Tocolíticos para retrasar el parto prematuro: un metanálisis en red
Resumen
Antecedentes
El parto prematuro es la principal causa de muerte de neonatos y niños. Los fármacos tocolíticos tienen como objetivo retrasar el parto prematuro reduciendo las contracciones uterinas para dar tiempo a la administración de corticosteroides para la maduración pulmonar del feto, sulfato de magnesio para la neuroprotección y al transporte a un centro con instalaciones de atención neonatal adecuadas. Sin embargo, sigue habiendo incertidumbre sobre su efectividad y seguridad.
Objetivos
Estimar la efectividad relativa y los perfiles de seguridad de las diferentes clases de fármacos tocolíticos para retrasar el parto prematuro, y proporcionar una clasificación de los fármacos disponibles.
Métodos de búsqueda
Se realizaron búsquedas en el Registro de ensayos del Grupo Cochrane de Embarazo y parto (Cochrane Pregnancy and Childbirth), en ClinicalTrials.gov (21 de abril de 2021) y en las listas de referencias de los estudios identificados.
Criterios de selección
Se incluyeron todos los ensayos controlados aleatorizados que evaluaron la efectividad o los efectos adversos de los fármacos tocolíticos para retrasar el parto prematuro. Se excluyeron los ensayos cuasialeatorizados y no aleatorizados. Todos los estudios se evaluaron según criterios predefinidos para valorar su fiabilidad.
Obtención y análisis de los datos
Al menos dos autores de la revisión evaluaron de forma independiente los ensayos en cuanto a la inclusión y el riesgo de sesgo, y extrajeron los datos. Se realizaron metanálisis pareados y en red para determinar los efectos relativos y establecer una clasificación de todos los tocolíticos disponibles. Se utilizó el método GRADE para calificar la certeza de las estimaciones del efecto del metanálisis en red para cada tocolítico versus placebo o ningún tratamiento.
Resultados principales
Este metanálisis en red incluye 122 ensayos (13 697 mujeres) con seis clases de tocolíticos, combinaciones de tocolíticos y placebo o ningún tratamiento. La mayoría de los ensayos incluyeron mujeres con embarazo único, de 24 a 34 semanas de gestación con riesgo de parto prematuro. Se consideró que 25 (20%) estudios tenían bajo riesgo de sesgo. En general, la certeza de la evidencia varió.
Los efectos relativos del metanálisis en red sugieren que todos los tocolíticos son probablemente eficaces para retrasar el parto prematuro en comparación con el placebo o ningún tratamiento tocolítico. Los betamiméticos son posiblemente eficaces para retrasar el parto prematuro por 48 horas (razón de riesgos [RR] 1,12; intervalo de confianza [IC] del 95%: 1,05 a 1,20; evidencia de certeza baja) y siete días (RR 1,14; IC del 95%: 1,03 a 1,25; evidencia de certeza baja). Los inhibidores de la COX posiblemente sean eficaces para retrasar 48 horas el parto prematuro (RR 1,11; IC del 95%: 1,01 a 1,23; evidencia de certeza baja). Los bloqueadores de los canales de calcio posiblemente sean eficaces para retrasar 48 horas el parto prematuro (RR 1,16; IC del 95%: 1,07 a 1,24; evidencia de certeza baja), probablemente sean eficaces para retrasar siete días el parto prematuro (RR 1,15; IC del 95%: 1,04 a 1,27; evidencia de certeza moderada) y prolongan el embarazo cinco días (0,1 más a 9,2 más; evidencia de certeza alta). Es probable que el sulfato de magnesio sea eficaz para retrasar el parto prematuro por 48 horas (RR 1,12; IC del 95%: 1,02 a 1,23; evidencia de certeza moderada). Los antagonistas de los receptores de oxitocina probablemente sean eficaces para retrasar 48 horas el parto prematuro (RR 1,13; IC del 95%: 1,05 a 1,22; evidencia de certeza moderada), son eficaces para retrasar siete días el parto prematuro (RR 1,18; IC del 95%: 1,07 a 1,30; evidencia de certeza alta) y posiblemente prolonguen el embarazo diez días (IC del 95%: 2,3 más a 16,7 más). Los donantes de óxido nítrico probablemente son eficaces para retrasar el parto prematuro por 48 horas (RR 1,17; IC del 95%: 1,05 a 1,31; evidencia de certeza moderada) y siete días (RR 1,18; IC del 95%: 1,02 a 1,37; evidencia de certeza moderada). Es probable que las combinaciones de tocolíticos sean eficaces para retrasar el parto prematuro por 48 horas (RR 1,17; IC del 95%: 1,07 a 1,27; evidencia de certeza baja) y siete días (RR 1,19; IC del 95%: 1,05 a 1,34; evidencia de certeza moderada).
Los donantes de óxido nítrico se situaron el primer puesto en cuanto al retraso del parto prematuro por 48 horas y siete días, y en el retraso del parto (desenlace continuo), seguidos de los bloqueadores de los canales de calcio, los antagonistas de los receptores de oxitocina y las combinaciones de tocolíticos.
Los betamiméticos (RR 14,4; IC del 95%: 6,11 a 34,1; evidencia de certeza moderada), los bloqueadores de los canales de calcio (RR 2,96; IC del 95%: 1,23 a 7,11; evidencia de certeza moderada), el sulfato de magnesio (RR 3,90; IC del 95%: 1,09 a 13,93; evidencia de certeza moderada) y las combinaciones de tocolíticos (RR 6,87; IC del 95%: 2,08 a 22,7; evidencia de certeza baja) probablemente sean más propensos a provocar la interrupción del tratamiento.
Los bloqueadores de los canales de calcio posiblemente reduzcan el riesgo de morbilidad del neurodesarrollo (RR 0,51; IC del 95%: 0,30 a 0,85; evidencia de certeza baja) y la morbilidad respiratoria (RR 0,68; IC del 95%: 0,53 a 0,88; evidencia de certeza baja), y den lugar a un menor número de neonatos con un peso al nacer inferior a 2000 g (RR 0,49; IC del 95%: 0,28 a 0,87; evidencia de certeza baja). Los donantes de óxido nítrico posiblemente den lugar a neonatos con mayor peso al nacer (diferencia de medias [DM] 425,53 g más; IC del 95%: 224,32 más a 626,74 más; evidencia de certeza baja), menos neonatos con peso al nacer inferior a 2500 g (RR 0,40; IC del 95%: 0,24 a 0,69; evidencia de certeza baja) y una edad gestacional más avanzada (DM 1,35 semanas más; IC del 95%: 0,37 más a 2,32 más; evidencia de certeza baja). Las combinaciones de tocolíticos posiblemente den lugar a un menor número de neonatos con un peso al nacer inferior a 2500 g (RR 0,74; IC del 95%: 0,59 a 0,93; evidencia de certeza baja).
En cuanto a los efectos adversos maternos, los betamiméticos probablemente causen disnea (RR 12,09; IC del 95%: 4,66 a 31,39; evidencia de certeza moderada), palpitaciones (RR 7,39; IC del 95%: 3,83 a 14,24; evidencia de certeza moderada), vómitos (RR 1.91; IC del 95%: 1,25 a 2,91; evidencia de certeza moderada) y posiblemente causen cefalea (RR 1,91; IC del 95%: 1,07 a 3,42; evidencia de certeza baja) y taquicardia (RR 3,01; IC del 95%: 1,17 a 7,71; evidencia de certeza baja) en comparación con el placebo o ningún tratamiento. Los inhibidores de la COX podrían provocar vómitos (RR 2,54; IC del 95%: 1,18 a 5,48; evidencia de certeza baja). Los bloqueadores de los canales de calcio (RR 2,59; IC del 95%: 1,39 a 4,83; evidencia de certeza baja) y los donantes de óxido nítrico probablemente causen cefalea (RR 4,20; IC del 95%: 2,13 a 8,25; evidencia de certeza moderada).
Conclusiones de los autores
En comparación con el placebo o ningún tratamiento tocolítico, todas las clases de fármacos tocolíticos que se evaluaron (betamiméticos, bloqueadores de los canales de calcio, sulfato de magnesio, antagonistas de los receptores de oxitocina, donantes de óxido nítrico) y sus combinaciones, fueron probable o posiblemente eficaces para retrasar el parto prematuro por 48 horas y siete días. Los fármacos tocolíticos se asociaron a una serie de efectos adversos (de leves a potencialmente graves) en comparación con el placebo o ningún tratamiento tocolítico, aunque los betamiméticos y los tocolíticos combinados tuvieron más probabilidades de provocar la interrupción del tratamiento. Los efectos del uso de tocolíticos en los desenlaces neonatales, como la mortalidad neonatal y perinatal, y en los desenlaces de seguridad, como la infección materna y neonatal, fueron inciertos.
PICOs
Resumen en términos sencillos
¿Los medicamentos que retrasan el inicio del trabajo de parto (tocolíticos) son eficaces para retrasar el parto prematuro?
Mensajes clave
• Todos los tocolíticos que se evaluaron (betamiméticos, bloqueadores de los canales de calcio, sulfato de magnesio, antagonistas de los receptores de oxitocina, donantes de óxido nítrico) y sus combinaciones, fueron probable o posiblemente eficaces para retrasar el parto prematuro por 48 horas y siete días, en comparación con el placebo (un tratamiento ficticio) o ningún tratamiento tocolítico.
• Los tocolíticos provocan una amplia gama de efectos no deseados (de leves a potencialmente graves) en comparación con el placebo o ningún tratamiento tocolítico. Las mujeres que tomaron betamiméticos y combinaciones de tocolíticos fueron más propensas a dejar de tomarlos como resultado de los efectos no deseados.
• Los efectos de los tocolíticos sobre la mortalidad de los niños antes y después del nacimiento, y en la infección de las madres y los niños no estuvieron claros.
¿Cuál es el problema?
El nacimiento prematuro es el motivo más frecuente por el que un recién nacido podría morir, y es la principal causa de muerte en niños menores de cinco años. El nacimiento pretérmino (o prematuro) se define como el nacimiento de un niño antes de las 37 semanas completas de embarazo. Cuanto más temprano se produzca el nacimiento, peor es el desenlace. Los recién nacidos prematuros no solo corren un mayor riesgo de morir, sino también de sufrir enfermedades graves. Son más propensos a sufrir complicaciones respiratorias, dificultades en la alimentación y en la regulación de la temperatura corporal. Las complicaciones a largo plazo incluyen la discapacidad asociada a la función cerebral y las complicaciones pulmonares e intestinales.
¿Por qué es esto importante?
El objetivo de los tocolíticos es retrasar el parto prematuro y dar tiempo a que las mujeres reciban medicamentos que puedan ayudar a la respiración y la alimentación del recién nacido si nace prematuro, y medicamentos que reducen la posibilidad de que el recién nacido presente parálisis cerebral. Lo más importante es que un breve retraso en el parto pretérmino puede permitir que las mujeres lleguen a recibir atención especializada. El objetivo de esta revisión Cochrane fue averiguar qué tocolítico es más eficaz para retrasar el parto pretérmino y tiene el menor número de efectos no deseados. Se recopilaron y analizaron todos los estudios para responder esta pregunta (fecha de la búsqueda: 21 de abril de 2021).
¿Qué evidencia se encontró?
Se buscaron pruebas y se identificaron 122 estudios con 13 697 mujeres que incluían seis clases de tocolíticos (betamiméticos, inhibidores de la COX, bloqueadores de los canales de calcio, sulfato de magnesio, antagonistas de los receptores de oxitocina y donantes de óxido nítrico), combinaciones de tocolíticos y placebo o ningún tratamiento tocolítico. De los 122 estudios, se consideró que 25 (20%) proporcionaron las pruebas más fiables. En general, la calidad de las pruebas fue muy diversa y la confianza en los resultados varió entre muy baja y alta. Se compararon los diferentes tocolíticos entre sí, así como con el placebo o ningún tratamiento.
Retraso en el parto por 48 horas y siete días
• Los betamiméticos podrían ser eficaces para retrasar el parto prematuro por 48 horas (9853 mujeres) y siete días (7143 mujeres).
• Los bloqueadores de los canales de calcio podrían ser eficaces para retrasar el parto prematuro por 48 horas y probablemente para retrasar el parto prematuro por siete días.
• El sulfato de magnesio podría ser eficaz para retrasar el parto prematuro por 48 horas.
• Los antagonistas de los receptores de oxitocina son eficaces para retrasar el parto prematuro por siete días, podrían ser eficaces para retrasar el parto por 48 horas y, posiblemente, provocan la prolongación del embarazo en una media de diez días (5093 mujeres).
• Los donantes de óxido nítrico podrían ser eficaces para retrasar el parto prematuro por 48 horas y siete días.
• Los inhibidores de la COX podrían ser eficaces para retrasar el parto prematuro por 48 horas.
• Las combinaciones de tocolíticos (más comúnmente el sulfato de magnesio combinado con betamiméticos) podrían ser eficaces para retrasar el parto prematuro por 48 horas y siete días.
• Los tocolíticos más eficaces para retrasar el parto prematuro por 48 horas y siete días fueron los donantes de óxido nítrico, los bloqueadores de los canales de calcio, los antagonistas de los receptores de oxitocina y las combinaciones de tocolíticos.
Efectos no deseados graves e interrupción del tratamiento debido a los efectos no deseados
• Los tocolíticos se asocian con un amplio abanico de efectos no deseados graves (6983 mujeres) en comparación con el placebo o ningún tratamiento.
• Los betamiméticos y las combinaciones de tocolíticos fueron los que causaron más efectos no deseados, lo que llevó a la mayoría de las mujeres a interrumpir el tratamiento.
• Los tocolíticos se asocian con un amplio abanico de efectos del tratamiento en comparación con el placebo o ningún tratamiento tocolítico con respecto a la muerte neonatal a los 28 días (8395 recién nacidos) y la infección materna (1399 mujeres); por lo que sus efectos fueron inciertos.
Authors' conclusions
Summary of findings
| Delay in birth by 48 hours | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.27 (1.11 to 1.45) | ⊕⊕⊕⊖ Moderatea | 1.04 (0.96 to 1.12) | ⊕⊕⊖⊖ Lowb | 1.12 (1.05 to 1.20) | ⊕⊕⊖⊖ Lowc | 645 per 1000 | 722 per 1000 | 77 more per 1000 (from 32 to 129 more) |
| COX inhibitors | 2.02 (0.81 to 5.08 | ⊕⊖⊖⊖ Very lowd | 1.10 (0.98 to 1.23) | ⊕⊖⊖⊖ Very lowe | 1.11 (1.01 to 1.23) | ⊕⊕⊖⊖ Lowf | 645 per 1000 | 716 per 1000 | 71 more per 1000 (from 6 to 148 more) |
| Calcium channel blockers | 1.87 (1.06 to 3.28) | ⊕⊕⊖⊖ Lowg | 1.17 (1.08 to 1.26) | ⊕⊕⊖⊖ Lowb | 1.16 (1.07 to 1.24) | ⊕⊕⊖⊖ Lowh | 645 per 1000 | 748 per 1000 | 103 per 1000 (from 45 to 155 more) |
| Magnesium sulphate | 1.06 (0.88 to 1.29) | ⊕⊕⊖⊖ Lowi | 1.14 (1.02 to 1.28) | ⊕⊖⊖⊖ Very lowe | 1.12 (1.02 to 1.23) | ⊕⊕⊕⊖ Moderatej | 645 per 1000 | 722 per 1000 | 77 more per 1000 (from 13 to 148 more) |
| Oxytocin receptor antagonists | 1.07 (0.91 to 1.27) | ⊕⊕⊖⊖ Lowk | 1.17 (1.06 to 1.29) | ⊕⊕⊕⊖ Moderatel | 1.13 (1.05 to 1.22) | ⊕⊕⊕⊖ Moderatem | 645 per 1000 | 729 per 1000 | 84 more per 1000 (from 32 to 142 more) |
| Nitric oxide donors | 1.18 (0.76 to 1.84 | ⊕⊕⊖⊖ Lown | 1.20 (1.06 to 1.36) | ⊕⊕⊕⊖ Moderatel | 1.17 (1.05 to 1.31) | ⊕⊕⊕⊖ Moderatem | 645 per 1000 | 755 per 1000 | 110 per 1000 (from 32 to 200 more) |
| Combinations of tocolytics | 1.05 (0.84 to 1.31) | ⊕⊖⊖⊖ Very lowo | 1.18 (1.08 to 1.30) | ⊕⊕⊕⊖ Moderatel | 1.17 (1.07 to 1.27) | ⊕⊕⊕⊖ Moderatem | 645 per 1000 | 755 per 1000 | 110 per 1000 (from 45 to 174 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded once due to multiple limitations in trial design. | |||||||||
| Delay in birth by 7 days | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.47 (1.09 to 1.97) | ⊕⊕⊕⊖ Moderatea | 1.07 (0.96 to 1.20) | ⊕⊕⊖⊖ Lowb | 1.14 (1.03 to 1.25) | ⊕⊕⊖⊖ Lowc | 742 per 1000 | 846 per 1000 | 104 more per 1000 (from 22 to 186 more) |
| COX inhibitors | 2.05 (0.41 to 10.33) | ⊕⊕⊖⊖ Lowd | 1.01 (0.84 to 1.21) | ⊕⊖⊖⊖ Very lowe | 1.04 (0.88 to 1.24) | ⊕⊕⊕⊖ Moderatef | 742 per 1000 | 772 per 1000 | 30 more per 1000 (from 89 fewer to 178 more) |
| Calcium channel blockers | 1.25 (0.86 to 1.82) | ⊕⊕⊖⊖ Lowg | 1.22 (1.10 to 1.36) | ⊕⊕⊕⊖ Moderateh | 1.15 (1.04 to 1.27) | ⊕⊕⊕⊖ Moderatei | 742 per 1000 | 853 per 1000 | 111 per 1000 (from 30 to 200 more) |
| Magnesium sulphate | 0.82 (0.63 to 1.08) | ⊕⊖⊖⊖ Very lowj | 0.99 (0.75 to 1.30) | ⊕⊖⊖⊖ Very lowe | 0.91 (0.74 to 1.12) | ⊕⊖⊖⊖ Very lowk | 742 per 1000 | 675 per 1000 | 67 fewer per 1000 (from 193 fewer to 89 more) |
| Oxytocin receptor antagonists | 1.23 (1.11 to 1.37) | ⊕⊕⊕⊕ High | 1.14 (0.99 to 1.30) | ⊕⊕⊖⊖ Lowl | 1.18 (1.07 to 1.30) | ⊕⊕⊕⊕ High | 742 per 1000 | 876 per 1000 | 134 more per 1000 (from 52 to 223 more) |
| Nitric oxide donors | No estimate possible | Not applicable | 1.18 (1.02 to 1.37) | ⊕⊕⊕⊖ Moderateh | 1.18 (1.02 to 1.37) | ⊕⊕⊕⊖ Moderatei | 742 per 1000 | 876 per 1000 | 134 per 1000 (from 15 to 275 more) |
| Combinations of tocolytics | 0.92 (0.67 to 1.28) | ⊕⊖⊖⊖ Very lowj | 1.22 (1.07 to 1.40) | ⊕⊕⊕⊖ Moderateh | 1.19 (1.05 to 1.34) | ⊕⊕⊕⊖ Moderatei | 742 per 1000 | 883 per 1000 | 141 per 1000 (from 37 to 252 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded once due to multiple limitations in trial design. | |||||||||
| Neonatal death before 28 days | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 0.94 (0.56 to 1.59) | ⊕⊕⊖⊖ Lowa | 1.46 (0.56 to 3.79) | ⊕⊖⊖⊖ Very lowb | 1.01 (0.66 to 1.55) | ⊕⊕⊖⊖ Lowc | 66 per 1000 | 67 per 1000 | 1 more per 1000 (from 22 fewer to 36 more) |
| COX inhibitors | 0.77 (0.22 to 2.72) | ⊕⊕⊖⊖ Lowd | 1.42 (0.53 to 3.81) | ⊕⊖⊖⊖ Very lowb | 1.12 (0.51 to 2.45) | ⊕⊕⊖⊖ Lowc | 66 per 1000 | 74 per 1000 | 8 more per 1000 (from 32 fewer to 96 more) |
| Calcium channel blockers | 5.18 (0.26 to 103.15) | ⊕⊖⊖⊖ Very lowe | 0.77 (0.40 to 1.47) | ⊕⊕⊖⊖ Lowf | 0.84 (0.44 to 1.57) | ⊕⊕⊖⊖ Lowg | 66 per 1000 | 55 per 1000 | 11 fewer per 1000 (from 37 fewer to 38 more) |
| Magnesium sulphate | 0.89 (0.15 to 5.09) | ⊕⊖⊖⊖ Very lowe | 1.75 (0.61 to 4.99) | ⊕⊖⊖⊖ Very lowb | 1.19 (0.55 to 2.58) | ⊕⊖⊖⊖ Very lowh | 66 per 1000 | 79 per 1000 | 13 more per 1000 (from 30 fewer to 104 more) |
| Oxytocin receptor antagonists | 4.10 (0.88 to 19.13) | ⊕⊕⊖⊖ Lowd | 0.60 (0.21 to 1.68) | ⊕⊖⊖⊖ Very lowb | 1.08 (0.46 to 2.56) | ⊕⊖⊖⊖ Very lowi | 66 per 1000 | 71 per 1000 | 5 more per 1000 (from 36 fewer to 103 more) |
| Nitric oxide donors | 0.49 (0.07 to 3.64) | ⊕⊕⊖⊖ Lowd | 0.79 (0.15 to 4.29) | ⊕⊖⊖⊖ Very lowb | 0.65 (0.18 to 2.36) | ⊕⊕⊖⊖ Lowc | 66 per 1000 | 43 per 1000 | 23 fewer per 1000 (from 54 fewer to 90 more) |
| Combinations of tocolytics | Not estimable | Not applicable | 0.55 (0.18 to 1.66) | ⊕⊖⊖⊖ Very lowb | 0.55 (0.18 to 1.66) | ⊕⊖⊖⊖ Very lowj | 66 per 1000 | 36 per 1000 | 30 fewer per 1000 (from 54 fewer to 44 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded twice due to multiple limitations in trial design and serious imprecision. | |||||||||
| Pregnancy prolongation (time from trial entry to birth in days) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.86 (−2.24 to 5.95) | ⊕⊕⊖⊖ Lowa | −0.10 (−6.18 to 5.98) | ⊕⊕⊕⊖ Moderateb | 0.83 (−3.12 to 4.78) | ⊕⊕⊕⊖ Moderatec | 20 days more | 21 days more | 1 day more (from 3 days fewer to 5 days more ) |
| COX inhibitors | −0.30 (−6.32 to 5.72) | ⊕⊕⊖⊖ Lowd | 5.45 (−4.35 to 15.24) | ⊕⊖⊖⊖ Very lowe | 3.31 (−4.41 to 11.03) | ⊕⊕⊖⊖ Lowf | 20 days more | 23 days more | 3 days more (from 4 days fewer to 11 days more) |
| Calcium channel blockers | 4.71 (0.32 to 9.10) | ⊕⊕⊕⊖ Moderateg | 4.72 (−0.59 to 10.02) | ⊕⊕⊖⊖ Lowh | 4.66 (0.13 to 9.19) | ⊕⊕⊕⊕ Highi | 20 days more | 25 days more | 5 days more (from 0 days to 9 days more) |
| Magnesium sulphate | 0.33 (−3.39 to 4.04) | ⊕⊖⊖⊖ Very lowj | 0.09 (−8.11 to 8.29) | ⊕⊖⊖⊖ Very lowk | 0.34 (−5.01 to 5.69) | ⊕⊖⊖⊖ Very lowl | 20 days more | 20 days more | 0 days (from 5 days fewer to 6 days more) |
| Oxytocin receptor antagonists | Not estimable | Not applicable | 9.54 (2.35 to 16.73) | ⊕⊕⊖⊖ Lowh | 9.54 (2.35 to 16.73) | ⊕⊕⊖⊖ Lowm | 20 days more | 30 days more | 10 days more (from 2 days more to 17 days more) |
| Nitric oxide donors | 11.91 (3.53 to 20.28) | ⊕⊕⊕⊖ Moderateg | 3.94 (−6.13 to 14.01) |
⊕⊕⊖⊖ Lowh | 7.44 (−0.44 to 15.32) | ⊕⊕⊕⊖ Moderaten | 20 days more | 27 days more | 7 days more (from 0 days to 15 days more) |
| Combinations of tocolytics | −6.10 (−13.54 to 1.34) | ⊕⊖⊖⊖ Very lowj | 4.30 (−3.56 to 12.16) | ⊕⊖⊖⊖ Very lowe | 1.55 (−5.31 to 8.40) | ⊕⊖⊖⊖ Very lowl | 20 days more | 22 days more | 2 days more (from 5 days fewer to 8 days more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded twice due to multiple limitations in trial design and serious imprecision. | |||||||||
| Serious adverse effects of drugs | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | We do not present summaries of relative and absolute effects because of high risk of bias, heterogeneous definitions, and serious imprecision.
| ||||||||
| COX inhibitors | |||||||||
| Calcium channel blockers | |||||||||
| Magnesium sulphate | |||||||||
| Oxytocin receptor antagonists | |||||||||
| Nitric oxide donors | |||||||||
| Combinations of tocolytics | |||||||||
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| Maternal infection | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.44 (0.82 to 2.51 | ⊕⊖⊖⊖ Very lowa | 33.26 (0.02 to 62,648.30) | ⊕⊖⊖⊖ Very lowb | 1.52 (0.76 to 3.02) | ⊕⊖⊖⊖ Very lowc | 290 per 1000 | 441 per 1000 | 151 more per 1000 (from 70 fewer to 586 more) |
| COX inhibitors | 1.46 (0.64 to 3.34) | ⊕⊕⊖⊖ Lowd | 0.32 (0.01 to 12.79) | ⊕⊖⊖⊖ Very lowb | 1.37 (0.51 to 3.69) | ⊕⊕⊖⊖ Lowe | 290 per 1000 | 397 per 1000 | 107 more per 1000 (from 142 fewer to 780 more) |
| Calcium channel blockers | Not estimable | Not applicable | 6.74 (0.29 to 155.05) | ⊕⊖⊖⊖ Very lowb | 6.74 (0.29 to 155.05) | ⊕⊖⊖⊖ Very lowf | 290 per 1000 | 1000 per 1000 | 710 more per 1000 (from 206 fewer to 1000 more) |
| Magnesium sulphate | 2.38 (0.24 to 23.84) | ⊕⊖⊖⊖ Very lowa | 0.76 (0.06 to 8.84) | ⊕⊖⊖⊖ Very lowb | 1.16 (0.24 to 5.60) | ⊕⊖⊖⊖ Very lowc | 290 per 1000 | 336 per 1000 | 46 more per 1000 (from 220 fewer to 1000 more) |
| Oxytocin receptor antagonists | Not estimable | Not applicable | 1.09 (0.02 to 50.70) | ⊕⊖⊖⊖ Very lowb | 1.09 (0.02 to 50.70) | ⊕⊖⊖⊖ Very lowf | 290 per 1000 | 316 per 1000 | 26 more per 1000 (from 284 fewer to 1000 more) |
| Nitric oxide donors | Not estimableg | Not applicableg | Not estimableg | Not applicableg | Not estimableg | Not applicableg | Not estimableg | ||
| Combinations of tocolytics | Not estimable | Not applicable | 1.31 (0.16 to 10.71) | ⊕⊖⊖⊖ Very lowb | 1.31 (0.16 to 10.71) | ⊕⊖⊖⊖ Very lowf | 290 per 1000 | 380 per 1000 | 90 more per 1000 (from 244 fewer to 1000 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded three times due to multiple limitations in trial design and very serious imprecision. | |||||||||
| Cessation of treatment due to adverse effects | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 9.62 (4.33 to 21.36) | ⊕⊕⊕⊖ Moderatea | 20.49 (6.29 to 66.76) | ⊕⊕⊖⊖ Lowb | 14.44 (6.11 to 34.11) | ⊕⊕⊕⊖ Moderatec | 108 per 1000 | 1000 per 1000 | 892 more per 1000 (from 552 more to 1000 more) |
| COX inhibitors | Not estimable | Not applicable | 2.34 (0.50 to 10.97) | ⊕⊖⊖⊖ Very lowd | 2.34 (0.50 to 10.97) | ⊕⊖⊖⊖ Very lowe | 108 per 1000 | 253 per 1000 | 145 more per 1000 (from 54 fewer to 1000 more) |
| Calcium channel blockers | 1.13 (0.67 to 1.88) | ⊕⊕⊖⊖ Lowf | 4.54 (1.51 to 13.63) | ⊕⊕⊕⊖ Moderateg | 2.96 (1.23 to 7.11) | ⊕⊕⊕⊖ Moderateh | 108 per 1000 | 320 per 1000 | 212 more per 1000 (from 25 to 660 more) |
| Magnesium sulphate | 9.82 (1.25 to 77.31) | ⊕⊕⊖⊖ Lowi | 2.99 (0.58 to 15.48) | ⊕⊖⊖⊖ Very lowd | 3.90 (1.09 to 13.93) | ⊕⊕⊕⊖ Moderatej | 108 per 1000 | 421 per 1000 | 313 more per 1000 (from 10 more to 1000 more) |
| Oxytocin receptor antagonists | 4.02 (2.05 to 7.85) | ⊕⊕⊕⊕ High | 0.63 (0.21 to 1.90) | ⊕⊕⊕⊖ Moderateg | 1.24 (0.46 to 3.35) | ⊕⊕⊕⊖ Moderatek | 108 per 1000 | 134 per 1000 | 26 more per 1000 (from 58 fewer to 254 more) |
| Nitric oxide donors | Not estimable | Not applicable | 4.31 (0.90 to 20.67) | ⊕⊖⊖⊖ Very lowd | 4.31 (0.90 to 20.67) | ⊕⊖⊖⊖ Very lowe | 108 per 1000 | 465 per 1000 | 357 more per 1000 (from 11 fewer to 1000 more) |
| Combinations of tocolytics | Not estimable | Not applicable | 6.87 (2.08 to 22.65) | ⊕⊕⊖⊖ Lowl | 6.87 (2.08 to 22.65) | ⊕⊕⊖⊖ Lowm | 108 per 1000 | 742 per 1000 | 634 more per 1000 (from 117 to 1000 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded once due to multiple limitations in trial design. | |||||||||
Background
Description of the condition
In 2019, five million children under five years of age died. Almost half of these deaths occurred in the first month of life (UNIGME 2020). Preterm birth is the most important contributing factor for high newborn death rates, and is the leading cause of death in children under five (Liu 2016). Preterm birth (previously called premature birth) is defined as birth before 37 completed weeks of pregnancy. In addition to altering the survival chances of newborns, preterm birth also causes significant morbidity. Preterm infants are at increased risk of short‐term complications such as breathing complications and difficulties with feeding and body temperature regulation, and long‐term complications including neurodevelopmental, respiratory, and gastrointestinal complications (Escobar 2006; Kinney 2006; Wang 2004). Despite advances in medicine, the number of preterm births appears to be rising in most countries (WHO 2018).
