Sex-Specific Differences in Late Preterm Neonatal Outcomes

Objective To estimate sex-specific differences in late preterm outcomes and evaluate whether betamethasone modifies this association. Study Design We conducted a secondary analysis of a multicenter trial of women at risk for late preterm birth randomized to receive betamethasone or placebo. We included women who delivered at 34 to 37 weeks and excluded major fetal anomalies. The primary outcome was severe neonatal morbidity (mechanical ventilation, respiratory distress syndrome, bronchopulmonary dysplasia, sepsis, necrotizing enterocolitis, and intraventricular hemorrhage). Maternal characteristics were compared using chi-square test, t -test, or Mann-Whitney U -test. Multivariable logistic regression estimated the association between sex and morbidity, and likelihood ratio testing assessed for effect modification by betamethasone. Results Of 2,831 women in the primary trial, 2,331 met the inclusion criteria: 1,236 delivered males and 1,095 delivered females. Betamethasone modified the association between sex and severe morbidity ( p = 0.047). Among those who received betamethasone, male sex was associated with higher odds of severe morbidity (adjusted odds ratio: 1.95, 95% confidence interval: 1.25-3.05), compared with female sex. Among those who did not receive betamethasone, there was no significant association between sex and morbidity. Conclusion Male sex is a risk factor for adverse late preterm outcomes, including severe neonatal morbidity after betamethasone receipt.