Comment on “Antenatal Corticosteroid in Twin-pregnant Women at Risk of Late Preterm Delivery: A Randomized Clinical Trial”

Twin pregnancies have been on the rise worldwide, driven by advancing maternal age and the use of assisted reproductive technology. In the United States, the twin birth rate rose from 1.9% to 3.1% from 1980 to 2022. In Korea, the annual twin birth rate rose from 7% to 10% after its government began supporting the cost of assisted reproduction. Twin pregnancies are at higher risk of neonatal morbidity and mortality than singleton pregnancies, largely due to preterm birth. Preterm birth occurs in about 37% to 61% of twin pregnancies and typically occurs during the late preterm period. Antenatal corticosteroids have been recommended for uncomplicated pregnancies at risk of early preterm birth (<34 wks), regardless of the number of fetuses. Recently, clinical guidelines were updated based on the Antenatal Late Preterm Steroids trial, which showed that antenatal corticosteroid injections reduced neonatal respiratory complications in singleton pregnancies at risk of late preterm birth (34 to 36+6 wk). However, this trial did not include twin pregnancies, and evidence remains limited on the use of corticosteroids in late preterm twin pregnancies. The aim of this study was to assess whether corticosteroid injection reduces the risk of neonatal respiratory morbidity in late preterm twin neonates. The Antenatal Corticosteroids in Twin Late Preterm Neonates trial was a double-blind, randomized clinical trial conducted at 8 university-based clinical centers in Korea between May 2018 and July 2024. Included were twin pregnancies between 34 weeks and 36+5 weeks at high risk of late preterm delivery. Participants were randomly assigned 1:1 to receive either antenatal corticosteroid injections of betamethasone or a placebo. The primary outcome was prenatal death or severe neonatal respiratory morbidity within 72 hours after birth. A total of 812 participants were included in the analysis, with 410 in the betamethasone group and 402 in the placebo group. Of the 99 neonates who experienced the primary outcome, the risk was less likely in the betamethasone group than the placebo group [4.8% vs 7.5%, respectively; relative risk (RR), 0.64; 95% CI, 0.42-0.98]. The betamethasone group was also less likely to require continuous positive airway pressure for 12 hours or more than the placebo group (2.3% vs 4.7%; RR, 0.50; 95% CI, 0.29-0.87). A lower risk of the primary outcome and mild respiratory morbidities was observed only in neonates delivered ≥12 hours and <7 days after the first administration of betamethasone (primary outcome: RR, 0.56; 95% CI, 0.35-0.89; mild respiratory morbidities: RR, 0.62; 95% CI, 0.39-0.97). The neonates whose mothers were randomized to betamethasone had higher rates of neonatal hypoglycemia as well (15.6% vs 11.7%, P < 0.05). In conclusion, the use of antenatal corticosteroids significantly reduced the risk of severe neonatal respiratory morbidity or perinatal death in late-term, twin pregnancies. This benefit was observed when corticosteroids were given between 12 hours and 7 days before delivery. (Summarized from Lee SM, Park HS, Choi SR, et al. Antenatal corticosteroid in twin-pregnant women at risk of late preterm delivery: A randomized clinical trial. JAMA Pediatr 2025;179(12):1275-1282. doi: https://doi.org/10.1001/jamapediatrics.2025.3284)