Prenatal Magnesium Sulfate Exposure Is Not Associated with Different Neurodevelopmental Outcomes by Sex in Extremely Preterm Infants

<b>Background/Objectives</b>: Magnesium sulfate (MgSO₄) has historically been used in obstetrics as a tocolytic and to prevent eclamptic seizures. MgSO₄ has also been investigated as a potential neonatal neuroprotectant for infants born preterm. However, randomized controlled trials of prenatal MgSO₄ have shown mixed results, with single-center observational studies also suggesting differential effects by sex. We sought to evaluate sex-dependent associations between prenatal MgSO₄ exposure and standardized neurodevelopmental outcomes in a large, multi-center cohort of extremely preterm neonates (24-0/7 to 27-6/7 weeks' gestation) from the Preterm Erythropoietin Neuroprotection Trial (PENUT). <b>Methods</b>: The relationship between maternal MgSO₄ exposure and neurodevelopmental outcomes assessed at 2 years using the Bayley Scales of Infant and Toddler Development Index, 3rd edition was examined by sex in <i>n</i> = 666 infants (<i>n</i> = 328 female, <i>n</i> = 338 male). To account for confounding by indication, we performed both matching and inverse probability weighting using 17 maternal predictors of MgSO₄ exposure. <b>Results</b>: In both unadjusted and adjusted (weighted and matched) analyses, no relationship between MgSO₄ exposure and neurodevelopmental outcomes was seen, either overall or by sex. <b>Conclusions</b>: This study reaffirms the safety of MgSO₄, but appropriate clinical trials of MgSO₄ in extremely preterm infants are still required to better understand any effects on neurodevelopmental outcomes.