The multifactorial aetiology of preterm birth means that it is difficult to predict and prevent. Several risk factors have been identified, including multiple pregnancy, infection, maternal medical conditions, and previous history of miscarriage and preterm birth (Blondel 2006; Lee 2008). Preterm birth can either be spontaneous (occurring without medical intervention) or iatrogenic (when the pregnancy is interrupted with medical intervention). The cause of spontaneous preterm labour often remains uncertain (Menon 2008). Iatrogenic preterm birth occurs only in cases where the continuation of the pregnancy poses greater risks to the mother or the fetus (or both), and its prevention should focus on preventing contributing conditions such as pre‐eclampsia (Kalra 2008; Mukhopadhaya 2007).
Description of the intervention
Tocolytic drugs have been used for delaying preterm birth since the 1950s. Tocolytic drugs aim to delay preterm birth by suppressing uterine contractions. Specifically, they induce smooth muscle relaxation by engaging slightly different mechanisms of action, and as a result each has different adverse effects and different administration challenges. Even within individual drug classes there is significant variation in administration regimens. There are many different types of tocolytic drugs, however most fall within the following tocolytic drug classes.
-
Betamimetics (e.g. ritodrine)
-
Calcium channel blockers (e.g. nifedipine)
-
Magnesium sulphate
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Oxytocin receptor antagonists (e.g. atosiban)
-
Nitric oxide donors (e.g. glyceryl trinitrate)
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Cyclo‐oxygenase (COX) inhibitors (e.g. indomethacin)
-
Combinations of tocolytics (e.g. betamimetics plus magnesium sulphate)
Betamimetics (e.g. ritodrine, terbutaline, and salbutamol) have been widely used, especially in resource‐poor countries. Betamimetics are beta receptor agonists mimicking the actions of both adrenaline ‐ and noradrenalise ‐, in the heart and lungs, and in smooth muscle tissue. Their use has declined over time due to their adverse effects (NICE 2015). They can cause heart palpitations, tremor, nausea, vomiting, headaches, nervousness, anxiety, chest pain, shortness of breath, and biochemical disturbances such as hyperglycaemia. Rarely, they can cause heart failure and pulmonary oedema (Medicines.org.uk 2020). Betamimetics cross the placenta and cause fetal tachycardia and neonatal hypoglycaemia (Medicines.org.uk 2020). They can be administered orally, subcutaneously, intramuscularly, and intravenously.
Calcium channel blockers (e.g. nifedipine, nicardipine) are used for the treatment of hypertension in pregnancy, and are increasingly also used as tocolytic drugs. Calcium channel blockers are administered orally. They are generally tolerated but are associated with cardiovascular adverse effects, such as headache, hypotension, dyspnoea, pulmonary oedema, and even myocardial infarction (Medicines.org.uk 2020).
Magnesium sulphate is used widely in obstetrics for the prevention and treatment of eclampsia. It is also an established fetal neuroprotective drug, and is recommended for women at risk of imminent preterm birth for the prevention of cerebral palsy in infants and children (WHO 2015). It can also be used as a tocolytic drug as it decreases the frequency of depolarisation of smooth muscle, which in turn inhibits uterine contractions. Magnesium sulphate can be administered intravenously or intramuscularly. In current clinical practice, intramuscular administration regimens are recommended only if intravenous access is not possible. Adverse effects are dose‐dependent and include nausea, vomiting, headache, heart palpitations, and, rarely, pulmonary oedema (Medicines.org.uk 2020). Concentrations above the recommended therapeutic range can lead to respiratory depression, respiratory arrest, and cardiac arrest (Crowther 2014).
Oxytocin receptor antagonists (e.g. atosiban) are the only drugs that have been purposefully developed to delay preterm birth. They block oxytocin receptors, and by blocking the action of oxytocin they are able to prevent uterine contractions and relax the uterus. They can only be administered intravenously, and are associated with adverse effects such as nausea, vomiting, headache, chest pain, and hypotension (Medicines.org.uk 2020). Important issues for consideration with oxytocin receptor antagonists are their cost and availability.
Nitric oxide donors (e.g. glyceryl trinitrate, isosorbide dinitrate) have also been used as tocolytic drugs. Nitric oxide is a free radical that induces smooth muscle relaxation, cervical ripening, and vasodilation. The effect of nitric oxide donors on the uterus is fast, which can be of great value in obstetric emergencies. They can be administered intravenously, transdermally or sublingually, and are typically associated with maternal adverse effects related to vasodilation, such as headache, flushing, hypotension and tachycardia (Duckitt 2014). Nitric oxide donors could adversely affect the developing fetus because they induce changes to the uterine blood flow (Duckitt 2014).
Cyclo‐oxygenase (COX) inhibitors (e.g. indomethacin) can easily be administered orally or rectally. They have a different adverse effect profile compared with betamimetics (Babay 1998). However, COX inhibitors easily cross the placenta and can interfere with the fetal prostaglandin homeostasis. A meta‐analysis published in 2006 found that even short‐term use of COX inhibitors in late gestations is associated with a 15‐fold increase of premature ductal closure (Koren 2006). Because of these concerns, COX inhibitors are currently contraindicated in the third trimester. In view of this contraindication, COX inhibitors are largely limited to use in the second trimester because of this effect.
Combinations of tocolytic drugs from different classes (e.g. betamimetics plus magnesium sulphate) have been used together to delay preterm birth. Using tocolytic drugs from different classes suppresses uterine contractions by targeting different pathways in the myometrium. Using a combination of tocolytic drugs could have the benefit of improving the desirable effects. A combination of tocolytic drug classes may mean also that a lower dose of the combination drugs could be used to achieve the desirable effect, resulting in fewer adverse effects.
How the intervention might work
Tocolytics can potentially delay preterm birth by suppressing uterine contractions (Haas 2009). The rationale for tocolysis is that the delay in preterm birth can allow time for administration of corticosteroids for fetal lung maturation, magnesium sulphate for neuroprotection, and time for the pregnant woman to be transported to a facility with appropriate neonatal care facilities.
Why it is important to do this review
With the increasing contribution of neonatal deaths to overall child mortality, it is critical to address the determinants of poor outcomes related to preterm birth to achieve further reductions in infant mortality. Infant mortality and morbidity can be reduced through interventions delivered to the mother before or during pregnancy, and to the infant after birth. The most beneficial set of maternal interventions are those that are aimed at improving outcomes for preterm infants when preterm birth is inevitable (e.g. antenatal corticosteroids, and magnesium sulphate; WHO 2015). The success of these interventions is dependent on appropriate timing. For example, corticosteroids are more beneficial when administered more than 24 hours before birth, but no more than seven days before birth; magnesium sulphate needs to be administered no more than 24 hours prior to birth; and transfer takes time to arrange. Therefore, once a diagnosis of preterm labour is made, prompt action is vital for maximising survival and reducing complications for the infant.
Tocolytics could potentially delay preterm birth, which in turn could enhance the beneficial effects of the interventions mentioned above. However, there is still uncertainty about whether they are effective in improving neonatal health outcomes. Current guidelines indicate inconsistencies; the World Health Organization (WHO) state that tocolytic drugs are not recommended for women at risk of imminent preterm birth for the purpose of improving neonatal outcomes (WHO 2015), while others suggest that tocolytic drugs should be offered. The evidence informing these guidelines was based on low‐certainty evidence from several individual Cochrane Reviews containing small‐ to medium‐sized trials (Bain 2013; Crowther 2014; Duckitt 2014; Flenady 2014a; Flenady 2014b; Neilson 2014; Reinebrant 2015; Su 2014).
The comparisons of interest for this review are those of tocolytic drugs versus placebo or no treatment with tocolytics, to determine if tocolytics are effective in delaying preterm birth and improving neonatal outcomes. The comparison of tocolytic drugs with each other is also of interest, for determining which tocolytic drug is the most effective. Where several competing drug options exist, not all of which have been directly compared, a network meta‐analysis may allow for more comparisons to be made and a more comprehensive synthesis of relative effects for all available tocolytic drugs (Caldwell 2005; Caldwell 2010). A network meta‐analysis, unlike conventional Cochrane Reviews, simultaneously pools all direct and indirect evidence into one single coherent analysis. Indirect evidence is obtained by inferring the relative effectiveness of two competing drugs through a common comparator, even when these two drugs have not been compared directly. A network meta‐analysis also calculates the probability for each competing drug to constitute the most effective drug with the fewest adverse effects, thereby allowing ranking of the available tocolytic drugs (Caldwell 2005).
Objectives
To estimate relative effectiveness and safety profiles for different classes of tocolytic drugs for delaying preterm birth, and provide rankings of the available drugs.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials or cluster‐randomised trials comparing tocolytic drugs with other tocolytic drugs, placebo or no treatment were eligible for inclusion. Cross‐over trials and quasi‐randomised trials were excluded. The cross‐over trial design is inappropriate to investigate the effectiveness of tocolytic drugs, and quasi‐randomisation rather than true randomisation introduces an elevated risk of bias that we wish to eliminate for the purpose of this review. Randomised trials published only as abstracts were eligible only if sufficient information could be retrieved.
Types of participants
This review included trials involving women with live fetus(es), with signs and symptoms of preterm labour, defined as uterine activity with or without ruptured membranes; or ruptured membranes with or without cervical dilatation or shortening, or biomarkers consistent with a high risk of preterm birth. We considered studies conducted in all settings.
Types of interventions
Trials were eligible if they administered tocolytic drugs of any dosage, route, or regimen for delaying preterm birth, and compared them with another tocolytic drug, placebo, or no treatment. We excluded trials that exclusively compared different dosages, routes or regimens of the same tocolytic drug. Eligible interventions include the tocolytic classes listed below.
-
Betamimetics (ritodrine, terbutaline, nylidrin, fenoterol, isoxsuprine salbutamol)
-
COX inhibitors (indomethacin, rofecoxib, celecoxib)
-
Calcium channel blockers (nifedipine, nicardipine)
-
Magnesium sulphate
-
Oxytocin receptor antagonists (atosiban, retosiban, barusiban)
-
Nitric oxide donors (isosorbide dinitrate, glyceryl trinitrate)
-
Combinations of tocolytics (betamimetics plus magnesium sulphate, betamimetic plus calcium channel blockers, COX inhibitors plus betamimetics, calcium channel blockers plus oxytocin antagonist receptors)
We grouped all tocolytic drugs from the same class in the same node regardless of dose, regime (bolus +/‐ maintenance) or route. We addressed the effect of regime (bolus +/‐ maintenance) through subgroup analyses. We would consider splitting the nodes if we found subgroup effects with a specific dose or route. There is no pre‐existing evidence that a specific dose or route is superior or inferior to another one.
Participants in the network could in principle be randomised to any of the tocolytic drugs being compared. We included trials in which adjuvant co‐interventions such as progesterone or cervical cerclage (inserting a stitch around the cervix) were administered in combination with tocolytic drugs; we tested the effects of such co‐interventions through sensitivity analyses. We have included information about co‐interventions aimed at improving maternal and neonatal status antenatally (corticosteroids, antibiotics, magnesium sulphate for neuroprotection, where documented within the included studies) in the Characteristics of included studies.
Types of outcome measures
Outcomes are based on WHO critical outcomes for preterm birth and include both neonatal and maternal outcomes (WHO 2015). Outcome measure time points were as reported in the primary studies.
Primary outcomes
The main (primary) outcomes are as follows. These outcomes feature in the summary of findings tables.
-
Delay in birth by 48 hours
-
Delay in birth by 7 days
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Neonatal death before 28 days
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Pregnancy prolongation (time from trial entry to birth)
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Serious adverse effects of drugs
-
Maternal infection after trial entry
-
Cessation of treatment due to adverse effects
Secondary outcomes
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Birth prior to 28 weeks of gestation
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Birth prior to 32weeks of gestation
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Birth prior to 34 weeks of gestation
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Birth prior to 37 weeks of gestation
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Maternal death
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Pulmonary oedema
-
Dyspnoea
-
Palpitation
-
Headaches
-
Nausea or vomiting
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Tachycardia
-
Maternal cardiac arrhythmias
-
Maternal hypotension
-
Perinatal mortality
-
Stillbirth
-
Neonatal death before 7 days
-
Neurodevelopmental morbidity
-
Gastrointestinal morbidity
-
Respiratory morbidity
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Mean birthweight
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Birthweight less than 2000 g
-
Birthweight less than 2500 g
-
Gestational age at birth
-
Neonatal infection
Search methods for identification of studies
Electronic searches
We searched Cochrane Pregnancy and Childbirth’s Trials Register by contacting their Information Specialist (21 April 2021).
Cochrane Pregnancy and Childbirth’s Trials Register is a database containing over 27,000 reports of controlled trials in the field of pregnancy and childbirth. It represents over 30 years of searching. For full current search methods used to populate Pregnancy and Childbirth’s Trials Register including the detailed search strategies for CENTRAL, MEDLINE, Embase and CINAHL; the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service, please follow this link.
Briefly, Cochrane Pregnancy and Childbirth’s Trials Register is maintained by their Information Specialist and contains trials identified from:
-
monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL), which contains Cochrane's centralised searches of WHO International Clinical Trials Registry Platform (ICTRP);
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weekly searches of MEDLINE (Ovid);
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weekly searches of Embase (Ovid);
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monthly searches of CINAHL (EBSCO);
-
handsearches of 30 journals and the proceedings of major conferences;
-
weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.
Two people screen the search results and review the full text of all relevant trial reports identified through the searching activities described above. Based on the intervention described, they assign each trial report a number that corresponds to a specific Pregnancy and Childbirth review topic (or topics), and it is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set that has been fully accounted for in the relevant review sections (Included studies, Excluded studies, Studies awaiting classification or Ongoing studies).
In addition, we searched ClinicalTrials.gov for unpublished, planned and ongoing trial reports (21 April 2021) using the search methods detailed in Appendix 1.
Searching other resources
We retrieved additional relevant references cited in papers identified through the above search strategy and we searched for the full texts of trials initially identified as abstracts. For randomised trials published only as abstracts, we sought information from primary authors to investigate whether these studies met our eligibility criteria before including them. Trials that compared at least two of the agents were eligible and we searched for all possible comparisons. We did not apply any language or date restrictions.
Data collection and analysis
Selection of studies
At least two review authors independently assessed for inclusion all the potential studies we identified as a result of the search strategy (AW, VAH, EJM, ADM, EL). We resolved any disagreement through discussion or, if required, we consulted a third person (KM or IG). We created a flow diagram to present the number of records identified, included and excluded (Liberati 2009; Figure 1).
Study flow diagram
Screening eligible studies for scientific integrity/trustworthiness
Two review authors evaluated all studies that met our inclusion criteria against predefined criteria to select studies that, based on available information, we deemed to be sufficiently trustworthy to be included in the analysis. These criteria are developed by Cochrane Pregnancy and Childbirth (see Appendix 2).
Where a trial is classified as being at ‘high risk’ for one or more of the predefined criteria, we attempted to contact the trial authors to address any possible lack of information and concerns. If adequate information remained unavailable, we categorised the trial as ‘awaiting classification’, and described the concerns and communications with the author (or lack thereof) in detail (Characteristics of studies awaiting classification). The process is described fully in Figure 2.
Process for using the Cochrane Pregnancy and Childbirth criteria for assessing the trustworthiness of a study
Data extraction and management
We extracted data from each eligible report using a pre‐designed form. For eligible studies, at least two review authors (AW, VAH, EJM, ADM, EL) independently extracted the data using the agreed form. We resolved discrepancies through discussion, or, if required, through consultation with a third person (KM or IG). We entered data into Review Manager 5 (Review Manager 2020), and checked them for accuracy. When information regarding any of the above was unclear, we attempted to contact authors of the original reports to provide further details.
Assessment of risk of bias in included studies
Two review authors (AW, VAH, EJM, ADM, EL) independently assessed risk of bias for each trial using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We resolved any disagreement by discussion or by involving a third assessor (KM or IG).
We made explicit judgements about whether studies are at high risk of bias, according to the criteria given in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We assessed the likely magnitude and direction of the bias and whether we considered it likely to impact on the findings. We explored the impact of the level of bias through undertaking sensitivity analyses (see Sensitivity analysis).
Measures of treatment effect
We summarised relative treatment effects for dichotomous outcomes as risk ratios (RR) and for continuous outcomes as mean difference (MD) with 95% confidence intervals (CI). These are summarised in forest plots displaying the results from pairwise, indirect and network (combining direct and indirect) analyses for the comparisons of tocolytic drugs versus placebo or no treatment and the comparisons of tocolytics with other tocolytic drugs.
Unit of analysis issues
Cluster‐randomised trials
We planned to include cluster‐randomised trials in the analyses along with individually randomised trials. We planned to adjust their sample sizes using the methods described in the Cochrane Handbook for Systematic Reviews of interventions (Higgins 2021), using an estimate of the intracluster correlation coefficient (ICC) derived from the trial (if possible), from a similar trial, or from a trial of a similar population. If we had used ICCs from other sources, we planned to report this and to conduct sensitivity analyses to investigate the effect of variation in the ICC. Had we identified both cluster‐randomised trials and individually randomised trials, we planned to synthesise the relevant information. In cluster‐randomised trials, particular biases to consider include: recruitment bias; baseline imbalance; loss of clusters; incorrect analysis; and comparability with individually randomised trials. We would have considered it reasonable to combine the results from both cluster‐randomised trials and individually randomised trials if there was little heterogeneity between the trial designs, and the interaction between the effect of intervention and the choice of randomisation unit was considered to be unlikely. We planned to also acknowledge heterogeneity in the randomisation unit and perform a sensitivity analysis to investigate the effects of the randomisation unit. We planned to include cluster‐randomised trials in the analyses along with individually‐randomised trials, but none were found.
Cross‐over trials
Cross‐over trials were not eligible for inclusion in this review.
Multi‐arm trials
We included multi‐arm trials and accounted for the correlation between the effect sizes in the network meta‐analysis. We treated multi‐arm studies as multiple independent comparisons in pairwise meta‐analyses.
Dealing with missing data
For included studies, we noted levels of attrition. We explored the impact of including studies with high levels of missing data (> 10%) in the overall assessment of treatment effect by using sensitivity analysis. We imputed missing standard deviations and errors using standard techniques where possible (Deeks 2021). For all outcomes, we performed analyses, as far as possible, on a modified intention‐to‐treat basis, that is, we attempted to include all participants randomised to each group in the analyses, and we analysed all participants in the group to which they were allocated, regardless of whether or not they received the allocated intervention. The denominator for each outcome in each trial was the number randomised minus any participants whose outcomes were known to be missing.
Assessment of heterogeneity
Assessment of clinical and methodological heterogeneity
To evaluate the presence of clinical heterogeneity, we examined trial and trial population characteristics across all eligible trials that compared each pair of interventions. We assessed the presence of clinical heterogeneity within each pairwise comparison by comparing these characteristics.
Assessment of transitivity across treatment comparisons
We assessed the assumption of transitivity by comparing the distribution of potential effect modifiers across the different pairwise comparisons. In this context we expect that the transitivity assumption will hold assuming the following:
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the common treatment used to compare different tocolytic drugs indirectly is similar when it appears in different trials (e.g. betamimetics are administered in a similar way in betamimetics versus magnesium sulphate trials and in betamimetics versus calcium channel blockers trials);
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all pairwise comparisons do not differ with respect to the distribution of effect modifiers (e.g. the design and trial characteristics of betamimetics versus magnesium sulphate trials are similar to betamimetics versus calcium channel blockers trials).
We evaluated the assumption of intransitivity epidemiologically by comparing the clinical and methodological characteristics of sets of studies from the various treatment comparisons.
Assessment of statistical heterogeneity and inconsistency
Assumptions when estimating heterogeneity
In standard pairwise meta‐analyses we estimated different heterogeneity variances for each pairwise comparison. In the network meta‐analysis, we assumed a common estimate for the heterogeneity variance across the different comparisons.
Measures and tests for heterogeneity
We assessed statistically the presence of heterogeneity within each pairwise comparison using the I² statistic and its 95% CI that measures the percentage of variability that cannot be attributed to random error (Higgins 2002). We based the assessment of statistical heterogeneity in the entire network on the magnitude of the heterogeneity variance parameter (Tau²) estimated from the network meta‐analysis models. For dichotomous outcomes we compared the magnitude of the heterogeneity variance with the empirical distribution as derived by Turner (Turner 2012). We also estimated a total I² statistic value for heterogeneity in the network as described elsewhere (Higgins 2002). We downgraded the certainty of the evidence for inconsistency where I² is greater than 60%.
Assessment of statistical inconsistency
We used global and local approaches to evaluate the statistical agreement between the various sources of evidence in a network of interventions (consistency) to complement the evaluation of transitivity. To evaluate the presence of inconsistency locally we used the loop‐specific approach. This method evaluates the consistency assumption in each closed loop of the network separately as the difference between direct and indirect estimates for a specific comparison in the loop (inconsistency factor). Then, the magnitude of the inconsistency factors and their 95% CIs can be used to infer the presence of inconsistency in each loop. We assumed a common heterogeneity estimate within each loop. To check the assumption of consistency in the entire network we used the 'design‐by‐treatment' model as described by Higgins and colleagues (Higgins 2012). This method accounts for different sources of inconsistency that can occur when studies with different designs (two‐arm trials versus three‐arm trials) give different results as well as disagreement between direct and indirect evidence. Using this approach we inferred the presence of inconsistency from any source in the entire network based on a Chi² test. We performed the design‐by‐treatment model in STATA using the mvmeta command (StataCorp 2019).
Assessment of reporting biases
We aimed to minimise the potential impact of reporting biases by ensuring a comprehensive search for eligible studies and by being alert to duplication of data. If there were 10 or more studies in any of the direct comparisons, we investigated reporting biases (such as publication bias) using funnel plots to explore the possibility of small‐study effects (a tendency for estimates of the intervention effect to be more beneficial in smaller studies) as part of the assessment of the certainty of the direct evidence.
Data synthesis
Methods for direct treatment comparisons
We performed standard pairwise meta‐analyses using a random‐effects model in Review Manager 5 (Review Manager 2020), for every treatment comparison for all outcomes (DerSimonian 1986). We used a random‐effects method for this analysis to mitigate for the high level of heterogeneity observed (DerSimonian 1986). This method incorporates an assumption that the different studies are estimating different, yet related, intervention effects. The standard errors of the trial‐specific estimates are therefore adjusted to incorporate a measure of the extent of heterogeneity. This results in wider confidence intervals in the presence of heterogeneity, and corresponding claims of statistical significance are more conservative.
Methods for indirect and network comparisons
We initially generated and assessed the network diagrams to determine if a network meta‐analysis was feasible. Then we performed the network meta‐analysis on all outcomes within a frequentist framework using multivariate meta‐analysis estimated by restricted maximum likelihood. We used Stata statistical software, release 17 (StataCorp, College Station, TX) to carry out all analyses. We used the network suite of Stata commands designed for this purpose (White 2015), and other Stata commands for visualising and reporting results in network meta‐analysis (Chaimani 2015).
Relative treatment ranking
We estimated the cumulative probabilities for each tocolytic class being at each possible rank and obtained a treatment hierarchy using the surface under the cumulative ranking curve (SUCRA); the larger the SUCRA the higher its rank among all available agents (Salanti 2011). The probabilities to rank the treatments are estimated under a Bayesian model with flat priors, assuming that the posterior distribution of the parameter estimates is approximated by a normal distribution with mean and variance equal to the frequentist estimates and variance‐covariance matrix. Rankings are constructed drawing 1000 samples from their approximate posterior density. For each draw, the linear predictor is evaluated for each trial, and the largest linear predictor is noted (White 2011).
Subgroup analysis and investigation of heterogeneity
For the primary outcomes we had planned to carry out the following prespecified subgroup analyses by using the following effect modifiers.
Population
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Gestational age at trial entry (fewer than 32 completed weeks versus 32 completed weeks or more)
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Status of amniotic membranes (women with ruptured membranes versus women with intact membranes)
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Number of fetuses (singleton versus multiple pregnancy)
Intervention
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Duration of tocolysis (acute suppression alone versus acute suppression plus long‐term maintenance)
Sensitivity analysis
For the primary outcomes we had planned to perform sensitivity analysis for the following.
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Risk of bias (restricted to studies with low risk of bias only): we planned to rank studies as low risk of bias if they were double‐blinded and had allocation concealment with little loss to follow‐up (less than 10%). We would consider protocol publication in advance of the results to be an unsuitable criterion for sensitivity analyses, because protocol publication only became widespread in recent years.
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Co‐intervention (we planned to remove trials where participants received co‐interventions such as progesterone)
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Choice of relative effect measure (risk ratio versus odds ratio)
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Use of fixed‐effect versus random‐effects model
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Randomisation unit (cluster versus individual)
In addition to the prespecified sensitivity analysis, we also carried out a post‐hoc sensitivity analysis by removing trials published before 1990.
We assessed differences by evaluating the relative effects and assessment of model fit.
Summary of findings and assessment of the certainty of the evidence
The summary of findings tables present evidence comparing all methods with a reference comparator, placebo or no tocolytic treatment. Each table describes key features of the evidence relating to a single outcome. There is a table for each primary outcome in accordance with the GRADE approach. These outcomes are:
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delay in birth by 48 hours;
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delay in birth by 7 days;
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neonatal death before 28 days;
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pregnancy prolongation (time from trial entry to birth in days);
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serious adverse effects of drugs;
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maternal infection; and
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cessation of treatment due to adverse effects.
We assessed the certainty of the evidence using the GRADE approach as outlined in the GRADE handbook in order to assess the certainty of the body of evidence relating to each outcome for all comparisons Schünemann 2013).
In order to create summary of findings tables, we used GRADEpro GDT to import data from Review Manager 5 (Review Manager 2020). We used the GRADE working group’s approach for rating the certainty of the network meta‐analysis effect estimates for all the comparisons and all outcomes (Brignardello‐Petersen 2018; Puhan 2014). We appraised the certainty of the direct, indirect, and network evidence sequentially (in this order).
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First, we assessed the certainty of the direct evidence (where available) for a given outcome, and rated the evidence using the standard GRADE approach based on consideration of: trial design limitations (risk of bias); inconsistency; imprecision; indirectness and publication bias (Schünemann 2021). For the outcomes where network meta‐analysis was possible, we display the certainty of the direct evidence in the network diagrams using a colour‐coded key (green lines for high‐certainty evidence; light green lines for moderate‐certainty evidence; orange lines for low‐certainty evidence and red lines for very low‐certainty evidence).
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Then we rated the certainty of the indirect evidence for the same given outcomes, based on the lower of the certainty ratings of the two direct arms forming the dominant ‘first‐order’ loop in the network diagram for this outcome.
