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Prophylactic oral betamimetics for reducing preterm birth in women with a twin pregnancy

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Abstract

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Background

Twin pregnancies are associated with a high risk of neonatal mortality and morbidity due to an increased rate of preterm birth. Betamimetics can decrease contraction frequency or delay preterm birth in singleton pregnancies by 24 to 48 hours. The efficacy of oral betamimetics in women with a twin pregnancy is unproven.

Objectives

To assess the effectiveness of prophylactic oral betamimetics for the prevention of preterm labour and birth for women with twin pregnancies.

Search methods

We searched the Cochrane Pregnancy and Childbirth Group Trials Register (31 January 2012), the Central Register of Controlled Trials (The Cochrane Library 2012, Issue 2), MEDLINE (January 1966 to 1 February 2012) and EMBASE (January 1985 to 1 February 2012).

Selection criteria

Randomised controlled trials in twin pregnancies comparing oral betamimetics with placebo or any intervention with the specific aim of preventing preterm birth. Quasi‐randomised controlled trials, cluster‐randomised trials and cross‐over trials were not included.

Data collection and analysis

Two review authors independently assessed trials for inclusion and trial quality. Two review authors extracted data. Data were checked for accuracy.

Main results

Six trials (374 twin pregnancies) were included, but only five trials (344 twin pregnancies) contributed data. All trials compared oral betamimetics with placebo.

Betamimetics reduced the incidence of preterm labour (one trial, 50 twin pregnancies, risk ratio (RR) 0.40; 95% confidence interval (CI) 0.19 to 0.86). However, betamimetics did not reduce preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10) or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50). Mean neonatal birthweight in the betamimetic group was significantly higher than in the placebo group (three trials, 478 neonates, mean difference 111.22 g; 95% CI 22.2 to 200.2). Nevertheless, there was no evidence of an effect of betamimetics in reduction of low birthweight (two trials, 366 neonates, average RR 1.19; 95% CI 0.77 to 1.85, random‐effects) or small‐for‐gestational age neonates (two trials, 178 neonates, RR 0.92; 95% CI 0.52 to 1.65). Two trials (388 neonates) showed that betamimetics significantly reduced the incidence of respiratory distress syndrome but the difference was not significant when the analysis was adjusted for correlation of babies from twins. Three trials (452 neonates) showed no evidence of an effect of betamimetics in reducing neonatal mortality (RR 0.80; 95% CI 0.35 to 1.82).

Authors' conclusions

There is insufficient evidence to support or refute the use of prophylactic oral betamimetics for preventing preterm birth in women with a twin pregnancy.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

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Oral betamimetics for the prevention of preterm labour and birth for women with twin pregnancies

There is insufficient evidence from randomised controlled trials to support or otherwise the routine use of oral betamimetics (drugs that reduce or prevent uterine contraction) to prevent preterm birth of twins.

When babies are born too early they can suffer from ill health, which is sometimes severe and very occasionally babies die. This may be due to their lungs and other organs not being mature enough. The problems related to preterm birth may also result in long‐term disabilities including cerebral palsy. Twins are more likely to be born early, have intrauterine growth restriction, and suffer from these problems. Drugs that reduce labour contractions (betamimetics) have been found to delay preterm birth when the mothers are carrying a single baby. However, this review of six trials (374 twin pregnancies) with only five trials (344 twin pregnancies) contributing data, found insufficient evidence to support the routine use of oral betamimetics. The results of one small study suggested that betamimetics can reduce the incidence of preterm labour but the results from four trials did not show a reduction in preterm births at less than 37 weeks gestation. There was no evidence of an effect of betamimetics in reducing the number of low or small‐for‐gestational age babies or deaths in newborns. The difference in the incidence of respiratory distress syndrome with betamimetics was not clear. Betamimetic drugs can cause maternal adverse effects such as heart palpitations.

The gestational age at trial entry ranged from 20 weeks to 34 weeks. The types and doses of betamimetics used in the trials varied and the outcomes reported were incomplete and defined in different ways. None of the included trials described whether or not steroids were used before birth to improve the baby’s lung maturity.