The Impact of Offspring Sex on Pregnancy and Neonatal Outcomes in Individuals with Pregestational Diabetes

Pregestational diabetes mellitus (PGDM) is increasing in prevalence among pregnant individuals and is associated with adverse outcomes. Prior work suggests that offspring sex influences placental responses and may impact risk for adverse outcomes. We sought to assess the impact of offspring sex on adverse pregnancy and neonatal outcomes in individuals with PGDM. We conducted a retrospective cohort study of 503 pregnant individuals with PGDM and known offspring sex with care at a major urban academic center between 1998 and 2016. We assessed two co-primary composite outcomes: (1) a composite adverse pregnancy outcome of small for gestational age (SGA), hypertensive disorder of pregnancy (HDP), and stillbirth and (2) a composite adverse neonatal outcome of large for gestational age (LGA), hypoglycemia, hyperbilirubinemia, shoulder dystocia, and respiratory distress syndrome (RDS). Secondary outcomes of spontaneous preterm birth (PTB) and admission to the neonatal intensive care unit (NICU) were assessed. Mixed effects logistic regression models, accounting for multiple pregnancies and adjusting for first trimester body mass index (BMI), insurance, parity, and maternal race/ethnicity, were analyzed. Of the 503 pregnant individuals with PGDM, 67% had a diagnosis of type 2 DM and 33% had type 1 DM. The composite adverse pregnancy outcome occurred in 79 of 258 (31%) pregnancies with a female fetus and 76 of 245 (31%) pregnancies with a male fetus. The composite neonatal outcome occurred in 163 of 245 males (67%) and 154 of 258 females (60%). Male infants had significantly higher odds of requiring admission to the NICU (adjusted odds ratio 1.79 [95% confidence interval: 1.13, 2.80], p = 0.01). There were no observed sex differences in the incidence of spontaneous PTB. We identified high rates of both composite outcomes in pregnancies with PGDM, regardless of fetal sex. The significantly higher rate of NICU admission among males suggests an increased risk of neonatal morbidity in males exposed to PGDM.