Sex Differences in Combined Effects of Maternal Pre‐Pregnancy BMI and OGTT Response Patterns on Early Neurodevelopment in Offspring: A Cohort Study

INTRODUCTION: Maternal pre-pregnancy overweight/obesity and gestational hyperglycemia are linked to adverse offspring neurodevelopment, but the role of oral glucose tolerance test (OGTT) response patterns remains unclear. We investigated the independent and combined effects of maternal pre-pregnancy BMI and OGTT response patterns on neurodevelopment in 2-year-old offspring. METHODS: This cohort study included 2639 mother-child pairs from Wuhan, China. A 75-g OGTT was performed at 24-28 gestational weeks, with glucose measured at fasting, 1 and 2 h. Group-based trajectory modeling identified distinct OGTT response patterns. Offspring neurodevelopment was assessed at 2 years using the Bayley Scales of Infant Development. Associations were examined with generalized linear and logistic regression models, and additive interaction was evaluated using RERI and AP. RESULTS: Three OGTT response patterns were identified; pattern 3 showed the most pronounced glycemic response. Maternal pre-pregnancy overweight/obesity alone showed nominal associations with lower MDI scores in the overall population and in girls, but these associations did not remain significant after FDR correction. In girls exposed to both maternal overweight/obesity and pattern 3, MDI was markedly lower (β = -13.73, 95% CI: -23.06 to -4.39), and the risk of suboptimal mental development was higher (OR = 2.88, 95% CI: 1.03 to 8.09), with significant additive interaction (RERI = 0.76; AP = 0.42). CONCLUSIONS: Maternal pre-pregnancy overweight/obesity and OGTT response patterns alone showed limited independent associations with offspring neurodevelopment. However, combined exposure may be associated with poorer mental developmental performance, with more consistent evidence in girls.