Environmental risk factors for autistic behaviors in a cohort study

队列研究中自闭症行为的环境危险因素

• 批准号: 9118996
• 负责人: SUSAN A KORRICK
• 金额: $ 27.38万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-10 至 2019-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9118996
• 关键词: Adolescence; Adolescent; Adolescent and Young Adult; Adult; Affect; Age; Anxiety; Anxiety Disorders; Area; Behavior; Behavioral; Biological Markers; Birth; Case-Control Studies; Child; Chlorinated Hydrocarbons; Clinical; Cohort Studies; Communication; Comorbidity; Complement; Data; Development; Diagnosis; Disease; Environmental Pollutants; Environmental Pollution; Environmental Risk Factor; Evaluation Studies; Exposure to; Female; General Population; Goals; Hair; Health; Impairment; Individual; Intelligence; Internet; Joints; Lead; Life; Longevity; Manganese; Measures; Medical; Mental Depression; Mercury; Metal exposure; Metals; Methods; Morbidity - disease rate; Nail plate; Online Systems; Participant; Performance; Persons; Pesticides; Polychlorinated Biphenyls; Predisposition; Prevalence; Prospective Studies; Public Health; Publishing; Quality of life; Reproducibility; Research; Research Design; Research Infrastructure; Resources; Risk Factors; Sampling; Schools; Serum; Sex Characteristics; Social Interaction; Specific qualifier value; Symptoms; System; Testing; Umbilical Cord Blood; Validation; Work; autism spectrum disorder; autistic behaviour; cohort; cost; design; developmental disease; disorder risk; early childhood; emerging adult; flexibility; follow up assessment; follow-up; genetic risk factor; insight; instrument; male; neurobehavioral; neurotoxic; non-genetic; novel strategies; organochlorine exposure; organochlorine pesticide; pollutant; prenatal; prenatal exposure; prospective; sex; skills; social; social communication; web based interface; young adult

 DESCRIPTION (provided by applicant): The potential for prenatal exposures to environmental contaminants to contribute to increasing prevalence of autism spectrum disorders (ASDs) is a growing public health concern. ASDs are diverse developmental disorders that share deficiencies in social interactions, communication and behavioral flexibility. Although typically diagnosed in early childhood, ASDs can result in significant impairment across the life span. After several decades of alarming increases in ASDs, currently 1 in 68 U.S. school children are estimated to be affected. Genetic risk factors contribute but recent data suggest that much of ASD risk is due to non-genetic factors, including prenatal contaminant exposures. The male:female ratio of ASD diagnoses is estimated to be 4:1 consistent with sex differences in susceptibility. Much of the published research on environmental risk factors for ASDs has been case-control studies wherein prenatal exposure is not measured. A key goal of this study is to use a novel approach to assess the relationship of measured prenatal exposures with ASDs and, in so doing, to develop methods for long term follow up of birth cohorts, in general, including our study cohort. Even among individuals with typical development, there is a range of performance on tasks which are deficient in ASDs. We will leverage this variability in normal behavior to explore the relation of prenatal exposure to common environmental contaminants with ASD behaviors in an established prospective birth cohort, the New Bedford Cohort (NBC). Extensive prenatal exposure biomarkers available on the NBC include cord serum levels of organochlorines (OC) (polychlorinated biphenyls and OC pesticides), and cord blood and maternal peripartum hair and nail levels of neurotoxic metals (e.g., lead, mercury, manganese). Although developmental testing has been done in the NBC from birth through age 16 yrs, testing to date has not included routine assessment for ASD behaviors and has been performed via extensive in-person examinations. The NBC are now older adolescents and young adults and are moving from the study area such that in person testing is not feasible. Thus study aims include: (1) development and validation of a web-based system for neurobehavioral assessment of the NBC that does not rely on in-person testing; (2) utilization of the web infrastructure to evaluate a focused set of behavioral skills that can be affected by ASDs; and (3) assessment of the relation of prenatal OC and metal exposures with ASD behaviors in the NBC. We will explore potential sex differences in exposure susceptibility and whether contaminant mixtures enhance the independent association of individual contaminants with ASD behaviors. The proposed study provides unique opportunities: (1) to expand research capacity for long-term prospective studies of early life environmental determinants of disease risk, in general, and ASD risk, in particular; and (2) to expand the scope of research on ASDs. We thereby hope to gain insight into potentially remediable environmental risk factors for ASDs, disorders of substantial public health importance given their increasing prevalence, morbidity, and associated social and medical costs.

 描述（由申请人提供）：产前接触环境污染物可能会导致自闭症谱系障碍 (ASD) 患病率增加，这是一个日益引起公众健康关注的问题。ASD 是多种发育障碍，在社交互动、沟通和行为方面都有缺陷。灵活性 虽然自闭症谱系障碍通常在儿童早期被诊断出来，但它可能会在整个生命周期中造成严重损害。几十年来，自闭症谱系障碍数量惊人地增加，目前估计每 68 名美国学童中就有 1 人受到影响。遗传风险因素有所影响，但最近的数据表明，大部分 ASD 风险是由非遗传因素造成的，包括产前污染物暴露，ASD 诊断的男性与女性比例估计为 4:1，这与易感性的性别差异一致。尽管未测量产前暴露，已发表的关于自闭症谱系障碍环境风险因素的研究一直是病例对照研究，本研究的一个主要目标是使用一种新方法来评估测量的产前暴露与自闭症谱系障碍的关系，在此过程中，我们将开发对出生群体（包括我们的研究群体）进行长期随访的方法，即使在具有典型发育的个体中，也存在一系列缺乏自闭症谱系障碍的任务表现。在已建立的前瞻性出生队列中，新贝德福德队列 (NBC) 中的正常行为探讨了产前接触常见环境污染物与 ASD 行为的关系，NBC 上提供的广泛产前暴露生物标志物包括有机氯的脐带血清水平。 (OC)（多氯联苯和 OC 杀虫剂），以及脐带血和母亲围产期头发和指甲中神经毒性金属（例如铅、汞、锰）的水平，尽管 NBC 已对从出生到 16 岁的儿童进行了发育测试，迄今为止，测试不包括对 ASD 行为的常规评估，而是通过广泛的现场检查进行的，NBC 现在正在从研究区域转移。因此，研究目标包括：(1) 开发和验证基于网络的 NBC 神经行为评估系统，该系统不依赖于现场测试；(2) 利用网络基础设施来进行 NBC 神经行为评估。评估一系列可能受 ASD 影响的行为技能；(3) 评估 NBC 中产前 OC 和金属暴露与 ASD 行为之间的关系，以及污染物混合物是否会增强 ASD 行为。独立的拟议的研究提供了独特的机会：（1）扩大对疾病风险（特别是 ASD 风险）的早期生命环境决定因素的长期前瞻性研究的研究能力；（2） ）以扩大自闭症谱系障碍的研究范围，因此我们希望深入了解自闭症谱系障碍的潜在可补救的环境风险因素，鉴于其日益增加的患病率、发病率以及相关的社会和医疗成本，这些疾病对公共卫生具有重大意义。