The Impact of Infant Sex on Perinatal Outcomes Following Exposure to Multiple Courses Versus a Single Course of Antenatal Corticosteroids: A Secondary Analysis of the MACS Randomized Controlled Trial

Abstract

Objective: Animal literature has suggested that the impact of antenatal corticosteroids (ACS) may vary by infant sex. Our objective was to assess the impact of infant sex on the use of multiple courses versus a single course of ACS and perinatal outcomes. Study Design: We conducted a secondary analysis of the Multiple Courses of Antenatal Corticosteroids (MACS) for Preterm Birth trial. Our primary outcome was a composite of perinatal mortality or clinically significant neonatal morbidity (including neonatal death, stillbirth, severe respiratory distress syndrome, intraventricular hemorrhage [grade III or IV], cystic periventricular leukomalacia, and necrotising enterocolitis [stage II or III]). Secondary outcomes included individual components of the primary outcome as well as anthropometric measures. Baseline characteristics were compared between participants who received multiple courses versus a single course of ACS. Multivariable regression analyses were conducted with adjustment for pre-defined covariates including an interaction between exposure to ACS and infant sex. Results: Data on 2304 infants were analyzed. The interaction term between treatment status (multiple courses versus a single course of ACS) and infant sex was not significant in the adjusted model for the primary outcome (p=0.86), nor for any of the secondary outcomes. Exposure to multiple courses versus a single course of ACS was not associated with the primary outcome either before or after adjustment (aOR 0.99, 95% CI 0.67 to 1.45, n=2292 infants). However, exposure to multiple courses versus a single course of ACS resulted in significantly lower birth length (p=0.02) and head circumference at birth (p=0.04) although not birthweight (p=0.06). Conclusions: Infant sex did not modify the association between exposure to ACS and perinatal outcomes including perinatal mortality or neonatal morbidity or anthropometric outcomes. However, animal literature indicates that sex specific differences after exposure to ACS may emerge over time and thus investigating long-term sex-specific outcomes warrants further attention.