PROJECT SUMMARY Autism Spectrum Disorder (ASD) risk is primarily of genetic origins with an estimated heritability of 80% but non-heritable factors are also important in understanding the underlying etiology. One source through which environmental effects may be influential is preterm birth (birth before 37 weeks gestation) which constitutes 10% of all births in the US. The etiology of preterm birth is primarily of environmental origin, usually due to disease in the pregnant woman or her fetus. The processes underlying preterm birth may initiate the development of ASD. This hypothesis has not been previously studied, and if true the heritability of ASD may be lower in children born preterm, and before the optimal gestational age for delivery at week 39 to 40, suggesting that children born preterm define a subset of the general population where environmental risk plays a larger role for ASD risk. The goal of this project is to examine the etiology of ASD in children born preterm and to determine if the etiology is different compared to term-born children, and across gestational age; to identify risk factors for ASD in PTB children, compared to term born, and to estimate the public health consequences of these risk factors, how much can be attributed to confounding factors instead of the risk factors per se and if there are differences in genetic architecture. To achieve this goal, we will create a prospective cohort of all children born in Sweden and Finland 1996 to 2020 followed for clinical diagnosis of ASD, and link information from Swedish and Finnish National registers until the end of 2024. We will replicate analyses in a sample from California and examine genetic markers in two large genetic databases for ASD research. In Aim 1 we will determine the epidemiology of ASD in children born preterm, and characterize the risk factors for these children. Aim 2 will estimate population measures of risk (heritability and proportion susceptible) and estimate public health consequences of the risk factors from aim 1 by calculating the proportion attributable fractions for the risk factors. Aim 3 will replicate the analyses in aim 1&2 in a similar database from California. Aim 4 will test if the genetic architecture of ASD differs in preterm and term-born children.