Abstract
OBJECTIVE: The aim of this study was to investigate the mediating role of child brain structure in the relationship between prenatal gestational diabetes mellitus (GDM) exposure and child adiposity. METHODS: This was a cross-sectional study of 9- to 10-year-old participants and siblings across the US. Data were obtained from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study®. Brain structure was evaluated by magnetic resonance imaging. GDM exposure was self-reported, and discordance for GDM exposure within biological siblings was identified. Mixed effects and mediation models were used to examine associations among prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates. RESULTS: The sample included 8521 children (7% GDM-exposed), among whom there were 28 sibling pairs discordant for GDM exposure. Across the entire study sample, prenatal exposure to GDM was associated with lower global and regional cortical gray matter volume (GMV) in the bilateral rostral middle frontal gyrus and superior temporal gyrus. GDM-exposed siblings also demonstrated lower global cortical GMV than unexposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers. CONCLUSIONS: The results identify brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM.