Effects of maternal obesity and inflammation on offspring brain development

项目总结 孕妇肥胖是孕妇及其后代的一个突出的健康问题。近期 研究表明，母亲怀孕期间肥胖与认知能力之间存在负相关 在儿童身上发挥作用。我们的初步研究也表明，新生儿的大脑存在显著差异。 与母亲肥胖有关，表明母亲肥胖在宫内对胎儿大脑有影响 发展。重要的问题仍有待回答，并将在这项提案中得到解决，例如 “大脑的结构和功能受影响最大的是什么？”、“这些影响是持久的吗？”以及“什么可能？” 这些大脑变化背后的潜在机制是什么？这个项目的目标是描述 孕期肥胖对婴儿大脑发育的影响，揭示神经发育 并找出造成这些影响的可能机制。总体假设是 孕期母亲肥胖会使胎儿暴露在影响婴儿大脑的炎性环境中 结构和功能发育，从而导致神经发育结果。为了检验这一假设， 将招募体重正常和肥胖的孕妇，与肥胖相关的炎症标记物 怀孕将被检查，并将与他们的后代大脑发育相关，使用 先进的核磁共振成像和使用神经发育测试评估结果。具体目标是：1)检测 新生儿大脑结构和功能发育的全球和区域变化与母亲 肥胖。在两周大的时候，将使用先进的磁共振成像来评估和比较大脑的许多特征 方法包括灰质体积计量学和皮质表面形态计量学，脑白质显微结构和 可能受到母体肥胖影响的地区之间的连通性和功能连通性。2)确定 如果与母亲肥胖有关的大脑差异在婴儿期持续存在并影响神经发育 结果。将在1岁和2岁时重复核磁共振检查，以确定母亲肥胖相关的大脑是否发生变化 坚持到新生儿年龄以后。神经发育结果也将在2岁时进行评估，这 将在不同组之间进行比较，并与新生儿的MRI结果相关联。3)测量 炎性环境与母亲肥胖相关，与婴儿大脑发育相关。 孕妇的循环促炎介质将被测量并与母体相关 妊娠早期肥胖。脐带血样本也将在出生时接受炎症标志物检查。 炎症标志物水平将与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，并为我们提供了潜在的促进大脑发育的策略 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.