Identifying Newborns at Risk of Adverse Neurodevelopmental Outcomes and Obesity from Air Pollution.

项目总结： 哥伦比亚儿童环境健康中心(CCCEH)的目标是为回声做出贡献 并开发、验证和实施一种迫切需要的新生物标记物，可在 易于获取的小容量脐带血样本，反映产前暴露于广泛的环境中 污染物，多环芳烃(PAH)，并预测在 肥胖和神经发育的领域。识别风险增加的新生儿将允许 早期干预。一旦在用于PAH的CCCEH队列中得到验证，此方法将可扩展到ECHO 并可应用于预防其他环境暴露的风险。哥伦比亚号 儿童环境健康中心(CCCEH)出生队列，由以下母亲和儿童组成 低收入和少数族裔(主要是非洲裔美国人和拉丁裔)将为回声做出独特的贡献 财团(“虚拟队列”)。他们包括母亲和新生儿，兄弟姐妹和公平开始出生队列， 目前共有886名儿童入学，目前的资金允许到2010年共有1048名儿童入学 2018年。该项目将利用CCCEH已经获得的关于关联的综合数据集 在产前暴露于广泛的有毒污染物多环芳烃(PAH)和 不良后果包括智商下降、多动症以及童年时期的肥胖。在一系列可行性中 UG3研究，关于产前多环芳烃暴露的广泛数据(通过个人空气监测，多环芳烃尿液 脐带血中的代谢物和多环芳烃-DNA加合物)和DNA甲基化将用于开发和验证 新的表观遗传生物标记物将识别产前接触多环芳烃的新生儿。与PAH相关的 然后将对甲基组进行测试，以确定它是否可以用于预测出生后的不良反应 神经发育和肥胖结果(“多环芳烃相关风险甲基组”)。机械的目标将评估 PAH相关的脑结构改变是否介导了PAH相关的甲基组对 神经发育结果。此外，为了更好地了解各种排放源的贡献 对于由PAH甲基组估计的总体PAH暴露，将使用各种指标，包括建模 黑碳(BC)暴露，模拟居民区与道路的距离，脐带中的多环芳烃-血红蛋白加合物 通过被动腕带采样器测量血液和PAH。在授权的UH3阶段，甲基组 方法将在更大的回声队列中进行测试，以交叉验证和评估预测模型 全国各地不同的人口。CCCEH的队列将通过ECHO扩展价值 回答与早期生活环境对儿童健康的作用有关的关键问题。

PROJECT SUMMARY: The goal of the Columbia Center for Children’s Environmental Health (CCCEH) is to contribute to the ECHO consortium and to develop, validate, and implement an urgently needed new biomarker measurable in an easy-to-obtain, small-volume cord blood sample that reflects prenatal exposure to widespread environmental pollutants, polycyclic aromatic hydrocarbons (PAH), and is predictive of risk of adverse outcomes in the domains of obesity and neurodevelopment. Identification of newborns at increased risk will allow for needed early interventions. Once validated in CCCEH cohorts for PAH, this approach will be scalable to the ECHO Consortium and can be applied to the prevention of risks from other environmental exposures. The Columbia Center for Children’s Environmental Health (CCCEH) birth cohorts, comprised of mothers and children who are low income and minority (largely African-American and Latino), will make a unique contribution to the ECHO Consortium (“Virtual Cohort”). They include the Mothers and Newborns, Sibling, and Fair Start birth cohorts, for a total of 886 children presently enrolled, current funding allows for a total of 1,048 children to be enrolled by 2018. This project will leverage the comprehensive dataset already acquired by CCCEH on the associations between prenatal exposure to a widespread toxic pollutant, polycyclic aromatic hydrocarbons (PAH), and adverse outcomes including reduced IQ and ADHD as well as obesity in childhood. In a series of feasibility studies in UG3, extensive data on prenatal PAH exposure (via personal air monitoring, PAH urinary metabolites and PAH-DNA adducts) and DNA methylation in cord blood will be used to develop and validate a novel epigenetic biomarker that will identify newborns who had high prenatal PAH exposure. The PAH-related methylome will then be tested to determine whether it can be used to predict adverse postnatal neurodevelopmental and obesogenic outcomes (“PAH-related risk methylome”). A mechanistic aim will assess whether PAH-related structural brain changes are mediating the effect of the PAH-related methylome on neurodevelopmental outcomes. In addition, to better understand the contribution of various emission sources to overall PAH exposure estimated by the PAH methylome, a variety of metrics will be used including modeled black carbon (BC) exposure, modeled residential distance to roadways, PAH-hemoglobin adducts in cord blood and PAH measured via passive wristband samplers. In the UH3 phase of the grant, the methylomic approach will be tested in the larger ECHO cohort to cross-validate and evaluate the prediction models in different populations across the country. The cohorts of the CCCEH will extend the value by the ECHO consortium to answer critical questions relating to the role of the early life environment on children’s health.