Pesticide Exposure and Childhood Autism

项目概要/摘要 孤独症是最常见的神经发育障碍之一， 10，000在美国的儿童（5，11）。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， 尽管公众非常关注，但环境仍然难以捉摸。基于人口的研究 完全需要有效和可靠的接触评估方法。在这里，我们建议审查 在脆弱时期，特别是在胎儿期， 发展，决定了自闭症障碍（AD）的后续发展的风险。 加州是研究环境对AD的潜在贡献的绝佳地点。的 加州发展服务部（CA-DDS）运营着一个全州范围的区域中心系统， 自闭症服务，并为所有客户保持电子记录。加州在美国各州中排名第一， 农业生产，占美国农业农药使用总量的1/4（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。基于这一独特的资源，我们的团队 在加州有超过15年研究杀虫剂对健康影响的经验。在此之前，我们开发了一个 地理农药暴露评估工具（GRAPES），利用独特的加州农药使用 报告系统，结合农业土地利用图， 住宅暴露（17，18），使我们能够捕获特定月份/三个月的农业农药暴露 全州范围内 在全州范围内，我们预计将确定> 20，000例自闭症病例，诊断年龄为72个月， CA-DDS数据库1997-2009年出生于加利福尼亚州，来自农业地区的人数超过1，700人，年龄性别匹配比例为1：10 出生记录（51）这将提供有史以来最大的队列，以解决假设， 特定化学品（如神经毒性或内分泌干扰剂）在易受影响的 发展时期。具体来说，我们将研究AD是否与围概念和胎儿 接触特定的农药，重点是神经发育毒素以及大量使用的农药; 采用先进的基于记录的接触评估技术，确定农药接触情况， 避免由于病例父母过度报告暴露而导致的回忆偏差。我们有迄今为止最 一个精炼的、最先进的客观农药评估工具，为我们提供个人水平的暴露 在一个延长的观察期内，在一个大的地区和一个大的人口（加州州）。 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，并可能提供科学见解， 自闭症发展的生物学机制。

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.