Effects of maternal obesity and inflammation on offspring brain development

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PROJECT SUMMARY Maternal obesity is a prominent health concern for both pregnant women and their offspring. Recent studies have revealed negative associations between maternal obesity during pregnancy and cognitive functioning in children. Preliminary studies by us also indicated significant brain differences in newborns associated with maternal obesity, suggesting that there are in utero effects of maternal obesity on fetal brain development. Important questions remain to be answered and will be addressed in this proposal, such as “What are the brain structures and functions most affected?”, “Are these effects persistent?”, and “What may be the underlying mechanisms behind these brain changes?”. The goals of this project are to characterize the effects of maternal obesity during pregnancy on infant brain development, reveal the neurodevelopmental consequences, and identify possible mechanisms causing these effects. The overall hypothesis is that maternal obesity during pregnancy exposes the fetus to an inflammatory environment that affects infant brain structural and functional development and consequently neurodevelopmental outcome. To test the hypothesis, normal-weight and obese pregnant women will be recruited, inflammatory markers associated with obese pregnancy will be examined, and will be correlated with their offspring brain development evaluated using advanced MRI and outcomes evaluated using neurodevelopmental tests. The specific aims are: 1) To detect global and regional changes in newborn brain structural and functional development associated with maternal obesity. A number of brain characteristics will be evaluated and compared at age 2 weeks using advanced MRI methods, including grey matter volumetrics and cortical surface morphometry, white matter microstructure and connectivity, and functional connectivity between regions likely impacted by maternal obesity. 2) To determine if brain differences associated with maternal obesity persist in infancy and impact neurodevelopmental outcomes. MRI will be repeated at age 1 and 2 years to determine if maternal obesity-related brain changes persist beyond the newborn age. Neurodevelopmental outcomes will also be assessed at age 2 years, which will be compared between groups and correlated with MRI findings from newborns. 3) To measure the inflammatory environment associated with maternal obesity and correlate with infant brain development. Circulating pro-inflammatory mediators in pregnant women will be measured and correlated with maternal adiposity at early pregnancy. Cord blood samples will also be examined for inflammatory markers at birth. Levels of inflammatory markers will be correlated to MRI measurements of brain structure and function at newborn, 1 year, and 2 years of age. Results of this project will help us better understand the negative impact of maternal obesity on offspring health and inform us potential strategies to promote brain development in children born to obese women.