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

TL;DR

This study shows that the timing of antenatal betamethasone affects neonatal respiratory outcomes differently depending on gestational age and the time between drug administration and delivery.

Contribution

The study identifies specific gestational age and timing windows where betamethasone provides respiratory benefits but also increases metabolic risks.

Findings

Late betamethasone exposure reduced respiratory distress syndrome (RDS) and composite respiratory morbidity but increased neonatal hypoglycemia.

Exposure within 7 days before delivery at 34 weeks significantly reduced RDS, but no benefit was seen at 35 or 36 weeks or with longer intervals.

The effects of betamethasone varied by gestational age and exposure-to-delivery interval, suggesting a non-uniform impact on neonatal outcomes.

Abstract

Objectives: 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. Methods: 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. Results: 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. Conclusions: 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.