Associations between antenatal corticosteroids and neonatal morbidities in a prospective cohort: role of course, timing, and gestational age

Background: Antenatal corticosteroids (ACS) have been widely used to enhance fetal lung maturation in pregnant women at risk of preterm delivery, but gaps remain in understanding how number of courses, gestational age at the first dose, and last dose-to-delivery interval affect neonatal morbidities across different gestational age groups. This study aimed to investigate the associations between ACS, particularly the number of courses, gestational age at the first dose, and last dose-to-delivery interval, and neonatal morbidities. Methods: This prospective study included 78,642 singleton infants born at 29-43 weeks of gestation between July 2018 and June 2024. Detailed information of ACS exposure and neonatal morbidities was obtained from electronic health records. Logistic regression was applied to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for neonatal morbidities. Subgroup analyses were performed by stratifying the gestational age at birth. Results: A total of 2827 (3.59%) infants were exposed to ACS. Compared with unexposed infants, those exposed to ACS had higher risks of respiratory, metabolic, infectious/inflammatory, and neurological morbidities, but not of asphyxia. Multiple ACS courses demonstrated the strongest association with higher risk of neurological morbidity (OR, 2.99; 95% CI 1.68-5.31), along with increased risks of metabolic (OR, 1.43; 95% CI 1.12-1.83) and infectious/inflammatory morbidities (OR, 1.45; 95% CI 1.11-1.89). The timing of the first ACS dose was associated with increased risks of specific neonatal morbidities, regardless of the gestational age at initiation. A last dose-to-delivery interval of 14 days or more was associated with higher risks of metabolic (OR, 1.25; 95% CI 1.14-1.37), infectious/inflammatory (OR, 1.26; 95% CI 1.13-1.40), and neurological (OR, 1.84; 95% CI 1.31-2.59) morbidities. No association was found for infants born before 34 weeks. Conclusions: ACS exposure, particularly multiple courses or a last dose-to-delivery interval of 14 days or more, was associated with higher risks of neonatal morbidities among infants born at 34 weeks of gestation or later.