Autism spectrum disorders (ASD, which include autism, Asperger syndrome, and pervasive developmental disorder not-otherwise-specified), are a growing public health concern; autism is currently the sixth most commonly classified disability in the United States, and an estimated 6 in 1,000 children have an ASD. Reports of increasing prevalence of ASD have fueled concerns regarding the risk factors and etiology of these debilitating developmental disorders. Although there is ample evidence implicating a strong genetic component, specific genes remain elusive, and evidence is accumulating that environmental factors are etiologically important. In 2005, participants in the Nurses' Health Study II (NHS II) cohort, a large United States national sample, were asked to report whether they had any children with an ASD. Approximately 800 women with biological children responded affirmatively to this question. The NHS II has a wealth of data on maternal factors collected prospectively and without any relationship to the child's condition, making it an attractive sample for a study of ASD. We will use information from biennial questionnaires, as well as follow-up questionnaires, to compare 700 cases and 1,400 controls matched on child's age and gender for maternal risk factors. With the wealth of information on reproductive factors collected in the NHS II sample, we will be able to address the debate over the role of obstetric complications in relationship to ASD. In addition, our group's expertise in dietary and lifestyle risk factors for neurological conditions will be useful in novel analyses of potential risk factors for ASD within this sample. This investigation of maternal dietary factors will be an innovative direction for the field of autism research and is supported by growing evidence of the role of dietary factors in the etiology of other psychiatric disorders. Finally, availability and continued collection of biosamples allows investigation of both environmental toxins as well as genetic factors in this sample. We anticipate the results of our study will have the following impacts: A better understanding of how demographic and reproductive factors may affect risk could influence obstetric practice. Investigating maternal dietary factors could reveal as yet unidentified risk factors for ASD, thereby guiding future research and potentially impacting public health recommendations for nutrition of women of child-bearing age. Replicating and expanding on the results of previous studies, including a recent air pollution study, as well as a recent whole genome association study, could advance the field by confirming one or more risk factors in a large national sample. Understanding biological risk factors, including genetic factors, involved in the disorder will clarify disease etiology, and, in turn, lead to more effective treatments. Ultimately, our aims are to determine whether modifiable risk factors for ASD can be identified so that incidence and/or severity may be reduced.