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Oxytocin receptor antagonists for inhibiting preterm labour.

Abstract

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 STRATEGY

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2004), CENTRAL (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to June 2004), EMBASE (1988 to June 2004).

SELECTION CRITERIA

Randomised trials of oxytocin receptor antagonists for tocolysis in the management of women in 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

Six trials (1695 women) were included. Compared with placebo, atosiban did not reduce incidence 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).Compared 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). Atosiban was associated with 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.

Authors+Show Affiliations

Department of Obstetrics and Gynaecology, Amphia Hospital Breda, Langendijk 75, Breda, Netherlands, 4819 EV. hoog.pap@wxs.nlNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Review
Systematic Review

Language

eng

PubMed ID

16034931

Citation

Papatsonis, D, et al. "Oxytocin Receptor Antagonists for Inhibiting Preterm Labour." The Cochrane Database of Systematic Reviews, 2005, p. CD004452.
Papatsonis D, Flenady V, Cole S, et al. Oxytocin receptor antagonists for inhibiting preterm labour. Cochrane Database Syst Rev. 2005.
Papatsonis, D., Flenady, V., Cole, S., & Liley, H. (2005). Oxytocin receptor antagonists for inhibiting preterm labour. The Cochrane Database of Systematic Reviews, (3), CD004452.
Papatsonis D, et al. Oxytocin Receptor Antagonists for Inhibiting Preterm Labour. Cochrane Database Syst Rev. 2005 Jul 20;(3)CD004452. PubMed PMID: 16034931.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxytocin receptor antagonists for inhibiting preterm labour. AU - Papatsonis,D, AU - Flenady,V, AU - Cole,S, AU - Liley,H, Y1 - 2005/07/20/ PY - 2005/7/22/pubmed PY - 2005/12/13/medline PY - 2005/7/22/entrez SP - CD004452 EP - CD004452 JF - The Cochrane database of systematic reviews JO - Cochrane Database Syst Rev IS - 3 N2 - 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 STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2004), CENTRAL (The Cochrane Library, Issue 3, 2004), MEDLINE (1965 to June 2004), EMBASE (1988 to June 2004). SELECTION CRITERIA: Randomised trials of oxytocin receptor antagonists for tocolysis in the management of women in 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: Six trials (1695 women) were included. Compared with placebo, atosiban did not reduce incidence 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).Compared 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). Atosiban was associated with 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. SN - 1469-493X UR - https://www.unboundmedicine.com/medline/citation/16034931/Oxytocin_receptor_antagonists_for_inhibiting_preterm_labour_ DB - PRIME DP - Unbound Medicine ER -