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Our final step was to determine the certainty of network evidence based on:
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the higher certainty rating of the direct and indirect evidence;
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whether the relevant network exhibited ‘transitivity’, that is, whether all the comparisons contributing data to the estimate were directly consistent with the PICO question;
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consideration of coherence between direct and indirect effect estimates; and
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precision of the network effect estimate.
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At each of these stages, two review authors (AW, AP) independently appraised the certainty ratings for the direct, indirect and network evidence. We resolved disagreements between authors through discussion and consultation with a third review author (IG) where necessary. We rated the certainty of network evidence for each outcome as ‘high’, ‘moderate’, ‘low’ or ‘very low’ in accordance with the GRADE approach.
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High certainty: we are very confident that the true effect lies close to that of the effect.
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Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different.
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Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect.
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Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect.
For ease of comparison when interpreting the relative effects of all tocolytic drugs versus placebo or no treatment, the summary of findings tables include the effect estimate and certainty judgements for the direct evidence, the indirect evidence and the network meta‐analysis, describing all the findings for a single outcome in each table. We also include the anticipated absolute effects, based on the network effect estimate for each treatment intervention in comparison with placebo or no treatment. The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis.
Results
Description of studies
Results of the search
6The results of the search are summarised in the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) flow diagram (Liberati 2009; Figure 1). The search of Cochrane Pregnancy and Childbirth's (CPC) Trials Register on 21 April 2021 retrieved in total 696 available records. No further records from additional searches or manual searching of reference lists were obtained. We excluded eight records as duplicates and screened out 231 on title and abstract. We examined the full text of 457 records and included in the network meta‐analysis 122 randomised trials (196 reports; Characteristics of included studies). We contacted the authors from 46 references for additional data or clarifications. We were able to obtain additional data or clarifications from trial authors for two randomised trials (Ozhan Baykal 2015; Thornton 2015). We excluded 169 studies (186 reports) (Characteristics of excluded studies), 44 studies (56 reports) could not be classified (Characteristics of studies awaiting classification), and 17 studies (19 reports) were still ongoing (Characteristics of ongoing studies).
Screening eligible studies for trustworthiness
In 457 records identified from the search we judged that 45 trials did not meet our criteria for trustworthiness for the following reasons.
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Two studies were published only as trial registry entries and we have not been able to confirm with the trial authors that the data were from the final analyses (IRCT2015042621947N1; NCT00486824).
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We had concerns about the randomisation process in 32 studies, where there was no explanation for substantial imbalances between the numbers allocated to each group (Akhtar 2018; Ali 2013; Al Jawady 2020; Aziz 2018; Badshah 2019; Bina 2012; Chawanpaiboon 2011; Chawanpaiboon 2012; Eftekhari 2012; Esmaeilzadeh 2017; Faisal 2020; Faraji 2013; Ghomian 2015; Hamza 2016; Jamil 2020; Khooshideh 2017; Lotfalizadeh 2010; Madkour 2013; Mesdaghinia 2012; Mirteimoori 2009; Mirzamoradi 2014; Nikbakht 2014; Ozhan Baykal 2015; PriyadarshiniBai 2013; Saadati 2014; Sachan 2012; Shafaie 2014; Shirazi 2015; Toghroli 2020; Xu 2016; Yasmin 2016; Zangooei 2011).
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Six studies published since 2010 demonstrated no evidence of prospective registration (Caliskan 2015; Dhawle 2013; Nankali 2014; Nauman 2020; Songthamwat 2018; Tabassum 2016).
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We were unable to obtain translations for four studies (Kim 2001; Lee 2004; Song 2002a; Song 2002b)
In all cases we made every effort to contact the authors and either identified no contact details at all or the authors did not respond to our queries (see Studies awaiting classification).
Included studies
This review included 122 randomised trials, published between 1966 and 2021, involving 13,697 women. All trials were individually randomised; there were no cluster‐randomised trials. Most trials were two‐arm trials and we also included three, three‐arm trials. For the purposes of the network meta‐analysis, we combined multi‐arm trials that included arms with the same intervention. Most trials were reported in English (88%, 107/122); we obtained 16 translations (Amorim 2009; Aramayo 1990; Asgharnia 2002; Cabar 2008; Francioli 1988; Janky 1990; Kara 2009; Kose 1995; Matsuda 1993; Nonnenmacher 2009; Sakamoto 1985; Szulc 2000; Tohoku 1984; Wang 2000; Zhang 2002; Zhu 1996).
The trials were conducted across 39 countries (including high‐, middle‐ and low‐income countries). The median size of the trials was 80 participants (interquartile range (IQR) 50 to 120). Most were single‐centre trials (66%, 81/122); 41 were multi‐centre trials (34%, 41/122).
The dates in which the trials were conducted varied, with the earliest being conducted in 1965 (Adam 1966). Similar numbers of included trials were conducted across the 1980s, 1990s and 2000s. Fewer trials were conducted from 2010 onwards. Most trials did not report any conflicts of interests. Thirteen reported receiving support from the pharmaceutical industry (de Heus 2009; European Atosiban Study 2001; French and Australian Atosiban Investigators 2001; Goodwin 1994; Goodwin 1996; Leake 1983; Lees 1999; Romero 2000; Saade 2021; Shim 2006; Spellacy 1979; Thornton 2009; Thornton 2015). Many studies did not report the source of funding.
Typically studies recruited women from 24 weeks to 34 weeks of gestation (range from 20 to 36 weeks of gestation). Most studies (71%, 87/122) recruited women with intact membranes, seven studies (6%, 7/122) recruited women with ruptured membranes, 28 studies (23%) recruited a mixed population or did not clearly specify the population. Half of the studies recruited women with a singleton pregnancy (50%, 61/122), no studies recruited women with multiple pregnancies, and 61 studies (50%) recruited a mixed population or did not specify the population. Sixty‐seven studies (55%) administered tocolysis to suppress contractions in the acute phase of preterm labour, whereas 49 studies (40%) maintained tocolysis for more than 48 hours and, in the majority of cases, throughout the pregnancy. Six studies (5%) did not specify the duration of tocolysis. The majority of studies excluded women in advanced preterm labour, recruiting women less than 4 cm dilated.
Of the 122 included studies, 120 (98%) contributed data to the analysis, while two studies did not report any outcomes of interest to this review (de Heus 2009; Parsons 1987).
The 122 trials (247 trial arms), used the following agents, either as intervention or comparison:
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betamimetics, 74 trial arms (30%);
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COX inhibitors, 13 trial arms (5%);
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calcium channel blockers, 44 trial arms (18%);
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magnesium sulphate, 21 trial arms (9%);
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oxytocin receptor antagonists, 20 trial arms (8%);
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nitric oxide donors, 13 trial arms (5%);
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combinations of tocolytics, 23 trial arms (9%);
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placebo or no treatment, 39 trial arms (16%).
Excluded studies
We excluded 169 studies (for details see Characteristics of excluded studies). The most common reasons for exclusion were that studies compared acute‐phase tocolysis with a maintenance dose of tocolysis (Alavi 2015a; Bivins 1993; Brown 1981; Carr 1999; Guinn 1998; Gummerus 1985; How 1994; Matijevic 2006; Newton 1991; Parilla 1993; Ricci 1990; Sanchez Ramos 1997; Sayin 2004; Wenstrom 1997) or they compared doses or routes of the same tocolytic drugs (Cabero 1988; Chhabra 1998; Holleboom 1996; Kawagoe 2011; Kullander 1985; Motazedian 2010; Parry 2014; Rezk 2015; Rios Anez 2001; Ryden 1977; Spatling 1989; Stika 2002; Zygmunt 2003), or were quasi‐randomised studies or not randomised (Calder 1985; Dunstan Boone 1990; Kurki 1991a; Leake 1980b; Maitra 2007; Malik 2007; Singh 2011; Sirohiwal 2001).
Risk of bias in included studies
We present summaries of the risk of bias of the included studies for each of the domains that we assessed across all studies (Figure 3), and for each included trial (Figure 4).
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Allocation
Seventy‐one of 122 trials (58%) used adequate sequence generation and we judged these trials to be at low risk of bias. Fifty‐one of 122 trials (42%) did not clearly state the description of sequence generation and hence they were at unclear risk of bias. Sixty‐four of 122 trials (52%) gave a clear description of adequate allocation concealment. However, in 58 of 122 trials (48%) the description of allocation concealment was inadequate and so these trials were at unclear risk of bias. Many of the trials with inadequate information about sequence generation or allocation concealment were abstracts or other forms of short communications, which had limited word counts. Most of the trials that had an inadequate description of random sequence generation also gave inadequate information regarding allocation concealment.
Blinding
Only 31 of 122 trials (25%) blinded participants and personnel and hence we judged them to be at low risk of bias. Sixty‐three of 122 trials (52%) gave unclear information regarding blinding of participants and personnel and we therefore judged them to be at unclear risk of bias. The remaining 28 trials (23%) were unblinded to either participants or personnel, or both, and therefore at high risk of bias. In the majority of these unblinded trials, the nature of the intervention and comparator, for example intravenous betamimetics versus oral calcium channel blockers, meant blinding was more difficult to achieve. Seventy‐seven (63%) trials inadequately described blinding of the outcome assessor of the primary outcomes, meaning we judged them to be at unclear risk of bias. In 10 of 122 trials (8%) the outcome assessor was unblinded meaning these were at high risk of bias. Only 35 of 122 trials (29%) clearly stated that the outcome assessor was blinded, meaning these trials were at low risk of bias.
Incomplete outcome data
Ninety‐five of 122 trials (78%) had minimal missing outcome data (less than 10%) and were balanced in numbers across intervention groups with similar reasons for missing data across groups. They were therefore at low risk of attrition bias. We judged 21 of 122 trials (17%) to be at high risk of attrition bias due to losing more than 10% of their participant population to follow‐up. We judged six of 122 trials (5%) to be at unclear risk of attrition bias as they did not provide enough information to assess whether or not their handling of incomplete data was appropriate.
Selective reporting
Only nine of 122 trials (7%) prespecified all outcomes in publicly available trial protocols and we judged them to be at low risk of reporting bias. We were unable to identify a published protocol for most trials (113 of 122 trials; 93%), and we judged the risk of reporting bias to be unclear.
Other potential sources of bias
We detected no other potential sources of bias in 94 of 122 trials (77%) and so we judged them to be at low risk of bias. We judged 28 of 122 trials (23%) to be at unclear risk of bias. The majority of comparisons contained fewer than 10 studies, therefore investigation of publication bias was not valid. The only comparison that we downgraded for publication bias was calcium channel blockers versus betamimetics for delay in birth by 48 hours.
Effects of interventions
See: Summary of findings 1 Delay in birth by 48 hours; Summary of findings 2 Delay in birth by 7 days; Summary of findings 3 Neonatal death before 28 days; Summary of findings 4 Pregnancy prolongation (time from trial entry to birth in days); Summary of findings 5 Serious adverse effects of drugs; Summary of findings 6 Maternal infection; Summary of findings 7 Cessation of treatment due to adverse effects
See summary of findings tables for the comparisons of tocolytics with placebo or no treatment.
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summary of findings Table 1 Delay in birth by 48 hours
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summary of findings Table 2 Delay in birth by 7 days
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summary of findings Table 3 Neonatal death before 28 days
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summary of findings Table 4 Pregnancy prolongation
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summary of findings Table 5 Serious adverse effects of drugs
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summary of findings Table 6 Maternal infection
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summary of findings Table 7 Cessation of treatment due to adverse effects
Please note that all of the analyses presented in the Data and analyses relate to the ’direct evidence’ and we used them to grade the evidence, as described in our methods. We do not describe direct evidence where network evidence is available. The following section presents the results as reported in all of the figures. The figures present the results as network diagrams, forest plots with pairwise, indirect and network (combining direct and indirect) effect estimates, and cumulative rankograms for all the outcomes with available data. The figures present the results for different tocolytics in comparison to placebo or no treatment. The certainty of the evidence (grading of the results) considers the heterogeneity and inconsistency for all outcomes, and all of the tocolytic comparisons stated in the results.
Primary outcomes
1. Delay in birth by 48 hours
Network evidence
The network diagram for delay in birth by 48 hours is presented in Figure 5. Relative effects from the network meta‐analysis of 86 trials (9853 women) suggested that all tocolytics are probably effective in delaying preterm birth when compared with placebo or no treatment (Figure 6). Moderate‐certainty evidence suggests that magnesium sulphate (RR 1.12, 95% CI 1.02 to 1.23), oxytocin receptor antagonists (RR 1.13, 95% CI 1.05 to 1.22), nitric oxide donors (RR 1.17, 95% CI 1.05 to 1.31), and combinations of tocolytics (the most common combination was magnesium sulphate with betamimetics; RR 1.17, 95% CI 1.07 to 1.27) are probably effective in delaying preterm birth by 48 hours. Meanwhile, low‐certainty evidence suggests that betamimetics (RR 1.12, 95% CI 1.05 to 1.20), COX inhibitors (1.11, 95% CI 1.01 to 1.23), and calcium channel blockers (RR 1.16, 95% CI 1.07 to 1.24), are possibly effective in delaying preterm birth by 48 hours compared with placebo or no treatment.
Network diagram for delay in birth by 48 hours. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for delay in birth by 48 hours.
Based on these results, about 645 per 1000 women with placebo or no treatment would have a delay in preterm birth by 48 hours compared with 722 with betamimetics or magnesium sulphate, 716 with COX inhibitors, 748 with calcium channel blockers, 729 with oxytocin receptor antagonists, and 755 with nitric oxide donors or combinations of tocolytics (summary of findings Table 1).
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for delaying birth by 48 hours are shown in Figure 7. Treatment hierarchies are presented with the surface under the cumulative ranking curve (SUCRA); the larger the SUCRA the higher its rank among all available agents. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, and so on. A SUCRA of 100% means the tocolytic drug is the best and a SUCRA of 0% means the drug is the worst. The tocolytics ranked highest for delaying preterm birth by 48 hours are the combinations of tocolytics (SUCRA 76%), nitric oxide donors (SUCRA 74%), and calcium channel blockers (SUCRA 72%), followed by oxytocin receptor antagonists (SUCRA 50%), magnesium sulphate (SUCRA 44%), COX inhibitors (SUCRA 42%) and betamimetics (SUCRA 42%) with placebo or no treatment being ranked the lowest (SUCRA 0%).
Cumulative rankograms comparing each of the tocolytic drugs for delay in birth by 48 hours. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x‐axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
2. Delay in birth by 7 days
Network evidence
The network diagram for the outcome of delay in birth by 7 days is presented in Figure 8. Relative effects from the network meta‐analysis of 60 trials (7143 women) suggested that oxytocin receptor antagonists (RR 1.18, 95% CI 1.07 to 1.30; high‐certainty evidence) are effective in delaying birth by 7 days compared with placebo or no treatment (Figure 9). Calcium channel blockers (RR 1.15, 95% CI 1.04 to 1.27; moderate‐certainty evidence), nitric oxide donors (RR 1.18, 95% CI 1.02 to 1.37; moderate‐certainty evidence), and combinations of tocolytics (RR 1.19, 95% CI 1.05 to 1.34; moderate‐certainty evidence) are probably effective, while betamimetics (RR 1.14, 95% CI 1.03 to 1.25; low‐certainty evidence) are possibly effective in delaying birth by 7 days compared with placebo or no treatment. There is moderate‐certainty evidence that COX inhibitors probably make little to no difference to this outcome compared with placebo or no treatment. The effects of magnesium sulphate were unclear because the certainty of the evidence was very low.
Network diagram for delay in birth by 7 days. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for delay in birth by 7 days.
Based on these results, about 742 per 1000 women with placebo or no treatment would experience a delay in preterm birth by 7 days compared with 846 with betamimetics, 772 with COX inhibitors, 853 with calcium channel blockers, 675 with magnesium sulphate, 876 with oxytocin receptor antagonists and nitric oxide donors, and 883 with combinations of tocolytics
Tocolytic ranking*
The cumulative probabilities for each agent being at each possible rank for delaying birth by 7 days are shown in Figure 10. The highest ranked tocolytics for delaying preterm birth by 7 days are the combinations of tocolytics (SUCRA 79%), oxytocin receptor antagonists (78%), and nitric oxide donors (SUCRA 76%), followed by the calcium channel blockers (SUCRA 61%) and betamimetics (SUCRA 55%). COX inhibitors (SUCRA 30%), placebo or no treatment (SUCRA 16%), and magnesium sulphate (SUCRA 6%) ranked the lowest.
Cumulative rankograms comparing each of the tocolytic drugs for delay in birth by 7 days. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
3. Neonatal death before 28 days
Network evidence
The network diagram for the outcome of neonatal death before 28 days is presented in Figure 11. Relative effects from the network meta‐analysis of 73 trials (8395 babies) suggested that all tocolytics are associated with a wide range of effects for neonatal death before 28 days when compared with placebo or no treatment as there were few neonatal deaths (Figure 12; summary of findings Table 3).
Network diagram for neonatal death before 28 days. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for neonatal death before 28 days.
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for neonatal death before 28 days are shown in Figure 13. The ranking for tocolytics was not clear for this outcome due to few events.
Cumulative rankograms comparing each of the tocolytic drugs for neonatal death before 28 days. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
4. Pregnancy prolongation (time from trial entry to birth in days)
Network evidence
The network diagram for pregnancy prolongation as a continuous outcome is presented in Figure 14. Network meta‐analysis of 47 trials (5093 women) suggested that tocolytics except calcium channel blockers and oxytocin antagonists make little to no difference to pregnancy prolongation from trial entry to birth in days as a continuous outcome when compared with placebo or no treatment (Figure 15). When compared with placebo or no treatment, calcium channel blockers result in an average pregnancy prolongation of 4.66 days (95% CI 0.13 more to 9.19 more; high‐certainty evidence; summary of findings Table 4). Low‐certainty evidence suggests that oxytocin antagonists also possibly result in an average pregnancy prolongation of 9.54 days (95% CI 2.35 more to 16.73 more; summary of findings Table 4) compared with placebo or no treatment. There is probably little or no difference between betamimetics (MD 0.83 days more, 95% CI 3.12 fewer to 4.78 more; moderate‐certainty evidence), nitric oxide donors (MD 7.44 days more, 95% CI 0.44 fewer to 15.32 more; moderate‐certainty evidence), and possibly for COX inhibitors (MD 3.31 days more, 95% CI 4.41 fewer to 11.03 more; low‐certainty evidence) compared with placebo or no treatment. The effects of magnesium sulphate and combinations of tocolytics were unclear because the certainty of the evidence was very low.
Network diagram for pregnancy prolongation (time from trial entry to birth). The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for pregnancy prolongation (time from trial entry to birth).
Tocolytic ranking
Figure 16 shows the cumulative probabilities for each agent being at each possible rank for pregnancy prolongation as a continuous outcome. The highest ranked tocolytics were oxytocin receptor antagonists (SUCRA 92%) and lowest ranked were the betamimetics (SUCRA 28%), magnesium sulphate (SUCRA 25%) and placebo or no treatment (SUCRA 20%).
Cumulative rankograms comparing each of the tocolytic drugs for pregnancy prolongation (time from trial entry to birth). Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
5. Serious adverse effects of drugs
Network evidence
The network diagram for serious (maternal) adverse effects of drugs is presented in Figure 17. Relative effects from the network meta‐analysis of 62 trials (6983 women) suggested that all tocolytics are associated with a wide range of effects for serious adverse effects when compared with placebo or no treatment as there were only few events (Figure 18; summary of findings Table 5).
Network diagram for serious adverse effects of the drugs. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for serious adverse effects of the drugs.
Tocolytic ranking*
The cumulative probabilities for each tocolytic being at each possible rank for serious adverse events are shown in Figure 19. The ranking for tocolytics was not clear for this outcome due to few events.
Cumulative rankograms comparing each of the tocolytic drugs for serious adverse effects of the drugs. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
6. Maternal infection after trial entry
Network evidence
The network diagram for maternal infection is presented in Figure 20. Relative effects from the network meta‐analysis of 13 trials (1399 women) suggested that tocolytics are associated with a wide range of effects when compared with placebo or no treatment as there were only few events (Figure 21, summary of findings Table 6).
Network diagram for maternal infection. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for maternal infection.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for maternal infection are shown in Figure 22. The ranking for tocolytics was not clear for this outcome due to few events.
Cumulative rankograms comparing each of the tocolytic drugs for maternal infection. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
7. Cessation of treatment due to adverse effects
Network evidence
The network diagram for cessation of treatment due to adverse effects is presented in Figure 23. Relative effects from the network meta‐analysis of 68 trials (8122 women) suggested that several tocolytics are more likely to result in cessation of treatment due to adverse effects when compared with placebo or no treatment (Figure 24). When compared with placebo or no treatment, moderate‐certainty evidence suggests that betamimetics (RR 14.44, 95% CI 6.11 to 34.11), calcium channel blockers (RR 2.96 (95% CI 1.23 to 7.11), and magnesium sulphate (RR 3.90 (95% CI 1.09 to 13.93) probably result to more frequent cessation of treatment due to adverse effects. The combinations of tocolytics possibly also result in more frequent cessation due to adverse effects (RR 6.87, 95% CI 2.08 to 22.65; low‐certainty evidence). Oxytocin receptor antagonists are associated with a wide range of effects (RR 1.24, 95% CI 0.46 to 3.35; moderate‐certainty evidence) compared with placebo or no treatment. The effects of COX inhibitors, and nitric oxide donors were unclear because the certainty of the evidence was very low (summary of findings Table 7).
Network diagram for cessation of treatment due to adverse effects. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for cessation of treatment due to adverse effects.
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for this outcome are shown in Figure 25. The lowest ranked tocolytics for this outcome were betamimetics (SUCRA 2%) and combinations of tocolytics (SUCRA 23%). Highest ranked were oxytocin receptor antagonists (SUCRA 85%) and placebo or no treatment (SUCRA 92%).
Cumulative rankograms comparing each of the tocolytic drugs for cessation of treatment due to adverse effects. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Secondary outcomes
8. Birth before 28 weeks of gestation
Network evidence
The network diagram for birth before 28 weeks of gestation is presented in Figure 26. Due to the small number of trials (8 trials) reporting this outcome, network meta‐analysis was not possible, and so were unable to produce network relative effects and a rankogram. Direct evidence is presented only from pairwise meta‐analysis (Data and analyses). One trial (501 women) suggests that oxytocin receptor antagonists probably result in fewer births before 28 weeks of gestation compared with placebo or no treatment (RR 3.11, 95% CI 1.02 to 9.51; moderate‐certainty evidence; Analysis 5.8; Appendix 3). One trial (153 women) for nitric oxide donors (RR 0.50, 95% CI 0.23 to 1.09; low‐certainty evidence; Analysis 6.8) suggests that they are associated with a wide range of effects compared with placebo or no treatment. The evidence for magnesium sulphate is of very low certainty for this outcome. There is no direct evidence comparing betamimetics, COX inhibitors, calcium channel blockers or combinations of tocolytics to placebo or no treatment (Appendix 3).
Network diagram for birth before 28 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
9. Birth before 32 weeks of gestation
Network evidence
The network diagram for birth before 32 weeks of gestation is presented in Figure 27. Relative effects from the network meta‐analysis of 11 trials (1954 women) suggested that tocolytics are associated with a wide range of effects for this outcome when compared with placebo or no treatment as there were insufficient studies contributing to this analysis (Figure 28; Appendix 3).
Network diagram for birth before 32 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birth before 32 weeks of gestation.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for birth before 32 weeks of gestation are shown in Figure 29. The ranking for tocolytics was not clear for this outcome due to few studies in this analysis.
Cumulative rankograms comparing each of the tocolytic drugs for birth before 32 weeks of gestation. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
10. Birth before 34 weeks of gestation
Network evidence
The network diagram for birth before 34 weeks of gestation is presented in Figure 30. Relative effects from the network meta‐analysis of 19 trials (2265 women) suggested that nitric oxide donors are associated with a wide range of effects for this outcome (RR 0.86, 95% CI 0.59 to 1.27; low‐certainty evidence) when compared with placebo or no treatment (Figure 31; Appendix 3). The comparisons of the other tocolytics with placebo or no treatment are of very low certainty, hence the effects remain uncertain.
Network diagram for birth before 34 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birth before 34 weeks of gestation.
Tocolytic ranking*
The cumulative probabilities for each tocolytic being at each possible rank for birth before 34 weeks of gestation are shown in Figure 32. The ranking for tocolytics was not clear for this outcome because of the low number of studies in this analysis.
Cumulative rankograms comparing each of the tocolytic drugs for birth before 34 weeks of gestation. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
11. Birth before 37 weeks of gestation
Network evidence
The network diagram for birth before 37 weeks of gestation is presented in Figure 33. Relative effects from the network meta‐analysis of 51 trials (6104 women) suggested that betamimetics (RR 0.97, 95% CI 0.83 to 1.13; low‐certainty evidence), calcium channel blockers (RR 0.91, 95% CI 0.78 to 1.07; low‐certainty evidence), oxytocin receptor antagonists (1.10, 95% CI 0.89 to 1.36; moderate‐certainty evidence), and nitric oxide donors (RR 0.77, 95% CI 0.59 to 1.00; low‐certainty evidence) are associated with a wide range of effects for this outcome when compared with placebo or no treatment (Figure 34; Appendix 3). The comparisons of COX inhibitors, magnesium sulphate and combinations of tocolytics compared with placebo or no treatment are of very low certainty, hence the effects remain uncertain.
Network diagram for birth before 37 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birth before 37 weeks of gestation.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for birth before 37 weeks of gestation are shown in Figure 35. The highest ranked tocolytics for birth before 37 weeks of gestation are the nitric oxide donors (SUCRA 94%), combinations of tocolytics (SUCRA 77%), and calcium channel blockers (SUCRA 70%).
Cumulative rankograms comparing each of the tocolytic drugs for birth before 37 weeks of gestation. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
12. Maternal death
Network evidence
There were no maternal deaths in 13 studies (2631 women) that reported this outcome and relative effects for the tocolytics compared with placebo or no treatment were not estimable.
13. Pulmonary oedema
Network evidence
The network diagram for pulmonary oedema as a serious adverse effect from tocolysis is presented in Figure 36. Relative effects from the network meta‐analysis of 32 trials (4344 women) found that evidence for all comparisons of tocolytics with placebo was of very low certainty, so their effects remain uncertain (Figure 37; Appendix 3).
Network diagram for pulmonary oedema. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for pulmonary oedema.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for pulmonary oedema are shown in Figure 38. The ranking for tocolytics was not clear for this outcome because of the low number of events in this analysis.
Cumulative rankograms comparing each of the tocolytic drugs for pulmonary oedema. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
14. Dyspnoea
Network evidence
The network diagram for dyspnoea from tocolysis is presented in Figure 39. Relative effects from the network meta‐analysis of 24 trials (3357 women) suggested that betamimetics (RR 12.09, 95% CI 4.66 to 31.39; moderate‐certainty evidence) probably cause dyspnoea; the other tocolytics are associated with a wide range of effects when compared with placebo or no treatment (Figure 40; Appendix 3).
Network diagram for dyspnoea. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for dyspnoea.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for dyspnoea are shown in Figure 41. The lowest ranked tocolytics for this outcome were betamimetics (SUCRA 3%). Highest ranked were the nitric oxide donors (SUCRA 81%) and placebo or no treatment (SUCRA 78%).
Cumulative rankograms comparing each of the tocolytic drugs for dyspnoea. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
15. Palpitations
Network evidence
The network diagram for palpitations from tocolysis is presented in Figure 42. Relative effects from the network meta‐analysis of 35 trials (4229 women) suggested that betamimetics (RR 7.39, 95% CI 3.83 to 14.24; moderate‐certainty evidence) probably cause palpitations, meanwhile the other tocolytics are associated with a wide range of effects when compared with placebo or no treatment (Figure 43; Appendix 3).
Network diagram for palpitations. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for palpitations.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for palpitations are shown in Figure 44. The lowest ranked tocolytics for this outcome were betamimetics (SUCRA 6%) and combinations of tocolytics (SUCRA 17%). Highest ranked were the COX inhibitors (SUCRA 81%) and nitric oxide donors (SUCRA 80%), oxytocin receptor antagonists (SUCRA 68%) and placebo or no treatment (SUCRA 65%).
Cumulative rankograms comparing each of the tocolytic drugs for palpitations. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
16. Headaches
Network evidence
The network diagram for headaches from tocolysis is presented in Figure 45. Relative effects from the network meta‐analysis of 55 trials (6132 women) suggested that nitric oxide donors (RR 4.20, 95% CI 2.13 to 8.25; moderate‐certainty evidence) probably cause headache. There is low‐certainty evidence that betamimetics (RR 1.91, 95% CI 1.07 to 3.42) and calcium channel blockers (RR 2.59, 95% CI 1.39 to 4.83) could possibly cause headache as well. COX inhibitors, magnesium sulphate, and oxytocin receptor antagonists are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for the combinations of tocolytics are of very low certainty, hence the effects remain uncertain (Figure 46; Appendix 3).
