Tocolytics for preterm premature rupture of membranes

Mackeen AD, Seibel-Seamon J, Grimes-Dennis J, Baxter JK, Berghella V

Published Online:

October 5, 2011

Preterm premature rupture of membranes (PPROM) accounts for one-third of preterm births. Infants who are born before 37 weeks may suffer from problems related to prematurity, including death. Medications that aim to stop labor are often given in an attempt to prevent preterm birth. It is unclear whether these medications should be used in women with PPROM. This review of eight studies (involving 408 women) found that these medications do not effect perinatal death, but do increase latency and may increase maternal (e.g., chorioamnionitis) and neonatal morbidity (e.g., five-minute Apgar of less than seven and increased need for ventilation of the neonate).

Abstract (click to read)

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 strategy:

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (6 April 2011), CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE (1966 to 6 April 2011) and EMBASE (1974 to 6 April 2011).

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, T2 = 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 patients 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.

This record should be cited as:

Mackeen AD, Seibel-Seamon J, Grimes-Dennis J, Baxter JK, Berghella V. Tocolytics for preterm premature rupture of membranes. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD007062. DOI: 10.1002/14651858.CD007062.pub2

Assessed as up to date:

September 5, 2011

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Primary Review Group:

Pregnancy and Childbirth Group

Health topics:

Pregnancy & childbirth > Pre-labour rupture of membranes > Preterm

Cochrane Summaries^beta

Independent high-quality evidence for health care decision making

Tocolytics for preterm premature rupture of membranes

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