Project Summary Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder that impacts approximately 1.5% of children in the United States. Individuals with ASD experience deficits in social communication or restricted interests and repetitive behavior; but the severity and patterns vary greatly and convey lifelong impairment for some. It is unclear how the presentation of ASD changes from early childhood into adolescence or adulthood. The causes of ASD are also unknown, though substantial evidence supports the contribution of both genes and environmental factors. These gaps in knowledge exist because US studies to date have lacked the sample size, depth of data collection, or appropriate life course timing to address these questions. The Study to Explore Early Development (SEED) is now able to address these prior limitations. SEED is a large case- control study of children ages 2-5 years and their families, implemented across eight states over three phases. SEED collected detailed data on children's core ASD symptoms, cognitive status, and presence of co- occurring conditions in early childhood, along with extensive risk factors related to maternal health and the perinatal environment as well as genomics. The SEED sample includes 2044 children with ASD, 1950 children with non-ASD developmental disabilities (DD), and 2285 population control children (POP), making this the largest etiologic study of ASD in the US. Recent ancillary studies - the SEED Teen Pilot and SEED COVID studies -- will soon add data on adolescent health and the consequences of the pandemic, respectively, for some SEED participants. The work proposed here, SEED Follow-up Studies (SEED FU), will maximize the impact of extant SEED data through analyses that characterize ASD phenotypes and assess the potential interplay between genetic and modifiable risk factors. SEED FU will also facilitate new data collection in middle childhood, adolescence and early adulthood to characterize changes in ASD phenotype across developmental stages, and the associated health, educational, and service needs across the early life course. These data will further enable prospective analyses of associations between early life factors and later childhood through early adulthood outcomes. Studying risk factors in relation to life course phenotypic subgroups may also help elucidate etiologies previously masked in ASD case-control studies. The MO SEED Team in combination with the SEED Network's collaborative infrastructure and extensive extant data resources, will ensure the successful implementation of the SEED FU Study in Missouri and contribute to success across the network. SEED is well-powered for making significant contributions to our understanding of the complex autism phenotype and identifying factors associated with ASD risk in the population. The knowledge gained by SEED FU will greatly advance our ability prevent adverse developmental outcomes and to support individuals with ASD and their families to ensure optimal wellbeing through early adulthood.

Project Narrative This study will shed light on a wide variety of genetic, prenatal, early-life and family factors that influence the risk for autism spectrum disorder (ASD) and on differences and similarities in the behaviors, abilities, and health of preschoolers with ASD. It will also provide insights into the experiences of adolescents with ASD as they mature. By helping to explain the causes of ASD and how ASD affects children, youth and young adults, this project will contribute to efforts to reduce the risk of ASD and improve the outcomes of affected children.