Associations between prenatal exposure to gestational diabetes mellitus and child adiposity markers: mediating effects of brain structure

Objectives To investigate neural mechanisms underlying increased obesity risk in children prenatally exposed to gestational diabetes mellitus (GDM). Research Design and Methods This was a cross-sectional study of 9-10-year-old participants and siblings across the United States. Data was obtained from the baseline assessment of the Adolescent Brain and Cognitive Development (ABCD) Study® in which brain structure was evaluated by magnetic resonance imaging. Adiposity markers included age- and sex-specific body mass index (BMI z- scores), waist circumference and waist-to-height ratio. 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 between prenatal GDM exposure, brain structure, and adiposity markers with sociodemographic covariates. Results The sample included 8,521 children (age: 9.9±0.6 years; 51% males; 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. In a subset of sample only including siblings, GDM-exposed siblings also demonstrated lower global cortical GMV than un-exposed siblings. Global cortical GMV partially mediated the associations between prenatal GDM exposure and child adiposity markers. Conclusions Our results establish robust and generalizable brain markers of prenatal GDM exposure and suggest that low cortical GMV may explain increased obesity risk for offspring prenatally exposed to GDM. Twitter summary Prenatal exposure to gestational diabetes mellitus #GDM is associated with smaller cortical gray matter volume #brain, which in turn relates to larger adiposity markers #BMI in a large and diverse cohort of 8521 children. Article Highlights Prenatal exposure to gestational diabetes mellitus (GDM) is associated with smaller cortical gray matter volume (GMV) in a large and diverse cohort of 8521 children, independent from genetics and shared environment. Cortical GMV partially mediated the associations of prenatal GDM exposure and adiposity markers in children. These results establish robust and generalizable brain markers of prenatal GDM exposure and provide neurobiological underpinnings of increased obesity risk in offspring prenatally exposed to GDM.