Sex-specific white matter alterations in children exposed to high pregestational BMI

<p dir="ltr">Objective: This study investigated whether exposure to high pregestational BMI (≥ 25 kg/m²) is associated with alterations in white matter microstructure in early childhood, explored sex-specific effects, and examined associations with cognitive performance.</p><p dir="ltr">Methods: A total of 90 children from the Alberta Pregnancy Outcomes and Nutrition (APrON) cohort underwent diffusion tensor imaging between ages 2 and 7 years. Data were processed using ExploreDTI to obtain mean fractional anisotropy (FA) and mean diffusivity (MD). Pregestational weight was self-reported by pregnant individuals, height was measured at enrollment, and child cognitive outcomes were assessed at ages 3 to 4 years using the Wechsler Preschool and Primary Scale of Intelligence.</p><p dir="ltr">Results: Children exposed to high pregestational BMI had lower FA, but not higher MD, in the superior longitudinal fasciculus and in the body and splenium of the corpus callosum compared with unexposed children (BMI 18.5-24.9 kg/m²). This association persisted when analyzing pregestational obesity and overweight categories separately. Altered FA in splenium of the corpus callosum was associated with poorer cognitive outcomes in exposed children. Exposed male children had higher FA in the fornix, whereas female children had lower FA in the body and splenium of the corpus callosum compared with unexposed peers.</p><p dir="ltr">Conclusions: High pregestational BMI was associated with alterations in white matter microstructure during early childhood in a sex-specific manner. Promoting healthy lifestyles and weight management among individuals of childbearing age is crucial.</p>