Autism and spectrum disorders (ASD) are serious and debilitating neurodevelopmental disorders that incursubstantial suffering for patients and major challenges to our health care system. It is now estimated that ASDaffects about 1 in 68 children, with a male:female ratio of 4:1. Both genetic and environmental factorscontribute to ASD, but environmental factors have been understudied. Because environmental factors arepotentially modifiable they should be a research priority. This effort has been hampered by the challenges ofacquiring accurate and relevant exposure measures in large, unbiased, epidemiologic cohorts.Among the many environmental exposures to which humans are exposed, endocrine disrupting chemicals(EDs) have perhaps the best-known effects on neurodevelopment in pediatric populations. Several of thesechemicals, particularly when exposure is prenatal, have been linked to autism-related phenotypes, and sex-differences in these associations have been documented. EDs have been shown to affect GABA andglutamate neurotransmission, which have prominent roles in ASD. Therefore, EDs are promising candidates asenvironmental triggers for ASD. To our knowledge, no prior study has been able to robustly link prenatal EDexposure to ASD.The goal of this application is to determine whether prenatal exposure to five classes of EDs impacts ASD risk.To achieve this, we will use stored samples from a serum biobank in southern Sweden and link these topopulation-based registries that include individual-level perinatal, diagnostic, medical, and demographicinformation (117,318 births in the years 1998-2007). We will randomly select and validate 600 ASD cases(oversampling females to include 200 females, 400 males) and 600 controls with similar sex and birth yeardistributions. By measuring concentrations of 38 EDs in five chemical classes in maternal serum samples wewill address the following three integrated specific aims: First, determine the associations between ASD riskand prenatal serum concentration of our target EDs and their mixtures; Second, determine whether gendermodifies sensitivity to prenatal ED exposure resulting in sex-dimorphic ED-ASD associations; Third, determinewhether concentrations of EDs, singly and in combination, contribute to differences in ASD phenotype andtheir severity.
Interagency Autism Coordinating Committee (IACC)
Autism Research Database (AFD)