Network diagram for headache. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for headache.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for headache are shown in Figure 47. The lowest ranked tocolytics for this outcome were the nitric oxide donors (SUCRA 1%), calcium channel blockers (SUCRA 16%), and betamimetics (SUCRA 34%).
Cumulative rankograms comparing each of the tocolytic drugs for headache. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
17. Nausea or vomiting
Network evidence
The network diagram for nausea or vomiting from tocolysis is presented in Figure 48. Relative effects from the network meta‐analysis of 52 trials (6129 women) suggested that betamimetics probably (RR 1.91, 95% CI 1.25 to 2.91; moderate‐certainty evidence) and COX inhibitors possibly (RR 2.54, 95% CI 1.18 to 5.48; low‐certainty evidence) cause nausea or vomiting. Low certainty evidence suggests that calcium channel blockers (RR 0.67, 95% CI 0.39 to 1.15), oxytocin receptor antagonists (RR 0.96, 95% CI 0.56 to 1.64), and combinations of tocolytics (RR 1.33, 95% CI 0.69 to 2.54) are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for the magnesium sulphate, and nitric oxide donors, is of very low certainty, hence the effects remain uncertain (Figure 49; Appendix 3).
Network diagram for nausea or vomiting. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for nausea or vomiting.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for nausea or vomiting are shown in Figure 50. The lowest ranked tocolytics for this outcome were the COX inhibitors (SUCRA 10%), magnesium sulphate (SUCRA 15%), and betamimetics (SUCRA 24%).
Cumulative rankograms comparing each of the tocolytic drugs for nausea or vomiting. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
18. Tachycardia
Network evidence
The network diagram for tachycardia from tocolysis is presented in Figure 51. Relative effects from the network meta‐analysis of 41 trials (4939 women) suggested that betamimetics (RR 3.01, 95% CI 1.17 to 7.71; low‐certainty evidence) possibly cause tachycardia. According to low‐certainty evidence, oxytocin receptor antagonists (RR 0.23, 95% CI 0.08 to 0.67), and nitric oxide donors (RR 0.16, 95% CI 0.04 to 0.70) are associated with a lower risk of tachycardia compared with placebo or no treatment. COX inhibitors (RR 0.18, 95% CI 0.02 to 1.60) and combinations of tocolytics (RR 1.62, 95% CI 0.49 to 5.31) are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for calcium channel blockers, and magnesium sulphate is of very low certainty, hence the effects remain uncertain (Figure 52; Appendix 3).
Network diagram for tachycardia. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for tachycardia.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for tachycardia are shown in Figure 53. The lowest ranked tocolytics for this outcome were betamimetics (SUCRA 1%), and combinations of tocolytics (SUCRA 19%). Highest ranked were the nitric oxide donors (SUCRA 84%), COX inhibitors (SUCRA 79%), and oxytocin receptor antagonists (SUCRA 75%).
Cumulative rankograms comparing each of the tocolytic drugs for tachycardia. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
19. Maternal cardiac arrhythmias
Network evidence
The network diagram for maternal cardiac arrhythmias from tocolysis is presented in Figure 54. Due to insufficient trials reporting this outcome (10 trials, 1661 women), network meta‐analysis was not possible, and so were unable to produce network relative effects and a rankogram. Direct evidence is presented only from pairwise meta‐analysis (Data and analyses). Four trials compared betamimetics to placebo or no treatment resulting in very low‐certainty evidence, so the effects for this comparison remain uncertain (Analysis 1.19; Appendix 3). There is no direct evidence comparing COX inhibitors, calcium channel blockers, magnesium sulphate, oxytocin receptor antagonists, nitric oxide donors, or combinations of tocolytics to placebo or no treatment (Appendix 3).
Network diagram for maternal cardiac arrhythmias. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
20. Maternal hypotension
Network evidence
The network diagram for maternal hypotension from tocolysis is presented in Figure 55. Relative effects from low‐certainty evidence from the network meta‐analysis of 44 trials (4998 women) suggested that betamimetics (RR 2.51, 95% CI 0.58 to 10.89), oxytocin receptor antagonists (RR 0.95, 95% CI 0.18 to 5.06), and nitric oxide donors (RR 1.95, 95% CI 0.50 to 7.53) are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for COX inhibitors, calcium channel blockers, magnesium sulphate, and combinations of tocolytics is of very low certainty, hence the effects remain uncertain (Figure 56; Appendix 3).
Network diagram for hypotension. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for hypotension.
Tocolytic ranking
Cumulative probabilities for each tocolytic being at each possible rank for maternal hypotension are shown in Figure 57. The lowest ranked tocolytics for this outcome were calcium channel blockers (SUCRA 15%) and betamimetics (SUCRA 18%).
Cumulative rankograms comparing each of the tocolytic drugs for hypotension. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
21. Perinatal death
Network evidence
The network diagram for the outcome of perinatal death, including stillbirths and neonatal deaths before 28 days, is presented in Figure 58. Relative effects from the network meta‐analysis of 79 trials (9547 babies) suggested that all tocolytics are associated with a wide range of effects for perinatal death when compared with placebo or no treatment as there were only few events (Figure 59; Appendix 3).
Network diagram for perinatal death. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for perinatal death.
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for perinatal death are shown in Figure 60. The ranking for tocolytics was not clear for this outcome due to few events.
Cumulative rankograms comparing each of the tocolytic drugs for perinatal death. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
22. Stillbirth
Network evidence
The network diagram for the outcome of stillbirth, is presented in Figure 61. Relative effects from the network meta‐analysis of 55 trials (6736 babies) suggested that all tocolytics are associated with a wide range of effects for stillbirth when compared with placebo or no treatment as there were few events (Figure 62; Appendix 3). There were no studies involving combinations of tocolytics.
Network diagram for stillbirth. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for stillbirth.
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for stillbirth are shown in Figure 63. The ranking for tocolytics was not clear for this outcome due to few events.
Cumulative rankograms comparing each of the tocolytic drugs for stillbirth. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
23. Neonatal death before 7 days
Network evidence
The network diagram for neonatal death before 7 days is presented in Figure 64. Due to the small number of events in the trials reporting this outcome (40 trials, 4501 babies), network meta‐analysis was not possible, and so we were unable to produce network relative effects and a rankogram. Direct evidence is presented only from pairwise meta‐analysis (Data and analyses). Direct evidence between betamimetics (Analysis 1.23), COX inhibitors (Analysis 2.23), calcium channel blockers (,Analysis 3.23) magnesium sulphate (Analysis 4.23), and oxytocin receptor antagonists (Analysis 5.23) versus placebo or no treatment is available, resulting in a wide range of effects (Appendix 3). There is no direct evidence comparing nitric oxide donors, and combinations of tocolytics to placebo or no treatment (Appendix 3).
Network diagram for neonatal death before 7 days. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
24. Neurodevelopmental morbidity
Network evidence
The network diagram for neurodevelopmental morbidity is presented in Figure 65. Relative effects from low‐certainty evidence from the network meta‐analysis of 41 trials (6378 babies) suggested that calcium channel blockers (RR 0.51, 95% CI 0.30 to 0.85; low‐certainty evidence) possibly reduce the risk of neurodevelopmental morbidity. Betamimetics (RR 0.86, 95% CI 0.59 to 1.25; low‐certainty evidence), oxytocin receptor antagonists (RR 0.74, 95% CI 0.47 to 1.16; moderate‐certainty evidence), and nitric oxide donors (RR 0.39, 95% CI 0.12 to 1.32; low‐certainty evidence) are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for COX inhibitors, magnesium sulphate, and combinations of tocolytics is of very low certainty, hence the effects remain uncertain (Figure 66; Appendix 3).
Network diagram for neurodevelopmental morbidity. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for neurodevelopmental morbidity.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for neurodevelopmental morbidity are shown in Figure 67. The highest ranked tocolytics for this outcome were the calcium channel blockers (SUCRA 80%), and nitric oxide donors (SUCRA 80%), meanwhile placebo or no treatment was ranked the lowest (SUCRA 14%).
Cumulative rankograms comparing each of the tocolytic drugs for neurodevelopmental morbidity. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
25. Gastrointestinal morbidity
Network evidence
The network diagram for gastrointestinal morbidity is presented in Figure 68. Relative effects from low certainty evidence from the network meta‐analysis of 32 trials (4549 babies) suggested that COX inhibitors (RR 1.12, 95% CI 0.47 to 2.64), oxytocin receptor antagonists (RR 0.38, 95% CI 0.12 to 1.22), and nitric oxide donors (RR 0.88, 95% CI 0.29 to 2.71) are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for betamimetics, calcium channel blockers, magnesium sulphate, and combinations of tocolytics is of very low certainty, hence the effects remain uncertain (Figure 69; Appendix 3).
Network diagram for gastrointestinal morbidity. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for gastrointestinal morbidity.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for gastrointestinal morbidity are shown in Figure 70. The highest ranked tocolytics for this outcome were the oxytocin receptor antagonists (SUCRA 88%), and the calcium channel blockers (SUCRA 73%). COX inhibitors (SUCRA 31%), and placebo or no treatment (SUCRA 37%) were ranked the lowest.
Cumulative rankograms comparing each of the tocolytic drugs for gastrointestinal morbidity. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
26. Respiratory morbidity
Network evidence
The network diagram for respiratory morbidity is presented in Figure 71. Relative effects of from the network meta‐analysis of 60 trials (8091 babies) suggested that calcium channel blockers (RR 0.68, 95% CI 0.53 to 0.88; low‐certainty evidence) possibly reduce the risk of respiratory morbidity, meanwhile betamimetics (RR 0.95, 95% CI 0.81 to 1.13; moderate‐certainty evidence) probably make little to no difference. COX inhibitors (RR 0.94, 95% CI 0.70 to 1.28; low‐certainty evidence), magnesium sulphate (RR 0.94, 95% CI 0.72 to 1.23; low‐certainty evidence), and oxytocin receptor antagonists (RR 1.07, 95% CI 0.86 to 1.33; moderate‐certainty evidence) are associated with a wide range of effects for this outcome compared with placebo or no treatment. The evidence for nitric oxide donors and combinations of tocolytics is of very low certainty, hence the effects remain uncertain (Figure 72; Appendix 3).
Network diagram for respiratory morbidity. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for respiratory morbidity.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for respiratory morbidity are shown in Figure 73. The highest ranked tocolytics for this outcome were the calcium channel blockers (SUCRA 90%) and nitric oxide donors (SUCRA 86%). Oxytocin receptor antagonists (SUCRA 22%) and combinations of tocolytics (SUCRA 23%) were ranked the lowest.
Cumulative rankograms comparing each of the tocolytic drugs for respiratory morbidity. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
27. Mean birthweight
Network evidence
The network diagram for birthweight as a continuous outcome in grams is presented in Figure 74. Network meta‐analysis of 77 trials (8258 babies) suggested that nitric oxide donors (MD 425.53 grams more, 95% CI 224.32 more to 626.74 more; low‐certainty evidence) possibly result in neonates with a higher birthweight (Figure 75; Appendix 3). Moderate‐certainty evidence suggests that there is probably little or no difference between betamimetics (MD 5.52 grams fewer, 95% CI 85.23 fewer to 74.18 more), calcium channel blockers (MD 84.08 grams more, 95% CI 3.22 fewer to 171.38 more), oxytocin receptor antagonists (MD 0.21 grams more, 95% CI 97.80 fewer to 98.22 more), and possibly with magnesium sulphate (MD 21.07 grams more, 95% CI 78.12 fewer to 120.27 more) compared with placebo or no treatment (Figure 75; Appendix 3). The effects for COX inhibitors and combinations of tocolytics were unclear because the certainty of the evidence was very low (Appendix 3).
Network diagram for mean birthweight. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for mean birthweight.
Tocolytic ranking
Figure 76 shows the cumulative probabilities for each agent being at each possible rank for birthweight as a continuous outcome. The highest ranked tocolytics were the nitric oxide donors (SUCRA 100%) and lowest ranked were betamimetics (SUCRA 19%) and placebo or no treatment (SUCRA 23%).
Cumulative rankograms comparing each of the tocolytic drugs for mean birthweight. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
28. Birthweight less than 2000 g
Network evidence
The network diagram for neonate birthweight less than 2000 g is presented in Figure 77. Relative effects from the network meta‐analysis of seven trials (522 babies) suggested that calcium channel blockers (RR 0.49, 95% CI 0.28 to 0.87; low‐certainty evidence) possibly reduce the risk of a neonate being born with a birthweight less than 2000 g, meanwhile other tocolytics are associated with a wide range of effects for this outcome when compared with placebo or no treatment as there were insufficient studies (Figure 78; Appendix 3). There is no direct, indirect or network evidence comparing oxytocin receptor antagonists, and nitric oxide donors with placebo or no treatment (Appendix 3).
Network diagram for birthweight of less than 2000 g. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birthweight of less than 2000 g.
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for birthweight less than 2000 g are shown in Figure 79. The ranking for tocolytics was not clear for this outcome due to few studies.
Cumulative rankograms comparing each of the tocolytic drugs for birthweight of less than 2000 g. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
29. Birthweight less than 2500 g
Network evidence
The network diagram for neonate birthweight less than 2500 g is presented in Figure 80. Relative effects from the network meta‐analysis of 27 trials (3592 babies) suggested that betamimetics (RR 0.92, 95% CI 0.85 to 1.00; moderate‐certainty evidence), and calcium channel blockers (RR 0.80, 95% CI 0.69 to 0.93; moderate‐certainty evidence) probably result in fewer neonates born with a birthweight less than 2500 g. Low‐certainty evidence suggests that COX inhibitors (RR 0.21, 95% CI 0.07 to 0.62), nitric oxide donors (RR 0.40, 95% CI 0.24 to 0.69), and combinations of tocolytics (RR 0.74, 95% CI 0.59 to 0.93) also possibly result in fewer neonates born with a birthweight less than 2500 g. Magnesium sulphate (RR 0.94, 95% CI 0.84 to 1.06), and oxytocin receptor antagonists (RR 0.94, 95% CI 0.79 to 1.12) possibly make little or no difference to this outcome (Figure 81; Appendix 3).
Network diagram for birthweight of less than 2500 g. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birthweight of less than 2500 g.
Tocolytic ranking
The cumulative probabilities for each agent being at each possible rank for birthweight less than 2500 g are shown in Figure 82. The highest ranked tocolytics were the COX inhibitors (SUCRA 97%), and nitric oxide donors (SUCRA 87%) and lowest ranked was placebo or no treatment (SUCRA 7%).
Cumulative rankograms comparing each of the tocolytic drugs for birthweight of less than 2500 g. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
30. Gestational age at birth
Network evidence
The network diagram for gestational age at birth as a continuous outcome in weeks is presented in Figure 83. Network meta‐analysis of 66 trials (7451 women) suggested that nitric oxide donors (MD 1.35 weeks more, 95% CI 0.37 more to 2.32 more; low‐certainty evidence) possibly result in neonates with a more advanced gestational age at birth (Figure 84; Appendix 3). Moderate‐certainty evidence suggests that there is probably little or no difference between betamimetics (MD 0.23 weeks fewer (95% CI 0.70 fewer to 0.23 more), calcium channel blockers (MD 0.24 weeks more, 95% CI 0.25 fewer to 0.73 more) than placebo or no treatment (Figure 84; Appendix 3). Similarly, oxytocin receptor antagonists possibly make little to no difference (MD 0.08 weeks fewer, 95% CI 0.70 fewer to 0.55 more) to this outcome. The effects for COX inhibitors, magnesium sulphate, and combinations of tocolytics were unclear because the certainty of the evidence was very low (Appendix 3).
Network diagram for gestational age at birth. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for gestational age at birth.
Tocolytic ranking
Figure 85 shows the cumulative probabilities for each agent being at each possible rank for gestational age at birth as a continuous outcome. The highest ranked tocolytics were the nitric oxide donors (SUCRA 98%) and COX inhibitors (SUCRA 82%) and lowest ranked were the betamimetics (SUCRA 13%).
Cumulative rankograms comparing each of the tocolytic drugs for gestational age at birth. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
31. Neonatal infection
Network evidence
The network diagram for neonatal infection is presented in Figure 86. Relative effects from the network meta‐analysis of 33 trials (5070 babies) suggested that tocolytics are associated with a wide range of effects for neonatal infection when compared with placebo or no treatment (Figure 87; Appendix 3). There were no studies involving nitric oxide donors and the effects for combinations of tocolytics were unclear because the certainty of the evidence was very low (Appendix 3)
Network diagram for neonatal infection. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for neonatal infection.
Tocolytic ranking
The cumulative probabilities for each tocolytic being at each possible rank for neonatal infection are shown in Figure 88. The highest ranked tocolytics were the magnesium sulphate (SUCRA 81%) and COX inhibitors (SUCRA 75%) and lowest ranked were the combinations of tocolytics (SUCRA 14%).
Cumulative rankograms comparing each of the tocolytic drugs for neonatal infection. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
The certainty of the evidence (grading of the results) considers the heterogeneity and inconsistency for all outcomes mentioned above, and all of the tocolytic comparisons stated in the results.
Subgroup analyses
Subgroup analyses did not reveal any substantial differences in the effects of different tocolytics by the duration of tocolysis (suppression alone versus suppression plus long‐term maintenance). We carried out a post hoc subgroup analysis according to the use of rescue tocolysis and the effects were consistent in both subgroups. Rescue tocolysis was defined as instances where the first tocolytic failed to delay preterm labour and another tocolytic had to be used. In addition, we planned a subgroup analysis according to the gestational age at trial entry, whether amniotic membranes were ruptured or not and whether the trial included singleton or multiple pregnancies, but sufficient studies were not available for these subgroup analyses.
Sensitivity analysis
We carried out prespecified sensitivity analyses by restricting our analyses to studies with no co‐interventions such as progesterone, to studies at low risk of bias and studies that were placebo‐controlled. We also performed sensitivity analyses according to the choice of relative effect measure (risk ratio versus odds ratio), the statistical model (fixed‐effect versus random‐effects model), and by removing studies conducted before 1990. The sensitivity analyses show that the overall results are not affected by the above mentioned criteria or decisions.
Discussion
Summary of main results
The network meta‐analysis involved six tocolytic drug classes, combinations of tocolytic drugs, and placebo or no tocolytic treatment. Most trials included women in threatened preterm birth, with a singleton pregnancy between 24 and 34 weeks. Overall, the evidence presented varied widely in quality, and our confidence in the effect estimates ranged from very low to high.
Primary outcomes
Delay in birth
Relative effects from the network meta‐analysis suggested that all the classes of tocolytics that we assessed are probably effective in delaying preterm birth when compared with placebo or no treatment. Specifically, betamimetics are possibly effective in delaying preterm birth by 48 hours, and 7 days. COX inhibitors are possibly effective in delaying preterm birth by 48 hours. Calcium channel blockers are possibly effective in delaying preterm birth by 48 hours, probably effective in delaying preterm birth by 7 days, and result in a significant pregnancy prolongation. Magnesium sulphate is probably effective in delaying preterm birth by 48 hours. Oxytocin receptor antagonists are effective in delaying preterm birth by 7 days, and probably by 48 hours, and also possibly result in a mean pregnancy prolongation of 10 days. Nitric oxide donors are probably effective in delaying preterm birth by 48 hours, and 7 days. Combinations of tocolytics ‐ largely based on the combination of betamimetics with magnesium sulphate ‐ are probably effective in delaying preterm birth by 48 hours, and 7 days.
The highest ranked tocolytics for delaying preterm birth by 48 hours, 7 days, and delay in birth as a continuous outcome are the nitric oxide donors, calcium channel blockers, oxytocin receptor antagonists and combinations of tocolytics.
Cessation of treatment due to adverse effects
Relative effects from the network meta‐analysis suggested that betamimetics, calcium channel blockers, magnesium sulphate and combinations of tocolytics are probably more likely to result in cessation of treatment due to adverse effects.
Neonatal death, serious adverse effects and maternal infection
For the remaining pre‐specified primary outcomes including neonatal death at 28 days, serious adverse effects and maternal infection, tocolytics are associated with a wide range of treatment effects compared with placebo or no treatment for so their effects remain uncertain.
Secondary outcomes
Neonatal morbidity, gestational age and birthweight
For the secondary outcomes, calcium channel blockers possibly reduce the risk of neurodevelopmental morbidity, and the risk of respiratory morbidity, and result in fewer neonates born with a birthweight less than 2000 g. Nitric oxide donors possibly result in neonates with a higher birthweight, fewer neonates born with a birthweight less than 2500 g, and a more advanced gestational age at birth. Combinations of tocolytics possibly result in fewer neonates born with a birthweight less than 2500 g.
Maternal adverse effects
In terms of adverse effects, betamimetics probably cause dyspnoea, palpitations, nausea or vomiting, and possibly headache, and tachycardia compared with placebo or no treatment. COX inhibitors possibly cause nausea or vomiting. Calcium channel blockers possibly cause headache. Nitric oxide donors probably cause headache.
Subgroup analyses
Subgroup analyses did not reveal any substantial differences in the effects of different tocolytics by the duration of tocolysis (acute suppression alone versus acute suppression plus long‐term maintenance). We carried out a post hoc subgroup analysis according to the use of rescue tocolysis and the effects were consistent in both subgroups. There are insufficient data to perform subgroup analyses by: gestational age at trial entry (fewer than 32/40 completed weeks versus 32/40 completed weeks or more); status of amniotic membranes (women with ruptured membranes versus women with intact membranes); and number of fetuses (singleton versus multiple pregnancy).
Overall completeness and applicability of evidence
This network meta‐analysis provides the relative effectiveness of all tocolytics in a coherent and methodologically robust way across important clinical outcomes by combining both direct and indirect evidence, thus increasing the statistical power and confidence in the results. We found that most of the included trials reported several of the primary outcomes and most of the secondary outcomes. This increased the power across most of our analyses and contributed to the consistency in the ranking across most outcomes.
We were thorough in our evaluation of the important potential treatment effect modifiers (gestational age, amniotic membranes, multiple pregnancy, and duration of tocolysis). We did not encounter important differences in the distribution of the effect modifiers between the different comparisons. The results of the network meta‐analyses were mostly consistent and where there was significant inconsistency this was likely due to unstable estimates from a low number of events.
Women recruited to the included studies were predominantly between 24 to 34 weeks of gestation, in hospital settings and with singleton pregnancies. Our findings may not be readily generalisable to other gestations or multiple pregnancies. Trials often varied in the regimen used for the tocolytics with several studies using a short course of tocolysis for up to 48 hours while others continued use of tocolysis for longer; in some trials up to the time of birth. The observed effects for the tocolytics were consistent in both subgroups.
Quality of the evidence
We acknowledge that there is no single established approach for assessing the certainty of the effect estimates generated by the network meta‐analysis. We applied the rigorous method for appraising quality of network evidence as proposed by the GRADE Working group. Overall, the evidence presented varied widely in quality, and our confidence in the effect estimates ranged from very low to high certainty. When we compared placebo or no treatment with all tocolytic drugs and combinations of tocolytics, most individual outcomes included a range in quality of evidence, and this was equally true for our most important outcomes. Our reasons for downgrading the evidence also varied across comparisons and outcomes.
Potential biases in the review process
The evidence for this review is derived from trials identified from a detailed, systematic search process without language restriction. This search was conducted in consultation with Cochrane Pregnancy and Childbirth's Information Specialist. It is possible (but unlikely) that additional trials have been published but not identified. It is also possible that there are other trials, additional to those of which we are aware, that have been conducted but are not yet published. Should any such trials be identified, we will include them in updates of this review. We performed a systematic search but we cannot be sure we identified all relevant trials. We prepublished and followed our protocol (New Reference). At least two review authors (AW, EM, AM, EL, AP, VAH, IG) independently assessed all studies, extracted data and graded evidence. At least two review authors (AW, VAH, IG) appraised studies published during and after 2010 for trustworthiness in accordance with set criteria (Appendix 2).
Before we could carry out the GRADE assessment of the network meta‐analysis evidence, we had to determine the methodology for this process because there is no well‐established approach or accompanying tools such as software. At least two review authors (AW, AP, VAH) undertook all GRADE assessments, in consultation with IG where additional decision making was required.
The earliest included trial was conducted in 1966 (Adam 1966), and in the decades since, clinical care for newborns has dramatically improved. These temporal changes could have contributed to heterogeneity and increased the uncertainty of findings. However, we carried out a sensitivity analysis by removing trials published before 1990 and this did not vary the ranking of the tocolytics substantially. As administration of corticosteroids for fetal lung maturation, and magnesium sulphate for neuroprotection have become increasingly available this could perhaps have also led to apparent changes in neonatal outcomes.
A source of heterogeneity and inconsistency was the use of rescue tocolysis where the first tocolytic failed to delay preterm labour. This varied substantially with some studies routinely administering a second‐line tocolytic, while others did not describe or use any rescue tocolysis if the first tocolytic was judged as failed. We did carry out a post‐hoc subgroup analysis to examine subgroup effects of the rescue tocolysis and the effects were consistent in both subgroups.
The trials included in the review recruited women with varied clinical characteristics, and it is important to consider this when interpreting results. The inclusion criteria were not always reported in detail and, when they were, these varied across trials. Lastly, not all trials reported data on adverse effects, hence these analyses were often underpowered.
Data from 17 ongoing studies may inform future updates of this review.
Agreements and disagreements with other studies or reviews
Our results agree with existing Cochrane Reviews (Crowther 2014; Duckitt 2014; Flenady 2014a; Flenady 2014b; Neilson 2014; Reinebrant 2015), that focus on the comparison of a tocolytic drug versus another (direct comparisons). However, this network meta‐analysis has several more studies than included in the previous reviews because of its nature of comparing all available tocolytic drugs in one single analysis and because it is the most up‐to‐date, including recently published trials. Hence, some estimates differ slightly, as expected.
A similar network meta‐analysis on this topic has previously been conducted (Haas 2012), which concluded that COX inhibitors and calcium channel blockers had the highest probability to delay preterm birth by 48 hours. This review was conducted almost a decade ago with fewer trials included, which resulted in lower power and may account for the different conclusions reached. We have also applied the trustworthiness tool from Cochrane, which may have resulted in some trials with implausible results (e.g. massive risk reduction for main outcomes with small sample size) to be eliminated from the review.
Process for using the Cochrane Pregnancy and Childbirth criteria for assessing the trustworthiness of a study
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies
Risk of bias summary: review authors' judgements about each risk of bias item for each included study
Network diagram for delay in birth by 48 hours. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for delay in birth by 48 hours.
Cumulative rankograms comparing each of the tocolytic drugs for delay in birth by 48 hours. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x‐axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for delay in birth by 7 days. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for delay in birth by 7 days.
Cumulative rankograms comparing each of the tocolytic drugs for delay in birth by 7 days. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for neonatal death before 28 days. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for neonatal death before 28 days.
Cumulative rankograms comparing each of the tocolytic drugs for neonatal death before 28 days. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for pregnancy prolongation (time from trial entry to birth). The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for pregnancy prolongation (time from trial entry to birth).
Cumulative rankograms comparing each of the tocolytic drugs for pregnancy prolongation (time from trial entry to birth). Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for serious adverse effects of the drugs. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for serious adverse effects of the drugs.
Cumulative rankograms comparing each of the tocolytic drugs for serious adverse effects of the drugs. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for maternal infection. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for maternal infection.
Cumulative rankograms comparing each of the tocolytic drugs for maternal infection. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for cessation of treatment due to adverse effects. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for cessation of treatment due to adverse effects.
Cumulative rankograms comparing each of the tocolytic drugs for cessation of treatment due to adverse effects. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for birth before 28 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Network diagram for birth before 32 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birth before 32 weeks of gestation.
Cumulative rankograms comparing each of the tocolytic drugs for birth before 32 weeks of gestation. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for birth before 34 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birth before 34 weeks of gestation.
Cumulative rankograms comparing each of the tocolytic drugs for birth before 34 weeks of gestation. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for birth before 37 weeks of gestation. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birth before 37 weeks of gestation.
Cumulative rankograms comparing each of the tocolytic drugs for birth before 37 weeks of gestation. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for pulmonary oedema. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for pulmonary oedema.
Cumulative rankograms comparing each of the tocolytic drugs for pulmonary oedema. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for dyspnoea. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for dyspnoea.
Cumulative rankograms comparing each of the tocolytic drugs for dyspnoea. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for palpitations. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for palpitations.
Cumulative rankograms comparing each of the tocolytic drugs for palpitations. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for headache. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for headache.
Cumulative rankograms comparing each of the tocolytic drugs for headache. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for nausea or vomiting. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for nausea or vomiting.
Cumulative rankograms comparing each of the tocolytic drugs for nausea or vomiting. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for tachycardia. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for tachycardia.
Cumulative rankograms comparing each of the tocolytic drugs for tachycardia. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for maternal cardiac arrhythmias. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Network diagram for hypotension. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for hypotension.
Cumulative rankograms comparing each of the tocolytic drugs for hypotension. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for perinatal death. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for perinatal death.
