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 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 two small studies 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 34 or 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, although this was not reported in the included trials. The quality of evidence is low because there were small numbers of participants and few outcomes in the included trials.

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.

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.

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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 strategy: 

We searched the Cochrane Pregnancy and Childbirth Group Trials Register (21 September 2015), MEDLINE (January 1966 to 31 July 2015), EMBASE (January 1985 to 31 July 2015) and reference lists of retrieved studies.

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 eligible for inclusion.

Data collection and analysis: 

Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Two authors assessed the quality of the evidence using the GRADE approach.

Main results: 

Overall, the quality of evidence is low for the primary outcomes. All of the included trials had small numbers of participants and few events. Preterm birth, the most important primary outcome, had wide confidence intervals crossing the line of no effect.

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 (two trials, 194 twin pregnancies, risk ratio (RR) 0.37; 95% confidence interval (CI) 0.17 to 0.78; low quality evidence). However, betamimetics did not reduce prelabour rupture of membranes (one trial, 144 twin pregnancies, RR 1.42; 95% CI 0.42 to 4.82; low quality evidence), preterm birth less than 37 weeks' gestation (four trials, 276 twin pregnancies, RR 0.85; 95% CI 0.65 to 1.10; low quality evidence), or less than 34 weeks' gestation (one trial, 144 twin pregnancies, RR 0.47; 95% CI 0.15 to 1.50; low quality evidence). 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 22.21 to 200.24). 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, average RR 0.90; 95% CI 0.41 to 1.99, random-effects). Two trials showed that betamimetics significantly reduced the incidence of respiratory distress syndrome (388 neonates, RR 0.30; 95% CI 0.12 to 0.77), but the difference was not significant when the analysis was adjusted to account for the non-independence of twins (194 twins, RR 0.35; 95% CI 0.11 to 1.16). Three trials showed no evidence of an effect of betamimetics in reducing neonatal mortality, either with the unadjusted analysis, assuming twins are completely independent of each other (452 neonates, average RR 0.90; 95% CI 0.15 to 5.37, random-effects), or in the adjusted analysis, assuming non-independence of twins (226 twins, average RR 0.74; 95% CI 0.23 to 2.38, random-effects). A maternal death was reported in one trial without a significant difference between the groups (144 women, RR 2.84; 95% CI 0.12 to 68.57).

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