# 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.

## Key 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.