Environmental exposures, early iron deficiency and child neurological development

环境暴露、早期缺铁和儿童神经发育

• 批准号: 8761542
• 负责人: BETSY LOZOFF
• 金额: $ 3.87万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-08-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8761542
• 关键词: Address; Adverse effects; Affect; Affective; Age-Months; Animals; Arts; Base of the Brain; Behavior; Biological; Biological Assay; Biological Markers; Biological Monitoring; Birth; Blood; Blood specimen; Brain; Brain region; Child; China; Chinese People; Cognition; Cognitive; Country; Coupled; Data; Development; Developmental Disabilities; Environmental Exposure; Exposure to; Funding; Health Policy; Heavy Metals; Herbicides; Human; Industrial fungicide; Infant; Insecticides; Intervention; Iron; Lead; Life; Light; Malnutrition; Manganese; Measures; Metabolism; Metals; Methods; Motor; Neurodevelopmental Disorder; Neurologic; Neurotoxins; Nutrient; Outcome; Outcome Study; Pathway interactions; Pattern; Pesticides; Predisposition; Pregnancy; Pregnant Women; Prevalence; Process; Psyche structure; Public Health; Randomized Controlled Trials; Reliance; Reporting; Research; Risk; Role; Rural; Sampling; Sensory; Smoking; System; Testing; Time; Tobacco smoke; Toxic effect; Umbilical Cord Blood; United States National Institutes of Health; Urine; Work; base; behavior measurement; brain behavior; cohort; cost effective; design; early life exposure; environmental agent; fetal; in utero; infancy; innovation; iron deficiency; iron supplementation; men; neurodevelopment; neurophysiology; neurotoxic; neurotoxicity; social; stressor; trend; uptake

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.

描述（由申请人提供）：使用国家数据的最新研究报告说，发育障碍很普遍（每6个孩子中高达1个），并且在美国和其他地方的增长。尽管这些趋势的原因尚不清楚，但人们担心暴露于环境神经毒性的潜在作用。越来越多的动物证据表明，许多人或大多数人都以不同水平暴露的特工，包括当代农药，重金属和二手烟草烟雾（STS）是神经毒性的。除铅外，缺乏对这些药物与神经发育相关的人类研究，无论是单独且作为混合物》的研究。在许多环境中，升高暴露于这些药物的情况可能伴有营养缺乏，铁缺乏症（ID）是最常见的。通过通过类似的机械途径或增加暴露易感性作用，这可能会导致更大的神经毒性。由于发育中的大脑的脆弱性，怀孕和婴儿期是最关心的时期。拟议的研究旨在：1）研究神经发育与早期寿命与农药，金属（锰和铅）的相关性，以及单独和组合的ST（即添加剂和乘法效应）； 2）在神经发育结果上测试这些药物与ID之间的相互作用； 3）确定妊娠和/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。该研究将利用在中国农村进行的两项大型NIH持续支持的ID和神经发育研究（n〜2500），其中已记录了较高的暴露以及广泛的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，9个月和18个月大的感觉，运动，认知，情感社会和调节功能的详细措施。暴露生物标志物将在早期发育中的多个时间点中测量尿液和血液样本，包括敏感的新方法，以量化绳索血液中的45种农药。这项研究的预期结果是提供有关环境暴露对神经发育的影响和暴露风险的优先次序的新的急需信息潜在的干预措施通过减少暴露或补充铁减少这些影响。鉴于全球范围内广泛接触这些代理商，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神经发育结果较差，因此这项研究可能会对公共卫生政策产生重大影响。