Cumulative rankograms comparing each of the tocolytic drugs for perinatal death. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for stillbirth. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for stillbirth.
Cumulative rankograms comparing each of the tocolytic drugs for stillbirth. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for neonatal death before 7 days. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Network diagram for neurodevelopmental morbidity. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for neurodevelopmental morbidity.
Cumulative rankograms comparing each of the tocolytic drugs for neurodevelopmental morbidity. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for gastrointestinal morbidity. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for gastrointestinal morbidity.
Cumulative rankograms comparing each of the tocolytic drugs for gastrointestinal morbidity. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for respiratory morbidity. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for respiratory morbidity.
Cumulative rankograms comparing each of the tocolytic drugs for respiratory morbidity. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for mean birthweight. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for mean birthweight.
Cumulative rankograms comparing each of the tocolytic drugs for mean birthweight. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for birthweight of less than 2000 g. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birthweight of less than 2000 g.
Cumulative rankograms comparing each of the tocolytic drugs for birthweight of less than 2000 g. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for birthweight of less than 2500 g. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for birthweight of less than 2500 g.
Cumulative rankograms comparing each of the tocolytic drugs for birthweight of less than 2500 g. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for gestational age at birth. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for gestational age at birth.
Cumulative rankograms comparing each of the tocolytic drugs for gestational age at birth. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Network diagram for neonatal infection. The nodes represent an intervention and their size is proportional to the number of trials comparing this intervention to any other in the network. The lines connecting each pair of interventions represent a direct comparison and are drawn proportional to the number of trials making each direct comparison. The colour of the line is green for high‐certainty evidence; light green for moderate‐certainty evidence; orange for low‐certainty evidence and red for very low‐certainty evidence. Multi‐arm trials contribute to more than one comparison.
Forest plot with relative risk ratios and 95% confidence intervals from pairwise, indirect and network (combining direct and indirect) analyses for neonatal infection.
Cumulative rankograms comparing each of the tocolytic drugs for neonatal infection. Ranking indicates the cumulative probability of being the best agent, the second best, the third best, etc. The x axis shows the relative ranking and the y‐axis the cumulative probability of each ranking. We estimate the SUrface underneath this Cumulative RAnking line (SUCRA); the larger the SUCRA the higher its rank among all available agents.
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 12: Maternal death
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 15: Palpitations
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 16: Headaches
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 1: Betamimetics vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 12: Maternal death
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 15: Palpitations
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 16: Headaches
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 2: COX inhibitors vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 12: Maternal death
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 15: Palpitations
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 16: Headaches
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 3: Calcium channel blockers vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 12: Maternal death
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 15: Palpitations
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 16: Headaches
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 4: Magnesium sulphate vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 12: Maternal death
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 15: Palpitations
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 16: Headaches
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 5: Oxytocin receptor antagonists vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 4: Pregnancy prolongation (Time from trial entry to birth in days)
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 12: Maternal death
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 15: Palpitations
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 16: Headaches
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 6: Nitric oxide donors vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 1: Delay in birth by 48 hours
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 2: Delay in birth by 7 days
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 3: Neonatal death before 28 days
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 5: Serious adverse effects of drugs
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 6: Maternal infection
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 7: Cessation of treatment due to adverse effects
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 8: Birth before 28 weeks' gestation
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 9: Birth before 32 weeks' gestation
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 10: Birth before 34 weeks' gestation
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 11: Birth before 37 weeks' gestation
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 12: Maternal death
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 13: Pulmonary oedema
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 14: Dyspnoea
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 15: Palpitations
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 16: Headaches
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 17: Nausea or vomiting
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 18: Tachycardia
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 19: Maternal cardiac arrhythmias
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 20: Maternal hypotension
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 21: Perinatal death
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 22: Stillbirth
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 23: Neonatal death before 7 days
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 24: Neurodevelopmental morbidity
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 25: Gastrointestinal morbidity
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 26: Respiratory morbidity
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 27: Mean birthweight
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 28: Birthweight < 2000 g
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 29: Birthweight < 2500 g
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 30: Gestational age at birth
Comparison 7: Combinations of tocolytics vs placebo or no treatment, Outcome 31: Neonatal infection
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 1: Delay in birth by 48 hours
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 2: Delay in birth by 7 days
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 3: Neonatal death before 28 days
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 5: Serious adverse effects of drugs
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 6: Maternal infection
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 7: Cessation of treatment due to adverse effects
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 8: Birth before 28 weeks' gestation
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 9: Birth before 32 weeks' gestation
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 10: Birth before 34 weeks' gestation
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 11: Birth before 37 weeks' gestation
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 12: Maternal death
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 13: Pulmonary oedema
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 14: Dyspnoea
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 15: Palpitations
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 16: Headaches
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 17: Nausea or vomiting
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 18: Tachycardia
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 19: Maternal cardiac arrhythmias
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 20: Maternal hypotension
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 21: Perinatal death
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 22: Stillbirth
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 23: Neonatal death before 7 days
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 24: Neurodevelopmental morbidity
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 25: Gastrointestinal morbidity
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 26: Respiratory morbidity
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 27: Mean birthweight
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 28: Birthweight < 2000 g
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 29: Birthweight < 2500 g
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 30: Gestational age at birth
Comparison 8: Betamimetics vs calcium channel blockers, Outcome 31: Neonatal infection
Comparison 9: Betamimetics vs COX inhibitors, Outcome 1: Delay in birth by 48 hours
Comparison 9: Betamimetics vs COX inhibitors, Outcome 2: Delay in birth by 7 days
Comparison 9: Betamimetics vs COX inhibitors, Outcome 3: Neonatal death before 28 days
Comparison 9: Betamimetics vs COX inhibitors, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 9: Betamimetics vs COX inhibitors, Outcome 5: Serious adverse effects of drugs
Comparison 9: Betamimetics vs COX inhibitors, Outcome 6: Maternal infection
Comparison 9: Betamimetics vs COX inhibitors, Outcome 7: Cessation of treatment due to adverse effects
Comparison 9: Betamimetics vs COX inhibitors, Outcome 8: Birth before 28 weeks' gestation
Comparison 9: Betamimetics vs COX inhibitors, Outcome 9: Birth before 32 weeks' gestation
Comparison 9: Betamimetics vs COX inhibitors, Outcome 10: Birth before 34 weeks' gestation
Comparison 9: Betamimetics vs COX inhibitors, Outcome 11: Birth before 37 weeks' gestation
Comparison 9: Betamimetics vs COX inhibitors, Outcome 12: Maternal death
Comparison 9: Betamimetics vs COX inhibitors, Outcome 13: Pulmonary oedema
Comparison 9: Betamimetics vs COX inhibitors, Outcome 14: Dyspnoea
Comparison 9: Betamimetics vs COX inhibitors, Outcome 15: Palpitations
Comparison 9: Betamimetics vs COX inhibitors, Outcome 16: Headaches
Comparison 9: Betamimetics vs COX inhibitors, Outcome 17: Nausea or vomiting
Comparison 9: Betamimetics vs COX inhibitors, Outcome 18: Tachycardia
Comparison 9: Betamimetics vs COX inhibitors, Outcome 19: Maternal cardiac arrhythmias
Comparison 9: Betamimetics vs COX inhibitors, Outcome 20: Maternal hypotension
Comparison 9: Betamimetics vs COX inhibitors, Outcome 21: Perinatal death
Comparison 9: Betamimetics vs COX inhibitors, Outcome 22: Stillbirth
Comparison 9: Betamimetics vs COX inhibitors, Outcome 23: Neonatal death before 7 days
Comparison 9: Betamimetics vs COX inhibitors, Outcome 24: Neurodevelopmental morbidity
Comparison 9: Betamimetics vs COX inhibitors, Outcome 25: Gastrointestinal morbidity
Comparison 9: Betamimetics vs COX inhibitors, Outcome 26: Respiratory morbidity
Comparison 9: Betamimetics vs COX inhibitors, Outcome 27: Mean birthweight
Comparison 9: Betamimetics vs COX inhibitors, Outcome 28: Birthweight < 2000 g
Comparison 9: Betamimetics vs COX inhibitors, Outcome 29: Birthweight < 2500 g
Comparison 9: Betamimetics vs COX inhibitors, Outcome 30: Gestational age at birth
Comparison 9: Betamimetics vs COX inhibitors, Outcome 31: Neonatal infection
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 1: Delay in birth by 48 hours
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 2: Delay in birth by 7 days
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 3: Neonatal death before 28 days
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 5: Serious adverse effects of drugs
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 6: Maternal infection
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 7: Cessation of treatment due to adverse effects
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 8: Birth before 28 weeks' gestation
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 9: Birth before 32 weeks' gestation
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 10: Birth before 34 weeks' gestation
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 11: Birth before 37 weeks' gestation
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 12: Maternal death
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 13: Pulmonary oedema
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 14: Dyspnoea
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 15: Palpitations
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 16: Headaches
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 17: Nausea or vomiting
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 18: Tachycardia
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 19: Maternal cardiac arrhythmias
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 20: Maternal hypotension
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 21: Perinatal death
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 22: Stillbirth
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 23: Neonatal death before 7 days
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 24: Neurodevelopmental morbidity
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 25: Gastrointestinal morbidity
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 26: Respiratory morbidity
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 27: Mean birthweight
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 28: Birthweight < 2000 g
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 29: Birthweight < 2500 g
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 30: Gestational age at birth
Comparison 10: Betamimetics vs nitric oxide donors, Outcome 31: Neonatal infection
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 1: Delay in birth by 48 hours
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 2: Delay in birth by 7 days
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 3: Neonatal death before 28 days
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 5: Serious adverse effects of drugs
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 6: Maternal infection
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 7: Cessation of treatment due to adverse effects
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 8: Birth before 28 weeks' gestation
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 9: Birth before 32 weeks' gestation
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 10: Birth before 34 weeks' gestation
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 11: Birth before 37 weeks' gestation
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 12: Maternal death
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 13: Pulmonary oedema
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 14: Dyspnoea
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 15: Palpitations
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 16: Headaches
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 17: Nausea or vomiting
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 18: Tachycardia
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 19: Maternal cardiac arrhythmias
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 20: Maternal hypotension
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 21: Perinatal death
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 22: Stillbirth
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 23: Neonatal death before 7 days
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 24: Neurodevelopmental morbidity
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 25: Gastrointestinal morbidity
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 26: Respiratory morbidity
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 27: Mean birthweight
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 28: Birthweight < 2000 g
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 29: Birthweight < 2500 g
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 30: Gestational age at birth
Comparison 11: Betamimetics vs magnesium sulphate, Outcome 31: Neonatal infection
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 1: Delay in birth by 48 hours
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 2: Delay in birth by 7 days
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 3: Neonatal death before 28 days
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 5: Serious adverse effects of drugs
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 6: Maternal infection
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 7: Cessation of treatment due to adverse effects
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 8: Birth before 28 weeks' gestation
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 9: Birth before 32 weeks' gestation
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 10: Birth before 34 weeks' gestation
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 11: Birth before 37 weeks' gestation
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 12: Maternal death
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 13: Pulmonary oedema
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 14: Dyspnoea
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 15: Palpitations
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 16: Headaches
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 17: Nausea or vomiting
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 18: Tachycardia
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 19: Maternal cardiac arrhythmias
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 20: Maternal hypotension
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 21: Perinatal death
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 22: Stillbirth
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 23: Neonatal death before 7 days
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 24: Neurodevelopmental morbidity
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 25: Gastrointestinal morbidity
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 26: Respiratory morbidity
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 27: Mean birthweight
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 28: Birthweight < 2000 g
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 29: Birthweight < 2500 g
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 30: Gestational age at birth
Comparison 12: Betamimetics vs oxytocin receptor antagonists, Outcome 31: Neonatal infection
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 1: Delay in birth by 48 hours
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 2: Delay in birth by 7 days
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 3: Neonatal death before 28 days
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 5: Serious adverse effects of drugs
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 6: Maternal infection
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 7: Cessation of treatment due to adverse effects
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 8: Birth before 28 weeks' gestation
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 9: Birth before 32 weeks' gestation
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 10: Birth before 34 weeks' gestation
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 11: Birth before 37 weeks' gestation
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 12: Maternal death
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 13: Pulmonary oedema
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 14: Dyspnoea
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 15: Palpitations
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 16: Headaches
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 17: Nausea or vomiting
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 18: Tachycardia
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 19: Maternal cardiac arrhythmias
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 20: Maternal hypotension
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 21: Perinatal death
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 22: Stillbirth
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 23: Neonatal death before 7 days
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 24: Neurodevelopmental morbidity
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 25: Gastrointestinal morbidity
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 26: Respiratory morbidity
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 27: Mean birthweight
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 28: Birthweight < 2000 g
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 29: Birthweight < 2500 g
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 30: Gestational age at birth
Comparison 13: Betamimetics vs combinations of tocolytics, Outcome 31: Neonatal infection
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 1: Delay in birth by 48 hours
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 2: Delay in birth by 7 days
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 3: Neonatal death before 28 days
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 5: Serious adverse effects of drugs
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 6: Maternal infection
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 7: Cessation of treatment due to adverse effects
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 8: Birth before 28 weeks' gestation
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 9: Birth before 32 weeks' gestation
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 10: Birth before 34 weeks' gestation
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 11: Birth before 37 weeks' gestation
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 12: Maternal death
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 13: Pulmonary oedema
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 14: Dyspnoea
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 15: Palpitations
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 16: Headaches
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 17: Nausea or vomiting
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 18: Tachycardia
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 19: Maternal cardiac arrhythmias
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 20: Maternal hypotension
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 21: Perinatal death
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 22: Stillbirth
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 23: Neonatal death before 7 days
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 24: Neurodevelopmental morbidity
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 25: Gastrointestinal morbidity
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 26: Respiratory morbidity
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 27: Mean birthweight
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 28: Birthweight < 2000 g
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 29: Birthweight < 2500 g
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 30: Gestational age at birth
Comparison 14: Calcium channel blockers vs COX inhibitors, Outcome 31: Neonatal infection
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 1: Delay in birth by 48 hours
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 2: Delay in birth by 7 days
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 3: Neonatal death before 28 days
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 5: Serious adverse effects of drugs
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 6: Maternal infection
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 7: Cessation of treatment due to adverse effects
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 8: Birth before 28 weeks' gestation
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 9: Birth before 32 weeks' gestation
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 10: Birth before 34 weeks' gestation
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 11: Birth before 37 weeks' gestation
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 12: Maternal death
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 13: Pulmonary oedema
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 14: Dyspnoea
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 15: Palpitations
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 16: Headaches
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 17: Nausea or vomiting
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 18: Tachycardia
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 19: Maternal cardiac arrhythmias
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 20: Maternal hypotension
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 21: Perinatal death
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 22: Stillbirth
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 23: Neonatal death before 7 days
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 24: Neurodevelopmental morbidity
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 25: Gastrointestinal morbidity
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 26: Respiratory morbidity
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 27: Mean birthweight
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 28: Birthweight < 2000 g
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 29: Birthweight < 2500 g
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 30: Gestational age at birth
Comparison 15: Calcium channel blockers vs magnesium sulphate, Outcome 31: Neonatal infection
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 1: Delay in birth by 48 hours
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 2: Delay in birth by 7 days
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 3: Neonatal death before 28 days
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 5: Serious adverse effects of drugs
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 6: Maternal infection
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 7: Cessation of treatment due to adverse effects
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 8: Birth before 28 weeks' gestation
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 9: Birth before 32 weeks' gestation
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 10: Birth before 34 weeks' gestation
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 11: Birth before 37 weeks' gestation
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 12: Maternal death
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 13: Pulmonary oedema
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 14: Dyspnoea
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 15: Palpitations
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 16: Headaches
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 17: Nausea or vomiting
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 18: Tachycardia
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 19: Maternal cardiac arrhythmias
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 20: Maternal hypotension
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 21: Perinatal death
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 22: Stillbirth
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 23: Neonatal death before 7 days
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 24: Neurodevelopmental morbidity
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 25: Gastrointestinal morbidity
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 26: Respiratory morbidity
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 27: Mean birthweight
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 28: Birthweight < 2000 g
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 29: Birthweight < 2500 g
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 30: Gestational age at birth
Comparison 16: Calcium channel blockers vs nitric oxide donors, Outcome 31: Neonatal infection
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 1: Delay in birth by 48 hours
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 2: Delay in birth by 7 days
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 3: Neonatal death before 28 days
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 5: Serious adverse effects of drugs
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 6: Maternal infection
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 7: Cessation of treatment due to adverse effects
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 8: Birth before 28 weeks' gestation
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 9: Birth before 32 weeks' gestation
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 10: Birth before 34 weeks' gestation
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 11: Birth before 37 weeks' gestation
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 12: Maternal death
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 13: Pulmonary oedema
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 14: Dyspnoea
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 15: Palpitations
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 16: Headaches
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 17: Nausea or vomiting
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 18: Tachycardia
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 19: Maternal cardiac arrhythmias
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 20: Maternal hypotension
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 21: Perinatal death
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 22: Stillbirth
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 23: Neonatal death before 7 days
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 24: Neurodevelopmental morbidity
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 25: Gastrointestinal morbidity
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 26: Respiratory morbidity
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 27: Mean birthweight
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 28: Birthweight < 2000 g
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 29: Birthweight < 2500 g
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 30: Gestational age at birth
Comparison 17: Calcium channel blockers vs oxytocin receptor antagonists, Outcome 31: Neonatal infection
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 1: Delay in birth by 48 hours
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 2: Delay in birth by 7 days
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 3: Neonatal death before 28 days
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 5: Serious adverse effects of drugs
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 6: Maternal infection
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 7: Cessation of treatment due to adverse effects
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 8: Birth before 28 weeks' gestation
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 9: Birth before 32 weeks' gestation
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 10: Birth before 34 weeks' gestation
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 11: Birth before 37 weeks' gestation
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 12: Maternal death
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 13: Pulmonary oedema
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 14: Dyspnoea
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 15: Palpitations
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 16: Headaches
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 17: Nausea or vomiting
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 18: Tachycardia
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 19: Maternal cardiac arrhythmias
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 20: Maternal hypotension
