Tocolytics for preterm premature rupture of membranes

Cochrane Database Syst Rev. 2014 Feb 27:(2):CD007062. doi: 10.1002/14651858.CD007062.pub3.


Background: In women with preterm labor, tocolysis has not been shown to improve perinatal mortality; however, it is often given for 48 hours to allow for the corticosteroid effect for fetal maturation. In women with preterm premature rupture of membranes (PPROM), the use of tocolysis is still controversial. In theory, tocolysis may prolong pregnancy in women with PPROM, thereby allowing for the corticosteroid benefit and reducing the morbidity and mortality associated with prematurity.

Objectives: To assess the potential benefits and harms of tocolysis in women with preterm premature rupture of membranes.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (15 January 2014).

Selection criteria: We included pregnant women with singleton pregnancies and PPROM (23 weeks to 36 weeks and six days). We included any tocolytic therapy compared to no tocolytic, placebo, or another tocolytic.

Data collection and analysis: All review authors assessed the studies for inclusion. We extracted and quality assessed data.

Main results: We included eight studies with a total of 408 women. Seven of the studies compared tocolysis to no tocolysis. One study compared nifedipine to terbutaline. Compared to no tocolysis, tocolysis was not associated with a significant effect on perinatal mortality in women with PPROM (risk ratio (RR) 1.67; 95% confidence interval (CI) 0.85 to 3.29). Tocolysis was associated with longer latency (mean difference (MD) 73.12 hours; 95% CI 20.21 to 126.03; three trials of 198 women) and fewer births within 48 hours (average RR 0.55; 95% CI 0.32 to 0.95; six trials of 354 women; random-effects, Tau² = 0.18, I² = 43%) compared to no tocolysis. However, tocolysis was associated with increased five-minute Apgar of less than seven (RR 6.05; 95% CI 1.65 to 22.23; two trials of 160 women) and increased need for ventilation of the neonate (RR 2.46; 95% CI 1.14 to 5.34; one trial of 81 women). In the subgroup analysis comparing betamimetic to no betamimetics, tocolysis was associated with increased latency and borderline significance for chorioamnionitis. Prophylactic tocolysis with PPROM was associated with increased overall latency, without additional benefits for maternal/neonatal outcomes. For women with PPROM before 34 weeks, there was a significantly increased risk of chorioamnionitis in women who received tocolysis. However, neonatal outcomes were not significantly different. There were no significant differences in maternal/neonatal outcomes in subgroup analyses comparing cox inhibitor versus no tocolysis, calcium channel blocker versus betamimetic, antibiotic, corticosteroid or combined antibiotic/corticosteroid.

Authors' conclusions: Our review suggests there is insufficient evidence to support tocolytic therapy for women with PPROM, as there was an increase in maternal chorioamnionitis without significant benefits to the infant. However, studies did not consistently administer latency antibiotics and corticosteroids, both of which are now considered standard of care.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones / therapeutic use
  • Adrenergic beta-Agonists / therapeutic use
  • Anti-Bacterial Agents / therapeutic use
  • Female
  • Fetal Membranes, Premature Rupture / drug therapy*
  • Humans
  • Nifedipine / adverse effects
  • Nifedipine / therapeutic use
  • Pregnancy
  • Randomized Controlled Trials as Topic
  • Terbutaline / adverse effects
  • Terbutaline / therapeutic use
  • Tocolysis / methods
  • Tocolytic Agents / adverse effects
  • Tocolytic Agents / therapeutic use*


  • Adrenal Cortex Hormones
  • Adrenergic beta-Agonists
  • Anti-Bacterial Agents
  • Tocolytic Agents
  • Nifedipine
  • Terbutaline