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

项目概要： 哥伦比亚儿童环境健康中心（CCCEH）的目标是为ECHO做出贡献。 联盟，并开发，验证和实施一个迫切需要的新的生物标志物，可在一个 容易获得的小体积脐带血样本，反映了产前暴露于广泛的环境 污染物，多环芳烃（PAH），并预测不良后果的风险， 肥胖和神经发育的领域。识别风险增加的新生儿将允许必要的 早期干预。一旦在CCCEH PAH队列中得到验证，该方法将可扩展至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，由母亲和儿童组成， 低收入和少数民族（主要是非洲裔美国人和拉丁美洲人）将为ECHO做出独特的贡献 联合会（“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，目前的资金允许共有1 048名儿童入学， 2018.该项目将利用CCCEH已经获得的关于协会的综合数据集 产前暴露于广泛的有毒污染物多环芳烃（PAH）， 不良后果包括智商降低和多动症以及儿童期肥胖。在一系列的可行性 UG 3研究，产前PAH暴露的广泛数据（通过个人空气监测，PAH尿 代谢物和PAH-DNA加合物）和DNA甲基化将用于开发和验证一种 一种新的表观遗传生物标志物，将识别产前PAH暴露较高的新生儿。PAH相关 然后将测试甲基化组，以确定它是否可以用来预测不良产后 神经发育和致肥胖结局（“PAH相关风险甲基化组”）。一个机械的目标将评估 PAH相关的脑结构变化是否介导PAH相关的甲基化对 神经发育结果。此外，为了更好地了解各种排放源的贡献， 对于通过PAH甲基化组估计的总体PAH暴露，将使用各种指标，包括模型 黑碳（BC）暴露，模拟住宅与道路的距离，脐带中PAH-血红蛋白加合物 通过被动腕带采样器测量血液和PAH。在赠款的UH 3阶段，甲基组学 该方法将在更大的ECHO队列中进行测试，以交叉验证和评估预测模型， 全国不同的人群。CCCEH的队列将扩展ECHO的值 联合会回答有关早期生活环境对儿童健康的作用的关键问题。

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.