Defining the Timing Window: Week- and Interval-Specific Effects of Antenatal Betamethasone in Late-Preterm Births

<b>Objectives:</b> To evaluate the association between antenatal betamethasone exposure and neonatal respiratory morbidity among late-preterm births. We further examined whether gestational age at delivery and the exposure-to-delivery interval modify this association. <b>Methods:</b> We conducted a retrospective cohort study of singleton live births at 34-36 + 6 weeks in a tertiary center (2011-2023). Betamethasone exposure was classified as none, early (<34 weeks), or late (34-36 + 6 weeks). Among exposed pregnancies, the interval from first dose to delivery was categorized as ≤7 or >7 days and evaluated separately at 34, 35, and 36 weeks. Primary outcomes were RDS and composite respiratory morbidity (RDS, TTN, or ≥3 days of respiratory support); neonatal hypoglycemia was secondary. Adjusted odds ratios were estimated using multivariable logistic regression including maternal age, parity, delivery mode, and birthweight. <b>Results</b>: The study included 2668 late-preterm infants, of whom 2356 (88.3%) were unexposed and 312 (11.7%) were exposed to antenatal corticosteroids (ACSs). Among exposed pregnancies, 138 (44.2%) received early ACS and 174 (55.8%) late ACS; 163 (52.2%) delivered ≤7 days and 149 (47.8%) >7 days after administration. Late ACS exposure was associated with lower odds of RDS (aOR 0.37, 95% CI 0.17-0.69) and composite respiratory morbidity (aOR 0.55, 95% CI 0.31-0.92), but with increased odds of neonatal hypoglycemia (aOR 2.72, 95% CI 1.26-5.31). Among pregnancies delivering at 34 weeks, exposure within ≤7 days was associated with a marked reduction in RDS (aOR 0.25, 95% CI 0.07-0.79; NNT ≈ 3), whereas no respiratory benefit was observed at 35 or 36 weeks or when the interval exceeded 7 days. <b>Conclusions</b>: Antenatal betamethasone exposure among late-preterm births was not uniformly associated with neonatal respiratory outcomes, with associations varying by gestational age at delivery and the exposure-to-delivery interval. These findings may be interpreted in the context of potential respiratory benefit alongside accompanying metabolic risk, with exploratory analyses suggesting a more pronounced signal among deliveries at 34 weeks within ≤7 days.