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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.

To examine the mediating role of child brain structure in the relationships between prenatal exposure to maternal diabetes and child adiposity.

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).

Prenatal exposure to maternal diabetes was determined via self-reported questionnaire.

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.

The sample consisted of 8,521 children (age_m: 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 (β (95% CI) = 0.175 (0.093, 0.256; FDR corrected P<0.001), waist circumference (β (95% CI …