Protecting Neurodevelopment in Latino Migrant Children by Reduced Exposure to Organophosphate Pesticides

通过减少有机磷农药的接触来保护拉丁裔移民儿童的神经发育

• 批准号: 9309585
• 负责人: LISA L SATTERWHITE
• 金额: $ 26.14万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-03-01 至 2019-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9309585
• 关键词: 11 year old; 2,4-Dichlorophenoxyacetic Acid; Address; Adult; Age; Age-Years; Agriculture; Animal Model; Area; Arsenic; Atrazine; Attention deficit hyperactivity disorder; Biological Assay; Biological Markers; Blood; Brain; Cadmium; Carbamates; Case-Control Studies; Cell model; Child; Child health care; Childhood Autism Risks from Genetics and the Environment; Chlorpyrifos; Clinical Treatment; Cognitive; Communities; Complex; Consensus; Data; Development; Developmental Delay Disorders; Diazinon; Diet; Down-Regulation; EPHA2 gene; Environmental Exposure; Environmental Health; Epidemiology; Excision; Exposure to; Family; Frequencies; Gender; Gene Expression; Gene Expression Profile; Genes; Health; Heavy Metals; Herbicides; Human; Individual; Latino; Lead; Link; Low Birth Weight Infant; MAP4K4 gene; Malathion; Manganese; Masks; Measurable; Measures; Metals; Modeling; Molecular; Monitor; Mothers; Motor; Neurodevelopmental Deficit; Neurotoxins; Nomads; Organophosphates; Outcome; Parathion; Participant; Pathway interactions; Pesticides; Policies; Prospective Studies; Race; Research; Research Support; Rest Tremor; Salinas Valley; Seasons; Stream; Stress; Structural defect; Structure; Testing; Time; Tremor; Underserved Population; Urine; Work; autism spectrum disorder; axonal guidance; clinical Diagnosis; cohort; differential expression; drinking water; farm worker; follow-up; functional restoration; genome-wide; glyphosate; improved; inner city; neurodevelopment; neurotoxic; pesticide exposure; population based; prenatal; prenatal exposure; pyrethroid; social; treatment planning; urinary

Abstract This study will assess neurodevelopment and blood biomarkers in a cohort of 200 Latino migrant children and young people 12-24 years of age before and after the EPA revokes all tolerances for the heavily used organophosphate pesticide chlorpyrifos, slated for December 2016. This policy change creates a unique and time limited opportunity to collect baseline blood, urine and neurodevelopmental measures before the end of the 2016 growing season and again in the following year to test the general hypothesis that lower exposure to chlorpyrifos will improve neurodevelopmental endpoints in eastern stream Latino migrant children who work in agriculture or reside nearby. Here we propose a population-based case control study that will assess ADHD, ASD, and tremor, exposure to individual pesticides, herbicides, and heavy metals through urinary profiling, and blood gene expression signatures specific to high levels of chlorpyrifos to determine if reduced exposure to chlorpyrifos will improve neurodevelopmental endpoints and restore function in axonal guidance pathways. Aim 1 will examine whether frequency of neurodevelopmental deficits, assayed by screens for ADHD, ASD and tremor, correlates with increased levels of specific urinary pesticide metabolites and metals. ADHD will be screened using the Conners 3-SR Scale in participants ages 12-17 and the Conners' Adult ADHD Rating Scale (CARRS)-SR will be used in participants ages 18-24. ASD will be scored using the Social Responsiveness Scale (SRS-2) in ages 18-24. Resting tremor will be scored using the Fahn-Tolosa-Marin Tremor Rating (FTM) Scale. Environmental exposures will be determined by levels of urinary pesticide metabolites for the organophosphates (chlorpyrifos, diazinon, malathion, parathion, pirimphos-methyl), pyrethroids, carbamates, herbicides (2,4-D, atrazine, glyphosate) and total metals including V, Cr, Mn, Fe, Cu, Zn, As, Se, Sr, Cd, Sn, Sb, Pb, and U. Reduced levels of chlorpyrifos and any compensatory increases in other pesticides will be confirmed in year 2 and association studies conducted between neurodevelopmental scores and levels of individual pesticides and metals. Aim 2 will determine the relationship between neurodevelopmental deficits and differential expression in key genes of the axonal guidance pathway specific to farmwork and pesticide exposure which include EPHA2, EPHA7, EFNA3, EFNA4, SLA, MAPT, MAP4K4, and GNAS. Expression signatures will be correlated with levels of individual pesticides, herbicides and metals. Bayesian sparse factor regression approaches will model neurodevelopment scores, gene expression and exposure data. Our molecular epidemiological approach will allow association studies between scores on assessments for ADHD, ASD and tremor with blood-derived gene expression in the same cohort for the first time and will determine immediate impact of chlorpyrifos revocation on Latino migrant children's health.

摘要 这项研究将评估200名拉丁裔移民儿童的神经发育和血液生物标志物， 年轻人12-24岁之前和之后，美国环保署撤销了所有的宽容，为大量使用 有机磷农药毒死蜱，定于2016年12月。这一政策变化创造了一个独特的， 在研究结束前有时间限制地收集基线血液、尿液和神经发育指标 2016年生长季节，并再次在接下来的一年，以测试一般假设， 毒死蜱将改善在东部工作的拉丁美洲移民儿童的神经发育终点， 农业或居住在附近。在这里，我们提出了一个基于人群的病例对照研究，将评估多动症， ASD和震颤，通过尿液分析暴露于单独的杀虫剂，除草剂和重金属，以及 血液基因表达特征的具体高水平毒死蜱，以确定是否减少接触 毒死蜱将改善神经发育终点并恢复轴突引导途径的功能。 目的1将检查是否神经发育缺陷的频率，通过ADHD，ASD筛查测定， 和震颤，与特定的尿农药代谢物和金属的水平增加相关。ADHD将 在12-17岁的参与者中使用Conners 3-SR量表和Conners成人ADHD评定量表进行筛选 （CARRS）-SR将用于18-24岁的参与者。ASD将使用社会反应性进行评分 量表（SRS-2），18-24岁。将使用Fahn-Tolosa-Marin震颤评级（FTM）对静息震颤进行评分 规模环境暴露将通过尿中农药代谢物的水平来确定， 有机磷酸酯（毒死蜱、二嗪农、马拉硫磷、氯磷、甲基嘧啶），拟除虫菊酯，氨基甲酸酯， 除草剂（2，4-D、莠去津、草甘膦）和总金属，包括V、Cr、Mn、Fe、Cu、Zn、As、Se、Sr、Cd、Sn， 锑铅和铀。降低毒死蜱的含量和任何补偿性增加其他杀虫剂的含量将是 在第2年证实，并进行了神经发育评分和水平之间的关联研究， 个别农药和金属。目的2将确定神经发育缺陷之间的关系 以及农作物和农药特异性轴突导向途径关键基因的差异表达 暴露，包括EPHA 2、EPHA 7、EFNA 3、EFNA 4、SLA、MAPT、MAP 4K 4和GNAS。表达 特征将与单独的杀虫剂、除草剂和金属的水平相关。贝叶斯稀疏因子 回归方法将模拟神经发育评分、基因表达和接触数据。我们 分子流行病学方法将允许ADHD评估分数之间的关联研究， ASD和震颤与血液来源的基因表达在同一队列中的第一次，并将确定 撤销毒死蜱对拉丁美洲移民儿童健康的直接影响。