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名儿童中有1名），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，但人们对接触环境神经毒物的潜在作用表示关切。越来越多的动物证据表明，许多人或大多数人以不同水平接触的物质，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，缺乏对这些药物单独或混合在一起与神经发育有关的人体研究。在许多情况下，暴露于这些试剂的升高可能伴随着营养缺乏，其中缺铁（ID）是最常见的。这可能通过类似的机制途径或增加对接触的敏感性而导致更大的神经毒性。由于大脑发育的脆弱性，怀孕和婴儿期是最令人担忧的时期。拟议的研究旨在：1）调查神经发育与生命早期暴露于农药、金属（锰和铅）和STS单独和组合（即，累加和倍增效应）; 2）测试这些药剂和ID之间对神经发育结果的相互作用;和3）确定妊娠期和/或婴儿期的铁补充是否改善环境暴露对神经发育结果的不利影响。该研究将利用两项正在进行的由NIH支持的关于ID和神经发育的大型研究（n ~ 2500），这些研究在中国农村进行，那里已经记录了高暴露以及广泛的ID。该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周龄、9个月和18个月时感觉、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的尿液和血液样本中测量暴露生物标志物，包括量化脐带血中>45种农药的敏感新方法。本研究的预期成果是提供新的和急需的信息，环境暴露对神经发育的影响和暴露风险的优先顺序，特定的过程和敏感的暴露窗口涉及的多重暴露和ID对这些终点的同时影响，并通过减少暴露或补铁的潜在干预措施，以减轻这些影响的证据。该研究可能会对公共卫生政策产生重大影响，因为全球范围内广泛暴露于这些药物，ID的全球患病率，以及越来越多的证据表明许多环境暴露导致神经发育结果较差。

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.