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 21: Perinatal death
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 22: Stillbirth
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 23: Neonatal death before 7 days
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 24: Neurodevelopmental morbidity
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 25: Gastrointestinal morbidity
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 26: Respiratory morbidity
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 27: Mean birthweight
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 28: Birthweight < 2000 g
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 29: Birthweight < 2500 g
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 30: Gestational age at birth
Comparison 18: Calcium channel blockers vs combinations of tocolytics, Outcome 31: Neonatal infection
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 1: Delay in birth by 48 hours
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 2: Delay in birth by 7 days
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 3: Neonatal death before 28 days
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 5: Serious adverse effects of drugs
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 6: Maternal infection
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 7: Cessation of treatment due to adverse effects
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 8: Birth before 28 weeks' gestation
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 9: Birth before 32 weeks' gestation
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 10: Birth before 34 weeks' gestation
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 11: Birth before 37 weeks' gestation
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 12: Maternal death
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 13: Pulmonary oedema
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 14: Dyspnoea
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 15: Palpitations
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 16: Headaches
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 17: Nausea or vomiting
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 18: Tachycardia
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 19: Maternal cardiac arrhythmias
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 20: Maternal hypotension
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 21: Perinatal death
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 22: Stillbirth
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 23: Neonatal death before 7 days
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 24: Neurodevelopmental morbidity
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 25: Gastrointestinal morbidity
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 26: Respiratory morbidity
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 27: Mean birthweight
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 28: Birthweight < 2000 g
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 29: Birthweight < 2500 g
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 30: Gestational age at birth
Comparison 19: COX inhibitors vs magnesium sulphate, Outcome 31: Neonatal infection
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 1: Delay in birth by 48 hours
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 2: Delay in birth by 7 days
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 3: Neonatal death before 28 days
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 5: Serious adverse effects of drugs
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 6: Maternal infection
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 7: Cessation of treatment due to adverse effects
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 8: Birth before 28 weeks' gestation
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 9: Birth before 32 weeks' gestation
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 10: Birth before 34 weeks' gestation
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 11: Birth before 37 weeks' gestation
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 12: Maternal death
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 13: Pulmonary oedema
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 14: Dyspnoea
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 15: Palpitations
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 16: Headaches
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 17: Nausea or vomiting
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 18: Tachycardia
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 19: Maternal cardiac arrhythmias
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 20: Maternal hypotension
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 21: Perinatal death
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 22: Stillbirth
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 23: Neonatal death before 7 days
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 24: Neurodevelopmental morbidity
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 25: Gastrointestinal morbidity
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 26: Respiratory morbidity
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 27: Mean birthweight
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 28: Birthweight < 2000 g
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 29: Birthweight < 2500 g
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 30: Gestational age at birth
Comparison 20: COX inhibitors vs nitric oxide donors, Outcome 31: Neonatal infection
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 1: Delay in birth by 48 hours
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 2: Delay in birth by 7 days
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 3: Neonatal death before 28 days
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 5: Serious adverse effects of drugs
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 6: Maternal infection
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 7: Cessation of treatment due to adverse effects
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 8: Birth before 28 weeks' gestation
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 9: Birth before 32 weeks' gestation
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 10: Birth before 34 weeks' gestation
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 11: Birth before 37 weeks' gestation
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 12: Maternal death
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 13: Pulmonary oedema
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 14: Dyspnoea
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 15: Palpitations
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 16: Headaches
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 17: Nausea or vomiting
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 18: Tachycardia
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 19: Maternal cardiac arrhythmias
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 20: Maternal hypotension
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 21: Perinatal death
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 22: Stillbirth
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 23: Neonatal death before 7 days
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 24: Neurodevelopmental morbidity
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 25: Gastrointestinal morbidity
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 26: Respiratory morbidity
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 27: Mean birthweight
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 28: Birthweight < 2000 g
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 29: Birthweight < 2500 g
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 30: Gestational age at birth
Comparison 21: COX inhibitors vs oxytocin receptor antagonists, Outcome 31: Neonatal infection
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 1: Delay in birth by 48 hours
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 2: Delay in birth by 7 days
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 3: Neonatal death before 28 days
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 5: Serious adverse effects of drugs
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 6: Maternal infection
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 7: Cessation of treatment due to adverse effects
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 8: Birth before 28 weeks' gestation
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 9: Birth before 32 weeks' gestation
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 10: Birth before 34 weeks' gestation
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 11: Birth before 37 weeks' gestation
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 12: Maternal death
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 13: Pulmonary oedema
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 14: Dyspnoea
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 15: Palpitations
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 16: Headaches
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 17: Nausea or vomiting
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 18: Tachycardia
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 19: Maternal cardiac arrhythmias
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 20: Maternal hypotension
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 21: Perinatal death
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 22: Stillbirth
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 23: Neonatal death before 7 days
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 24: Neurodevelopmental morbidity
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 25: Gastrointestinal morbidity
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 26: Respiratory morbidity
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 27: Mean birthweight
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 28: Birthweight < 2000 g
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 29: Birthweight < 2500 g
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 30: Gestational age at birth
Comparison 22: COX inhibitors vs combinations of tocolytics, Outcome 31: Neonatal infection
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 1: Delay in birth by 48 hours
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 2: Delay in birth by 7 days
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 3: Neonatal death before 28 days
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 5: Serious adverse effects of drugs
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 6: Maternal infection
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 7: Cessation of treatment due to adverse effects
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 8: Birth before 28 weeks' gestation
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 9: Birth before 32 weeks' gestation
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 10: Birth before 34 weeks' gestation
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 11: Birth before 37 weeks' gestation
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 12: Maternal death
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 13: Pulmonary oedema
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 14: Dyspnoea
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 15: Palpitations
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 16: Headaches
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 17: Nausea or vomiting
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 18: Tachycardia
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 19: Maternal cardiac arrhythmias
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 20: Maternal hypotension
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 21: Perinatal death
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 22: Stillbirth
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 23: Neonatal death before 7 days
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 24: Neurodevelopmental morbidity
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 25: Gastrointestinal morbidity
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 26: Respiratory morbidity
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 27: Mean birthweight
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 28: Birthweight < 2000 g
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 29: Birthweight < 2500 g
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 30: Gestational age at birth
Comparison 23: Magnesium sulphate vs nitric oxide donors, Outcome 31: Neonatal infection
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 1: Delay in birth by 48 hours
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 2: Delay in birth by 7 days
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 3: Neonatal death before 28 days
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 5: Serious adverse effects of drugs
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 6: Maternal infection
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 7: Cessation of treatment due to adverse effects
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 8: Birth before 28 weeks' gestation
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 9: Birth before 32 weeks' gestation
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 10: Birth before 34 weeks' gestation
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 11: Birth before 37 weeks' gestation
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 12: Maternal death
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 13: Pulmonary oedema
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 14: Dyspnoea
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 15: Palpitations
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 16: Headaches
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 17: Nausea or vomiting
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 18: Tachycardia
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 19: Maternal cardiac arrhythmias
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 20: Maternal hypotension
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 21: Perinatal death
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 22: Stillbirth
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 23: Neonatal death before 7 days
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 24: Neurodevelopmental morbidity
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 25: Gastrointestinal morbidity
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 26: Respiratory morbidity
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 27: Mean birthweight
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 28: Birthweight < 2000 g
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 29: Birthweight < 2500 g
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 30: Gestational age at birth
Comparison 24: Magnesium sulphate vs oxytocin receptor antagonists, Outcome 31: Neonatal infection
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 1: Delay in birth by 48 hours
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 2: Delay in birth by 7 days
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 3: Neonatal death before 28 days
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 5: Serious adverse effects of drugs
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 6: Maternal infection
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 7: Cessation of treatment due to adverse effects
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 8: Birth before 28 weeks' gestation
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 9: Birth before 32 weeks' gestation
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 10: Birth before 34 weeks' gestation
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 11: Birth before 37 weeks' gestation
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 12: Maternal death
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 13: Pulmonary oedema
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 14: Dyspnoea
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 15: Palpitations
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 16: Headaches
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 17: Nausea or vomiting
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 18: Tachycardia
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 19: Maternal cardiac arrhythmias
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 20: Maternal hypotension
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 21: Perinatal death
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 22: Stillbirth
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 23: Neonatal death before 7 days
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 24: Neurodevelopmental morbidity
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 25: Gastrointestinal morbidity
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 26: Respiratory morbidity
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 27: Mean birthweight
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 28: Birthweight < 2000 g
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 29: Birthweight < 2500 g
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 30: Gestational age at birth
Comparison 25: Magnesium sulphate vs combinations of tocolytics, Outcome 31: Neonatal infection
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 1: Delay in birth by 48 hours
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 2: Delay in birth by 7 days
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 3: Neonatal death before 28 days
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 5: Serious adverse effects of drugs
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 6: Maternal infection
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 7: Cessation of treatment due to adverse effects
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 8: Birth before 28 weeks' gestation
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 9: Birth before 32 weeks' gestation
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 10: Birth before 34 weeks' gestation
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 11: Birth before 37 weeks' gestation
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 12: Maternal death
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 13: Pulmonary oedema
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 14: Dyspnoea
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 15: Palpitations
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 16: Headaches
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 17: Nausea or vomiting
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 18: Tachycardia
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 19: Maternal cardiac arrhythmias
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 20: Maternal hypotension
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 21: Perinatal death
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 22: Stillbirth
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 23: Neonatal death before 7 days
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 24: Neurodevelopmental morbidity
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 25: Gastrointestinal morbidity
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 26: Respiratory morbidity
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 27: Mean birthweight
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 28: Birthweight < 2000 g
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 29: Birthweight < 2500 g
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 30: Gestational age at birth
Comparison 26: Nitric oxide donors vs oxytocin receptor antagonists, Outcome 31: Neonatal infection
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 1: Delay in birth by 48 hours
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 2: Delay in birth by 7 days
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 3: Neonatal death before 28 days
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 5: Serious adverse effects of drugs
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 6: Maternal infection
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 7: Cessation of treatment due to adverse effects
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 8: Birth before 28 weeks' gestation
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 9: Birth before 32 weeks' gestation
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 10: Birth before 34 weeks' gestation
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 11: Birth before 37 weeks' gestation
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 12: Maternal death
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 13: Pulmonary oedema
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 14: Dyspnoea
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 15: Palpitations
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 16: Headaches
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 17: Nausea or vomiting
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 18: Tachycardia
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 19: Maternal cardiac arrhythmias
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 20: Maternal hypotension
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 21: Perinatal death
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 22: Stillbirth
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 23: Neonatal death before 7 days
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 24: Neurodevelopmental morbidity
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 25: Gastrointestinal morbidity
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 26: Respiratory morbidity
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 27: Mean birthweight
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 28: Birthweight < 2000 g
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 29: Birthweight < 2500 g
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 30: Gestational age at birth
Comparison 27: Nitric oxide donors vs combinations of tocolytics, Outcome 31: Neonatal infection
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 1: Delay in birth by 48 hours
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 2: Delay in birth by 7 days
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 3: Neonatal death before 28 days
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 4: Pregnancy prolongation (time from trial entry to birth in days)
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 5: Serious adverse effects of drugs
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 6: Maternal infection
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 7: Cessation of treatment due to adverse effects
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 8: Birth before 28 weeks' gestation
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 9: Birth before 32 weeks' gestation
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 10: Birth before 34 weeks' gestation
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 11: Birth before 37 weeks' gestation
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 12: Maternal death
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 13: Pulmonary oedema
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 14: Dyspnoea
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 15: Palpitations
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 16: Headaches
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 17: Nausea or vomiting
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 18: Tachycardia
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 19: Maternal cardiac arrhythmias
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 20: Maternal hypotension
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 21: Perinatal death
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 22: Stillbirth
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 23: Neonatal death before 7 days
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 24: Neurodevelopmental morbidity
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 25: Gastrointestinal morbidity
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 26: Respiratory morbidity
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 27: Mean birthweight
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 28: Birthweight < 2000 g
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 29: Birthweight < 2500 g
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 30: Gestational age at birth
Comparison 28: Oxytocin receptor antagonists vs combinations of tocolytics, Outcome 31: Neonatal infection
| Delay in birth by 48 hours | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.27 (1.11 to 1.45) | ⊕⊕⊕⊖ Moderatea | 1.04 (0.96 to 1.12) | ⊕⊕⊖⊖ Lowb | 1.12 (1.05 to 1.20) | ⊕⊕⊖⊖ Lowc | 645 per 1000 | 722 per 1000 | 77 more per 1000 (from 32 to 129 more) |
| COX inhibitors | 2.02 (0.81 to 5.08 | ⊕⊖⊖⊖ Very lowd | 1.10 (0.98 to 1.23) | ⊕⊖⊖⊖ Very lowe | 1.11 (1.01 to 1.23) | ⊕⊕⊖⊖ Lowf | 645 per 1000 | 716 per 1000 | 71 more per 1000 (from 6 to 148 more) |
| Calcium channel blockers | 1.87 (1.06 to 3.28) | ⊕⊕⊖⊖ Lowg | 1.17 (1.08 to 1.26) | ⊕⊕⊖⊖ Lowb | 1.16 (1.07 to 1.24) | ⊕⊕⊖⊖ Lowh | 645 per 1000 | 748 per 1000 | 103 per 1000 (from 45 to 155 more) |
| Magnesium sulphate | 1.06 (0.88 to 1.29) | ⊕⊕⊖⊖ Lowi | 1.14 (1.02 to 1.28) | ⊕⊖⊖⊖ Very lowe | 1.12 (1.02 to 1.23) | ⊕⊕⊕⊖ Moderatej | 645 per 1000 | 722 per 1000 | 77 more per 1000 (from 13 to 148 more) |
| Oxytocin receptor antagonists | 1.07 (0.91 to 1.27) | ⊕⊕⊖⊖ Lowk | 1.17 (1.06 to 1.29) | ⊕⊕⊕⊖ Moderatel | 1.13 (1.05 to 1.22) | ⊕⊕⊕⊖ Moderatem | 645 per 1000 | 729 per 1000 | 84 more per 1000 (from 32 to 142 more) |
| Nitric oxide donors | 1.18 (0.76 to 1.84 | ⊕⊕⊖⊖ Lown | 1.20 (1.06 to 1.36) | ⊕⊕⊕⊖ Moderatel | 1.17 (1.05 to 1.31) | ⊕⊕⊕⊖ Moderatem | 645 per 1000 | 755 per 1000 | 110 per 1000 (from 32 to 200 more) |
| Combinations of tocolytics | 1.05 (0.84 to 1.31) | ⊕⊖⊖⊖ Very lowo | 1.18 (1.08 to 1.30) | ⊕⊕⊕⊖ Moderatel | 1.17 (1.07 to 1.27) | ⊕⊕⊕⊖ Moderatem | 645 per 1000 | 755 per 1000 | 110 per 1000 (from 45 to 174 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded once due to multiple limitations in trial design. | |||||||||
| Delay in birth by 7 days | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.47 (1.09 to 1.97) | ⊕⊕⊕⊖ Moderatea | 1.07 (0.96 to 1.20) | ⊕⊕⊖⊖ Lowb | 1.14 (1.03 to 1.25) | ⊕⊕⊖⊖ Lowc | 742 per 1000 | 846 per 1000 | 104 more per 1000 (from 22 to 186 more) |
| COX inhibitors | 2.05 (0.41 to 10.33) | ⊕⊕⊖⊖ Lowd | 1.01 (0.84 to 1.21) | ⊕⊖⊖⊖ Very lowe | 1.04 (0.88 to 1.24) | ⊕⊕⊕⊖ Moderatef | 742 per 1000 | 772 per 1000 | 30 more per 1000 (from 89 fewer to 178 more) |
| Calcium channel blockers | 1.25 (0.86 to 1.82) | ⊕⊕⊖⊖ Lowg | 1.22 (1.10 to 1.36) | ⊕⊕⊕⊖ Moderateh | 1.15 (1.04 to 1.27) | ⊕⊕⊕⊖ Moderatei | 742 per 1000 | 853 per 1000 | 111 per 1000 (from 30 to 200 more) |
| Magnesium sulphate | 0.82 (0.63 to 1.08) | ⊕⊖⊖⊖ Very lowj | 0.99 (0.75 to 1.30) | ⊕⊖⊖⊖ Very lowe | 0.91 (0.74 to 1.12) | ⊕⊖⊖⊖ Very lowk | 742 per 1000 | 675 per 1000 | 67 fewer per 1000 (from 193 fewer to 89 more) |
| Oxytocin receptor antagonists | 1.23 (1.11 to 1.37) | ⊕⊕⊕⊕ High | 1.14 (0.99 to 1.30) | ⊕⊕⊖⊖ Lowl | 1.18 (1.07 to 1.30) | ⊕⊕⊕⊕ High | 742 per 1000 | 876 per 1000 | 134 more per 1000 (from 52 to 223 more) |
| Nitric oxide donors | No estimate possible | Not applicable | 1.18 (1.02 to 1.37) | ⊕⊕⊕⊖ Moderateh | 1.18 (1.02 to 1.37) | ⊕⊕⊕⊖ Moderatei | 742 per 1000 | 876 per 1000 | 134 per 1000 (from 15 to 275 more) |
| Combinations of tocolytics | 0.92 (0.67 to 1.28) | ⊕⊖⊖⊖ Very lowj | 1.22 (1.07 to 1.40) | ⊕⊕⊕⊖ Moderateh | 1.19 (1.05 to 1.34) | ⊕⊕⊕⊖ Moderatei | 742 per 1000 | 883 per 1000 | 141 per 1000 (from 37 to 252 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded once due to multiple limitations in trial design. | |||||||||
| Neonatal death before 28 days | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 0.94 (0.56 to 1.59) | ⊕⊕⊖⊖ Lowa | 1.46 (0.56 to 3.79) | ⊕⊖⊖⊖ Very lowb | 1.01 (0.66 to 1.55) | ⊕⊕⊖⊖ Lowc | 66 per 1000 | 67 per 1000 | 1 more per 1000 (from 22 fewer to 36 more) |
| COX inhibitors | 0.77 (0.22 to 2.72) | ⊕⊕⊖⊖ Lowd | 1.42 (0.53 to 3.81) | ⊕⊖⊖⊖ Very lowb | 1.12 (0.51 to 2.45) | ⊕⊕⊖⊖ Lowc | 66 per 1000 | 74 per 1000 | 8 more per 1000 (from 32 fewer to 96 more) |
| Calcium channel blockers | 5.18 (0.26 to 103.15) | ⊕⊖⊖⊖ Very lowe | 0.77 (0.40 to 1.47) | ⊕⊕⊖⊖ Lowf | 0.84 (0.44 to 1.57) | ⊕⊕⊖⊖ Lowg | 66 per 1000 | 55 per 1000 | 11 fewer per 1000 (from 37 fewer to 38 more) |
| Magnesium sulphate | 0.89 (0.15 to 5.09) | ⊕⊖⊖⊖ Very lowe | 1.75 (0.61 to 4.99) | ⊕⊖⊖⊖ Very lowb | 1.19 (0.55 to 2.58) | ⊕⊖⊖⊖ Very lowh | 66 per 1000 | 79 per 1000 | 13 more per 1000 (from 30 fewer to 104 more) |
| Oxytocin receptor antagonists | 4.10 (0.88 to 19.13) | ⊕⊕⊖⊖ Lowd | 0.60 (0.21 to 1.68) | ⊕⊖⊖⊖ Very lowb | 1.08 (0.46 to 2.56) | ⊕⊖⊖⊖ Very lowi | 66 per 1000 | 71 per 1000 | 5 more per 1000 (from 36 fewer to 103 more) |
| Nitric oxide donors | 0.49 (0.07 to 3.64) | ⊕⊕⊖⊖ Lowd | 0.79 (0.15 to 4.29) | ⊕⊖⊖⊖ Very lowb | 0.65 (0.18 to 2.36) | ⊕⊕⊖⊖ Lowc | 66 per 1000 | 43 per 1000 | 23 fewer per 1000 (from 54 fewer to 90 more) |
| Combinations of tocolytics | Not estimable | Not applicable | 0.55 (0.18 to 1.66) | ⊕⊖⊖⊖ Very lowb | 0.55 (0.18 to 1.66) | ⊕⊖⊖⊖ Very lowj | 66 per 1000 | 36 per 1000 | 30 fewer per 1000 (from 54 fewer to 44 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded twice due to multiple limitations in trial design and serious imprecision. | |||||||||
| Pregnancy prolongation (time from trial entry to birth in days) | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.86 (−2.24 to 5.95) | ⊕⊕⊖⊖ Lowa | −0.10 (−6.18 to 5.98) | ⊕⊕⊕⊖ Moderateb | 0.83 (−3.12 to 4.78) | ⊕⊕⊕⊖ Moderatec | 20 days more | 21 days more | 1 day more (from 3 days fewer to 5 days more ) |
| COX inhibitors | −0.30 (−6.32 to 5.72) | ⊕⊕⊖⊖ Lowd | 5.45 (−4.35 to 15.24) | ⊕⊖⊖⊖ Very lowe | 3.31 (−4.41 to 11.03) | ⊕⊕⊖⊖ Lowf | 20 days more | 23 days more | 3 days more (from 4 days fewer to 11 days more) |
| Calcium channel blockers | 4.71 (0.32 to 9.10) | ⊕⊕⊕⊖ Moderateg | 4.72 (−0.59 to 10.02) | ⊕⊕⊖⊖ Lowh | 4.66 (0.13 to 9.19) | ⊕⊕⊕⊕ Highi | 20 days more | 25 days more | 5 days more (from 0 days to 9 days more) |
| Magnesium sulphate | 0.33 (−3.39 to 4.04) | ⊕⊖⊖⊖ Very lowj | 0.09 (−8.11 to 8.29) | ⊕⊖⊖⊖ Very lowk | 0.34 (−5.01 to 5.69) | ⊕⊖⊖⊖ Very lowl | 20 days more | 20 days more | 0 days (from 5 days fewer to 6 days more) |
| Oxytocin receptor antagonists | Not estimable | Not applicable | 9.54 (2.35 to 16.73) | ⊕⊕⊖⊖ Lowh | 9.54 (2.35 to 16.73) | ⊕⊕⊖⊖ Lowm | 20 days more | 30 days more | 10 days more (from 2 days more to 17 days more) |
| Nitric oxide donors | 11.91 (3.53 to 20.28) | ⊕⊕⊕⊖ Moderateg | 3.94 (−6.13 to 14.01) |
⊕⊕⊖⊖ Lowh | 7.44 (−0.44 to 15.32) | ⊕⊕⊕⊖ Moderaten | 20 days more | 27 days more | 7 days more (from 0 days to 15 days more) |
| Combinations of tocolytics | −6.10 (−13.54 to 1.34) | ⊕⊖⊖⊖ Very lowj | 4.30 (−3.56 to 12.16) | ⊕⊖⊖⊖ Very lowe | 1.55 (−5.31 to 8.40) | ⊕⊖⊖⊖ Very lowl | 20 days more | 22 days more | 2 days more (from 5 days fewer to 8 days more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded twice due to multiple limitations in trial design and serious imprecision. | |||||||||
| Serious adverse effects of drugs | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | We do not present summaries of relative and absolute effects because of high risk of bias, heterogeneous definitions, and serious imprecision.
| ||||||||
| COX inhibitors | |||||||||
| Calcium channel blockers | |||||||||
| Magnesium sulphate | |||||||||
| Oxytocin receptor antagonists | |||||||||
| Nitric oxide donors | |||||||||
| Combinations of tocolytics | |||||||||
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| Maternal infection | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 1.44 (0.82 to 2.51 | ⊕⊖⊖⊖ Very lowa | 33.26 (0.02 to 62,648.30) | ⊕⊖⊖⊖ Very lowb | 1.52 (0.76 to 3.02) | ⊕⊖⊖⊖ Very lowc | 290 per 1000 | 441 per 1000 | 151 more per 1000 (from 70 fewer to 586 more) |
| COX inhibitors | 1.46 (0.64 to 3.34) | ⊕⊕⊖⊖ Lowd | 0.32 (0.01 to 12.79) | ⊕⊖⊖⊖ Very lowb | 1.37 (0.51 to 3.69) | ⊕⊕⊖⊖ Lowe | 290 per 1000 | 397 per 1000 | 107 more per 1000 (from 142 fewer to 780 more) |
| Calcium channel blockers | Not estimable | Not applicable | 6.74 (0.29 to 155.05) | ⊕⊖⊖⊖ Very lowb | 6.74 (0.29 to 155.05) | ⊕⊖⊖⊖ Very lowf | 290 per 1000 | 1000 per 1000 | 710 more per 1000 (from 206 fewer to 1000 more) |
| Magnesium sulphate | 2.38 (0.24 to 23.84) | ⊕⊖⊖⊖ Very lowa | 0.76 (0.06 to 8.84) | ⊕⊖⊖⊖ Very lowb | 1.16 (0.24 to 5.60) | ⊕⊖⊖⊖ Very lowc | 290 per 1000 | 336 per 1000 | 46 more per 1000 (from 220 fewer to 1000 more) |
| Oxytocin receptor antagonists | Not estimable | Not applicable | 1.09 (0.02 to 50.70) | ⊕⊖⊖⊖ Very lowb | 1.09 (0.02 to 50.70) | ⊕⊖⊖⊖ Very lowf | 290 per 1000 | 316 per 1000 | 26 more per 1000 (from 284 fewer to 1000 more) |
