Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth.Cochrane Database Syst Rev. 2020 12 25; 12:CD004454.CD
Respiratory morbidity including respiratory distress syndrome (RDS) is a serious complication of preterm birth and the primary cause of early neonatal mortality and disability. Despite early evidence indicating a beneficial effect of antenatal corticosteroids on fetal lung maturation and widespread recommendations to use this treatment in women at risk of preterm delivery, some uncertainty remains about their effectiveness particularly with regard to their use in lower-resource settings, different gestational ages and high-risk obstetric groups such as women with hypertension or multiple pregnancies. This updated review (which supersedes an earlier review Crowley 1996) was first published in 2006 and subsequently updated in 2017.
To assess the effects of administering a course of corticosteroids to women prior to anticipated preterm birth (before 37 weeks of pregnancy) on fetal and neonatal morbidity and mortality, maternal mortality and morbidity, and on the child in later life.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (3 September 2020), ClinicalTrials.gov, the databases that contribute to the WHO International Clinical Trials Registry Platform (ICTRP) (3 September 2020), and reference lists of the retrieved studies.
We considered all randomised controlled comparisons of antenatal corticosteroid administration with placebo, or with no treatment, given to women with a singleton or multiple pregnancy, prior to anticipated preterm delivery (elective, or following rupture of membranes or spontaneous labour), regardless of other co-morbidity, for inclusion in this review.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two review authors independently assessed trials for inclusion, assessed risk of bias, evaluated trustworthiness based on predefined criteria developed by Cochrane Pregnancy and Childbirth, extracted data and checked them for accuracy, and assessed the certainty of the evidence using the GRADE approach. Primary outcomes included perinatal death, neonatal death, RDS, intraventricular haemorrhage (IVH), birthweight, developmental delay in childhood and maternal death.
We included 27 studies (11,272 randomised women and 11,925 neonates) from 20 countries. Ten trials (4422 randomised women) took place in lower- or middle-resource settings. We removed six trials from the analysis that were included in the previous version of the review; this review only includes trials that meet our pre-defined trustworthiness criteria. In 19 trials the women received a single course of steroids. In the remaining eight trials repeated courses may have been prescribed. Fifteen trials were judged to be at low risk of bias, two had a high risk of bias in two or more domains and we ten trials had a high risk of bias due to lack of blinding (placebo was not used in the control arm. Overall, the certainty of evidence was moderate to high, but it was downgraded for IVH due to indirectness; for developmental delay due to risk of bias and for maternal adverse outcomes (death, chorioamnionitis and endometritis) due to imprecision. Neonatal/child outcomes Antenatal corticosteroids reduce the risk of: - perinatal death (risk ratio (RR) 0.85, 95% confidence interval (CI) 0.77 to 0.93; 9833 infants; 14 studies; high-certainty evidence; 2.3% fewer, 95% CI 1.1% to 3.6% fewer), - neonatal death (RR 0.78, 95% CI 0.70 to 0.87; 10,609 infants; 22 studies; high-certainty evidence; 2.6% fewer, 95% CI 1.5% to 3.6% fewer), - respiratory distress syndrome (RR 0.71, 95% CI 0.65 to 0.78; 11,183 infants; studies = 26; high-certainty evidence; 4.3% fewer, 95% CI 3.2% to 5.2% fewer). Antenatal corticosteroids probably reduce the risk of IVH (RR 0.58, 95% CI 0.45 to 0.75; 8475 infants; 12 studies; moderate-certainty evidence; 1.4% fewer, 95% CI 0.8% to1.8% fewer), and probably have little to no effect on birthweight (mean difference (MD) -14.02 g, 95% CI -33.79 to 5.76; 9551 infants; 19 studies; high-certainty evidence). Antenatal corticosteroids probably lead to a reduction in developmental delay in childhood (RR 0.51, 95% CI 0.27 to 0.97; 600 children; 3 studies; moderate-certainty evidence; 3.8% fewer, 95% CI 0.2% to 5.7% fewer). Maternal outcomes Antenatal corticosteroids probably result in little to no difference in maternal death (RR 1.19, 95% CI 0.36 to 3.89; 6244 women; 6 studies; moderate-certainty evidence; 0.0% fewer, 95% CI 0.1% fewer to 0.5% more), chorioamnionitis (RR 0.86, 95% CI 0.69 to 1.08; 8374 women; 15 studies; moderate-certainty evidence; 0.5% fewer, 95% CI 1.1% fewer to 0.3% more), and endometritis (RR 1.14, 95% CI 0.82 to 1.58; 6764 women; 10 studies; moderate-certainty; 0.3% more, 95% CI 0.3% fewer to 1.1% more) The wide 95% CIs in all of these outcomes include possible benefit and possible harm.