Z Geburtshilfe Neonatol
DOI: 10.1055/a-2217-9463
Original Article

Use and Impact of Pessary, Cerclage, and Progesterone for the Secondary Prevention of Preterm Birth: Data from the German Neonatal Network

Einsatz und Einfluss von Pessar, Cerclage und Progesteron auf die Sekundärprävention der Frühgeburtlichkeit: Daten des Deutschen Frühgeborenenentzwerkes
Kathrin Hanke
1   Department of Pediatrics, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Germany
,
Mats Ingmar Fortmann
1   Department of Pediatrics, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Germany
,
Gesa Henrike Auerswald
1   Department of Pediatrics, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Germany
,
Christoph Härtel
2   Department of Pediatrics, Universitätsklinikum Würzburg, Würzburg, Germany
,
Dirk Olbertz
3   Department of Neonatology, University of Rostock, Rostock, Germany
,
Claudia Roll
4   Neonatology and Paediatric Intensive Care, Vestische Kinder- und Jugendklinik Datteln, Datteln, Germany
,
Berthold Grüttner
5   Gynaecology, Uniklinik Köln, Köln, Germany
,
Christian Wieg
6   Department of Pediatrics, Klinikum Aschaffenburg-Alzenau gGmbH, Aschaffenburg, Germany
,
Stephanie Breunig
6   Department of Pediatrics, Klinikum Aschaffenburg-Alzenau gGmbH, Aschaffenburg, Germany
,
Achim Rody
7   Department of Obstetrics and Gynaecology, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Germany
,
Ursula Felderhoff-Müser
8   Department of Pediatrics, Universität Duisburg-Essen, Essen, Germany
,
Egbert Herting
1   Department of Pediatrics, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Germany
,
Wolfgang Göpel
1   Department of Pediatrics, Universitätsklinikum Schleswig-Holstein – Campus Lübeck, Lübeck, Germany
,
Verena Bossung
9   Department of Obstetrics, University Hospital Zurich, Zurich, Switzerland and 15 -University of Zurich, Zurich, Switzerland
› Author Affiliations

Abstract

Background To evaluate the use and effect of cervical stitch cerclage, pessary, and progesterone on pregnancy outcome in mothers of very low birth weight infants (VLBWI) born<32 weeks of gestation in the German Neonatal Network (GNN).

Methods The GNN is a population-based cohort study enrolling VLBWI since 2009. We included 575 neonates from 424 mothers into our analysis, who were born between 2015 and 2019, after prenatal intervention with cerclage, pessary, progesterone or a combination between 20/0 to 25/0 weeks of gestation to prevent preterm birth. Median intervention-to-birth interval was the primary endpoint.

Results 231 of 424 pregnant women had a cerclage only (54.5%), 76 women a pessary only (17.9%), and 27 were prescribed progesterone only (15.3%). The most common combination treatment (>1 intervention group) was cerclage plus progesterone (n=27), followed by cerclage plus pessary (n=13). The median intervention-to-birth interval for the whole cohort was 24 days (IQR 19.0 days). The earlier the intervention was started, the longer the intervention-to-birth interval lasted: When started at 20 weeks, the interval was 34 days in contrast to 11.5 days, when started at 25 weeks. The >1 group was born at a significantly higher median GA with 27.0 weeks (IQR 2.9 weeks) and a higher median birth weight of 980 g (IQR 394 g) accordingly.

Conclusion We propose that the earliest possible start of intervention leads to the most efficient pregnancy prolongation.

Zusammenfassung

Hintergrund Bewertung von Einsatz und Effektivität von Cerclage, Pessar und Progesteron auf den Schwangerschaftsverlauf bei Müttern von Frühgeborenen mit sehr niedrigem Geburtsgewicht (VLBWI), die im Rahmen des GNN unter der 32. Schwangerschaftswoche geboren wurden.

Methoden Wir haben 575 Neugeborene von 424 Müttern in unsere Analyse einbezogen, die zwischen 2015 und 2019 nach pränataler Intervention mit Cerclage, Pessar, Progesteron oder einer Kombinationstherapie zur Verhinderung einer Frühgeburt zwischen der 20. und 25. Schwangerschaftswoche geboren wurden. Der mittlere Zeitraum zwischen Intervention und Geburt war der primäre Endpunkt.

Ergebnisse 231 von 424 schwangeren Frauen erhielten nur eine Cerclage (54,5%), 76 Frauen nur ein Pessar (17,9%) und 27 Frauen erhielten nur Progesteron (15,3%). Die häufigste Kombinationsbehandlung (>1 Interventionsgruppe) war die Cerclage plus Progesteron (n=27), gefolgt von Cerclage plus Pessar (n=13). Das mittlere Intervall zwischen Intervention und Geburt betrug für die gesamte Kohorte 24 Tage (IQR 19.0 Tage). Je früher mit der Intervention begonnen wurde, desto länger dauerte das Intervall zwischen Intervention und Geburt: Bei Beginn mit 20 Wochen betrug das Intervall 34 Tage, im Gegensatz zu 11.5 Tagen bei Beginn mit 25 Wochen. Die Gruppe >1 wurde mit einem deutlich höheren mittleren GA von 27.0 Wochen (IQR 2.9 Wochen) und entsprechend höherem Geburtsgewicht von 980 g (IQR 394 g) geboren.

