Effects of maternal obesity and inflammation on offspring brain development

项目摘要 产妇肥胖是孕妇及其后代的一个突出健康问题。最近 研究表明，母亲在怀孕期间肥胖与认知能力之间存在负相关， 在儿童中发挥作用。我们的初步研究也表明新生儿的大脑有显著的差异 与母体肥胖相关，表明母体肥胖对胎儿大脑有宫内影响 发展重要的问题仍有待回答，本提案将解决这些问题，例如 “什么是大脑结构和功能最受影响？"，“这些影响是否持续存在？"，和“什么可能 是这些大脑变化背后的潜在机制？”该项目的目标是描述 母亲怀孕期间肥胖对婴儿大脑发育的影响，揭示了神经发育 的影响，并确定可能的机制，造成这些影响。总的假设是， 孕妇在怀孕期间的肥胖使胎儿暴露于影响婴儿大脑的炎症环境中 结构和功能发育以及因此神经发育结果。为了验证这个假设， 将招募体重正常和肥胖的孕妇，与肥胖相关的炎症标志物 怀孕将被检查，并将与他们的后代大脑发育评估使用 先进的MRI和使用神经发育测试评估的结果。具体目标是：1）检测 新生儿脑结构和功能发育的全球和区域变化与孕产妇 肥胖将在2周龄时使用先进的MRI评估和比较一些大脑特征 方法，包括灰质体积测量和皮质表面形态测量，白色物质显微结构和 连接性和可能受母体肥胖影响的区域之间的功能连接性。2)以确定 如果与母亲肥胖相关的大脑差异在婴儿期持续存在， 结果。将在1岁和2岁时重复MRI，以确定是否与母亲肥胖相关的大脑变化 持续到新生儿年龄之后。还将在2岁时评估神经发育结果， 将在组间进行比较，并与新生儿的MRI结果相关联。3)测量 炎症环境与母亲肥胖相关，并与婴儿大脑发育相关。 将测量孕妇中的循环促炎介质，并将其与母体 妊娠早期肥胖。还将在出生时检查脐带血样本的炎症标志物。 炎症标志物的水平将与MRI测量的大脑结构和功能相关， 新生儿、1岁和2岁。这个项目的结果将帮助我们更好地了解负面影响 母亲肥胖对后代健康的影响，并为我们提供促进大脑发育的潜在策略， 肥胖妇女所生的孩子

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.