The Early Autism Risk Longitudinal Investigation (EARLI) Network will establish and prospectively follow a cohort of mothers of children with an autism spectrum disorder (ASD) at the start of a subsequent pregnancy (with select preconception data collection). This enriched-risk cohort will have the potential to serve as a study population for a variety of observational studies on the etiology and natural history of ASDs. The Network includes an Administrative Center at the Drexel University School of Public Health, a Data Coordinating Center at University of California Davis, a Central Laboratory and Repository at the Johns Hopkins School of Public Health, and four field sites: 1) Drexel University School of Public Health / Children's Hospital of Philadelphia; 2) University of California Davis / MIND Institute; 3) Johns Hopkins University School of Public Health / Kennedy Krieger Institute; and 4) Northern California Kaiser Permanente. The EARLI Network will implement a core epidemiologic data collection protocol focusing on: 1) prospective documentation of exogenous exposure during pregnancy and early life; 2) collection and banking of biologic samples during pregnancy and early-life, allowing measurement of exposure biomarkers, endogenous risk biomarkers, genotypes, and gene-expression profiles; and 3) follow-up of the newborn sibling through 36 months of age to gather data on ASD diagnoses, continuous ASD behavioral domains, and other potential behavioral endophenotypes. The goal is to have data on 1,000 siblings of ASD probands from fetal life through 36 months of age. This will allow sufficiently-powered estimation of associations among exposures and biomarkers measured during the pre-, peri-, and neonatal periods and ASD risk as well as candidate gene, gene-environment interaction, epigenetic, and maternally-mediated genetic effects. Full data collection in the target sample size will require additional five-years beyond the initial award period; however, by the end of the award the Network will have followed 875 pregnancies and completed 250 24-month follow-up visits. The attached application describes a plan for establishing the cohort and presents a set of exemplary specific aims to be partially addressed during the initial award period and more completely addressed once data collection is completed. Other types of specific aims that could be addressed through additional analyses of EARLI Network cohort data are highlighted.