Oxytocin receptor antagonists for inhibiting preterm labour

BACKGROUND: Preterm birth, defined as birth before 37 completed weeks, is the single most important cause of perinatal mortality and morbidity in high-income countries. Oxytocin receptor antagonists have been proposed as effective tocolytic agents for women in preterm labour to postpone the birth, with fewer side-effects than other tocolytic agents. OBJECTIVES: To assess the effects on maternal, fetal and neonatal outcomes of tocolysis with oxytocin receptor antagonists for women with preterm labour compared with placebo or no intervention and compared with any other tocolytic agent. SEARCH METHODS: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2004), CENTRAL (The Cochrane Library 2004, Issue 3), MEDLINE (1965 to June 2004), EMBASE (1988 to June 2004). We updated the search of the Cochrane Pregnancy and Childbirth Group's Trials Register on 17 September 2009 and added the results to the awaiting classification section of the review. SELECTION CRITERIA: Randomised trials of oxytocin receptor antagonists for tocolysis of labour between 20 and 36 weeks' gestation. DATA COLLECTION AND ANALYSIS: Two authors independently evaluated methodological quality and extracted trial data. We sought additional information from trial authors. MAIN RESULTS: Two trials (651 women) compared atosiban with placebo. Atosiban did not reduce the risk of preterm birth or improve neonatal outcome. In one trial (583 infants), atosiban was associated with an increase in infant deaths at 12 months of age compared with placebo (relative risk (RR) 6.15; 95% confidence intervals (CI) 1.39 to 27.22). However, this trial randomised significantly more women to atosiban before 26 weeks' gestation. Use of atosiban resulted in lower infant birthweight (weighted mean difference -138.31 gm; 95% CI -248.76 to -27.86) and more maternal adverse drug reactions (RR 4.02; 95% CI 2.05 to 7.85, 2 trials, 613 women). Four trials (1044 women) compared atosiban with betamimetics. Atosiban increased the numbers of infants born under 1500 gm (RR 1.96; 95% CI 1.15 to 3.35, 2 trials, 575 infants), and resulted in fewer maternal drug reactions requiring treatment cessation (RR 0.04; 95% CI 0.02 to 0.11, number needed to treat 6; 95% CI 5 to 7, 4 trials, 1035 women). AUTHORS' CONCLUSIONS: This review failed to demonstrate the superiority of atosiban over betamimetics or placebo in terms of tocolytic efficacy or infant outcomes. The finding of an increase in infant deaths in one placebo controlled trial warrants caution. A recent Cochrane review suggests that calcium channel blockers (mainly nifedipine) are associated with better neonatal outcome and fewer maternal side-effects than betamimetics. However, a randomised comparison of nifedipine with placebo is not available. Further well-designed randomised controlled trials of tocolytic therapy are needed. Such trials should incorporate a placebo arm. [Note: The 24 citations in the awaiting classification section of the review may alter the conclusions of the review once assessed.]