Environmental exposures, early iron deficiency and child neurodevelopment

描述（由申请人提供）：最近使用国家数据进行的研究表明，发育障碍很普遍（每 6 个儿童中就有 1 个），并且在美国和其他地方呈上升趋势。虽然这些趋势的原因尚不清楚，但人们担心暴露于环境神经毒物的潜在作用。越来越多的动物证据表明，许多或大多数人不同程度接触的物质，包括当代使用的杀虫剂、重金属和二手烟草烟雾 (STS)，具有神经毒性。除铅外，还缺乏对这些药物与神经发育相关的人体研究，无论是单独使用还是作为混合物一起使用。在许多情况下，接触这些物质的增加可能会伴随营养缺乏，其中最常见的是缺铁（ID）。这可能会通过类似的机制途径发挥作用或增加对暴露的敏感性，从而导致更大的神经毒性。由于大脑发育的脆弱性，怀孕和婴儿期是最令人担忧的时期。拟议研究的目的是： 1) 研究神经发育与生命早期接触杀虫剂、金属（锰和铅）和 STS 的单独和组合（即加性和乘性效应）之间的关联； 2) 测试这些药物与 ID 之间的相互作用对神经发育结果的影响； 3) 确定妊娠期和/或婴儿期补充铁是否可以改善环境暴露对神经发育结果的不利影响。该研究将利用美国国立卫生研究院 (NIH) 支持的两项大型正在进行的智力障碍和神经发育 (n ~ 2500) 研究，这些研究在中国农村地区进行，那里的暴露水平较高，并且智力障碍广泛存在。该研究将利用最先进的方法来评估暴露和结果。正在进行的研究收集了出生时/6周、9个月和18个月时的感觉、运动、认知、情感社会和调节功能的详细测量结果。将在早期开发的多个时间点测量尿液和血液样本中的暴露生物标志物，包括定量脐带血中 > 45 种农药的敏感新方法。这项研究的预期结果是提供新的、急需的信息，涉及环境暴露对神经发育的影响和暴露风险的优先顺序、涉及多重暴露和 ID 对这些终点的同时影响的具体过程和敏感暴露窗口，以及通过减少暴露或补充铁来减轻这些影响的潜在干预措施的证据。鉴于全球范围内广泛接触这些物质、智力障碍在全球流行，以及越来越多的证据表明许多环境暴露会导致神经发育结果较差，这项研究可能会对公共卫生政策产生重大影响。

DESCRIPTION (provided by applicant): Recent studies using national data have reported that developmental disabilities are prevalent (as high as 1 in every 6 children) and on the rise in the US and elsewhere. While the cause(s) of these trends are unknown, there is concern for the potential role of exposures to environmental neurotoxicants. There is growing animal evidence that agents to which many or most people are exposed at varying levels, including contemporary-use pesticides, heavy metals, and secondhand tobacco smoke (STS), are neurotoxic. With the exception of lead, human studies of these agents in relation to neurodevelopment are lacking, both alone and together as mixtures. In many settings elevated exposure to these agents may be accompanied by nutritional deficiencies, with iron deficiency (ID) being the most common. This may result in greater neurotoxicity by acting through similar mechanistic pathways or increasing susceptibility to exposure. Pregnancy and infancy are the periods of greatest concern due to vulnerability of the developing brain. The proposed study aims to: 1) Investigate the association between neurodevelopment and early life exposure to pesticides, metals (manganese and lead), and STS individually and in combination (i.e., additive and multiplicative effects); 2) Test for interactions between these agents and ID on neurodevelopmental outcomes; and 3) Determine whether iron supplementation in pregnancy and/or in infancy ameliorates adverse impacts of environmental exposures on neurodevelopment outcome. The study will leverage two large ongoing NIH-supported studies of ID and neurodevelopment (n ~ 2500) taking place in rural China where elevated exposures, as well as widespread ID, have been documented. The study will utilize state-of-the-art approaches to assess exposures and outcomes. Detailed measures of sensory, motor, cognitive, affective-social and regulatory functions at birth/6 weeks, 9 months, and 18 months of age are collected in the ongoing studies. Exposure biomarkers will be measured in urine and blood samples from multiple time points in early development, including sensitive new methods to quantify >45 pesticides in cord blood. Expected outcomes of this study are to provide new and much needed information on the impacts of environmental exposures on neurodevelopment and prioritization of exposure risks, the specific processes and sensitive exposure windows involved the simultaneous effects of multiple exposures and ID on these endpoints, and evidence for potential interventions to lessen these effects through exposure reduction or iron supplementation. The study will likely have a significant impact on public health policy given widespread exposure to these agents worldwide, the global prevalence of ID, and increasing evidence that many environmental exposures contribute to poorer neurodevelopmental outcomes.