Maternal hyperglycemia during pregnancy is associated specifically with larger hypothalamic volumes at 12 years of age

Abstract Maternal hyperglycemia is associated with higher risk of metabolic diseases in offspring. Despite various hypotheses, the exact mechanisms remain unclear and the neural implication is yet to be fully investigated. The hypothalamus plays a critical role in energy regulation. In utero exposure to maternal hyperglycemia might selectively affect the developing hypothalamus. To test this hypothesis, we investigated associations between in utero exposure to maternal hyperglycemia and hypothalamic volume at 10–12 years of age. We included 82 mother–child pairs from the Gen3G prospective birth cohort, followed up 10–12 years after birth. Women underwent a 75g Oral Glucose Tolerance Test (OGTT) at 24–30 weeks of gestation, and we calculated the area-under-the-curve of glucose (AUCgluc) from maternal glucose measurements at fasting, 1h and 2h during OGTT to reflect prenatal hyperglycemia exposure. During the follow-up visit at 10–12 years of age, a subsample of children ( n = 82) completed 3 T brain magnetic resonance imaging (MRI) to quantify brain volumes with FreeSurfer 7. We used Pearson correlations and partial correlations with adjustments to test associations between the AUCgluc and offspring hypothalamic brain volumes. We found that higher maternal AUCgluc was associated with greater total offspring hypothalamic volume ( r = 0.30; p = 0.006). In comparison, no other brain region was significantly correlated with the maternal AUCgluc. Correlations remain significant when adjusted for maternal or offspring’s variables. Overall, we found that higher maternal glycemic response following OGTT in pregnancy appears associated with larger offspring hypothalamic volume. Our results suggest that prenatal exposure to hyperglycemia may lead to hypothalamic programming.