In this proposal, which is a renewal of a previously funded award, we will investigate maternal environmental factors during pregnancy and risk of childhood autism in the offspring from a national birth cohort in Finland (the Finnish Prenatal Study of Autism, FiPS-A). No previous study of autism has ever examined the proposed prenatal factors by maternal biomarkers and their relationship to perinatal complications and growth velocity of the child's head circumference during infancy. The putative risk factors include environmental toxins (including PCBs and insecticides) and infections (influenza and Chlamydia trachomatis). We aim to address these questions in pregnancies of a large sample of autism cases and matched controls using maternal serum samples that were drawn and stored in nearly all pregnancies in Finland over the course of the study. The children with autism and their matched controls have been identified from detailed databases that contain diagnoses on nearly all cases of autism in Finland. These subjects have been linked to the maternal serum samples and to other registries including data on perinatal complications. In this study, the maternal serum samples of autism cases and of matched controls will be analyzed for these environmental factors, and their occurrence during pregnancy will be compared between the cases and controls. We shall also test whether these maternal environmental factors during pregnancy are related to a select number of other pregnancy and birth complications and to abnormalities in the velocity of head circumference during infancy. This research has the potential to result in a better understanding of potential risk factors for autism and of convergen, as well as divergent, developmental pathways that lead to the illness. Since the risk factors investigated in this study are relatively common in the population, their discovery may lead to prevention of cases of autism by straightforward public measures in pregnant women, including reduction of exposure to environmental contaminants, and prevention of infections, such as influenza and sexually transmitted diseases during pregnancy. These studies could also result in an improved understanding of the mechanisms by which prenatal insults alter postnatal brain development in autism and, along with other measures, potentially target infants at high risk for the disorder for intervention. In summary, the proposed work builds on an existing national birth cohort, and is anticipated to have considerable impact on an emerging and potentially transformative area of research epidemiology and clinical/basic neuroscience, as well as lead to improvements in current public health policy recommendations for care during pregnancy.