Schlussfolgerung Der frühestmögliche Beginn einer Intervention führt zur effizientesten Verlängerung der Schwangerschaft.



Publication History

Received: 28 July 2023

Accepted: 07 November 2023

Article published online:
16 January 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Calvert C, Brockway MM, Zoega H. et al. Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries. Nat Hum Behav 2023; 7: 529-544
  • 2 IQTIQ. Bundesauswertung Perinatalmedizin: Geburtshilfe, Erfassungsjahr 2021 [Internet]. 2022 [cited 2023 Jan 3]. Available online: https://iqtig.org/downloads/auswertung/2021/pmgebh/DeQS_PM-GEBH_2021_BUAW_V01_2022-06-30.pdf
  • 3 Perin J, Mulick A, Yeung D. et al. Global, regional, and national causes of under-5 mortality in 2000-19: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet Child Adolesc Health 2022; 6: 106-115
  • 4 Manuck TA, Rice MM, Bailit JL. et al. Preterm neonatal morbidity and mortality by gestational age: A contemporary cohort. Am J Obstet Gynecol 2016; 215: 103.e1-103.e14
  • 5 Humberg A, Härtel C, Rausch TK. et al. Active perinatal care of preterm infants in the German Neonatal Network. Arch Dis Child Fetal Neonatal Ed 2019; 105: 190-195
  • 6 Katz TA, Vliegenthart RJS, Aarnoudse-Moens CSH. et al. Severity of bronchopulmonary dysplasia and neurodevelopmental outcome at 2 and 5 years corrected age. J Pediatr 2022; 243: 40-46.e2
  • 7 Villar J, Papageorghiou AT, Knight HE. et al. The preterm birth syndrome: A prototype phenotypic classification. Am J Obstet Gynecol 2012; 206: 119-123
  • 8 Romero R, Dey SK, Fisher SJ. Preterm labor: one syndrome, many causes. Science 2014; 345: 760-765
  • 9 Grobman WA, Lai Y, Iams JD. et al. Prediction of spontaneous preterm birth among nulliparous women with a short cervix. J Ultrasound Med 2016; 35: 1293-1297
  • 10 Van Baaren GJ, Vis JY, Wilms FF. et al. Predictive value of cervical length measurement and fibronectin testing in threatened preterm labor. Obstet Gynecol 2014; 123: 1185-1192
  • 11 Care A, Nevitt SJ, Medley N. et al. Interventions to prevent spontaneous preterm birth in women with singleton pregnancy who are at high risk: Systematic review and network meta-analysis. BMJ 2022; 376: e064547
  • 12 Berger R, Abele H, Bahlmann F, Doubek K. et al. Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) – Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature R. Geburtshilfe Frauenheilkd 2023; 83: 569-601
  • 13 Sneider K, Christiansen OB, Sundtoft IB, Langhoff-Roos J. Recurrence of second trimester miscarriage and extreme preterm delivery at 16-27 weeks of gestation with a focus on cervical insufficiency and prophylactic cerclage. Acta Obstet Gynecol Scand 2016; 95: 1383-1390
  • 14 Grabovac M, Lewis-Mikhael AM, McDonald SD. Interventions to try to prevent preterm birth in women with a history of conization: A systematic review and meta-analyses. J Obstet Gynaecol Can 2019; 41: 76-88.e7
  • 15 Di Renzo GC, Cabero Roura L, Facchinetti F. et al. Preterm labor and birth management: Recommendations from the European Association of Perinatal Medicine. J Matern Neonatal Med 2017; 30: 2011-2030
  • 16 Dodd JM, Jones L, Flenady V, Crowther CA. Prenatal administration of progesterone for preventing preterm birth in women considered to be at risk of preterm birth. Cochrane Database Syst Rev 2013; CD004947
  • 17 Di Renzo GC, Tosto V, Tsibizova V, Fonseca E. Prevention of preterm birth with progesterone. J Clin Med 2021; 10: 4511
  • 18 Romero R, Conde-Agudelo A, Rehal A, Da Fonseca E, Brizot ML, Rode L. et al. Vaginal progesterone for the prevention of preterm birth and adverse perinatal outcomes in twin gestations with a short cervix: an updated individual patient data meta-analysis. Ultrasound Obstet Gynecol 2022; 59: 263-266
  • 19 Prediction and Prevention of Spontaneous Preterm Birth: ACOG Practice Bulletin, Number 234. Obstet Gynecol 2021; 138: e65-e90
  • 20 Goya M, Pratcorona L, Merced C. et al. Cervical pessary in pregnant women with a short cervix (PECEP): an open-label randomised controlled trial. Lancet 2012; 379: 1800-1806
