Antenatal Corticosteroid in Twin-Pregnant Women at Risk of Late Preterm Delivery: A Randomized Clinical Trial.

Importance: Recent guidelines have recommended corticosteroid injection in women with singleton pregnancies at risk of late preterm delivery. However, the effectiveness of antenatal corticosteroid administration in women with twin pregnancies at risk of late preterm delivery has not been evaluated, and studies on this population are lacking. Objective: To evaluate whether antenatal betamethasone administration reduces the risk of neonatal respiratory morbidity in late preterm twin neonates. Design, Setting, and Participants: In this multicenter randomized trial, twin-pregnant women at 34 weeks 0 days to 36 weeks 5 days of gestation at risk of late preterm delivery were enrolled across 8 university-based clinical centers in Korea. Data were collected between May 2018 and July 2024. Intention-to-treat analysis was performed. Intervention: The participants received 2 injections of betamethasone or placebo after randomization (1:1). Main Outcomes and Measures: The primary outcome was perinatal death within 72 hours after birth or severe neonatal respiratory morbidity. The exploratory outcomes were mild neonatal respiratory morbidities, other neonatal respiratory morbidities, other neonatal complications, or maternal complications. Results: A total of 812 participants were randomized and analyzed, with 410 in the intervention group (median [IQR] age, 35 [33-37] years) and 402 in the placebo group (median [IQR] age, 35 [32-38] years). Among 1620 neonates (818 in the intervention group and 802 in the placebo group), there were no perinatal deaths in either group, and severe neonatal respiratory morbidity occurred in 99 neonates (6.1%), with lower risk in the betamethasone group than in the placebo group (39 [4.8%] vs 60 [7.5%]; relative risk [RR], 0.64 [95% CI, 0.42-0.98]). For the exploratory outcomes, continuous positive airway pressure use for 2 hours or more (RR, 0.58 [95% CI, 0.35-0.95]) and transient tachypnea of the newborn (RR, 0.47 [95% CI, 0.25-0.89]) were lower in the betamethasone group. The risk of primary outcome and mild respiratory morbidities was reduced only in neonates delivered between 12 hours or more and less than 7 days after the first betamethasone administration. The risk of neonatal hypoglycemia was increased in the betamethasone group (128 [15.6%] vs 94 [11.7%]; RR, 1.33 [95% CI, 1.01-1.75]), but the risk of neonatal sepsis or maternal chorioamnionitis did not differ between the 2 groups. Conclusions and Relevance: In this randomized clinical trial, antenatal betamethasone administration in women with twin pregnancies at risk of late preterm delivery significantly reduced the risk of neonatal respiratory morbidity. The outcomes from this study could serve as a valuable reference in clinical management of twin pregnancies at risk of late preterm delivery. Trial Registration: ClinicalTrials.gov Identifier: NCT03547791.