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 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.]

 

Plain language summary

Oxytocin receptor antagonists for inhibiting preterm labour

Atosiban, an oxytocin receptor antagonist, is no better than other drugs in delaying or preventing preterm birth but has fewer maternal side-effects.

Tocolytic agents may postpone preterm delivery long enough to improve neonatal outcome, allow corticosteroids to be given to help the baby's lungs and other organs to mature and, if necessary, to allow transfer of the mother to a hospital that has facilities to provide neonatal intensive care. Tocolytic drugs called oxytocin receptor antagonists work by inhibiting the hormone oxytocin that stimulates labour. This review found that, although the oxytocin receptor antagonist atosiban resulted in fewer maternal side-effects than other tocolytic drugs (betamimetics), no benefit was shown in delaying or preventing preterm birth, and atosiban was associated with more infant deaths in one placebo controlled trial. Further well-designed trials are needed.

 

摘要

背景

用於抑制早產的oxytocin受器拮抗劑

早產的定義為在37個完整周數之前出生，在高收入的國家中，它是引起周產而死亡與罹病的單一項最重要因素。針對婦女早產而用來延後出生的安胎藥物，人們認為oxytocin受器拮抗劑會跟它們一樣有效，而且會帶來比其他的安胎藥物更少的副作用。

目標

與安慰劑或不採取治療相比，以及與任何其他的安胎藥物相比，要評估針對早產的婦女以oxytocin受器拮抗劑所進行的安胎在母體、胎兒與新生兒狀況上的影響。

搜尋策略

我們搜尋了the Cochrane Pregnancy and Childbirth Group's Trials Register（2004年九月）、CENTRAL（The Cochrane Library，Issue 3，2004年）、MEDLINE（1965年到2004年六月）、EMBASE（1988年到2004年六月）。

選擇標準

針對介於20到36周孕期的妊娠安胎所進行關於oxytocin受器拮抗劑的隨機試驗。

資料收集與分析

有2位作者獨立評估了方法上的品質，並擷取出試驗資料。我們會從試驗的作者那尋求更多的資訊。

主要結論

有2份試驗（651名婦女）將atosiban與安慰劑進行比較。atosiban並不會降低早產的風險，或是改善新生兒的狀況。在某1份試驗中（583名嬰兒），跟安慰劑比較起來，atosiban會伴隨著12個月大的嬰兒之死亡數增加（relative risk （RR） 6.15; 95% confidence intervals （CI） 1.39 to 27.22）。然而，這份研究明顯的隨機分配了較多在26周的孕期之前的婦女到atosiban之中。使用atosiban會造成嬰兒出生時的體重較輕（加權平均差為−138.31克；95% CI −248.76 to −27.86），以及更多的母體之不良藥物反應（RR 4.02; 95% CI 2.05 to 7.85, 2 trials, 613 women）。有4組試驗（1044名婦女）將atosiban與betamimetics進行比較。atosiban會讓出生時體重低於1500克的嬰兒數目增加（RR 1.96; 95% CI 1.15 to 3.35, 2 trials, 575 infants），並帶來較少會讓治療停止的母體藥物反應（RR 0.04; 95% CI 0.02 to 0.11, number needed to treat 6; 95% CI 5 to 7, 4 trials, 1035 women）。

作者結論

若考慮到安胎的效用或是嬰兒的狀況，本篇回顧無法證實atosiban會優於betamimetics或是安慰劑。在某1組以安慰劑為對照的試驗中發現，嬰兒的死亡情形增加是值得注意的。有1份Cochrane評論認為鈣離子通道阻斷劑（calcium channel blockers）（以nifedipine為主）與較佳的新生兒狀況相關，而且跟betamimetics比較起來，母體的副作用也較少。然而，目前還沒有任何1份針對nifedipine與安慰劑所進行的隨機比較。關於安胎治療，還需要有更進一步且經過妥善設計的隨

翻譯人

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

屬於一種oxytocin受器拮抗劑的atosiban，在延遲或預防早產上並不會優於其他藥物，但是對母體的副作用較少。安胎藥物可能會讓早產的現象延後到足以改善新生兒狀況，給予corticosteroids 來輔助嬰兒的肺部及其他器官成熟，而且如果有必要的話，還可以讓母親轉到某家可以提供新生兒加護設備的醫院。那些被稱作oxytocin受器拮抗劑的安胎藥物，藉由抑制會刺激分娩的oxytocin荷爾蒙來產生作用。本篇回顧發現，雖然跟其他的安胎藥物（betamimetics）比較起來，atosiban這種oxytocin受器拮抗劑所帶來的母體副作用比較少，但是對於延緩或是預防早產方面並沒有助益，而且在1份以安慰劑為對照的試驗中，atosiban伴隨了更多與嬰兒死亡相關。還需要有更進一步且經過妥善設計的試驗。