The clinical efficacy of oral tocolytic therapy

doi:10.1016/S0002-9378(96)80009-3

American Journal of Obstetrics and Gynecology

Volume 175, Issue 4, Part 1, October 1996, Pages 838-842

Presented at the Sixteenth Annual Meeting of the Society of Perinatal Obstetricians, Kamuela, Hawaii, February 4-10, 1996.

https://doi.org/10.1016/S0002-9378(96)80009-3 Get rights and content

Abstract

OBJECTIVE: Our purpose was to determine whether maintenance oral tocolytic therapy after preterm labor stabilization decreases uterine activity, reduces the rate of recurrent preterm labor and subsequent preterm birth, or improves neonatal outcome. STUDY DESIGN: Women with documented idiopathic preterm labor stabilized with acute tocolytic therapy were randomized to three groups: placebo, terbutaline 5 mg, or magnesium chloride 128 mg, all given orally every 4 hours. Patients and providers were blinded to group assignment. All subjects were enrolled in a comprehensive system of preterm birth prevention that included preterm labor education, weekly clinic visits, home uterine contraction assessment, daily phone contact, and 24-hour perinatal nurse access. RESULTS: Of the 248 patients who were randomized, 39 were delivered before discharge and 4 were lost to follow-up, leaving 205 for final analysis: 68 placebo, 72 terbutaline, and 65 magnesium. The terbutaline group had significantly more side effects than the placebo group did. All groups had otherwise similar perinatal outcomes when confounding variables were controlled for. Overall, the three groups had a preterm birth rate <37 weeks of 55.6% delivery, <34 weeks of 15.6%, a 20.4% rate of newborn intensive care unit admission, and a mean neonatal length of stay of 6.3 days. CONCLUSIONS: Maintenance oral tocolytic therapy did not decrease uterine activity, reduce the rate of recurrent preterm labor or preterm birth, or improve perinatal outcome. Overall improvement in perinatal outcome may be achieved with a comprehensive program of preterm birth prevention without the use of maintenance oral tocolytic therapy. (Am J Obstet Gynecol 1996;175:838-42.)

Section snippets

MATERIAL AND METHODS

All patients admitted to the University of Mississippi Medical Center Labor and Delivery Unit in fiscal year 1995 with a diagnosis of idiopathic preterm labor (gestational age 24 to 34 weeks, regular contractions of more than four per hour, documented cervical change on serial digital examinations, intact membranes, and absence of any medical or obstetric condition requiring delivery) were given informed consent and considered for enrollment. Additional inclusion criteria included arrest of

RESULTS

During the investigational period 248 women were enrolled, randomized, and managed according to the study protocol. Thirty-nine patients were delivered after randomization and before discharge during the initial hospitalization because of various complications of pregnancy. The most common causes of delivery in this group were rapidly progressive preterm labor (n = 13), preterm premature rupture of the membranes (n = 9), and medically indicated delivery because of hypertensive disorders of

COMMENT

To date there have been two randomized studies of maintenance oral tocolytic therapy comparing the efficacy β-agonists with magnesium compounds.3, 4 These studies both reported similar outcomes. There are three randomized investigations of β-agonist oral tocolytic therapy versus no therapy.4, 5, 6 One of these studies also compared magnesium with no therapy.⁴ All three failed to demonstrate any benefit of therapy over no treatment. Two studies of β-agonist therapy were placebo controlled. The

References (11)

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JM Ricci et al.
Oral tocolysis with magnesium chloride: a randomized controlled prospective clinical trial
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HY How et al.
Oral terbutaline in the outpatient management of preterm labor
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BV Parilla et al.
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GA Macones et al.
Efficacy of oral β-agonist maintenance therapy in preterm labor: a meta-analysis
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There are more references available in the full text version of this article.

