Impact of pre- and postnatal chemical mixture exposures on child neurobehavior and neuroimaging

产前和产后化学混合物暴露对儿童神经行为和神经影像的影响

基本信息

批准号：
10441308
负责人：
Aimin Chen
金额：
$ 64.61万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-07-01 至 2026-04-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10441308
关键词：
12 year old Affect Age Air American Anatomy Anxiety Arsenic Attention Attention deficit hyperactivity disorder Behavior Biological Markers Birth Brain Brain imaging Cadmium Calcium Signaling Canada Chemicals Child Child Development Chlorinated Hydrocarbons Chlorpyrifos Cognition Cohort Studies Conduct Disorder Data Development Diet Dust Endocrine Disruptors Environment Environmental Health Environmental Pollution Epigenetic Process Exposure to Fetal Development Flame Retardants Fluorides Health Heavy Metals Height Human Milk Individual Infant Investigation Joints Lead Learning Learning Disabilities Least-Squares Analysis Life Literature Manganese Measures Mediation Mental Depression Mercury Metals Methods Methylmercury Compounds National Health and Nutrition Examination Survey Neuraxis Neurons Neurosecretory Systems Neurotoxins Neurotransmitters Organophosphates Outcome Outcome Measure Oxidative Stress Parabens Pesticides Phenols Placenta Policy Making Poly-fluoroalkyl substances Polychlorinated Biphenyls Predisposition Pregnancy Pregnant Women Problem behavior Prospective cohort Research Statistical Methods Structure Synapses Testing Tetrachloroethylene Tobacco smoke Toluene Toxicant exposure Triclosan Water adverse birth outcomes autism spectrum disorder base behavioral outcome bisphenol A chemical association cognitive ability cognitive function cohort design developmental neurotoxicity dichlorodiphenyltrichloroethane environmental chemical epidemiology study executive function follow-up migration myelination neural network neurobehavior neurobehavioral neurochemistry neurodevelopment neuroimaging neurotransmitter release neurotransmitter uptake organochlorine pesticide persistent organic pollutants phthalates polybrominated diphenyl ether postnatal prenatal pyrethroid sex white matter

项目摘要

Project Summary One in six children in the U.S. and Canada have one or more learning or behavioral problems, such as learning disability, anxiety, autism spectrum disorder, conduct disorder, depression, or attention deficit hyperactivity disorder (ADHD). Early brain development is sensitive to toxicant exposures, including heavy metals, persistent organic pollutants, and endocrine disrupting chemicals. Exposure to mixtures of environmental chemicals is a reality in children, and chemical mixtures may have different modes of action affecting neuronal proliferation, migration, differentiations, synaptic formation/trimming/plasticity, myelination, and neurotransmitters, resulting in adverse impact on the central nervous system. Majority of environmental epidemiologic studies have only examined the impact of a single chemical on neurobehavioral outcomes. Recent development and application of mixture statistical methods will provide great potential to reveal the impact of an individual chemical, interactions between chemicals, and cumulative exposure. These methods have only been applied in limited studies of child neurobehavior and none has been used for neuroimaging outcomes. We will use two existing birth cohorts to examine the impact of both pre- and postnatal exposures to chemical mixtures on child neurobehavior. The Health Outcomes and Measures of the Environment (HOME) Study is a Cincinnati-based birth cohort of 400 pregnant women with children followed up to age 12 years, and the Maternal-Infant Research on Environmental Chemicals (MIREC) is a Canadian study of 1983 pregnant women with children followed up to age 9-11 years. The two North American birth cohorts both measured over 60 environmental contaminants, including lead, mercury, cadmium, arsenic, polybrominated diphenyl ethers, polychlorinated biphenyls, perfluoroalkyl substances, organochlorine and organophosphate pesticides, bisphenol A, phthalates, triclosan, and organophosphate flame retardants, as well as child cognitive abilities (n>1000), behavior (n>1000), and neuroimaging (n=390). We will utilize advanced statistical methods for chemical mixtures, including Elastic Net (ENET) for variable selection, Sparse Partial Least Squares (SPLS) regression for individual chemical effect estimation, and Bayesian Kernel Machine Regression (BKMR) for interactions, nonlinearities, and joint effects. This project will be among the first to test and quantify the potential impact of prenatal and postnatal exposures to chemical mixtures on neurobehavioral and neuroimaging outcomes in well-established cohorts. The results have the potential to greatly increase our understanding of developmental neurotoxicity of chemical mixtures in children and affect environmental health policy making.

项目摘要美国和加拿大有六分之一的孩子有一个或多个学习或行为问题，例如学习障碍，焦虑，自闭症谱系障碍，行为障碍，抑郁或注意力不足多动症（ADHD）。早期大脑发育对毒物暴露敏感，包括重度金属，持续的有机污染物和内分泌破坏化学物质。暴露于混合物环境化学物质是儿童的现实，化学混合物可能具有不同的作用方式影响神经元增殖，迁移，分化，突触形成/修剪/可塑性，髓鞘，和神经递质，导致对中枢神经系统的不利影响。大多数环境流行病学研究仅研究了一种化学物质对神经行为结果的影响。混合统计方法的最新开发和应用将为揭示巨大的潜力单个化学物质的影响，化学物质之间的相互作用和累积暴露。这些方法仅应用于对儿童神经行为的有限研究，没有用于神经影像学结果。我们将使用两个现有的出生队列来检查产后和后暴露的影响儿童神经行为的化学混合物。环境的健康成果和衡量标准（家庭）研究是一个基于辛辛那提的出生队列，由400名儿童孕妇随访，直到12岁，孕产妇环境化学品研究（MIREC）是一项1983年的加拿大研究有孩子的妇女跟踪到9-11岁。两个北美出生队列都测量了 60种环境污染物，包括铅，汞，镉，砷，多溴二苯基醚，多氯联苯，全氟烷基物质，有机氯和有机磷酸盐农药，双苯酚A，邻苯二甲酸盐，三氯生和有机磷酸盐阻燃剂以及儿童认知能力（n> 1000），行为（n> 1000）和神经影像学（n = 390）。我们将利用高级统计方法化学混合物，包括用于可变选择的弹性网（ENET），稀疏的部分最小二乘（SPL）单个化学效应估计的回归和贝叶斯内核机回归（BKMR）的回归相互作用，非线性和关节效应。该项目将是最早测试和量化的项目之一产前和产后暴露对化学混合物对神经行为和神经影像学的成果在良好的队列中。结果有可能大大增加我们的了解儿童化学混合物的发育神经毒性并影响环境健康政策制定。