Fetal Sex and the Natural History of Maternal Risk of Diabetes During and After Pregnancy

Context: It has recentlyemergedthat carrying a male fetus is associated with poorer maternal beta-cell function in pregnancy and an increased risk of gestational diabetes mellitus (GDM). beta-cell dysfunction is the central pathophysiologic defect underlying bothGDMand subsequent postpartum progression to type 2 diabetes mellitus (T2DM). Objective: This was a retrospective cohort study that aimed to determine whether fetal sex influences the natural history of maternal risk of diabetes after delivery and in a subsequent pregnancy. Setting: The study was conducted using population-based administrative databases in Ontario, Canada. Patients: Allwomenwith a singleton live-birth first pregnancy between April 2000 and March 2010 (n = 642 987) were included. Exposure: Fetal sex was the exposure of interest (313 280 delivered a girl; 329 707 delivered a boy). Main Outcome Measure: Development of T2DM or a second pregnancy were the main outcome measures. Glucose tolerance in each pregnancy was classified as either GDM or non-GDM. Results: The population was followed for a median of 3.8 years. Carrying a boy yielded a higher risk of GDM in both the first pregnancy (odds ratio [OR] = 1.03; 95% confidence interval [CI], 1.0002-1.054) and second pregnancy (OR = 1.04, 95% CI, 1.01-1.08). For women with GDM in the first pregnancy, the likelihood of developing T2DM before a second pregnancy was higher if they delivered a girl (OR = 1.07; 95% CI, 1.01-1.12). Recurrence of GDM was not affected by fetal sex (P = .7). However, among women with a non-GDM first pregnancy while carrying a girl, having a boy in their second pregnancy predicted an increased risk of GDM (OR = 1.07, 95% CI, 1.01-1.14). Conclusions: Fetal sex is a previously unrecognized factor that is associated with maternal diabetic risk both after delivery and in a subsequent pregnancy.