Sexual dimorphism in the association between gestational diabetes mellitus and overweight in offspring at 5-7 years: The OBEGEST cohort study

Evidence from literature is mixed regarding a possible association of maternal gestational diabetes mellitus (GDM) and overweight in the offspring. Sexual dimorphism, or sex disparities in the pathogenesis linking GDM exposure to overweight, could be at play. The objective of this study was to investigate the association between GDM and child overweight at 5–7 years. Six hundred pairs (1:1) of Reunionese liveborn singletons selected from a hospital-based birth registry, matched for sex, gestational age, and birth period, underwent a prospective in-home follow-up and were analyzed with respect to their exposure to GDM. The primary outcome was child overweight at 5–7 years, as defined by the International Obesity Task Force. The association between GDM exposure and child overweight was estimated by the odds ratio (OR) using conditional logistic regression models. For the subset of children exposed to GDM with available maternal glycemic data, we analyzed the relationship between maternal glycemic levels during pregnancy and child body mass index (BMI) at 5–7 years with a linear regression model. In light of the significant interaction between sex and GDM, all statistical analyses were then stratified by sex. After controlling for pre-pregnancy BMI and maternal sociodemographic characteristics, the risk of overweight increased with exposure to GDM for boys (adjusted OR: 2.34; 95% confidence interval = 1.26–4.34, P = 0.007) but not for girls (adjusted OR: 0.56; 95%CI = 0.28–1.10, P = 0.093). Consistent with this, the linear increase of boys’ BMI at 5–7 years with maternal blood glucose levels during pregnancy, in the exposed group, displayed a dose-response relationship. Our findings indicate that exposure to GDM is a risk factor for childhood overweight in boys but not in girls, which adds to the growing body of evidence suggesting greater sensitivity of male offspring to intrauterine hyperglycemia.