| Nitric oxide donors | Not estimableg | Not applicableg | Not estimableg | Not applicableg | Not estimableg | Not applicableg | Not estimableg | ||
| Combinations of tocolytics | Not estimable | Not applicable | 1.31 (0.16 to 10.71) | ⊕⊖⊖⊖ Very lowb | 1.31 (0.16 to 10.71) | ⊕⊖⊖⊖ Very lowf | 290 per 1000 | 380 per 1000 | 90 more per 1000 (from 244 fewer to 1000 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded three times due to multiple limitations in trial design and very serious imprecision. | |||||||||
| Cessation of treatment due to adverse effects | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Patient or population: women with signs and symptoms of preterm labour Settings: hospital setting Intervention: betamimetics, calcium channel blockers, COX inhibitors, magnesium sulphate, nitric oxide donors, oxytocin receptor antagonists, combinations of tocolytics Comparison: placebo or no treatment | |||||||||
| Outcomes | Direct evidence | Indirect evidence | Network evidence | Anticipated absolute effects for network estimate | |||||
| RR | Certainty | RR | Certainty | RR | Certainty | Risk with placebo or no treatment | Risk with tocolytic agent | Risk difference with tocolytic agent | |
| Betamimetics | 9.62 (4.33 to 21.36) | ⊕⊕⊕⊖ Moderatea | 20.49 (6.29 to 66.76) | ⊕⊕⊖⊖ Lowb | 14.44 (6.11 to 34.11) | ⊕⊕⊕⊖ Moderatec | 108 per 1000 | 1000 per 1000 | 892 more per 1000 (from 552 more to 1000 more) |
| COX inhibitors | Not estimable | Not applicable | 2.34 (0.50 to 10.97) | ⊕⊖⊖⊖ Very lowd | 2.34 (0.50 to 10.97) | ⊕⊖⊖⊖ Very lowe | 108 per 1000 | 253 per 1000 | 145 more per 1000 (from 54 fewer to 1000 more) |
| Calcium channel blockers | 1.13 (0.67 to 1.88) | ⊕⊕⊖⊖ Lowf | 4.54 (1.51 to 13.63) | ⊕⊕⊕⊖ Moderateg | 2.96 (1.23 to 7.11) | ⊕⊕⊕⊖ Moderateh | 108 per 1000 | 320 per 1000 | 212 more per 1000 (from 25 to 660 more) |
| Magnesium sulphate | 9.82 (1.25 to 77.31) | ⊕⊕⊖⊖ Lowi | 2.99 (0.58 to 15.48) | ⊕⊖⊖⊖ Very lowd | 3.90 (1.09 to 13.93) | ⊕⊕⊕⊖ Moderatej | 108 per 1000 | 421 per 1000 | 313 more per 1000 (from 10 more to 1000 more) |
| Oxytocin receptor antagonists | 4.02 (2.05 to 7.85) | ⊕⊕⊕⊕ High | 0.63 (0.21 to 1.90) | ⊕⊕⊕⊖ Moderateg | 1.24 (0.46 to 3.35) | ⊕⊕⊕⊖ Moderatek | 108 per 1000 | 134 per 1000 | 26 more per 1000 (from 58 fewer to 254 more) |
| Nitric oxide donors | Not estimable | Not applicable | 4.31 (0.90 to 20.67) | ⊕⊖⊖⊖ Very lowd | 4.31 (0.90 to 20.67) | ⊕⊖⊖⊖ Very lowe | 108 per 1000 | 465 per 1000 | 357 more per 1000 (from 11 fewer to 1000 more) |
| Combinations of tocolytics | Not estimable | Not applicable | 6.87 (2.08 to 22.65) | ⊕⊕⊖⊖ Lowl | 6.87 (2.08 to 22.65) | ⊕⊕⊖⊖ Lowm | 108 per 1000 | 742 per 1000 | 634 more per 1000 (from 117 to 1000 more) |
| *The assumed risks in the placebo or no‐treatment group are based on weighted means of baseline risks from the studies with placebo or no treatment arms in the network meta‐analysis. The corresponding risks for each tocolytic drug (and their 95% CIs) are based on the assumed risk in the placebo or no‐treatment group and the relative effect of the individual treatment intervention, when compared with the placebo or no‐treatment group (and its 95% CI) as derived from the network meta‐analysis. | |||||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | |||||||||
| aDirect evidence downgraded once due to multiple limitations in trial design. | |||||||||
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 1.1 Delay in birth by 48 hours Show forest plot | 10 | 1399 | Risk Ratio (IV, Random, 95% CI) | 1.27 [1.11, 1.45] |
| 1.2 Delay in birth by 7 days Show forest plot | 8 | 1102 | Risk Ratio (IV, Random, 95% CI) | 1.46 [1.09, 1.97] |
| 1.3 Neonatal death before 28 days Show forest plot | 14 | 1763 | Risk Ratio (IV, Random, 95% CI) | 0.94 [0.56, 1.59] |
| 1.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 7 | 1176 | Mean Difference (IV, Random, 95% CI) | 1.86 [‐2.24, 5.95] |
| 1.5 Serious adverse effects of drugs Show forest plot | 5 | 344 | Risk Ratio (IV, Random, 95% CI) | 0.50 [0.05, 4.94] |
| 1.6 Maternal infection Show forest plot | 4 | 222 | Risk Ratio (IV, Random, 95% CI) | 1.44 [0.82, 2.51] |
| 1.7 Cessation of treatment due to adverse effects Show forest plot | 5 | 1081 | Risk Ratio (IV, Random, 95% CI) | 9.62 [4.33, 21.36] |
| 1.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 1.9 Birth before 32 weeks' gestation Show forest plot | 3 | 561 | Risk Ratio (IV, Random, 95% CI) | 0.86 [0.73, 1.01] |
| 1.10 Birth before 34 weeks' gestation Show forest plot | 2 | 209 | Risk Ratio (IV, Random, 95% CI) | 0.32 [0.04, 2.85] |
| 1.11 Birth before 37 weeks' gestation Show forest plot | 4 | 1024 | Risk Ratio (IV, Random, 95% CI) | 0.99 [0.58, 1.72] |
| 1.12 Maternal death Show forest plot | 3 | 825 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 1.13 Pulmonary oedema Show forest plot | 5 | 1012 | Risk Ratio (IV, Random, 95% CI) | 3.03 [0.12, 74.23] |
| 1.14 Dyspnoea Show forest plot | 2 | 814 | Risk Ratio (IV, Random, 95% CI) | 12.09 [4.66, 31.39] |
| 1.15 Palpitations Show forest plot | 7 | 1320 | Risk Ratio (IV, Random, 95% CI) | 8.55 [5.71, 12.79] |
| 1.16 Headaches Show forest plot | 4 | 974 | Risk Ratio (IV, Random, 95% CI) | 2.94 [1.17, 7.35] |
| 1.17 Nausea or vomiting Show forest plot | 5 | 1167 | Risk Ratio (IV, Random, 95% CI) | 1.77 [1.29, 2.41] |
| 1.18 Tachycardia Show forest plot | 5 | 493 | Risk Ratio (IV, Random, 95% CI) | 1.72 [0.57, 5.17] |
| 1.19 Maternal cardiac arrhythmias Show forest plot | 4 | 860 | Risk Ratio (IV, Random, 95% CI) | 3.43 [0.84, 13.89] |
| 1.20 Maternal hypotension Show forest plot | 2 | 136 | Risk Ratio (IV, Random, 95% CI) | 1.55 [0.12, 19.43] |
| 1.21 Perinatal death Show forest plot | 14 | 1702 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.75, 1.55] |
| 1.22 Stillbirth Show forest plot | 9 | 1298 | Risk Ratio (IV, Random, 95% CI) | 1.24 [0.66, 2.33] |
| 1.23 Neonatal death before 7 days Show forest plot | 10 | 1446 | Risk Ratio (IV, Random, 95% CI) | 1.02 [0.50, 2.05] |
| 1.24 Neurodevelopmental morbidity Show forest plot | 4 | 978 | Risk Ratio (IV, Random, 95% CI) | 0.71 [0.45, 1.14] |
| 1.25 Gastrointestinal morbidity Show forest plot | 2 | 149 | Risk Ratio (IV, Random, 95% CI) | 0.50 [0.12, 2.16] |
| 1.26 Respiratory morbidity Show forest plot | 10 | 1530 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.72, 1.33] |
| 1.27 Mean birthweight Show forest plot | 9 | 1298 | Mean Difference (IV, Random, 95% CI) | 68.28 [‐10.92, 147.49] |
| 1.28 Birthweight < 2000 g Show forest plot | 1 | 53 | Risk Ratio (IV, Random, 95% CI) | 1.74 [1.04, 2.91] |
| 1.29 Birthweight < 2500 g Show forest plot | 8 | 1400 | Risk Ratio (IV, Random, 95% CI) | 0.92 [0.79, 1.06] |
| 1.30 Gestational age at birth Show forest plot | 7 | 1241 | Mean Difference (IV, Random, 95% CI) | 0.09 [‐0.56, 0.75] |
| 1.31 Neonatal infection Show forest plot | 5 | 999 | Risk Ratio (IV, Random, 95% CI) | 1.47 [0.71, 3.06] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 2.1 Delay in birth by 48 hours Show forest plot | 3 | 113 | Risk Ratio (IV, Random, 95% CI) | 2.02 [0.81, 5.08] |
| 2.2 Delay in birth by 7 days Show forest plot | 2 | 83 | Risk Ratio (IV, Random, 95% CI) | 2.05 [0.41, 10.33] |
| 2.3 Neonatal death before 28 days Show forest plot | 3 | 114 | Risk Ratio (IV, Random, 95% CI) | 0.77 [0.22, 2.72] |
| 2.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 1 | 47 | Mean Difference (IV, Random, 95% CI) | ‐0.30 [‐6.32, 5.72] |
| 2.5 Serious adverse effects of drugs Show forest plot | 2 | 67 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.6 Maternal infection Show forest plot | 2 | 77 | Risk Ratio (IV, Random, 95% CI) | 1.46 [0.64, 3.34] |
| 2.7 Cessation of treatment due to adverse effects Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.11 Birth before 37 weeks' gestation Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | 0.21 [0.07, 0.62] |
| 2.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.17 Nausea or vomiting Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | 5.00 [0.26, 97.37] |
| 2.18 Tachycardia Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.20 Maternal hypotension Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.21 Perinatal death Show forest plot | 3 | 114 | Risk Ratio (IV, Random, 95% CI) | 0.63 [0.19, 2.09] |
| 2.22 Stillbirth Show forest plot | 3 | 114 | Risk Ratio (IV, Random, 95% CI) | 0.31 [0.01, 7.15] |
| 2.23 Neonatal death before 7 days Show forest plot | 1 | 31 | Risk Ratio (IV, Random, 95% CI) | 0.94 [0.15, 5.84] |
| 2.24 Neurodevelopmental morbidity Show forest plot | 1 | 47 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 2.25 Gastrointestinal morbidity Show forest plot | 2 | 78 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.25, 3.37] |
| 2.26 Respiratory morbidity Show forest plot | 2 | 78 | Risk Ratio (IV, Random, 95% CI) | 0.80 [0.47, 1.36] |
| 2.27 Mean birthweight Show forest plot | 2 | 67 | Mean Difference (IV, Random, 95% CI) | 713.61 [402.54, 1024.67] |
| 2.28 Birthweight < 2000 g Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | 0.50 [0.05, 5.04] |
| 2.29 Birthweight < 2500 g Show forest plot | 1 | 36 | Risk Ratio (IV, Random, 95% CI) | 0.21 [0.07, 0.62] |
| 2.30 Gestational age at birth Show forest plot | 3 | 114 | Mean Difference (IV, Random, 95% CI) | 2.61 [‐0.62, 5.84] |
| 2.31 Neonatal infection Show forest plot | 2 | 78 | Risk Ratio (IV, Random, 95% CI) | 0.51 [0.23, 1.14] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 3.1 Delay in birth by 48 hours Show forest plot | 4 | 311 | Risk Ratio (IV, Random, 95% CI) | 1.87 [1.06, 3.28] |
| 3.2 Delay in birth by 7 days Show forest plot | 5 | 384 | Risk Ratio (IV, Random, 95% CI) | 1.25 [0.86, 1.82] |
| 3.3 Neonatal death before 28 days Show forest plot | 2 | 143 | Risk Ratio (IV, Random, 95% CI) | 5.18 [0.26, 103.15] |
| 3.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 2 | 138 | Mean Difference (IV, Random, 95% CI) | 4.71 [0.32, 9.10] |
| 3.5 Serious adverse effects of drugs Show forest plot | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.7 Cessation of treatment due to adverse effects Show forest plot | 3 | 211 | Risk Ratio (IV, Random, 95% CI) | 1.13 [0.67, 1.88] |
| 3.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.10 Birth before 34 weeks' gestation Show forest plot | 1 | 73 | Risk Ratio (IV, Random, 95% CI) | 5.84 [0.74, 46.11] |
| 3.11 Birth before 37 weeks' gestation Show forest plot | 4 | 334 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.71, 1.35] |
| 3.12 Maternal death Show forest plot | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.16 Headaches Show forest plot | 2 | 162 | Risk Ratio (IV, Random, 95% CI) | 2.92 [0.29, 28.90] |
| 3.17 Nausea or vomiting Show forest plot | 1 | 73 | Risk Ratio (IV, Random, 95% CI) | 0.78 [0.23, 2.67] |
| 3.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.21 Perinatal death Show forest plot | 3 | 216 | Risk Ratio (IV, Random, 95% CI) | 5.02 [0.60, 41.80] |
| 3.22 Stillbirth Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.23 Neonatal death before 7 days Show forest plot | 2 | 143 | Risk Ratio (IV, Random, 95% CI) | 5.18 [0.26, 103.15] |
| 3.24 Neurodevelopmental morbidity Show forest plot | 2 | 128 | Risk Ratio (IV, Random, 95% CI) | 3.11 [0.13, 73.11] |
| 3.25 Gastrointestinal morbidity Show forest plot | 2 | 128 | Risk Ratio (IV, Random, 95% CI) | 5.98 [0.74, 48.42] |
| 3.26 Respiratory morbidity Show forest plot | 2 | 128 | Risk Ratio (IV, Random, 95% CI) | 0.66 [0.01, 31.39] |
| 3.27 Mean birthweight Show forest plot | 3 | 216 | Mean Difference (IV, Random, 95% CI) | 19.52 [‐258.79, 297.82] |
| 3.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 3.29 Birthweight < 2500 g Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.60, 1.54] |
| 3.30 Gestational age at birth Show forest plot | 3 | 211 | Mean Difference (IV, Random, 95% CI) | ‐0.01 [‐1.64, 1.62] |
| 3.31 Neonatal infection Show forest plot | 2 | 128 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.39, 2.45] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 4.1 Delay in birth by 48 hours Show forest plot | 4 | 311 | Risk Ratio (IV, Random, 95% CI) | 1.06 [0.88, 1.29] |
| 4.2 Delay in birth by 7 days Show forest plot | 2 | 191 | Risk Ratio (IV, Random, 95% CI) | 0.82 [0.63, 1.08] |
| 4.3 Neonatal death before 28 days Show forest plot | 5 | 473 | Risk Ratio (IV, Random, 95% CI) | 0.89 [0.15, 5.09] |
| 4.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 4 | 310 | Mean Difference (IV, Random, 95% CI) | 0.33 [‐3.39, 4.04] |
| 4.5 Serious adverse effects of drugs Show forest plot | 2 | 120 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.6 Maternal infection Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 2.38 [0.24, 23.84] |
| 4.7 Cessation of treatment due to adverse effects Show forest plot | 3 | 281 | Risk Ratio (IV, Random, 95% CI) | 9.82 [1.25, 77.31] |
| 4.8 Birth before 28 weeks' gestation Show forest plot | 1 | 145 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.60, 2.05] |
| 4.9 Birth before 32 weeks' gestation Show forest plot | 2 | 301 | Risk Ratio (IV, Random, 95% CI) | 1.14 [0.92, 1.43] |
| 4.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.11 Birth before 37 weeks' gestation Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 0.79 [0.15, 4.17] |
| 4.12 Maternal death Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.13 Pulmonary oedema Show forest plot | 2 | 65 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.16 Headaches Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 3.00 [0.13, 68.26] |
| 4.17 Nausea or vomiting Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.18 Tachycardia Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 4.20 Maternal hypotension Show forest plot | 1 | 156 | Risk Ratio (IV, Random, 95% CI) | 3.16 [0.13, 76.30] |
| 4.21 Perinatal death Show forest plot | 5 | 476 | Risk Ratio (IV, Random, 95% CI) | 1.07 [0.16, 7.15] |
| 4.22 Stillbirth Show forest plot | 3 | 410 | Risk Ratio (IV, Random, 95% CI) | 5.70 [0.28, 116.87] |
| 4.23 Neonatal death before 7 days Show forest plot | 3 | 351 | Risk Ratio (IV, Random, 95% CI) | 2.37 [0.43, 13.01] |
| 4.24 Neurodevelopmental morbidity Show forest plot | 4 | 445 | Risk Ratio (IV, Random, 95% CI) | 0.63 [0.20, 1.96] |
| 4.25 Gastrointestinal morbidity Show forest plot | 4 | 445 | Risk Ratio (IV, Random, 95% CI) | 0.90 [0.39, 2.12] |
| 4.26 Respiratory morbidity Show forest plot | 5 | 475 | Risk Ratio (IV, Random, 95% CI) | 1.10 [0.68, 1.78] |
| 4.27 Mean birthweight Show forest plot | 5 | 475 | Mean Difference (IV, Random, 95% CI) | 12.65 [‐99.04, 124.35] |
| 4.28 Birthweight < 2000 g Show forest plot | 2 | 191 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.82, 1.41] |
| 4.29 Birthweight < 2500 g Show forest plot | 2 | 202 | Risk Ratio (IV, Random, 95% CI) | 0.95 [0.83, 1.09] |
| 4.30 Gestational age at birth Show forest plot | 5 | 456 | Mean Difference (IV, Random, 95% CI) | ‐0.61 [‐1.35, 0.12] |
| 4.31 Neonatal infection Show forest plot | 3 | 219 | Risk Ratio (IV, Random, 95% CI) | 0.74 [0.26, 2.15] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 5.1 Delay in birth by 48 hours Show forest plot | 3 | 653 | Risk Ratio (IV, Random, 95% CI) | 1.07 [0.91, 1.27] |
| 5.2 Delay in birth by 7 days Show forest plot | 3 | 604 | Risk Ratio (IV, Random, 95% CI) | 1.23 [1.11, 1.37] |
| 5.3 Neonatal death before 28 days Show forest plot | 3 | 769 | Risk Ratio (IV, Random, 95% CI) | 4.10 [0.88, 19.13] |
| 5.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 5.5 Serious adverse effects of drugs Show forest plot | 4 | 799 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.7 Cessation of treatment due to adverse effects Show forest plot | 4 | 727 | Risk Ratio (IV, Random, 95% CI) | 4.02 [2.05, 7.85] |
| 5.8 Birth before 28 weeks' gestation Show forest plot | 1 | 501 | Risk Ratio (IV, Random, 95% CI) | 3.11 [1.02, 9.51] |
| 5.9 Birth before 32 weeks' gestation Show forest plot | 1 | 287 | Risk Ratio (IV, Random, 95% CI) | 1.33 [0.83, 2.14] |
| 5.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.11 Birth before 37 weeks' gestation Show forest plot | 3 | 690 | Risk Ratio (IV, Random, 95% CI) | 1.13 [0.98, 1.31] |
| 5.12 Maternal death Show forest plot | 2 | 524 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.16 Headaches Show forest plot | 2 | 176 | Risk Ratio (IV, Random, 95% CI) | 1.62 [0.13, 19.74] |
| 5.17 Nausea or vomiting Show forest plot | 2 | 176 | Risk Ratio (IV, Random, 95% CI) | 1.60 [0.27, 9.57] |
| 5.18 Tachycardia Show forest plot | 1 | 501 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.14, 7.07] |
| 5.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.21 Perinatal death Show forest plot | 2 | 729 | Risk Ratio (IV, Random, 95% CI) | 2.25 [0.79, 6.38] |
| 5.22 Stillbirth Show forest plot | 3 | 769 | Risk Ratio (IV, Random, 95% CI) | 0.41 [0.04, 4.08] |
| 5.23 Neonatal death before 7 days Show forest plot | 2 | 746 | Risk Ratio (IV, Random, 95% CI) | 6.15 [0.74, 50.73] |
| 5.24 Neurodevelopmental morbidity Show forest plot | 1 | 489 | Risk Ratio (IV, Random, 95% CI) | 0.85 [0.45, 1.62] |
| 5.25 Gastrointestinal morbidity Show forest plot | 1 | 575 | Risk Ratio (IV, Random, 95% CI) | 0.21 [0.02, 1.76] |
| 5.26 Respiratory morbidity Show forest plot | 5 | 939 | Risk Ratio (IV, Random, 95% CI) | 1.22 [0.90, 1.66] |
| 5.27 Mean birthweight Show forest plot | 4 | 779 | Mean Difference (IV, Random, 95% CI) | ‐68.13 [‐228.13, 91.88] |
| 5.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 5.30 Gestational age at birth Show forest plot | 2 | 135 | Mean Difference (IV, Random, 95% CI) | ‐0.39 [‐1.41, 0.62] |
| 5.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 6.1 Delay in birth by 48 hours Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 1.18 [0.76, 1.84] |
| 6.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.3 Neonatal death before 28 days Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 0.49 [0.07, 3.64] |
| 6.4 Pregnancy prolongation (Time from trial entry to birth in days) Show forest plot | 2 | 186 | Mean Difference (IV, Random, 95% CI) | 11.91 [3.53, 20.28] |
| 6.5 Serious adverse effects of drugs Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.8 Birth before 28 weeks' gestation Show forest plot | 1 | 153 | Risk Ratio (IV, Random, 95% CI) | 0.50 [0.23, 1.09] |
| 6.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.10 Birth before 34 weeks' gestation Show forest plot | 1 | 153 | Risk Ratio (IV, Random, 95% CI) | 0.93 [0.61, 1.41] |
| 6.11 Birth before 37 weeks' gestation Show forest plot | 2 | 303 | Risk Ratio (IV, Random, 95% CI) | 0.57 [0.17, 1.90] |
| 6.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.13 Pulmonary oedema Show forest plot | 1 | 33 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.16 Headaches Show forest plot | 2 | 309 | Risk Ratio (IV, Random, 95% CI) | 2.00 [1.35, 2.97] |
| 6.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.18 Tachycardia Show forest plot | 1 | 156 | Risk Ratio (IV, Random, 95% CI) | 4.63 [0.23, 94.99] |
| 6.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.20 Maternal hypotension Show forest plot | 2 | 309 | Risk Ratio (IV, Random, 95% CI) | 2.51 [0.31, 20.64] |
| 6.21 Perinatal death Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 0.41 [0.06, 3.00] |
| 6.22 Stillbirth Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 0.36 [0.01, 8.59] |
| 6.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.24 Neurodevelopmental morbidity Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 1.06 [0.16, 7.04] |
| 6.25 Gastrointestinal morbidity Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 0.75 [0.06, 9.46] |
| 6.26 Respiratory morbidity Show forest plot | 2 | 186 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.12, 1.00] |
| 6.27 Mean birthweight Show forest plot | 1 | 33 | Mean Difference (IV, Random, 95% CI) | 327.00 [‐272.13, 926.13] |
| 6.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 6.30 Gestational age at birth Show forest plot | 2 | 186 | Mean Difference (IV, Random, 95% CI) | 1.13 [‐0.46, 2.71] |
| 6.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 7.1 Delay in birth by 48 hours Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | 1.05 [0.84, 1.31] |
| 7.2 Delay in birth by 7 days Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | 0.92 [0.67, 1.28] |
| 7.3 Neonatal death before 28 days Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 1 | 54 | Mean Difference (IV, Random, 95% CI) | ‐6.10 [‐13.54, 1.34] |
| 7.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.11 Birth before 37 weeks' gestation Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | 1.32 [0.90, 1.95] |
| 7.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.21 Perinatal death Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.22 Stillbirth Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.23 Neonatal death before 7 days Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.24 Neurodevelopmental morbidity Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.25 Gastrointestinal morbidity Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.26 Respiratory morbidity Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.27 Mean birthweight Show forest plot | 1 | 54 | Mean Difference (IV, Random, 95% CI) | ‐287.00 [‐562.65, ‐11.35] |
| 7.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 7.30 Gestational age at birth Show forest plot | 1 | 54 | Mean Difference (IV, Random, 95% CI) | ‐0.80 [‐1.87, 0.27] |
| 7.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 8.1 Delay in birth by 48 hours Show forest plot | 20 | 1649 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.90, 1.01] |
| 8.2 Delay in birth by 7 days Show forest plot | 13 | 1092 | Risk Ratio (IV, Random, 95% CI) | 0.95 [0.86, 1.03] |
| 8.3 Neonatal death before 28 days Show forest plot | 17 | 1216 | Risk Ratio (IV, Random, 95% CI) | 1.22 [0.68, 2.20] |
| 8.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 12 | 887 | Mean Difference (IV, Random, 95% CI) | ‐3.91 [‐7.03, ‐0.79] |
| 8.5 Serious adverse effects of drugs Show forest plot | 18 | 1556 | Risk Ratio (IV, Random, 95% CI) | 4.25 [1.32, 13.66] |
| 8.6 Maternal infection Show forest plot | 1 | 49 | Risk Ratio (IV, Random, 95% CI) | 0.22 [0.01, 4.46] |
| 8.7 Cessation of treatment due to adverse effects Show forest plot | 18 | 1422 | Risk Ratio (IV, Random, 95% CI) | 4.35 [2.05, 9.25] |
| 8.8 Birth before 28 weeks' gestation Show forest plot | 1 | 91 | Risk Ratio (IV, Random, 95% CI) | 7.80 [0.41, 146.74] |
| 8.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 8.10 Birth before 34 weeks' gestation Show forest plot | 8 | 794 | Risk Ratio (IV, Random, 95% CI) | 1.25 [1.09, 1.44] |
| 8.11 Birth before 37 weeks' gestation Show forest plot | 14 | 1098 | Risk Ratio (IV, Random, 95% CI) | 1.11 [1.00, 1.23] |
| 8.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 8.13 Pulmonary oedema Show forest plot | 7 | 622 | Risk Ratio (IV, Random, 95% CI) | 3.39 [0.83, 13.79] |
| 8.14 Dyspnoea Show forest plot | 5 | 374 | Risk Ratio (IV, Random, 95% CI) | 5.59 [1.25, 25.07] |
| 8.15 Palpitations Show forest plot | 12 | 903 | Risk Ratio (IV, Random, 95% CI) | 5.18 [3.60, 7.44] |
| 8.16 Headaches Show forest plot | 16 | 1187 | Risk Ratio (IV, Random, 95% CI) | 0.66 [0.43, 1.03] |
| 8.17 Nausea or vomiting Show forest plot | 13 | 991 | Risk Ratio (IV, Random, 95% CI) | 3.43 [2.22, 5.30] |
| 8.18 Tachycardia Show forest plot | 10 | 596 | Risk Ratio (IV, Random, 95% CI) | 3.55 [1.80, 7.01] |
| 8.19 Maternal cardiac arrhythmias Show forest plot | 1 | 66 | Risk Ratio (IV, Random, 95% CI) | 5.00 [0.25, 100.32] |
| 8.20 Maternal hypotension Show forest plot | 14 | 1046 | Risk Ratio (IV, Random, 95% CI) | 1.56 [0.76, 3.24] |
| 8.21 Perinatal death Show forest plot | 19 | 1391 | Risk Ratio (IV, Random, 95% CI) | 1.33 [0.81, 2.18] |
| 8.22 Stillbirth Show forest plot | 15 | 1135 | Risk Ratio (IV, Random, 95% CI) | 1.85 [0.38, 8.98] |
| 8.23 Neonatal death before 7 days Show forest plot | 17 | 1226 | Risk Ratio (IV, Random, 95% CI) | 1.31 [0.70, 2.48] |
| 8.24 Neurodevelopmental morbidity Show forest plot | 8 | 654 | Risk Ratio (IV, Random, 95% CI) | 1.80 [1.14, 2.85] |
| 8.25 Gastrointestinal morbidity Show forest plot | 6 | 551 | Risk Ratio (IV, Random, 95% CI) | 4.79 [1.05, 21.90] |
| 8.26 Respiratory morbidity Show forest plot | 15 | 1191 | Risk Ratio (IV, Random, 95% CI) | 1.44 [1.08, 1.92] |
| 8.27 Mean birthweight Show forest plot | 19 | 1434 | Mean Difference (IV, Random, 95% CI) | ‐126.47 [‐207.03, ‐45.91] |
| 8.28 Birthweight < 2000 g Show forest plot | 1 | 53 | Risk Ratio (IV, Random, 95% CI) | 1.74 [1.04, 2.91] |
| 8.29 Birthweight < 2500 g Show forest plot | 5 | 292 | Risk Ratio (IV, Random, 95% CI) | 1.14 [0.92, 1.40] |
| 8.30 Gestational age at birth Show forest plot | 13 | 1098 | Mean Difference (IV, Random, 95% CI) | ‐0.76 [‐1.14, ‐0.38] |
| 8.31 Neonatal infection Show forest plot | 8 | 686 | Risk Ratio (IV, Random, 95% CI) | 1.31 [0.86, 2.00] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 9.1 Delay in birth by 48 hours Show forest plot | 2 | 100 | Risk Ratio (IV, Random, 95% CI) | 0.84 [0.72, 0.99] |
| 9.2 Delay in birth by 7 days Show forest plot | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.63, 1.51] |
| 9.3 Neonatal death before 28 days Show forest plot | 3 | 114 | Risk Ratio (IV, Random, 95% CI) | 0.73 [0.09, 5.66] |
| 9.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 2 | 78 | Mean Difference (IV, Random, 95% CI) | ‐7.07 [‐18.16, 4.01] |
| 9.5 Serious adverse effects of drugs Show forest plot | 3 | 120 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.7 Cessation of treatment due to adverse effects Show forest plot | 2 | 60 | Risk Ratio (IV, Random, 95% CI) | 3.63 [0.16, 84.11] |
| 9.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.11 Birth before 37 weeks' gestation Show forest plot | 2 | 80 | Risk Ratio (IV, Random, 95% CI) | 0.53 [0.28, 0.99] |
| 9.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.13 Pulmonary oedema Show forest plot | 2 | 80 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.14 Dyspnoea Show forest plot | 3 | 120 | Risk Ratio (IV, Random, 95% CI) | 9.79 [1.30, 73.81] |
| 9.15 Palpitations Show forest plot | 2 | 100 | Risk Ratio (IV, Random, 95% CI) | 10.10 [2.00, 51.05] |
| 9.16 Headaches Show forest plot | 1 | 40 | Risk Ratio (IV, Random, 95% CI) | 11.00 [1.53, 78.86] |
| 9.17 Nausea or vomiting Show forest plot | 3 | 120 | Risk Ratio (IV, Random, 95% CI) | 0.87 [0.47, 1.61] |
| 9.18 Tachycardia Show forest plot | 2 | 80 | Risk Ratio (IV, Random, 95% CI) | 11.00 [0.69, 175.86] |
| 9.19 Maternal cardiac arrhythmias Show forest plot | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.20 Maternal hypotension Show forest plot | 2 | 80 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.21 Perinatal death Show forest plot | 3 | 114 | Risk Ratio (IV, Random, 95% CI) | 0.73 [0.09, 5.66] |
| 9.22 Stillbirth Show forest plot | 1 | 20 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.23 Neonatal death before 7 days Show forest plot | 2 | 69 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.01, 8.12] |
| 9.24 Neurodevelopmental morbidity Show forest plot | 3 | 114 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.14, 2.59] |
| 9.25 Gastrointestinal morbidity Show forest plot | 2 | 69 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.01, 8.12] |
| 9.26 Respiratory morbidity Show forest plot | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.12, 3.71] |
| 9.27 Mean birthweight Show forest plot | 2 | 94 | Mean Difference (IV, Random, 95% CI) | ‐192.87 [‐590.66, 204.92] |
| 9.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 9.30 Gestational age at birth Show forest plot | 2 | 89 | Mean Difference (IV, Random, 95% CI) | ‐1.55 [‐3.49, 0.40] |
| 9.31 Neonatal infection Show forest plot | 2 | 69 | Risk Ratio (IV, Random, 95% CI) | 1.04 [0.07, 15.73] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 10.1 Delay in birth by 48 hours Show forest plot | 2 | 370 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.88, 1.20] |
| 10.2 Delay in birth by 7 days Show forest plot | 4 | 629 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.89, 1.12] |
| 10.3 Neonatal death before 28 days Show forest plot | 2 | 427 | Risk Ratio (IV, Random, 95% CI) | 1.28 [0.21, 7.89] |
| 10.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 2 | 365 | Mean Difference (IV, Random, 95% CI) | ‐4.15 [‐15.90, 7.60] |
| 10.5 Serious adverse effects of drugs Show forest plot | 3 | 559 | Risk Ratio (IV, Random, 95% CI) | 2.91 [0.12, 70.50] |
| 10.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.7 Cessation of treatment due to adverse effects Show forest plot | 3 | 394 | Risk Ratio (IV, Random, 95% CI) | 2.79 [0.05, 145.73] |
| 10.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.9 Birth before 32 weeks' gestation Show forest plot | 1 | 233 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.54, 1.84] |
| 10.10 Birth before 34 weeks' gestation Show forest plot | 2 | 365 | Risk Ratio (IV, Random, 95% CI) | 1.40 [0.70, 2.79] |
| 10.11 Birth before 37 weeks' gestation Show forest plot | 4 | 627 | Risk Ratio (IV, Random, 95% CI) | 1.26 [0.92, 1.72] |
| 10.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.13 Pulmonary oedema Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | 2.91 [0.12, 70.50] |
| 10.14 Dyspnoea Show forest plot | 2 | 217 | Risk Ratio (IV, Random, 95% CI) | 10.45 [2.13, 51.30] |
| 10.15 Palpitations Show forest plot | 3 | 349 | Risk Ratio (IV, Random, 95% CI) | 11.11 [2.61, 47.27] |
| 10.16 Headaches Show forest plot | 3 | 349 | Risk Ratio (IV, Random, 95% CI) | 0.24 [0.06, 0.93] |
| 10.17 Nausea or vomiting Show forest plot | 3 | 349 | Risk Ratio (IV, Random, 95% CI) | 1.91 [0.85, 4.31] |
| 10.18 Tachycardia Show forest plot | 2 | 323 | Risk Ratio (IV, Random, 95% CI) | 31.40 [9.12, 108.19] |
| 10.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.21 Perinatal death Show forest plot | 3 | 559 | Risk Ratio (IV, Random, 95% CI) | 1.98 [0.67, 5.86] |
| 10.22 Stillbirth Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | 2.91 [0.12, 70.50] |
| 10.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.24 Neurodevelopmental morbidity Show forest plot | 1 | 236 | Risk Ratio (IV, Random, 95% CI) | 4.14 [0.90, 19.08] |
| 10.25 Gastrointestinal morbidity Show forest plot | 1 | 236 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.45, 2.39] |
| 10.26 Respiratory morbidity Show forest plot | 1 | 236 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.43, 2.51] |
| 10.27 Mean birthweight Show forest plot | 1 | 132 | Mean Difference (IV, Random, 95% CI) | ‐481.00 [‐766.78, ‐195.22] |
| 10.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 10.29 Birthweight < 2500 g Show forest plot | 1 | 132 | Risk Ratio (IV, Random, 95% CI) | 2.28 [1.34, 3.88] |
| 10.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 10.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 11.1 Delay in birth by 48 hours Show forest plot | 2 | 64 | Risk Ratio (IV, Random, 95% CI) | 1.23 [0.84, 1.82] |
| 11.2 Delay in birth by 7 days Show forest plot | 2 | 64 | Risk Ratio (IV, Random, 95% CI) | 1.35 [0.71, 2.56] |
| 11.3 Neonatal death before 28 days Show forest plot | 2 | 89 | Risk Ratio (IV, Random, 95% CI) | 0.57 [0.07, 4.42] |
| 11.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 2 | 91 | Mean Difference (IV, Random, 95% CI) | 9.13 [4.93, 13.34] |
| 11.5 Serious adverse effects of drugs Show forest plot | 1 | 57 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.6 Maternal infection Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 2.11 [0.47, 9.42] |
| 11.7 Cessation of treatment due to adverse effects Show forest plot | 2 | 106 | Risk Ratio (IV, Random, 95% CI) | 4.25 [0.22, 82.57] |
| 11.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.11 Birth before 37 weeks' gestation Show forest plot | 4 | 219 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.53, 2.21] |
| 11.12 Maternal death Show forest plot | 2 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.13 Pulmonary oedema Show forest plot | 2 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.18 Tachycardia Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 4.25 [0.22, 82.57] |
| 11.19 Maternal cardiac arrhythmias Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 2.55 [0.11, 58.60] |
| 11.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.21 Perinatal death Show forest plot | 2 | 89 | Risk Ratio (IV, Random, 95% CI) | 0.57 [0.07, 4.42] |
| 11.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 11.23 Neonatal death before 7 days Show forest plot | 1 | 54 | Risk Ratio (IV, Random, 95% CI) | 0.33 [0.01, 7.84] |
| 11.24 Neurodevelopmental morbidity Show forest plot | 2 | 89 | Risk Ratio (IV, Random, 95% CI) | 2.41 [0.82, 7.07] |
| 11.25 Gastrointestinal morbidity Show forest plot | 2 | 89 | Risk Ratio (IV, Random, 95% CI) | 0.72 [0.09, 5.58] |
| 11.26 Respiratory morbidity Show forest plot | 2 | 88 | Risk Ratio (IV, Random, 95% CI) | 0.87 [0.46, 1.67] |
| 11.27 Mean birthweight Show forest plot | 3 | 145 | Mean Difference (IV, Random, 95% CI) | 144.92 [‐27.73, 317.58] |
| 11.28 Birthweight < 2000 g Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.60, 1.38] |
| 11.29 Birthweight < 2500 g Show forest plot | 2 | 66 | Risk Ratio (IV, Random, 95% CI) | 1.01 [0.86, 1.19] |
| 11.30 Gestational age at birth Show forest plot | 2 | 89 | Mean Difference (IV, Random, 95% CI) | 0.87 [‐1.38, 3.12] |
