Importance: Children prenatally exposed to maternal diabetes have a higher risk of developing obesity and metabolic disorders. Alterations in the brain development is hypothesized as a potential mechanism underlying this relationship but has not been fully tested in humans.
Objectives: To examine the mediating role of child brain structure in the relationships between prenatal exposure to maternal diabetes and child adiposity.
Design, setting and participants: This was a cross-sectional study of children (ages 9-to-10-years-old) from the baseline assessment of the Adolescent Brain and Cognitive Development (ABCD) Study (N=11,875).
Exposures: Prenatal exposure to maternal diabetes was determined via self-reported questionnaire.
Main outcomes and measures: Child adiposity markers included age- and sex-specific body mass index (BMI z-scores), waist circumference, and waist-to-height ratio (WHtR). T1-weighted magnetic resonance imaging (MRI) was used to assess brain structure. Linear mixed effects models examined associations of prenatal exposure to maternal diabetes with child adiposity markers and brain structure controlling for sociodemographic covariates. Mediation models were performed to investigate the mediating role of brain structure on the association between maternal diabetes exposure and child adiposity markers.
Results: The sample consisted of 8,521 children (age: 9.92+/-0.63 years; sex: 51.4% males; 7% exposed to maternal diabetes). Children prenatally exposed vs. unexposed to maternal diabetes had greater BMI z-scores, waist circumference and WHtR. Prenatal exposure to maternal diabetes was associated with reduction in global and regional cortical gray matter volume primarily in the frontal, temporal, and occipital areas. Whole-brain cortical gray matter volume partially mediated the association between prenatal exposure to maternal diabetes and WHtR.
Conclusion and relevance: Cortical gray matter volume partially mediated the link between prenatal exposure to maternal diabetes and WHtR. These results demonstrate a potential neurobiological mechanism by which prenatal exposure to maternal diabetes may be associated with increased risk for obesity and metabolic disorders in children.