Antenatal dexamethasone for late preterm birth: A multi-centre, two-arm, parallel, double-blind, placebo-controlled, randomized trial

BACKGROUND: There is currently insufficient evidence on the safety and efficacy of antenatal corticosteroids in preventing mortality and severe morbidity amongst late preterm newborns in low-resource countries. METHODS: We conducted a double-blind, randomized trial in four hospitals in India between 26 December 2017 to 21 May 2020. Pregnant women at risk of imminent preterm birth between 34 weeks 0 days and 36 weeks 0 days of gestation were recruited. Women were randomly assigned (1:1) to a course of 6 mg intramuscular dexamethasone or an identical placebo. All trial participants, research staff and outcome assessors were masked to allocation. Primary outcomes were neonatal death, any baby death (stillbirth or neonatal death), severe neonatal respiratory distress and possible maternal bacterial infection. The study was registered with ANZCTR (ACTRN12617001494325) and CTRI (CTRI/2017/05/008721). FINDINGS: We randomized 782 women, 391 to each arm. Neonatal death occurred in 11 of 412 liveborn babies (2.7%) in the dexamethasone group and 12 of 425 liveborn babies (2.8%) in the placebo group (RR 0.95; 95% CI 0.42–2.12). Any baby death occurred in 16 of 417 infants (3.8%) in the dexamethasone group and 19 of 432 infants (4.4%) in the placebo group (RR 0.87; 95% CI 0.45–1.67). Severe neonatal respiratory distress was infrequent in both groups (0.8% vs 0.5%; RR 1.56; 95% CI 0.26–9.29). Possible maternal bacterial infection did not differ between groups (2.3% vs. 3.8%, RR 0.60; 95% CI 0.27–1.35). Fewer neonates in the dexamethasone group required resuscitation at birth (RR 0.38, CI 0.15–0.97). Other secondary outcomes were similar in the two arms. The trial was stopped due to lower than expected prevalence of primary outcomes and slow recruitment. INTERPRETATION: Antenatal dexamethasone did not result in a reduction in neonatal death, stillbirth or neonatal death, or severe neonatal respiratory distress in this trial. The overall trend of effects suggests that potential benefit of dexamethasone in late preterm cannot be excluded, and further trials are required. FUNDING: This trial was primarily funded by the Bill and Melinda Gates Foundation (Grant OPP1136821). Additional support was provided by UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research; and Department of Maternal, Newborn, Child, Adolescent Health, and Ageing, of the World Health Organization, Geneva, Switzerland.