Pesticide Exposure and Childhood Autism

项目摘要/摘要 自闭症是最常见的神经发育障碍之一，发病率约为40-60%。 在美国儿童中有10,000人(5，11人)。基因和环境因素都导致了这种复杂的疾病。 (13)最近的研究表明，环境因素的作用更大(14)。然而，它的作用是 尽管公众非常关心，但环境仍然难以捉摸。基于人口的研究应用 完全需要有效和可靠的暴露评估方法。在这里，我们建议研究 假设在脆弱时期，特别是在胎儿时期，接触特定的杀虫剂 发展，决定了自闭症障碍(AD)的后续发展风险。 加州是研究阿尔茨海默病潜在环境贡献的绝佳地点。这个 加州发展服务部(CA-DDS)运营着全州范围的区域中心系统 自闭症服务和维护所有客户的电子记录。加利福尼亚州在美国各州中排名第一 农业生产，占美国农业农药总使用量的四分之一(15，16)，是唯一一个 它维护着全州范围内的农药使用报告系统。在这一独特资源的基础上，我们集团拥有 在加州研究农药对健康影响的经验超过15年。之前，我们开发了一种 利用独特的加州农药使用的地理农药暴露评估工具(GRPES) 报告系统，与农业土地利用图相结合，得出基于记录的历史估计 住宅暴露(17，18)，使我们能够捕获特定月/三个月的农业杀虫剂暴露 全州范围内。 在全州范围内，我们预计将识别20,000名确诊年龄在72个月前的自闭症患者。 CA-DDS数据库出生于1997年至2009年，1700人来自农业地区，年龄-性别匹配为1：10 来自出生记录的控制(51)。这将提供有史以来最大的队列来解决暴露于 易患阿尔茨海默病的特定化学物质(如神经毒性或内分泌干扰剂)导致AD 发展阶段。具体地说，我们将检查AD是否与围产期和胎儿有关 暴露于特定杀虫剂，集中于神经发育毒素以及大量使用杀虫剂； 应用复杂的基于记录的暴露评估技术来确定农药暴露，同时 避免由于病例父母过度报告暴露而导致的回忆偏差。我们有最新的 精细的、最先进的客观农药评估工具，为我们提供个人水平的暴露 在较长的观察期内，在较大的区域和较大的人口(加利福尼亚州)。 提高我们对环境毒素影响的认识将为环境卫生政策提供信息 农药监管，推进自闭症的初级预防，并有可能为 自闭症发生的生物学机制。

Project summary/Abstract Autism is one of the most common neurodevelopmental disorders with a prevalence of ~40- 60 in 10,000 in children in the US (5, 11). Both genes and environmental factors contribute to this complex disorder (13) with recent research suggesting a stronger role for environmental factors (14). However, the role of environment remains elusive even though the public is very concerned. Population-based research applying valid and reliable exposure assessment methods is thoroughly needed. Here, we propose to examine the hypothesis that exposure to specific pesticides during vulnerable periods, particularly during fetal development, determines risks of subsequent development of autistic disorder (AD). California is an excellent location for studying potential environmental contributions to AD. The California Department of Developmental Services (CA-DDS) operates a statewide system of regional centers for autism services and maintains electronic records for all clients. California ranks 1st among US states in agricultural production, with 1/4 of total agricultural pesticide use in the US (15, 16), and is the only state which maintains a statewide pesticide use reporting system. Building onto this unique resource, our group has over 15 years of experience studying health effects from pesticides in California. Previously, we developed a geographic pesticide exposure assessment tool (GRAPES) that utilizes the unique California Pesticide Use Report system, in combination with agricultural land-use maps, to derive record-based estimates of historical residential exposures (17, 18), allowing us to capture month/trimester specific agricultural pesticide exposures statewide. Statewide, we expect to identify >20,000 autism cases with diagnoses up to the age of 72 months from the CA-DDS database born in CA 1997-2009 and >1,700 from agricultural areas as well as 1:10 age-sex match controls from birth records (51). This will provide the largest cohort ever to address hypotheses that exposures to specific chemicals (e.g. neurotoxic or endocrine disrupting agents) contribute to AD during vulnerable periods of development. Specifically, we will examine whether AD is associated with peri-conceptional and fetal exposures to specific pesticides, focusing neurodevelopmental toxins as well as high volume use pesticides; applying sophisticated record based exposure assessment techniques to determine pesticide exposures while avoiding recall bias due to over-reporting of exposures among case parents. We have available the to-date most refined, state-of-the-art objective pesticide assessment tool that provides us with individual level exposures during an extended observation period, in a large area and for a large population (the state of California). Improving our understanding of impacts of environmental toxins will inform environmental health policy on pesticide regulation, advance primary prevention of autism, and potentially provide scientific insights into biologic mechanisms of autism development.