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Oxytocin Antagonists for suppressing preterm birth after an episode of preterm labour

Preterm labour is indicated by regular contractions of the uterus and changes in the cervix (the opening of the womb) before 37 weeks of pregnancy. Preterm labour and birth may be associated with illness or death of the baby, and often place a substantial emotional burden on families. Preterm birth may also result in childhood disability. Even a short-term prolongation of pregnancy after the onset of threatened or actual preterm labour can allow the administration of corticosteroids to the mother to hasten fetal lung maturation and transfer of the mother to a centre with neonatal intensive care facilities. A range of drugs (tocolytic) are used to suppress labour. The oxytocin antagonist atosiban is one of these. Once the episode of threatened preterm labour settles, maintenance treatment with a tocolytic can then be used to try to prevent any reoccurrence. This has to be balanced against potential adverse outcomes such as intrauterine infection, fetal death, an increase in severe disability for survivors, and side-effects of the drugs.

This review identified only one good quality multicentre controlled trial which showed that subcutaneously administered atosiban as maintenance therapy did not reduce the incidence of preterm birth or improve neonatal outcomes when compared with placebo treatment. The trial randomised 513 women in whom preterm labour (with intact membranes and limited cervical dilatation) ceased following intravenous treatment with atosiban. The mean gestation at enrolment was around 31 weeks and the proportion of multiple births was similar in the two groups. Atosiban infused at 6 mL/hr (30 µg/min) did not reduce preterm birth before 28, 32, or 37 weeks. Women on maintenance therapy were discharged home with a continuous subcutaneous infusion pump and daily nursing contact. There was an increase in injection site reaction for the atosiban group. There is insufficient evidence of benefit to justify this intervention.

研究背景

In some women, an episode of preterm labour settles and does not result in immediate preterm birth. Subsequent treatment with tocolytic agents such as oxytocin receptor antagonists may then have the potential to prevent the recurrence of preterm labour, prolonging gestation, and preventing the adverse consequences of prematurity for the infant.

研究目的

To assess the effects of maintenance therapy with oxytocin antagonists administered by any route after an episode of preterm labour in order to delay or prevent preterm birth.

检索策略

We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 July 2013), sought ongoing and unpublished trials by contacting experts in the field and searched the reference lists of relevant articles.

纳入排除标准

Randomised controlled trials comparing oxytocin antagonists with any alternative tocolytic agent, placebo or no treatment, used for maintenance therapy after an episode of preterm labour.

资料收集与分析

We used the standard methods of The Cochrane Collaboration and the Cochrane Pregnancy and Childbirth Group. Two review authors independently undertook evaluation of methodological quality and extracted trial data.

主要结果

This review includes one trial of 513 women. When compared with placebo, atosiban did not reduce preterm birth before 37 weeks (risk ratio (RR) 0.89; 95% confidence intervals (CI) 0.71 to 1.12), 32 weeks (RR 0.85; 95% CI 0.47 to 1.55), or 28 weeks (RR 0.75; 95% CI 0.28 to 2.01). No difference was shown in neonatal morbidity, or perinatal mortality.

作者结论

There is insufficient evidence to support the use of oxytocin receptor antagonists to inhibit preterm birth after a period of threatened or actual preterm labour. Any future trials using oxytocin antagonists or other drugs as maintenance therapy for preventing preterm birth should examine a variety of important infant outcome measures, including reduction of neonatal morbidity and mortality, and long-term infant follow-up. Future research should also focus on the pathophysiological pathways that precede preterm labour.

引用文献
Papatsonis DNM, Flenady V, Liley HG. Maintenance therapy with oxytocin antagonists for inhibiting preterm birth after threatened preterm labour. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD005938. DOI: 10.1002/14651858.CD005938.pub3.

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