Association of Antenatal Dexamethasone Administration Timing with Outcomes in Preterm Infants in a Low-and Middle-income Country

Vijay Kalrao^*Mamta Benda

• Bharati Vidyapeeth's Medical College, Pune, India

Background: Timely administration of antenatal corticosteroids improves preterm outcomes; however, in low-and middle-income countries (LMICs), multiple barriers often delay treatment. Whether exposure within 24 h before delivery confers benefits remains uncertain. We aimed to evaluate the association between antenatal dexamethasone-to-delivery intervals and preterm outcomes in an LMIC setting. Methods: This single-center prospective cohort study was conducted at a tertiary neonatal intensive care unit in India from June 2023 to December 2024. The participants were preterm infants born at 24 0/7 to 33 6/7 wk gestation. Exclusion criteria were major congenital anomalies, multiple courses of dexamethasone, administration-to-birth interval >7 d, and interfacility transfer. The exposure variable was maternal first dexamethasone dose-to-delivery interval, categorized as ≤24 h (n=167), >24 h–7 d (n=64), or no exposure (n=101). The primary outcome was in-hospital mortality. Secondary outcomes included severe necrotizing enterocolitis (NEC), intraventricular hemorrhage, respiratory distress syndrome, and a composite of death or severe morbidity. Propensity scores from 10 covariates generated inverse-probability-of-treatment-weights (IPTW). Adjusted risk ratios (aRRs) and 95% confidence intervals (CIs) were estimated using a doubly-robust, trimmed IPTW-modified Poisson model. Sensitivity analyses used doubly-robust overlap weighting and an entropy-balanced treatment-only model. Results: Of the 371 infants born during the study period, 332 met eligibility criteria (mean gestational age, 30.6 ± 2.2 wk; 60.5% male). Overall mortality was 7.8% (26/332): 11.9% (12/101) without dexamethasone, 6.6% (11/167) with ≤24 h exposure, and 4.7% (3/64) with >24 h–7 d exposure. Mortality did not differ by dexamethasone timing interval group: ≤24 h (aRR, 0.58; 95%CI 0.26–1.27) and >24 h–7 d (aRR, 0.33; 95%CI, 0.10–1.12) vs. no dexamethasone. Wide CIs were observed, reflecting imprecision due to lower-than-expected mortality in the unexposed group. Severe NEC was lower with ≤24 h exposure (1.8% [3/167] vs. 8.9% [9/101]; aRR, 0.15; 95%CI 0.04–0.54), persisting in sensitivity analyses (aRR, 0.11; 95%CI 0.03–0.38) and after multiple-comparison adjustment. No other secondary outcomes differed significantly. Conclusions: Dexamethasone administration within 24 h before delivery did not reduce mortality but significantly decreased the risk of severe NEC. Imprecise estimates due to lower-than-expected mortality, reduced statistical power, and potential residual confounding limit definitive conclusions.