Prenatal Exposure to Gestational Diabetes Mellitus is Associated with Greater Pre-pubertal BMI Growth and Faster Post-pubertal Cortical Thinning During Peri-adolescence.

Background: The longitudinal trajectory of body mass index (BMI) and brain structure development during peri-adolescence is not clearly defined in offspring prenatally exposed to gestational diabetes mellitus (GDM) vs. un-exposed offspring.

Methods: Participants between age 9 and 10 years (N=9,583) were included from the Adolescent Brain and Cognitive Development (ABCD) Study and followed yearly though 4-year follow-up. GDM and puberty status were self-reported. BMI was calculated yearly, and MRI assessed brain structure biennially. Mixed-effects models analyzed trajectories of BMI and brain structural measures between groups controlling for sociodemographic covariates, and linear spline was defined with a knot at onset of puberty.

Results: There was an interaction of exposure by age in change in BMI [β (95% CI) = 0.032 (0.008, 0.056), P =0.009] and mean cortical thickness [β (95% CI) = -0.038 (-0.071, -0.004), P =0.027]. The former was driven by greater pre-pubertal increases in BMI [β (95% CI) = 0.051 (0.002, 0.100), P =0.043], whereas the latter was driven by faster post-pubertal declines in cortical thickness among GDM-exposed offspring [β (95% CI) = -0.051 (-0.095, -0.007), P =0.046].

Conclusion: Prenatal GDM exposure is associated with greater pre-pubertal increases in BMI and faster post-pubertal cortical thinning in youth age between 9 and 15.

Practitioner points: - Prenatal GDM exposure is associated with greater pre-pubertal increases in BMI and faster post-pubertal cortical thinning in youth age between 9 and 15.- It is important to recognize puberty as a window of vulnerability for altered brain development among youth prenatally exposed to GDM.