The multicenter trial enrolled 812 women with twin pregnancies between 34 weeks 0 days and 36 weeks 5 days of gestation across eight university-based hospitals in Korea. Participants were randomly assigned to receive two injections of betamethasone or a placebo in a 1:1 ratio. The study analyzed outcomes for 1,620 neonates, with the primary focus on perinatal death within 72 hours or severe neonatal respiratory morbidity. Secondary outcomes included other respiratory complications, mild neonatal respiratory issues, and maternal complications.
The study led to the following notable findings:
- No perinatal deaths were reported in either the betamethasone or placebo groups.
- Severe neonatal respiratory morbidity occurred in 99 neonates (6.1%).
- The risk of severe neonatal respiratory morbidity was lower in the betamethasone group compared to placebo (4.8% vs 7.5%; RR, 0.64).
- Betamethasone reduced the need for continuous positive airway pressure (CPAP) for 2 hours or more (RR, 0.58).
- Rates of transient tachypnea of the newborn were lower in the betamethasone group (RR, 0.47).
- Protective effects of betamethasone were observed only when delivery occurred between 12 hours and less than 7 days after the first injection.
- Neonatal hypoglycemia was more frequent in the betamethasone group (15.6% vs 11.7%; RR, 1.33).
- Rates of neonatal sepsis and maternal chorioamnionitis were similar between the two groups.
- In subgroup analyses excluding neonates with congenital malformations, the primary outcome did not reach statistical significance, likely due to a smaller sample size.
The study had some limitations, including a lower-than-expected rate of severe respiratory morbidity compared to prior data from single centers, potential minor unblinding due to clinical cues, and inclusion of only Asian participants. Nevertheless, the trial demonstrated a clear protective effect of antenatal corticosteroid administration, with a larger-than-anticipated risk reduction.
In conclusion, antenatal betamethasone administration in twin pregnancies at risk of late preterm delivery effectively reduces the risk of severe neonatal respiratory complications, provided the timing of delivery aligns with the 12-hour to 7-day window post-injection. These findings support current recommendations for corticosteroid use in late preterm twin pregnancies and provide clinicians with important guidance for optimizing neonatal outcomes. Further research is warranted to assess long-term safety and applicability across diverse populations.
Reference:
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. Published online September 22, 2025. doi:10.1001/jamapediatrics.2025.3284
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