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

识别因空气污染而面临神经发育不良和肥胖风险的新生儿。

• 批准号: 10673231
• 负责人: Julie Beth Herbstman
• 金额: $ 9.2万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-21 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10673231
• 关键词: African American; Age; Air Pollution; Area; Aromatic Polycyclic Hydrocarbons; Attention deficit hyperactivity disorder; Behavior; Biological Markers; Biological Specimen Banks; Birth; Blood specimen; Brain; Brain imaging; Carbon Black; Child; Child Health; Childhood; Cognitive; Cohort Studies; Collection; Country; DNA Adducts; DNA Methylation; Data; Data Set; Databases; Early Intervention; Enrollment; Environment; Environmental Exposure; Environmental Health; Environmental Pollutants; Exposure to; Feasibility Studies; Funding; Genetic; Goals; Grant; Hemoglobin; Institutes; Latino; Life; Low Income Population; Low income; Magnetic Resonance Imaging; Measurable; Measurement; Measures; Mediating; Methods; Minority; Modeling; Mothers; Neurodevelopmental Problem; New York City; Newborn Infant; Obesity; Outcome; Participant; Phase; Phenotype; Population; Pregnancy; Prevention; Preventive measure; Probability; Problem behavior; Protocols documentation; Risk; Risk Marker; Role; Rural; Sampling; Secure; Series; Siblings; Source; Testing; Umbilical Cord Blood; Urban Population; Work; adduct; adverse outcome; air monitoring; base; brain magnetic resonance imaging; cognitive function; cohort; epigenetic marker; epigenomics; inner city; inter-individual variation; member; methylation pattern; methylome; methylomics; multi-ethnic; neonate; neurodevelopment; novel; obesogenic; pollutant; postnatal; predictive modeling; prenatal; prenatal exposure; prevent; prospective; study population; urinary; virtual

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.

项目摘要： 哥伦比亚儿童环境健康中心（CCCEH）的目标是为回声做出贡献 财团并开发，验证和实施迫切需要的新生物标志物，可在 易于访问的小体积脐带血样本，反映了产前暴露于宽度环境的环境 污染物，多环芳烃（PAH），并可以预测出现不良后果的风险 肥胖和神经发育领域。确定处于风险增加的新生儿将允许需要 早期干预措施。一旦在CCCEH队列中验证了PAH，此方法将可扩展到Echo 财团可以应用于预防其他环境暴露的风险。哥伦比亚 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”）。其中包括母亲和新生儿，兄弟姐妹和公平的开始出生队列 目前总共有886名儿童，目前的资金允许总共1,048名儿童参加 2018年。该项目将利用CCCEH已在协会中获得的综合数据集 在产前暴露于广泛的有毒污染物，多环芳烃（PAH）和 不良后果，包括减少智商和多动症以及童年时期的肥胖症。在一系列可行性中 在UG3中的研究，有关产前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）和脐带血中的DNA甲基化将用于发展和验证 新的表观遗传生物标志物将确定具有高产前PAH暴露的新生儿。与PAH有关 然后将测试甲基团，以确定是否可以用于预测产后不良后 神经发育和肥胖的结果（“与PAH相关的风险甲基组”）。机械目标将评估 与PAH相关的结构大脑的变化是否正在介导与PAH相关的甲基对 神经发育结果。此外，以更好地了解各种排放源的贡献 对于PAH甲基估计的总体PAH暴露，将使用各种指标，包括建模 黑碳（BC）暴露，建模的居住距离，距离道路，绳索中的PAH-Hemoglobin加合物 血液和PAH通过被动腕带样品测量。在赠款的UH3阶段，甲基甲基团 方法将在较大的回声队列中进行测试，以交叉估算和评估预测模型 全国不同的人口。 CCCEH的队列将通过回声扩展该值 财团回答有关早期生活环境对儿童健康的作用的关键问题。