Infant Subcortical Brain Volumes Associated with Maternal Obesity and Diabetes: A Large Multicohort Study

Area of Science:

• Neuroscience
• Developmental Biology
• Public Health

Background:

• Maternal diabetes (MD) and maternal obesity (MO) are known risk factors for offspring health.
• Fetal programming effects of MD and MO may differ by infant sex, but their impact on brain development is not fully understood.

Purpose of the Study:

• To investigate the independent and interactive effects of maternal diabetes, maternal obesity, and infant sex on subcortical brain volumes.
• To characterize sex-specific associations between prenatal exposures and infant brain structure.

Main Methods:

• Cross-sectional study of 1,966 infants from six international cohorts.
• MRI-based segmentation of subcortical brain volumes (thalamus, amygdala, hippocampus, pallidum, putamen, caudate).
• Mixed-effects models and backward elimination regression were used to analyze associations, controlling for covariates and applying FDR corrections.

Main Results:

• A significant three-way interaction between MD, MO, and sex was found in the thalamus.
• In females, MD and MO were independently associated with smaller thalamic volumes, and MO with smaller hippocampal volumes.
• In males, combined MD and MO exposure was associated with reduced thalamic volume.

Conclusions:

• Prenatal exposure to maternal diabetes and/or obesity has sex-specific associations with infant subcortical brain volumes.
• These findings highlight the critical role of sex in mediating the impact of the intrauterine environment on brain development.
• The observed alterations in brain structure may have long-term implications for metabolic and other health disorders in offspring.