Abstract
BACKGROUND: Corticosteroids are widely used in obstetric clinical practice for cases with signs of preterm labor to promote fetal lung maturity and reduce neonatal morbidity and mortality. Although short-term use is considered safe, there is ongoing debate regarding the dosage, therapeutic window, neonatal benefits, and maternal-fetal side effects, especially in high-risk pregnancies such as twins, where the impact remains unclear. METHODS: This retrospective study included 1,997 twin pregnancies, divided into two groups: those who received antenatal corticosteroid therapy (ACS) and those who did not. To correct for baseline imbalances, the optimal overlap weighting scheme was selected by calculating the Absolute Standardized Mean Difference (ASMD) to minimize intergroup differences. The primary outcome, neonatal respiratory distress syndrome (NRDS), and other adverse outcomes in twin neonates were analyzed for the effect of ACS using logistic regression, with subgroup and interaction analyses based on key maternal pregnancy characteristics. Lastly, the Restricted cubic spline (RCS) method was used to examine the effect of ACS on neonatal respiratory disease incidence across different gestational ages at delivery. RESULTS: After propensity score overlap weighting, results showed that although ACS treatment did not significantly improve the respiratory composite outcome in the overall preterm group, it effectively reduced the incidence of NRDS and pneumonia, while also decreasing the risk of low birth weight, small for gestational age (SGA), neonatal purpura, and neonatal hypoproteinemia. Notably, the risk of neonatal hypoglycemia and hyperbilirubinemia was significantly increased in the ACS treatment group. In both early and late preterm groups, there was no significant difference in the impact of ACS on NRDS and respiratory composite outcomes, but it remained effective in reducing the risks of neonatal pneumonia, low birth weight, and hypoproteinemia. In late preterm pregnancies, ACS significantly reduced the incidence of neonatal enteritis, lower gastrointestinal bleeding and neonatal infections, while in early preterm pregnancies, it significantly lowered the risk of neonatal hyperlacticemia. Subgroup analysis showed that for early preterm twin pregnancies with gestational diabetes mellitus (GDM), ACS treatment increased the incidence of NRDS and the neonatal respiratory composite outcome. Similarly, for twin pregnancies complicated by preeclampsia (PE), ACS treatment raised NRDS incidence in both overall and early preterm subgroups. Finally, RCS analysis indicated that ACS treatment may help reduce the risk of NRDS and other respiratory outcomes across different gestational ages at delivery, although this trend did not reach statistical significance. Sensitivity analysis showed similar results. CONCLUSION: Antenatal corticosteroids, whether in early or late preterm births, may not prevent NRDS and respiratory composite outcomes in twin neonates, but they are effective in reducing adverse neonatal outcomes such as pneumonia, low birth weight, and hypoproteinemia. However, the occurrence of neonatal hypoglycemia and hyperbilirubinemia should be noted.