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

• 批准号: 10620185
• 负责人: Aimin Chen
• 金额: $ 62.48万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 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/10620185
• 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; Central Nervous System; Chemicals; Child; Child Development; Chlorinated Hydrocarbons; Chlorpyrifos; Cognition; Cohort Studies; Conduct Disorder; Data; Development; Diet; Dust; Elasticity; Endocrine Disruptors; Environment; Environmental Epidemiology; Environmental Health; Environmental Pollutants; 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; Neurons; Neurosecretory Systems; Neurotoxins; Neurotransmitters; Organophosphates; Outcome; Oxidative Stress; Parabens; Pesticides; Phenols; Placenta; Policy Making; Poly-fluoroalkyl substances; Polychlorinated Biphenyls; Predisposition; Pregnancy; Pregnant Women; Problem behavior; Proliferating; Prospective cohort; Research; Statistical Methods; Structure; Synapses; Testing; Tetrachloroethylene; Tobacco smoke; Toluene; Toxicant exposure; Triclosan; Water; adverse birth outcomes; autism spectrum disorder; 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; prenatal exposure; pyrethroid; sex; white matter

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 在美国和加拿大，六分之一的儿童有一个或多个学习或行为问题，如 学习障碍、焦虑、自闭症谱系障碍、行为障碍、抑郁或注意力缺陷 多动症（ADHD）。早期的大脑发育对有毒物质的暴露很敏感， 金属、持久性有机污染物和干扰内分泌的化学品。接触以下物质的混合物 环境中的化学品是一个现实的儿童，化学混合物可能有不同的行动模式 影响神经元增殖、迁移、分化、突触形成/修整/可塑性，髓鞘形成， 和神经递质，对中枢神经系统产生不利影响。大多数环境 流行病学研究仅检查了单一化学品对神经行为结果的影响。 近年来混合统计方法的发展和应用为揭示这一问题提供了巨大的潜力。 单个化学品的影响、化学品之间的相互作用和累积接触。这些方法 仅用于儿童神经行为的有限研究，没有用于神经成像 结果。我们将使用两个现有的出生队列来研究产前和产后暴露对 对儿童神经行为的影响环境的健康结果和措施（HOME） 研究是一项基于先天性的出生队列研究，包括400名孕妇和随访至12岁的儿童， 母婴环境化学品研究（MIREC）是加拿大对1983年孕妇的一项研究。 对有子女的妇女进行随访，直至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、多溴联苯醚， 多氯联苯、全氟烷基物质、有机氯和有机磷酸盐农药， 双酚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）和神经成像（n=390）。我们将利用先进的统计方法， 化学混合物，包括用于变量选择的弹性网络（ENET），稀疏偏最小二乘（SPLS） 回归用于个体化学效应估计，贝叶斯核机器回归（BKMR）用于 交互作用、非线性和联合效应。该项目将是第一个测试和量化 产前和产后接触化学混合物对神经行为和 神经影像学结果在良好建立的队列。这些结果有可能大大提高我们的 了解化学混合物对儿童的发育神经毒性和对环境健康的影响 政策制定。