Environmental exposures, early iron deficiency and child neurodevelopment

描述（由申请人提供）：最近使用国家数据的研究报告称，发育障碍在美国和其他地方很普遍（高达每6个儿童中就有1个）并且呈上升趋势。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，许多或大多数人在不同程度上接触的物质，包括当代使用的杀虫剂、重金属和二手烟草烟雾（STS），都具有神经毒性。除铅外，这些物质单独或混合使用对神经发育的影响尚缺乏人体研究。在许多情况下，暴露于这些物质的增加可能伴随着营养缺乏，其中最常见的是缺铁（ID）。这可能通过类似的机制途径或增加对暴露的易感性而导致更大的神经毒性。由于大脑发育的脆弱性，怀孕和婴儿期是最受关注的时期。该研究旨在：1)研究神经发育与早期暴露于杀虫剂、金属（锰和铅）和STS之间的关系（即加性和乘法效应）；2)检测这些药物与ID对神经发育结局的相互作用；3)确定孕期和/或婴儿期补铁是否能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支持的两项正在进行的关于ID和神经发育的大型研究（n ~ 2500），这些研究在中国农村进行，在那里已经记录了高暴露和广泛的ID。这项研究将利用最先进的方法来评估暴露和结果。在正在进行的研究中收集了出生/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。暴露生物标志物将在早期发育的多个时间点的尿液和血液样本中进行测量，包括量化脐带血中bbbb45农药的灵敏新方法。本研究的预期结果是为环境暴露对神经发育的影响和暴露风险的优先级提供新的和急需的信息，具体过程和敏感暴露窗口涉及多重暴露和ID对这些终点的同时影响，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。鉴于全球范围内这些物质的广泛暴露，ID的全球流行，以及越来越多的证据表明许多环境暴露会导致较差的神经发育结果，该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. PUBLIC HEALTH RELEVANCE: Using innovative approaches to assess the risk of environmental exposures on child neurodevelopment, this study will have a significant impact on public health given widespread exposure to pesticides, heavy metals and STS worldwide, the global prevalence of iron deficiency, and concerns that environmental influences are contributing to the high and increasing rates of neurodevelopmental disorders.