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

项目概要 美国和加拿大有六分之一的儿童存在一种或多种学习或行为问题，例如 学习障碍、焦虑、自闭症谱系障碍、行为障碍、抑郁或注意力缺陷 多动症（ADHD）。早期大脑发育对有毒物质暴露很敏感，包括重度接触 金属、持久性有机污染物和内分泌干扰化学物质。暴露于以下混合物 环境化学物质在儿童中是现实存在的，化学混合物可能有不同的作用方式 影响神经元增殖、迁移、分化、突触形成/修剪/可塑性、髓鞘形成、 和神经递质，对中枢神经系统造成不良影响。大部分环保 流行病学研究仅考察了单一化学物质对神经行为结果的影响。 混合统计方法的最新发展和应用将为揭示 单个化学品的影响、化学品之间的相互作用以及累积暴露。这些方法 仅应用于有限的儿童神经行为研究，尚未用于神经影像学 结果。我们将使用两个现有的出生队列来检查产前和产后接触的影响 化学混合物对儿童神经行为的影响。环境的健康成果和措施（主页） 该研究是一项基于辛辛那提的出生队列，由 400 名孕妇及其子女进行随访，随访至 12 岁， 环境化学物质母婴研究 (MIREC) 是加拿大一项针对 1983 年孕妇的研究 有孩子的妇女的随访期为 9-11 岁。两个北美出生队列的测量值均超过 60种环境污染物，包括铅、汞、镉、砷、多溴二苯醚、 多氯联苯、全氟烷基物质、有机氯和有机磷酸酯农药、 双酚 A、邻苯二甲酸盐、三氯生和有机磷酸酯阻燃剂，以及儿童认知能力 (n>1000)、行为 (n>1000) 和神经影像 (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)、稀疏偏最小二乘法 (SPLS) 用于个体化学效应估计的回归，以及用于估计的贝叶斯核机器回归（BKMR） 相互作用、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行为的潜在影响 已建立的队列中的神经影像学结果。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及其对环境健康的影响 政策制定。

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.