| 11.31 Neonatal infection Show forest plot | 1 | 35 | Risk Ratio (IV, Random, 95% CI) | 2.95 [0.71, 12.24] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 12.1 Delay in birth by 48 hours Show forest plot | 7 | 1087 | Risk Ratio (IV, Random, 95% CI) | 0.99 [0.94, 1.04] |
| 12.2 Delay in birth by 7 days Show forest plot | 7 | 1087 | Risk Ratio (IV, Random, 95% CI) | 0.92 [0.81, 1.05] |
| 12.3 Neonatal death before 28 days Show forest plot | 7 | 1382 | Risk Ratio (IV, Random, 95% CI) | 1.52 [0.60, 3.87] |
| 12.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 2 | 206 | Mean Difference (IV, Random, 95% CI) | ‐21.26 [‐27.02, ‐15.50] |
| 12.5 Serious adverse effects of drugs Show forest plot | 6 | 986 | Risk Ratio (IV, Random, 95% CI) | 1.52 [0.39, 5.94] |
| 12.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 12.7 Cessation of treatment due to adverse effects Show forest plot | 6 | 1268 | Risk Ratio (IV, Random, 95% CI) | 17.82 [7.83, 40.54] |
| 12.8 Birth before 28 weeks' gestation Show forest plot | 2 | 324 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.63, 1.87] |
| 12.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 12.10 Birth before 34 weeks' gestation Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.95, 1.05] |
| 12.11 Birth before 37 weeks' gestation Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.95, 1.05] |
| 12.12 Maternal death Show forest plot | 1 | 45 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 12.13 Pulmonary oedema Show forest plot | 3 | 616 | Risk Ratio (IV, Random, 95% CI) | 1.61 [0.20, 12.95] |
| 12.14 Dyspnoea Show forest plot | 5 | 941 | Risk Ratio (IV, Random, 95% CI) | 9.77 [3.75, 25.44] |
| 12.15 Palpitations Show forest plot | 4 | 861 | Risk Ratio (IV, Random, 95% CI) | 8.69 [2.75, 27.48] |
| 12.16 Headaches Show forest plot | 6 | 1243 | Risk Ratio (IV, Random, 95% CI) | 1.98 [1.40, 2.80] |
| 12.17 Nausea or vomiting Show forest plot | 6 | 1243 | Risk Ratio (IV, Random, 95% CI) | 1.97 [1.18, 3.30] |
| 12.18 Tachycardia Show forest plot | 7 | 1288 | Risk Ratio (IV, Random, 95% CI) | 18.28 [8.16, 40.94] |
| 12.19 Maternal cardiac arrhythmias Show forest plot | 1 | 247 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.01, 8.44] |
| 12.20 Maternal hypotension Show forest plot | 4 | 861 | Risk Ratio (IV, Random, 95% CI) | 1.58 [0.60, 4.17] |
| 12.21 Perinatal death Show forest plot | 7 | 1382 | Risk Ratio (IV, Random, 95% CI) | 1.60 [0.65, 3.92] |
| 12.22 Stillbirth Show forest plot | 6 | 1088 | Risk Ratio (IV, Random, 95% CI) | 1.80 [0.17, 19.66] |
| 12.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 12.24 Neurodevelopmental morbidity Show forest plot | 5 | 1196 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.67, 1.80] |
| 12.25 Gastrointestinal morbidity Show forest plot | 1 | 292 | Risk Ratio (IV, Random, 95% CI) | 4.21 [0.27, 66.35] |
| 12.26 Respiratory morbidity Show forest plot | 6 | 1300 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.63, 1.46] |
| 12.27 Mean birthweight Show forest plot | 7 | 1176 | Mean Difference (IV, Random, 95% CI) | ‐25.73 [‐122.06, 70.60] |
| 12.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 12.29 Birthweight < 2500 g Show forest plot | 2 | 575 | Risk Ratio (IV, Random, 95% CI) | 1.02 [0.77, 1.36] |
| 12.30 Gestational age at birth Show forest plot | 7 | 1090 | Mean Difference (IV, Random, 95% CI) | ‐0.44 [‐1.21, 0.34] |
| 12.31 Neonatal infection Show forest plot | 6 | 1311 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.68, 1.72] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 13.1 Delay in birth by 48 hours Show forest plot | 8 | 687 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.89, 1.03] |
| 13.2 Delay in birth by 7 days Show forest plot | 5 | 391 | Risk Ratio (IV, Random, 95% CI) | 0.97 [0.88, 1.08] |
| 13.3 Neonatal death before 28 days Show forest plot | 4 | 296 | Risk Ratio (IV, Random, 95% CI) | 1.57 [0.53, 4.65] |
| 13.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 4 | 223 | Mean Difference (IV, Random, 95% CI) | 0.42 [‐8.91, 9.74] |
| 13.5 Serious adverse effects of drugs Show forest plot | 5 | 392 | Risk Ratio (IV, Random, 95% CI) | 2.90 [0.31, 26.80] |
| 13.6 Maternal infection Show forest plot | 2 | 128 | Risk Ratio (IV, Random, 95% CI) | 1.16 [0.17, 7.96] |
| 13.7 Cessation of treatment due to adverse effects Show forest plot | 9 | 580 | Risk Ratio (IV, Random, 95% CI) | 2.36 [0.62, 8.95] |
| 13.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.11 Birth before 37 weeks' gestation Show forest plot | 3 | 399 | Risk Ratio (IV, Random, 95% CI) | 1.14 [0.96, 1.36] |
| 13.12 Maternal death Show forest plot | 1 | 131 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.13 Pulmonary oedema Show forest plot | 3 | 315 | Risk Ratio (IV, Random, 95% CI) | 3.00 [0.13, 71.00] |
| 13.14 Dyspnoea Show forest plot | 2 | 149 | Risk Ratio (IV, Random, 95% CI) | 4.09 [0.69, 24.17] |
| 13.15 Palpitations Show forest plot | 2 | 191 | Risk Ratio (IV, Random, 95% CI) | 5.17 [0.84, 31.73] |
| 13.16 Headaches Show forest plot | 1 | 71 | Risk Ratio (IV, Random, 95% CI) | 2.06 [0.20, 21.68] |
| 13.17 Nausea or vomiting Show forest plot | 5 | 486 | Risk Ratio (IV, Random, 95% CI) | 0.80 [0.43, 1.50] |
| 13.18 Tachycardia Show forest plot | 5 | 556 | Risk Ratio (IV, Random, 95% CI) | 1.56 [1.05, 2.30] |
| 13.19 Maternal cardiac arrhythmias Show forest plot | 1 | 106 | Risk Ratio (IV, Random, 95% CI) | 2.89 [0.12, 69.40] |
| 13.20 Maternal hypotension Show forest plot | 4 | 313 | Risk Ratio (IV, Random, 95% CI) | 1.70 [0.79, 3.65] |
| 13.21 Perinatal death Show forest plot | 6 | 611 | Risk Ratio (IV, Random, 95% CI) | 1.60 [0.82, 3.12] |
| 13.22 Stillbirth Show forest plot | 4 | 369 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.23 Neonatal death before 7 days Show forest plot | 1 | 107 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.24 Neurodevelopmental morbidity Show forest plot | 1 | 97 | Risk Ratio (IV, Random, 95% CI) | 3.76 [0.44, 32.44] |
| 13.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 13.26 Respiratory morbidity Show forest plot | 1 | 70 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.24, 1.47] |
| 13.27 Mean birthweight Show forest plot | 6 | 391 | Mean Difference (IV, Random, 95% CI) | ‐70.71 [‐193.64, 52.22] |
| 13.28 Birthweight < 2000 g Show forest plot | 1 | 24 | Risk Ratio (IV, Random, 95% CI) | 1.18 [0.08, 16.78] |
| 13.29 Birthweight < 2500 g Show forest plot | 4 | 360 | Risk Ratio (IV, Random, 95% CI) | 1.33 [0.92, 1.92] |
| 13.30 Gestational age at birth Show forest plot | 3 | 239 | Mean Difference (IV, Random, 95% CI) | ‐0.17 [‐0.76, 0.42] |
| 13.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 14.1 Delay in birth by 48 hours Show forest plot | 3 | 342 | Risk Ratio (IV, Random, 95% CI) | 1.15 [0.90, 1.48] |
| 14.2 Delay in birth by 7 days Show forest plot | 3 | 342 | Risk Ratio (IV, Random, 95% CI) | 1.13 [0.87, 1.48] |
| 14.3 Neonatal death before 28 days Show forest plot | 1 | 222 | Risk Ratio (IV, Random, 95% CI) | 0.49 [0.15, 1.64] |
| 14.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 1 | 191 | Mean Difference (IV, Random, 95% CI) | ‐1.00 [‐7.09, 5.09] |
| 14.5 Serious adverse effects of drugs Show forest plot | 2 | 270 | Risk Ratio (IV, Random, 95% CI) | 3.57 [0.40, 31.81] |
| 14.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.7 Cessation of treatment due to adverse effects Show forest plot | 2 | 270 | Risk Ratio (IV, Random, 95% CI) | 1.13 [0.31, 4.18] |
| 14.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.10 Birth before 34 weeks' gestation Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | 1.09 [0.88, 1.35] |
| 14.11 Birth before 37 weeks' gestation Show forest plot | 2 | 263 | Risk Ratio (IV, Random, 95% CI) | 0.94 [0.84, 1.04] |
| 14.12 Maternal death Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.13 Pulmonary oedema Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.15 Palpitations Show forest plot | 1 | 79 | Risk Ratio (IV, Random, 95% CI) | 6.83 [0.36, 128.02] |
| 14.16 Headaches Show forest plot | 1 | 79 | Risk Ratio (IV, Random, 95% CI) | 6.83 [0.36, 128.02] |
| 14.17 Nausea or vomiting Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | 2.51 [0.10, 60.95] |
| 14.18 Tachycardia Show forest plot | 1 | 191 | Risk Ratio (IV, Random, 95% CI) | 7.53 [0.97, 58.27] |
| 14.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.20 Maternal hypotension Show forest plot | 3 | 342 | Risk Ratio (IV, Random, 95% CI) | 10.85 [2.05, 57.34] |
| 14.21 Perinatal death Show forest plot | 2 | 301 | Risk Ratio (IV, Random, 95% CI) | 0.44 [0.14, 1.33] |
| 14.22 Stillbirth Show forest plot | 1 | 222 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.24 Neurodevelopmental morbidity Show forest plot | 1 | 222 | Risk Ratio (IV, Random, 95% CI) | 0.62 [0.29, 1.33] |
| 14.25 Gastrointestinal morbidity Show forest plot | 1 | 222 | Risk Ratio (IV, Random, 95% CI) | 0.69 [0.19, 2.51] |
| 14.26 Respiratory morbidity Show forest plot | 1 | 222 | Risk Ratio (IV, Random, 95% CI) | 0.70 [0.49, 1.01] |
| 14.27 Mean birthweight Show forest plot | 2 | 294 | Mean Difference (IV, Random, 95% CI) | 101.46 [‐80.34, 283.27] |
| 14.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 14.30 Gestational age at birth Show forest plot | 3 | 342 | Mean Difference (IV, Random, 95% CI) | ‐0.24 [‐1.26, 0.78] |
| 14.31 Neonatal infection Show forest plot | 1 | 222 | Risk Ratio (IV, Random, 95% CI) | 0.67 [0.30, 1.45] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 15.1 Delay in birth by 48 hours Show forest plot | 4 | 623 | Risk Ratio (IV, Random, 95% CI) | 1.01 [0.95, 1.07] |
| 15.2 Delay in birth by 7 days Show forest plot | 1 | 189 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.84, 1.40] |
| 15.3 Neonatal death before 28 days Show forest plot | 4 | 642 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.18, 1.91] |
| 15.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 3 | 401 | Mean Difference (IV, Random, 95% CI) | ‐1.33 [‐7.20, 4.53] |
| 15.5 Serious adverse effects of drugs Show forest plot | 3 | 471 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.05, 2.61] |
| 15.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 15.7 Cessation of treatment due to adverse effects Show forest plot | 3 | 401 | Risk Ratio (IV, Random, 95% CI) | 1.95 [0.29, 13.02] |
| 15.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 15.9 Birth before 32 weeks' gestation Show forest plot | 2 | 312 | Risk Ratio (IV, Random, 95% CI) | 0.76 [0.52, 1.11] |
| 15.10 Birth before 34 weeks' gestation Show forest plot | 2 | 279 | Risk Ratio (IV, Random, 95% CI) | 0.93 [0.77, 1.12] |
| 15.11 Birth before 37 weeks' gestation Show forest plot | 4 | 591 | Risk Ratio (IV, Random, 95% CI) | 0.91 [0.84, 0.99] |
| 15.12 Maternal death Show forest plot | 1 | 189 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 15.13 Pulmonary oedema Show forest plot | 2 | 381 | Risk Ratio (IV, Random, 95% CI) | 0.18 [0.02, 1.61] |
| 15.14 Dyspnoea Show forest plot | 2 | 381 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.13, 0.95] |
| 15.15 Palpitations Show forest plot | 1 | 192 | Risk Ratio (IV, Random, 95% CI) | 0.31 [0.01, 7.44] |
| 15.16 Headaches Show forest plot | 3 | 434 | Risk Ratio (IV, Random, 95% CI) | 1.69 [0.92, 3.11] |
| 15.17 Nausea or vomiting Show forest plot | 4 | 623 | Risk Ratio (IV, Random, 95% CI) | 0.19 [0.09, 0.38] |
| 15.18 Tachycardia Show forest plot | 1 | 189 | Risk Ratio (IV, Random, 95% CI) | 7.36 [0.95, 56.91] |
| 15.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 15.20 Maternal hypotension Show forest plot | 5 | 713 | Risk Ratio (IV, Random, 95% CI) | 2.11 [0.56, 7.88] |
| 15.21 Perinatal death Show forest plot | 4 | 647 | Risk Ratio (IV, Random, 95% CI) | 0.69 [0.23, 2.11] |
| 15.22 Stillbirth Show forest plot | 4 | 642 | Risk Ratio (IV, Random, 95% CI) | 2.41 [0.10, 57.65] |
| 15.23 Neonatal death before 7 days Show forest plot | 3 | 428 | Risk Ratio (IV, Random, 95% CI) | 0.32 [0.01, 7.80] |
| 15.24 Neurodevelopmental morbidity Show forest plot | 2 | 430 | Risk Ratio (IV, Random, 95% CI) | 0.71 [0.34, 1.49] |
| 15.25 Gastrointestinal morbidity Show forest plot | 2 | 430 | Risk Ratio (IV, Random, 95% CI) | 0.64 [0.18, 2.31] |
| 15.26 Respiratory morbidity Show forest plot | 3 | 520 | Risk Ratio (IV, Random, 95% CI) | 0.77 [0.57, 1.04] |
| 15.27 Mean birthweight Show forest plot | 4 | 672 | Mean Difference (IV, Random, 95% CI) | ‐0.97 [‐61.12, 59.18] |
| 15.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 15.29 Birthweight < 2500 g Show forest plot | 2 | 306 | Risk Ratio (IV, Random, 95% CI) | 0.77 [0.55, 1.06] |
| 15.30 Gestational age at birth Show forest plot | 4 | 770 | Mean Difference (IV, Random, 95% CI) | 0.22 [‐0.11, 0.55] |
| 15.31 Neonatal infection Show forest plot | 2 | 430 | Risk Ratio (IV, Random, 95% CI) | 0.73 [0.36, 1.50] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 16.1 Delay in birth by 48 hours Show forest plot | 2 | 170 | Risk Ratio (IV, Random, 95% CI) | 0.90 [0.69, 1.17] |
| 16.2 Delay in birth by 7 days Show forest plot | 1 | 120 | Risk Ratio (IV, Random, 95% CI) | 0.79 [0.62, 1.00] |
| 16.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 16.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.7 Cessation of treatment due to adverse effects Show forest plot | 1 | 120 | Risk Ratio (IV, Random, 95% CI) | 5.00 [0.25, 102.00] |
| 16.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.16 Headaches Show forest plot | 2 | 170 | Risk Ratio (IV, Random, 95% CI) | 0.60 [0.13, 2.86] |
| 16.17 Nausea or vomiting Show forest plot | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.63 [0.30, 8.90] |
| 16.18 Tachycardia Show forest plot | 2 | 170 | Risk Ratio (IV, Random, 95% CI) | 3.24 [0.14, 75.91] |
| 16.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.20 Maternal hypotension Show forest plot | 2 | 170 | Risk Ratio (IV, Random, 95% CI) | 1.68 [0.82, 3.44] |
| 16.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.27 Mean birthweight Show forest plot | 1 | 120 | Mean Difference (IV, Random, 95% CI) | ‐277.00 [‐539.41, ‐14.59] |
| 16.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 16.30 Gestational age at birth Show forest plot | 2 | 220 | Mean Difference (IV, Random, 95% CI) | ‐1.21 [‐1.81, ‐0.61] |
| 16.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 17.1 Delay in birth by 48 hours Show forest plot | 3 | 728 | Risk Ratio (IV, Random, 95% CI) | 1.04 [0.96, 1.12] |
| 17.2 Delay in birth by 7 days Show forest plot | 3 | 728 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.95, 1.23] |
| 17.3 Neonatal death before 28 days Show forest plot | 1 | 189 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 3 | 728 | Mean Difference (IV, Random, 95% CI) | 3.14 [‐1.22, 7.49] |
| 17.5 Serious adverse effects of drugs Show forest plot | 1 | 503 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.6 Maternal infection Show forest plot | 1 | 503 | Risk Ratio (IV, Random, 95% CI) | 6.17 [0.75, 50.87] |
| 17.7 Cessation of treatment due to adverse effects Show forest plot | 2 | 646 | Risk Ratio (IV, Random, 95% CI) | 2.22 [0.95, 5.20] |
| 17.8 Birth before 28 weeks' gestation Show forest plot | 1 | 145 | Risk Ratio (IV, Random, 95% CI) | 0.47 [0.04, 5.03] |
| 17.9 Birth before 32 weeks' gestation Show forest plot | 1 | 172 | Risk Ratio (IV, Random, 95% CI) | 0.90 [0.70, 1.16] |
| 17.10 Birth before 34 weeks' gestation Show forest plot | 1 | 145 | Risk Ratio (IV, Random, 95% CI) | 0.59 [0.31, 1.12] |
| 17.11 Birth before 37 weeks' gestation Show forest plot | 1 | 145 | Risk Ratio (IV, Random, 95% CI) | 0.64 [0.47, 0.89] |
| 17.12 Maternal death Show forest plot | 1 | 499 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.13 Pulmonary oedema Show forest plot | 1 | 503 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.15 Palpitations Show forest plot | 2 | 225 | Risk Ratio (IV, Random, 95% CI) | 4.60 [0.53, 39.75] |
| 17.16 Headaches Show forest plot | 2 | 225 | Risk Ratio (IV, Random, 95% CI) | 1.33 [0.43, 4.13] |
| 17.17 Nausea or vomiting Show forest plot | 1 | 145 | Risk Ratio (IV, Random, 95% CI) | 2.80 [0.12, 67.68] |
| 17.18 Tachycardia Show forest plot | 2 | 225 | Risk Ratio (IV, Random, 95% CI) | 4.66 [0.82, 26.63] |
| 17.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.20 Maternal hypotension Show forest plot | 3 | 728 | Risk Ratio (IV, Random, 95% CI) | 3.53 [0.52, 23.91] |
| 17.21 Perinatal death Show forest plot | 2 | 780 | Risk Ratio (IV, Random, 95% CI) | 2.26 [0.94, 5.42] |
| 17.22 Stillbirth Show forest plot | 1 | 189 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.24 Neurodevelopmental morbidity Show forest plot | 2 | 780 | Risk Ratio (IV, Random, 95% CI) | 1.08 [0.21, 5.58] |
| 17.25 Gastrointestinal morbidity Show forest plot | 2 | 780 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.04, 8.60] |
| 17.26 Respiratory morbidity Show forest plot | 2 | 780 | Risk Ratio (IV, Random, 95% CI) | 0.58 [0.33, 1.03] |
| 17.27 Mean birthweight Show forest plot | 2 | 306 | Mean Difference (IV, Random, 95% CI) | 57.75 [‐40.38, 155.88] |
| 17.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 17.29 Birthweight < 2500 g Show forest plot | 1 | 189 | Risk Ratio (IV, Random, 95% CI) | 0.84 [0.66, 1.05] |
| 17.30 Gestational age at birth Show forest plot | 2 | 648 | Mean Difference (IV, Random, 95% CI) | 0.91 [0.30, 1.51] |
| 17.31 Neonatal infection Show forest plot | 2 | 780 | Risk Ratio (IV, Random, 95% CI) | 1.02 [0.61, 1.69] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 18.1 Delay in birth by 48 hours Show forest plot | 4 | 308 | Risk Ratio (IV, Random, 95% CI) | 0.97 [0.89, 1.05] |
| 18.2 Delay in birth by 7 days Show forest plot | 2 | 154 | Risk Ratio (IV, Random, 95% CI) | 0.88 [0.77, 1.02] |
| 18.3 Neonatal death before 28 days Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 5.25 [0.26, 106.01] |
| 18.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 1 | 77 | Mean Difference (IV, Random, 95% CI) | ‐2.80 [‐8.81, 3.21] |
| 18.5 Serious adverse effects of drugs Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.01, 8.34] |
| 18.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.7 Cessation of treatment due to adverse effects Show forest plot | 2 | 154 | Risk Ratio (IV, Random, 95% CI) | 0.12 [0.01, 2.10] |
| 18.8 Birth before 28 weeks' gestation Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 5.25 [0.26, 106.01] |
| 18.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.10 Birth before 34 weeks' gestation Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 1.21 [0.67, 2.21] |
| 18.11 Birth before 37 weeks' gestation Show forest plot | 3 | 234 | Risk Ratio (IV, Random, 95% CI) | 1.17 [0.78, 1.75] |
| 18.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.13 Pulmonary oedema Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 0.35 [0.01, 8.34] |
| 18.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.16 Headaches Show forest plot | 2 | 157 | Risk Ratio (IV, Random, 95% CI) | 4.45 [0.25, 77.71] |
| 18.17 Nausea or vomiting Show forest plot | 3 | 234 | Risk Ratio (IV, Random, 95% CI) | 1.05 [0.46, 2.37] |
| 18.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.20 Maternal hypotension Show forest plot | 2 | 157 | Risk Ratio (IV, Random, 95% CI) | 5.98 [1.79, 19.96] |
| 18.21 Perinatal death Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | 5.25 [0.26, 106.01] |
| 18.22 Stillbirth Show forest plot | 1 | 80 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.27 Mean birthweight Show forest plot | 4 | 308 | Mean Difference (IV, Random, 95% CI) | ‐112.94 [‐267.34, 41.45] |
| 18.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 18.30 Gestational age at birth Show forest plot | 3 | 234 | Mean Difference (IV, Random, 95% CI) | ‐0.78 [‐1.90, 0.34] |
| 18.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 19.1 Delay in birth by 48 hours Show forest plot | 4 | 610 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.83, 1.11] |
| 19.2 Delay in birth by 7 days Show forest plot | 1 | 172 | Risk Ratio (IV, Random, 95% CI) | 1.13 [0.87, 1.46] |
| 19.3 Neonatal death before 28 days Show forest plot | 3 | 424 | Risk Ratio (IV, Random, 95% CI) | 0.93 [0.30, 2.85] |
| 19.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 1 | 172 | Mean Difference (IV, Random, 95% CI) | 0.20 [‐10.11, 10.51] |
| 19.5 Serious adverse effects of drugs Show forest plot | 4 | 610 | Risk Ratio (IV, Random, 95% CI) | 0.33 [0.01, 7.89] |
| 19.6 Maternal infection Show forest plot | 2 | 316 | Risk Ratio (IV, Random, 95% CI) | 0.38 [0.02, 9.13] |
| 19.7 Cessation of treatment due to adverse effects Show forest plot | 3 | 506 | Risk Ratio (IV, Random, 95% CI) | 1.01 [0.01, 144.87] |
| 19.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.10 Birth before 34 weeks' gestation Show forest plot | 1 | 172 | Risk Ratio (IV, Random, 95% CI) | 0.85 [0.68, 1.05] |
| 19.11 Birth before 37 weeks' gestation Show forest plot | 1 | 172 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.87, 1.06] |
| 19.12 Maternal death Show forest plot | 2 | 292 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.13 Pulmonary oedema Show forest plot | 3 | 396 | Risk Ratio (IV, Random, 95% CI) | 0.33 [0.01, 7.89] |
| 19.14 Dyspnoea Show forest plot | 2 | 386 | Risk Ratio (IV, Random, 95% CI) | 5.19 [0.62, 43.69] |
| 19.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.16 Headaches Show forest plot | 1 | 214 | Risk Ratio (IV, Random, 95% CI) | 0.62 [0.15, 2.54] |
| 19.17 Nausea or vomiting Show forest plot | 2 | 386 | Risk Ratio (IV, Random, 95% CI) | 1.14 [0.07, 18.76] |
| 19.18 Tachycardia Show forest plot | 2 | 276 | Risk Ratio (IV, Random, 95% CI) | 0.98 [0.06, 15.37] |
| 19.19 Maternal cardiac arrhythmias Show forest plot | 1 | 214 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.20 Maternal hypotension Show forest plot | 2 | 276 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.21 Perinatal death Show forest plot | 3 | 424 | Risk Ratio (IV, Random, 95% CI) | 0.93 [0.30, 2.85] |
| 19.22 Stillbirth Show forest plot | 1 | 198 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.23 Neonatal death before 7 days Show forest plot | 1 | 194 | Risk Ratio (IV, Random, 95% CI) | 0.22 [0.01, 4.55] |
| 19.24 Neurodevelopmental morbidity Show forest plot | 3 | 424 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.61, 1.74] |
| 19.25 Gastrointestinal morbidity Show forest plot | 4 | 544 | Risk Ratio (IV, Random, 95% CI) | 1.35 [0.47, 3.88] |
| 19.26 Respiratory morbidity Show forest plot | 3 | 424 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.78, 1.36] |
| 19.27 Mean birthweight Show forest plot | 4 | 528 | Mean Difference (IV, Random, 95% CI) | ‐6.46 [‐138.66, 125.73] |
| 19.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 19.30 Gestational age at birth Show forest plot | 4 | 502 | Mean Difference (IV, Random, 95% CI) | 0.25 [‐0.35, 0.85] |
| 19.31 Neonatal infection Show forest plot | 2 | 392 | Risk Ratio (IV, Random, 95% CI) | 1.05 [0.55, 1.98] |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 20.1 Delay in birth by 48 hours Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 20.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.27 Mean birthweight Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 20.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 20.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 20.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 21.1 Delay in birth by 48 hours Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 21.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.27 Mean birthweight Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 21.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 21.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 21.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 22.1 Delay in birth by 48 hours Show forest plot | 1 | 77 | Risk Ratio (IV, Random, 95% CI) | 0.88 [0.75, 1.03] |
| 22.2 Delay in birth by 7 days Show forest plot | 1 | 77 | Risk Ratio (IV, Random, 95% CI) | 0.80 [0.64, 1.00] |
| 22.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 22.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.11 Birth before 37 weeks' gestation Show forest plot | 1 | 77 | Risk Ratio (IV, Random, 95% CI) | 1.81 [1.20, 2.72] |
| 22.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.20 Maternal hypotension Show forest plot | 1 | 77 | Risk Ratio (IV, Random, 95% CI) | 0.38 [0.02, 9.01] |
| 22.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.27 Mean birthweight Show forest plot | 1 | 77 | Mean Difference (IV, Random, 95% CI) | ‐541.00 [‐904.72, ‐177.28] |
| 22.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 22.30 Gestational age at birth Show forest plot | 1 | 77 | Mean Difference (IV, Random, 95% CI) | ‐2.60 [‐4.32, ‐0.88] |
| 22.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 23.1 Delay in birth by 48 hours Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 23.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.7 Cessation of treatment due to adverse effects Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 1.14 [0.08, 16.63] |
| 23.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.14 Dyspnoea Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 10.20 [0.60, 174.24] |
| 23.15 Palpitations Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 2.29 [0.23, 22.59] |
| 23.16 Headaches Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 0.42 [0.17, 1.01] |
| 23.17 Nausea or vomiting Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 1.47 [0.75, 2.90] |
| 23.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.20 Maternal hypotension Show forest plot | 1 | 30 | Risk Ratio (IV, Random, 95% CI) | 0.13 [0.01, 2.15] |
| 23.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.27 Mean birthweight Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 23.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 23.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 23.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 24.1 Delay in birth by 48 hours Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 24.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.27 Mean birthweight Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 24.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 24.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 24.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 25.1 Delay in birth by 48 hours Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.3 Neonatal death before 28 days Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 25.5 Serious adverse effects of drugs Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.6 Maternal infection Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.7 Cessation of treatment due to adverse effects Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.9 Birth before 32 weeks' gestation Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 1.05 [0.07, 16.21] |
| 25.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.11 Birth before 37 weeks' gestation Show forest plot | 1 | 86 | Risk Ratio (IV, Random, 95% CI) | 1.75 [0.55, 5.55] |
| 25.12 Maternal death Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.13 Pulmonary oedema Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.24 Neurodevelopmental morbidity Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 1.05 [0.07, 16.21] |
| 25.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.26 Respiratory morbidity Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 2.09 [0.40, 10.85] |
| 25.27 Mean birthweight Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 25.28 Birthweight < 2000 g Show forest plot | 1 | 88 | Risk Ratio (IV, Random, 95% CI) | 1.05 [0.07, 16.21] |
| 25.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 25.30 Gestational age at birth Show forest plot | 1 | 88 | Mean Difference (IV, Random, 95% CI) | ‐0.10 [‐1.76, 1.56] |
| 25.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 26.1 Delay in birth by 48 hours Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 26.5 Serious adverse effects of drugs Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.7 Cessation of treatment due to adverse effects Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.16 Headaches Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.17 Nausea or vomiting Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.18 Tachycardia Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.27 Mean birthweight Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 26.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 26.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 26.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 27.1 Delay in birth by 48 hours Show forest plot | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 1.12 [0.91, 1.39] |
| 27.2 Delay in birth by 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.3 Neonatal death before 28 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 27.5 Serious adverse effects of drugs Show forest plot | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.7 Cessation of treatment due to adverse effects Show forest plot | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 1.57 [0.32, 7.81] |
| 27.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.13 Pulmonary oedema Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.15 Palpitations Show forest plot | 1 | 50 | Risk Ratio (IV, Random, 95% CI) | 0.13 [0.04, 0.39] |
| 27.16 Headaches Show forest plot | 2 | 110 | Risk Ratio (IV, Random, 95% CI) | 4.88 [0.88, 26.94] |
| 27.17 Nausea or vomiting Show forest plot | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 1.50 [0.47, 4.78] |
| 27.18 Tachycardia Show forest plot | 1 | 60 | Risk Ratio (IV, Random, 95% CI) | 0.05 [0.01, 0.32] |
| 27.19 Maternal cardiac arrhythmias Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.20 Maternal hypotension Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.21 Perinatal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.23 Neonatal death before 7 days Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.24 Neurodevelopmental morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.25 Gastrointestinal morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.26 Respiratory morbidity Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.27 Mean birthweight Show forest plot | 1 | 50 | Mean Difference (IV, Random, 95% CI) | 399.00 [110.46, 687.54] |
| 27.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 27.30 Gestational age at birth Show forest plot | 0 | 0 | Mean Difference (IV, Random, 95% CI) | Not estimable |
| 27.31 Neonatal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| Outcome or subgroup title | No. of studies | No. of participants | Statistical method | Effect size |
| 28.1 Delay in birth by 48 hours Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 1.00 [0.89, 1.14] |
| 28.2 Delay in birth by 7 days Show forest plot | 1 | 84 | Risk Ratio (IV, Random, 95% CI) | 1.03 [0.89, 1.20] |
| 28.3 Neonatal death before 28 days Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.4 Pregnancy prolongation (time from trial entry to birth in days) Show forest plot | 1 | 92 | Mean Difference (IV, Random, 95% CI) | ‐7.70 [‐37.03, 21.63] |
| 28.5 Serious adverse effects of drugs Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.6 Maternal infection Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.7 Cessation of treatment due to adverse effects Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.19 [0.01, 3.89] |
| 28.8 Birth before 28 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.9 Birth before 32 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.10 Birth before 34 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.11 Birth before 37 weeks' gestation Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.12 Maternal death Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.13 Pulmonary oedema Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.14 Dyspnoea Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.15 Palpitations Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.16 Headaches Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.44 [0.18, 1.06] |
| 28.17 Nausea or vomiting Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.14, 6.51] |
| 28.18 Tachycardia Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.30 [0.14, 0.64] |
| 28.19 Maternal cardiac arrhythmias Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.20 Maternal hypotension Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.30 [0.14, 0.64] |
| 28.21 Perinatal death Show forest plot | 1 | 63 | Risk Ratio (IV, Random, 95% CI) | 1.24 [0.42, 3.64] |
| 28.22 Stillbirth Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.23 Neonatal death before 7 days Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.24 Neurodevelopmental morbidity Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.19 [0.01, 3.89] |
| 28.25 Gastrointestinal morbidity Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.32 [0.01, 7.64] |
| 28.26 Respiratory morbidity Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.96 [0.44, 2.08] |
| 28.27 Mean birthweight Show forest plot | 1 | 92 | Mean Difference (IV, Random, 95% CI) | 230.00 [‐499.21, 959.21] |
| 28.28 Birthweight < 2000 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.29 Birthweight < 2500 g Show forest plot | 0 | 0 | Risk Ratio (IV, Random, 95% CI) | Not estimable |
| 28.30 Gestational age at birth Show forest plot | 1 | 92 | Mean Difference (IV, Random, 95% CI) | 0.40 [‐1.10, 1.90] |
| 28.31 Neonatal infection Show forest plot | 1 | 92 | Risk Ratio (IV, Random, 95% CI) | 0.48 [0.13, 1.80] |
