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，发育障碍很普遍(高达每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(S)尚不清楚，但人们对暴露于环境神经毒物的潜在作用感到担忧。越来越多的动物证据表明，许多人或大多数人在不同程度上接触的制剂，包括当代使用的杀虫剂、重金属和二手烟烟雾(STS)，具有神经毒性。除了铅以外，人类对这些药物与神经发育关系的研究还很缺乏，无论是单独进行还是作为混合物一起进行。在许多情况下，暴露于这些制剂的增加可能伴随着营养缺乏，其中缺铁(ID)是最常见的。这可能会通过类似的机械途径或增加对暴露的敏感性而导致更大的神经毒性。由于发育中的大脑的脆弱性，怀孕和婴儿期是最令人担忧的时期。这项拟议的研究旨在：1)调查神经发育与早期单独和联合暴露于杀虫剂、金属(锰和铅)和STS(即相加和相乘效应)之间的关系；2)测试这些制剂与ID之间的相互作用对神经发育结果的影响；以及3)确定孕期和/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。这项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)，该研究在中国农村地区进行，在那里，高暴露和广泛的ID已被记录在案。这项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/6周、9个月和18个月大时感觉、运动、认知、情感社交和调节功能的详细测量。接触生物标记物将在早期开发的多个时间点的尿样和血液样本中进行测量，包括灵敏的新方法来定量脐带血中的&gt；45种农药。这项研究的预期结果是提供关于环境暴露对神经发育的影响和暴露风险的优先顺序的新的和迫切需要的信息，涉及多个暴露和ID对这些端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。这项研究可能会对公共卫生政策产生重大影响，因为全球范围内对这些制剂的广泛接触，ID的全球流行，以及越来越多的证据表明，许多环境暴露导致较差的神经发育结果。

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.