  • 21 Nicolaides KH, Syngelaki A, Poon LC. et al. A randomized trial of a cervical pessary to prevent preterm singleton birth. N Engl J Med 2016; 374: 1044-1052
  • 22 Groussolles M, Winer N, Sentilhes L. et al. Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE). Am J Obstet Gynecol 2022; 227: 271.e1-271.e13
  • 23 Grobman WA, Norman J, Jacobsson B. et al. FIGO good practice recommendations on the use of pessary for reducing the frequency and improving outcomes of preterm birth. Int J Gynecol Obstet 2021; 155: 23-25
  • 24 Berghella V, Ciardulli A, Rust OA. et al. Cerclage for sonographic short cervix in singleton gestations without prior spontaneous preterm birth: systematic review and meta-analysis of randomized controlled trials using individual patient-level data. Ultrasound Obstet Gynecol 2017; 50: 569-577
  • 25 Shennan A, Story L, Jacobsson B. et al. FIGO good practice recommendations on cervical cerclage for prevention of preterm birth. Int J Gynaecol Obstet 2021; 155: 19-22
  • 26 Geffers C, Baerwolff S, Schwab F, Gastmeier P. Incidence of healthcare-associated infections in high-risk neonates: results from the German surveillance system for very-low-birthweight infants. J Hosp Infect 2008; 68: 214-221
  • 27 Shennan AT, Dunn MS, Ohlsson A. et al. Abnormal pulmonary outcomes in premature infants: Prediction from oxygen requirement in the neonatal period. Pediatrics 1988; 82: 527-532
  • 28 Bell MJ, Ternberg JL, Feigin RD. et al. Ann Surg 1978; 187: 1-7
  • 29 Papile LA, Burstein J, Burstein R, Koffler H. Incidence and evolution of subependymal and intraventricular hemorrhage: A study of infants with birth weights less than 1,500 gm. J Pediatr 1978; 92: 529-534
  • 30 Conde-Agudelo A, Romero R. Vaginal progesterone for the prevention of preterm birth: Who can benefit and who cannot? Evidence-based recommendations for clinical use. J Perinat Med 2022; 51: 125-134 Epub ahead of print
  • 31 Booker WA, Reed EG, Power ML. et al. OBGYN practice patterns regarding combination therapy for prevention of preterm birth: A national survey. Eur J Obstet Gynecol Reprod Biol 2021; 266: 23-30
  • 32 DeFranco EA, Valent AM, Newman T. et al. Adjunctive therapies to cerclage for the prevention of preterm birth: A systematic review. Obstet Gynecol Int 2013; 2013: 528158
  • 33 Jarde A, Lewis-Mikhael AM, Dodd JM. et al. The more, the better? Combining interventions to prevent preterm birth in women at risk: a systematic review and meta-analysis. J Obstet Gynaecol Can 2017; 39: 1192-1202
  • 34 Ragab A, Mesbah Y. To do or not to do emergency cervical cerclage (a rescue stitch) at 24–28 weeks gestation in addition to progesterone for patients coming early in labor? A prospective randomized trial for efficacy and safety. Arch Gynecol Obstet 2015; 292: 1255-1260
  • 35 Park JY, Jung YM, Kook SY. et al. The effect of postoperative vaginal progesterone in ultrasound-indicated cerclage to prevent preterm birth. J Matern Fetal Neonatal Med 2021; 34: 2473-2480
  • 36 Jung EY, Oh KJ, Hong JS. et al. Addition of adjuvant progesterone to physical-exam-indicated cervical cerclage to prevent preterm birth. J Obstet Gynaecol Res 2016; 42: 1666-1672
  • 37 Liu J, Song G, Meng T, Zhao G. Vaginal progesterone combined with cervical pessary in preventing preterm birth: a meta-analysis. J Matern Fetal Neonatal Med 2021; 34: 3050-3056
  • 38 Conde-Agudelo A, Romero R, Nicolaides KH. Cervical pessary to prevent preterm birth in asymptomatic high-risk women: a systematic review and meta-analysis. Am J Obstet Gynecol 2020; 223: 42-65.e2
  • 39 Zhuang Y, Li H, Na Q. et al. Prevention of preterm birth by cervical pessary combined with vaginal progesterone: a systematic review and meta-analysis with trial sequential analysis. Reprod Sci 2023; 30: 93
  • 40 D’Antonio F, Berghella V, Di Mascio D. et al. Role of progesterone, cerclage and pessary in preventing preterm birth in twin pregnancies: A systematic review and network meta-analysis. Eur J Obstet Gynecol Reprod Biol 2021; 261: 166-177