Effects of maternal obesity and inflammation on offspring brain development

母亲肥胖和炎症对后代大脑发育的影响

• 批准号: 9795837
• 负责人: Xiawei Ou
• 金额: $ 60.5万
• 依托单位: ARKANSAS CHILDREN'S HOSPITAL RES INST
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-10 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9795837
• 关键词: 2 year old; Address; Affect; Age; Birth; Blood specimen; Brain; Characteristics; Child; Childhood; Cognitive; Detection; Development; Diffusion Magnetic Resonance Imaging; Enrollment; Ensure; Environment; Exposure to; Family; Fetus; Functional Magnetic Resonance Imaging; Goals; Growth and Development function; Health; Infant; Inflammation; Inflammation Mediators; Interleukin-6; Intervention; Lead; Life Style; Longitudinal Studies; Magnetic Resonance Imaging; Measurement; Measures; Methods; Neonatal; Newborn Infant; Obesity; Outcome; Pilot Projects; Prefrontal Cortex; Pregnancy; Pregnant Women; Research; Resolution; Rest; Structure; Surface; TNF gene; Testing; Time; Umbilical Cord Blood; Weight; Woman; cognitive function; cytokine; early pregnancy; experience; fetal; frontal lobe; gray matter; imaging biomarker; in utero; infancy; inflammatory marker; inflammatory milieu; maternal obesity; morphometry; neurobehavioral; neurodevelopment; neuroimaging; novel; nutrition; obese mothers; offspring; outcome prediction; psychologic; recruit; therapy design; white matter

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.

项目概要 母亲肥胖是孕妇及其后代的一个突出的健康问题。最近的 研究表明，孕期肥胖与认知能力呈负相关 在儿童中发挥作用。我们的初步研究也表明新生儿的大脑存在显着差异 与母亲肥胖有关，表明母亲肥胖在子宫内对胎儿大脑有影响 发展。重要问题仍有待回答，并将在本提案中解决，例如 “受影响最严重的大脑结构和功能是什么？”、“这些影响是否持续存在？”以及“什么可能会影响大脑？” 这些大脑变化背后的潜在机制是什么？”。该项目的目标是描述 孕期母亲肥胖对婴儿大脑发育的影响，揭示神经发育 后果，并确定导致这些影响的可能机制。总体假设是 怀孕期间母亲肥胖会使胎儿暴露在影响婴儿大脑的炎症环境中 结构和功能发育以及神经发育结果。为了检验假设， 将招募正常体重和肥胖孕妇，与肥胖相关的炎症标志物 将检查怀孕情况，并将其与后代大脑发育的相关性进行评估 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 与母亲相关的新生儿大脑结构和功能发育的全球和区域变化 肥胖。 2 周大时，将使用先进的 MRI 评估和比较许多大脑特征 方法，包括灰质体积测量和皮质表面形态测量、白质微观结构和 可能受孕产妇肥胖影响的区域之间的连通性和功能连通性。 2）确定 与母亲肥胖相关的大脑差异是否在婴儿期持续存在并影响神经发育 结果。 MRI 将在 1 岁和 2 岁时重复进行，以确定母亲肥胖相关的大脑是否发生变化 持续超过新生儿年龄。神经发育结果也将在 2 岁时进行评估，其中 将在各组之间进行比较，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。 将测量孕妇的循环促炎介质并将其与母体 怀孕早期肥胖。出生时还将检查脐带血样本的炎症标记物。 炎症标志物的水平将与大脑结构和功能的 MRI 测量结果相关 新生儿、1岁、2岁。该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，并告诉我们促进大脑发育的潜在策略 肥胖妇女所生的孩子。