DESCRIPTION (provided by applicant): This proposed competitive supplement will enhance 1-R01-ES015359 (2-01-08 to 1-31-12),"The CHARGE Study: Childhood Autism Risks from Genetics and the Environment" by expanding the exposure assessment to include additional chemicals and more sensitive analyses of previously included compounds. The CHARGE Study is a large, population-based case-control investigation of the underlying causes of autism, with a focus on environmental exposures, genetic susceptibility, and the interactions between these two domains. Currently, the primary exposure information sources in the CHARGE Study are an environmental exposure questionnaire, medical charts, and chemical analysis of metals in current blood, baby hair, and newborn blood spots, and of fipronil metabolites in urine. This supplement (a) adds the collection and laboratory analysis of dust samples from the home to obtain historical measures of polybrominated diphenyl ethers (PBDEs) and other home environmental exposures that cover the perinatal period, (b) expands the chemicals for which we will quantify exposures to encompass pyrethroid and organophosphate pesticides, phthalates and bisphenol-A, as well as some of their metabolites, and (c) adds a food frequency questionnaire for the pregnancy and early childhood periods focused on a short list of common dietary items that are known to have high levels of specified contaminants of interest. Thus, this supplement addresses two major pathways for exposures to pesticides, PBDEs, phthalates, and bisphenol-A, namely, dust and food. The chemicals selected for this project are found at increasing concentrations in environmental and biological media and have demonstrated neurotoxicity or endocrine disrupting activity, and hence are candidate etiologic factors in autism. Pyrethroids interfere with voltage-sensitive sodium channels in the brain, and compromise the blood-brain barrier; PBDEs alter responses to novel stimuli in rat pups exposed prenatally, and influence levels of precursors to thyroxine. Phthalates and bisphenol A are endocrine disruptors, the latter being estrogenic and the former, anti-androgenic. Because of the 4:1 male-female ratio in autism, sex steroids are hypothesized to play a role in susceptibility. Finally, because immune dysregulation is a correlate and possible mechanism in autism, this supplement will evaluate these newly measured compounds in relation to immune markers obtained through existing funding. By expanding the scope of the CHARGE study to include classes of compounds that have never been examined in relation to pervasive developmental disorders, this supplement will accelerate the rate of scientific discovery, bringing us closer to interventions that can prevent autism in at least some children. It will also address a major goal of the American Recovery and Reinvestment Act by the creation of 3.5 new jobs.
PUBLIC HEALTH RELEVANCE: The environmental causes of autism are not well understood. The public health urgency of this problem is underscored by recent estimates that one in 150 children in the U.S. will be diagnosed with an autism spectrum disorder by 8 years of age. Meanwhile, exposures to neurotoxic pesticides and brominated flame-retardants, as well as other compounds with potential developmental toxicity, have been increasing. The CHARGE (CHildhood Autism Risks from Genetics and the Environment) Study is the first large-scale investigation of autism and autism spectrum disorders in which clinically confirmed cases are being compared with population-based controls in order to determine the environmental influences. By expanding the scope of the CHARGE study to include classes of compounds that have never been examined in relation to autism spectrum disorders, this supplement will accelerate the rate of discovery of modifiable factors contributing to the caseload, and will thereby bring us closer to public health interventions, which may occur at the individual or societal level, that can prevent autism in at least some children. This supplement will also address a major goal of the American Recovery and Reinvestment Act by the creation of 3.5 new jobs.