Environmental risk factors for autistic behaviors in a cohort study

点击翻译按钮获取中文摘要

 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.