Autism and Prenatal Endocrine Disruptors (A-PED)

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Project Summary Autism and spectrum disorders (ASD) are serious and debilitating neurodevelopmental disorders that incur substantial suffering for patients and pose major challenges to our health care system. It is now estimated that ASD affects about 1 in 68 children, with a male:female ratio of 4:1. Both genetic and environmental factors contribute to ASD, but environmental factors have been understudied. Because environmental factors are potentially modifiable their study should be a research priority. Thus, there is an urgent need to understand the role of environmental factors in ASD risk. This effort has been hampered by the challenge of acquiring accurate and relevant exposure measures in epidemiologic cohorts of adequate size. The goal of our funded application is to determine the impact of prenatal exposure to multiple classes of endocrine disrupting chemicals (EDCs) on ASD risk. To achieve this, we are using stored samples from a serum biobank in South Sweden and corresponding population-based registries that include linkable, individual-level perinatal, diagnostic, medical, and demographic information for all births in the years 1998- 2007. We originally proposed to ascertain 600 ASD cases and 600 controls with similar sex and birth year distributions, measure levels of EDCs in maternal serum samples, and investigate three integrated specific aims: first, determine associations between ASD risk and prenatal serum concentration of our target EDCs and their mixtures; second, determine whether sex modifies these associations; third, determine whether prenatal exposure to EDCs, singly and combined, contributes to individual differences in ASD phenotype and severity. The current request is for supplemental funds to measure levels of EDCs in 397 ASD cases and controls in addition to the 600 cases and controls whose data collection is funded by the original grant. That initially proposed sample size reflects estimates of statistical power which were calculated on the basis of available (but non-representative) data. Pilot data obtained since study onset confirms that adding the requested subjects will provide sufficient statistical power to achieve the goals and accomplish the specific aims of the original application which cannot be met with the originally proposed sample size. All 997 cases have been identified, and the availability of their stored prenatal serum confirmed. In addition, because the expanded sample of 997 cases include all diagnosed ASD cases in the study region and time period, this study will provide the research community with the first-ever complete case ascertainment of all ASD cases diagnosed in a large clinically well-characterized population over a ten-year period. This study, including 997 ASD cases with extensive exposure and registry data, will then be the largest and most complete study of prenatal EDCs exposure undertaken to date and should set a new standard for future studies of this important question.