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.

抽象的 这项研究将评估200名拉丁裔移民儿童队列中的神经发育和血液生物标志物 EPA前后12-24岁的年轻人撤销了对大量使用的所有公差 有机磷酸农药毒性雌科，定于2016年12月。这项政策变化创造了独特的和 时间有限的机会在结束前收集基线血，尿液和神经发育措施 2016年的生长季节，并在第二年再次检验了一个普遍的假设，即接触较低 Chlorpyrifos将改善东部溪流拉丁裔移民儿童的神经发育终点 农业或居住在附近。在这里，我们提出了一项基于人群的案例对照研究，该研究将评估多动症， ASD和震颤，通过尿液分析暴露于单个农药，除草剂和重金属，并且 血液基因表达特定于高水平的毒死rif虫，以确定暴露于暴露于 Chlorpyrifos将改善神经发育终点并在轴突引导途径中恢复功能。 AIM 1将检查神经发育缺陷的频率是否由ASD，ASD屏幕测定 和震颤，与特定尿农药代谢物和金属的水平增加相关。多动症会 在12-17岁的参与者和Conners的成人ADHD评级量表中使用Conners 3-SR量表进行筛选 （CARRS）-SR将在18-24岁的参与者中使用。 ASD将使用社会响应得分 18-24岁的比例尺（SRS-2）。使用Fahn-Tolosa-Marin震颤（FTM），将得分静止震动 规模。环境暴露将由尿农药代谢物的水平确定 有机磷酸盐（Chlorpyrifos，Diazinon，Malathion，Parathion，乙酰甲基），拟除虫菊酯，氨基甲酸酯，氨基甲酸酯，碳酸盐， 除草剂（2,4-D，阿特拉津，草甘膦）和总金属，包括V，CR，MN，MN，Fe，Cu，Cu，Zn，AS，SE，SR，SR，CD，SN，SN，SN，SN，SN，SN，SN，SN，SN，SN， SB，PB和U.氯吡啶磷的水平降低，其他农药的任何补偿性增加将是 在2年级证实，神经发育评分和水平之间进行的关联研究 单个农药和金属。 AIM 2将确定神经发育缺陷之间的关系 轴突引导途径的关键基因中的差异表达 包括EPHA2，EPHA7，EFNA3，EFNA4，SLA，MAPT，MAP4K4和GNA的暴露。表达 签名将与单个农药，除草剂和金属的水平相关。贝叶斯稀疏因素 回归方法将模拟神经发育评分，基因表达和暴露数据。我们的 分子流行病学方法将允许在评估多动症评估之间进行关联研究， ASD和震颤第一次在同一队列中具有血液衍生的基因表达，并将确定 Chlorpyrifos撤销对拉丁裔移民儿童健康的直接影响。