Environmental risk factors for autistic behaviors in a cohort study

 描述(由申请人提供)：产前暴露于环境污染物可能导致自闭症谱系障碍(ASDS)患病率增加，这是一个日益严重的公共卫生问题。自闭症是一种不同的发育障碍，在社交、沟通和行为灵活性方面都存在缺陷。虽然通常在儿童早期被诊断为自闭症，但在整个生命周期中，自闭症可能会导致严重的损害。在经历了几十年令人震惊的自闭症增加之后，目前估计每68名美国学龄儿童中就有一名受到影响。遗传风险因素起了作用，但最近的数据表明，大部分自闭症风险是由非遗传因素造成的，包括产前接触污染物。据估计，ASD诊断的男性和女性比例为4：1，与易感性的性别差异一致。已发表的关于自闭症环境风险因素的大部分研究都是病例对照研究，其中没有测量产前暴露。这项研究的一个关键目标是使用一种新的方法来评估测量的产前暴露与自闭症的关系，并在这样做的过程中，开发出长期跟踪出生队列的方法，一般包括我们的研究队列。即使在具有典型发育的个体中，也有一系列自闭症缺陷任务的表现。我们将利用正常行为的这种变异性，在一个已建立的预期出生队列--新贝德福德队列(NBC)中，探索产前暴露于常见环境污染物与ASD行为的关系。NBC提供的广泛产前暴露生物标志物包括脐带血有机氯(OC)水平(多氯联苯和OC杀虫剂)，以及脐带血和产妇围产期头发和指甲中神经毒性金属的水平(例如，铅、汞、锰)。虽然NBC从出生到16岁都进行了发育测试，但到目前为止，测试还没有包括对ASD行为的常规评估，而是通过广泛的面对面检查进行的。NBC现在是年龄较大的青少年和年轻人，他们正在离开研究区域，因此亲自测试是不可行的。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，该系统不依赖于面对面测试；(2)利用网络基础设施来评估可受ASD影响的一组重点行为技能；以及(3)评估产前OC和金属暴露与NBC中ASD行为的关系。我们将探索暴露易感性的潜在性别差异，以及污染物混合物是否增强了单个污染物与ASD行为的独立关联。拟议的研究提供了独特的机会：(1)扩大对一般疾病风险的早期生活环境决定因素，特别是自闭症风险的长期前瞻性研究的研究能力；(2)扩大对自闭症的研究范围。因此，我们希望深入了解自闭症的潜在可补救的环境风险因素，鉴于其日益增长的患病率、发病率以及相关的社会和医疗成本，自闭症对公共卫生具有重要意义。

 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.