Antenatal betamethasone reduces neonatal morbidity in twin pregnancies

Data published in JAMA Network Open have indicated a significant reduction in neonatal respiratory morbidity among women with twin pregnancies at risk of late preterm delivery receiving antenatal betamethasone.¹

Twin pregnancies, which are at an increased risk of neonatal morbidity and mortality, have become more prevalent over time in the United States.² As antenatal corticosteroid administration has been linked to improved outcomes in singleton pregnancies, this regimen has also been recommended for use in twin pregnancies at risk of preterm birth.¹

“Guidelines pertaining to late preterm twin gestation are lacking,” wrote investigators. “Higher neonatal morbidity in late preterm neonates compared with full-term neonates…may support the use of antenatal corticosteroid in late preterm twin neonates.”

Antenatal corticosteroid vs placebo

The multicenter double-blind randomized clinical trial was conducted to evaluate the impact of antenatal betamethasone administration in twin pregnancies with late preterm births. Participants included twin pregnant women between 34 weeks’ and 36 weeks, 5 days’ gestation at great risk of late preterm delivery.

These patients were randomly assigned 1:1 to undergo either antenatal corticosteroid administration as 2 intramuscular injections of 12 mg/3 mL betamethasone or placebo administration as 2 intramuscular injections of 3 mL normal saline. All participants injected the doses 24 hours apart.

Baseline characteristics, pregnancy outcomes, and neonatal outcomes were obtained from the medical records of participants and neonates, collected by trained medical staff blinded to the randomization assignment. Additionally, neonatal outcomes were reevaluated 28 days after birth.

Patient characteristics and adverse events

Perinatal death or severe respiratory morbidity within 72 hours after birth were reported as primary outcomes. Morbidity outcomes included continuous positive airway pressure (CPAP) or high-flow nasal cannula use, supplementary oxygen administration, mechanical ventilation, and extracorporeal membrane oxygenation.

There were 812 participants included in the final analysis, 410 of whom were randomly assigned to the study group and 402 to the placebo group. Median maternal ages were 35 years in both groups, and nulliparity status was reported in 78.1%. Assisted reproduction was provided to 77.2%, and rates of monochorionic twins and congenital malformation were 18.7% and 5.5%, respectively.

The completion of both doses was reported by 68.5% of participants in the betamethasone group and 66.4% in the placebo group. Receiving only one dose was reported by 31% and 33.1%, respectively. No significant differences in adverse event rates were reported between groups, and events were mild, such as nausea and pain at the injection site.

Morbidity and mortality comparisons

A significantly reduced risk of neonatal morbidity and mortality was reported in patients receiving antenatal corticosteroids vs placebo, with rates of 4.8% and 7.5%, respectively. This indicated a relative risk (RR) of 0.64.

For 12 or more hours of CPAP use, the RR was 0.50, with rates of 2.3% and 4.7%, respectively. Based on this data, investigators stated 23 twin pregnancies would need antenatal corticosteroid injection to prevent a primary outcome in at least 1 neonate per twin pair.

The betamethasone group also had reduced risks of CPAP for 2 hours or more and transient tachypnea of the newborn, with RRs of 0.58 and 0.47, respectively. Neonatal hypoglycemia was reported in 15.6% of the betamethasone group and 11.7% of the placebo group, while 1% and 2.7%, respectively, reported feeding difficulty.

Implications

No significant differences in chorioamnionitis or postpartum endometritis risks were reported between groups. Overall, the data highlighted reduced neonatal respiratory morbidity in twin-pregnant patients at risk of late preterm delivery receiving antenatal betamethasone.

“Antenatal corticosteroid injection should be recommended in this population,” wrote investigators.

References

1. 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
2. Osterman MJK, Hamilton BE, Martin JA, Driscoll AK, Valenzuela CP. Births: final data for 2022. Natl Vital Stat Rep. 2024;73(2):1-56.