Antenatal dexamethasone for early preterm birth in low-resource countries

BACKGROUND: The safety and efficacy of antenatal glucocorticoids for women at risk of preterm birth in low-resource countries is unknown. METHODS: We conducted a multicountry, randomized trial involving pregnant women at risk of preterm birth between 26 weeks 0 days and 33 weeks 6 days of gestation. Participants were assigned to intramuscular dexamethasone or identical placebo. Primary outcomes were neonatal death, any baby death (stillbirth or neonatal death), and composite possible maternal bacterial infection outcome. We applied superiority hypothesis for the infant primary outcomes and non-inferiority hypothesis for the maternal primary outcome. RESULTS: The trial was stopped at the second interim analysis for benefits. We randomized 2852 women (and their 3070 babies) from 29 secondary and tertiary level hospitals across Bangladesh, India, Kenya, Nigeria, and Pakistan. Neonatal death occurred in 278 of 1417 infants (19.6%) in the dexamethasone group and 331 of 1406 infants (23.5%) in the placebo group (relative risk, 0.84; 95% confidence interval [CI] 0.72 to 0.97; P=0.03). Any baby death occurred in 393 of 1532 infants (25.7%) in the dexamethasone group and 444 of 1519 infants (29.2%) in the placebo group (relative risk, 0.88; 95% CI 0.78 to 0.99; P=0.04). Possible maternal bacterial infection did not differ between dexamethasone and placebo groups (4.8% vs. 6.3%, relative risk, 0.76; 95% CI 0.56 to 1.03), a finding consistent with noninferiority (P=0.002). Early neonatal death, severe respiratory distress at 24 hours, neonatal hypoglycemia at 6 hours, resuscitation at birth, and use of continuous positive airway pressure were lower in the dexamethasone group. Adverse events did not differ significantly between the groups. CONCLUSIONS: Antenatal dexamethasone treatment of women at risk of early preterm birth in low-resource countries resulted in a significantly lower risk of neonatal death and any baby death, and no increase in possible maternal bacterial infection. (Funded by Bill and Melinda Gates Foundation; Australia and New Zealand Clinical Trials Registry number ACTRN12617000476336; Clinical Trials Registry-India number, CTRI/2017/04/008326)