Cited by (68)

Endocrine Diseases of Pregnancy
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Physiological and endocrine adaptations occur in the mother in response to the demands of pregnancy. These demands include support of the fetus (volume support, nutritional and oxygen supply, and clearance of fetal waste), protection of the fetus (from starvation, drugs, toxins), preparation of the uterus for labor, and protection of the mother from potential cardiovascular injury at delivery. The presence of a preexisting endocrine disorder is likely to affect the ability of the mother to adapt to the demands of pregnancy and, as a result, may influence fetal growth and development. Drugs used to treat such disorders may also affect perinatal outcome. The most common preexisting endocrine disorders that can complicate pregnancy are diabetes mellitus, thyroid dysfunction, and obesity. Less common preexisting maternal endocrine disorders include pituitary tumors, diabetes insipidus, and hyperparathyroidism.
The physiological and endocrine adaptations that characterize pregnancy can also lead to the development of pregnancy-specific diseases in previously healthy women, the most common of which are gestational diabetes and disorders of the endocrine and sympathetic nervous systems associated with preeclampsia and preterm labor. This chapter is designed to review in detail the underlying pathophysiology of these pregnancy-specific diseases, as well as the effects of pregnancy on preexisting endocrine disorders. A better understanding of these conditions will improve the ability of clinicians to optimize maternal and perinatal outcome in such pregnancies.
Preterm Labor and Birth
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The effects of ritodrine and magnesium sulfate on maternal and fetal Doppler blood flow patterns in women with preterm labor
2010, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
Healthy pregnant women matched for gestational age and parity served as the controls (n = 83, Group III). As in other studies, preterm labor was diagnosed by regular uterine contractions of over four per hour with documented cervical change on serial digital examinations [14,15]. Exclusion criteria included twin or higher order pregnancy, fetal congenital anomalies, intrauterine growth restriction, cervical dilatation ≥4 cm or effacement ≥80%, preeclampsia–eclampsia, abruptio or placenta previa, chorioamnionitis, diabetes mellitus, maternal heart disease, women with a previous preterm labor episode in the index pregnancy or delivered before 48 h after initiating therapy.
To determine the effects of ritodrine and magnesium sulfate on maternal–fetal blood flows.
A total of 85 pregnant women between 26th and 36th weeks with preterm labor, and 83 healthy pregnant women were included. Patients in the study group were randomly assigned to receive either ritodrine (with the addition of verapamil) (n = 46) or magnesium sulfate (n = 39). Blood flow examinations on the umbilical artery (UA), middle cerebral artery (MCA), bilateral uterine arteries (Ut.A) and ductus venosus (DV) were performed before and 48 h after initiating therapy.
UA pulsatility index (PI) significantly differed in women receiving tocolysis compared to controls after 48 h. DV PI increased in women receiving MgSO₄, whereas it decreased in the ritodrine and control groups. Ut.A values did not significantly change after 48 h in the groups.
In women between the 26th and 32nd weeks, UA, MCA and DV PI did not significantly change after 48 h in the three groups. However, in women between the 32nd and 36th weeks UA and MCA PI significantly differed in the treatment groups compared to controls after 48 h. DV PI increased in women receiving MgSO₄, whereas it decreased in the ritodrine and control groups.
MgSO₄ and ritodrine affect blood flow patterns after 48 h in some maternal–fetal vessels. These effects on blood flow are particularly significant in women between 32nd and 36th weeks. The effects of both drugs on fetal and maternal Doppler flows seem similar, except the increased resistance to flow in DV in women receiving MgSO₄.
Endocrine diseases of pregnancy
2009, Yen & Jaffe's Reproductive Endocrinology: Expert Consult - Online and Print
Endocrine Diseases of Pregnancy
2009, Yen & Jaffe's Reproductive Endocrinology

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^☆: From the Departments of Obstetrics and Gynecology^aand Preventive Medicine,^bUniversity of Mississippi Medical Center.

^☆☆: Supported in part by the Vicksburg Hospital Medical Foundation.

^★: Reprint requests: Orion A. Rust, MD, c/o Janice Gordon, Publications Division, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 N. State St., Jackson, MS 39216-4505.

^★★: 0002-9378/96 $5.00 + 0 6/6/75297

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The clinical efficacy of oral tocolytic therapy☆,☆☆,★,★★

Abstract

Section snippets

MATERIAL AND METHODS

RESULTS

COMMENT

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Am J Obstet Gynecol

Obstet Gynecol