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

点击翻译按钮获取中文摘要

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.