In utero exposure to maternal diabetes or hypertension and childhood hypothalamic gliosis.

Exposure to maternal diabetes (DM) or hypertension (HTN) during pregnancy impacts offspring metabolic health in childhood and beyond. Animal models suggest that induction of hypothalamic inflammation and gliosis in the offspring's hypothalamus is a possible mechanism mediating this effect. We tested, in children, whether in utero exposures to maternal DM or HTN were associated with mediobasal hypothalamic (MBH) gliosis as assessed by brain magnetic resonance imaging (MRI). The study included a subsample of 306 children aged 9-11 years enrolled in the ABCD Study®; 49 were DM-exposed, 53 were HTN-exposed, and 204 (2:1 ratio) were age- and sex-matched children unexposed to DM and/or HTN in utero. We found a significant overall effect of group for the primary outcome of MBH/amygdala (AMY) T2 signal ratio (F(2,300):3.51, p = 0.03). Compared to unexposed children, MBH/AMY T2 signal ratios were significantly higher in the DM-exposed (ß:0.05, p = 0.02), but not the HTN-exposed children (ß:0.03, p = 0.13), findings that were limited to the MBH and independent of adiposity. We concluded that children exposed to maternal DM in utero display evidence of hypothalamic gliosis, suggesting that gestational DM may have a distinct influence on offspring's brain development and, by extension, children's long-term metabolic health.

Greater radiologic evidence of hypothalamic gliosis predicts adiposity gain in children at risk for obesity.

OBJECTIVE: This study investigated, in a large pediatric population, whether magnetic resonance imaging (MRI) evidence of mediobasal hypothalamic (MBH) gliosis is associated with baseline or change over 1 year in body adiposity. METHODS: Cross-sectional and prospective cohort analyses were conducted within the Adolescent Brain Cognitive Development Study. Study 1 included 169 children with usable baseline T2-weighted MRI images and anthropometrics from baseline and 1-year follow-up study visits. Signal ratios compared T2 signal intensity in MBH and two reference regions (amygdala [AMY] and putamen) as a measure of MBH gliosis. Study 2 included a distinct group of 238 children with overweight or obesity to confirm initial findings in an independent sample. RESULTS: In Study 1, MBH/AMY signal ratio was positively associated with BMI z score (ß = 4.27, p < 0.001). A significant interaction for the association of MBH/AMY signal ratio with change in BMI z score suggested that relationships differed by baseline weight status. Study 2 found that higher MBH/AMY signal ratios associated with an increase in BMI z score for children with overweight (ß = 0.58, p = 0.01), but not those with obesity (ß = 0.02, p = 0.91). CONCLUSIONS: Greater evidence of hypothalamic gliosis by MRI is associated with baseline BMI z score and predicts adiposity gain in young children at risk of obesity.