PROJECT SUMMARY/ABSTRACT Three percent of liveborn babies in the US have a major structural birth defect. The emotional, psychological and economic impact of birth defects on families, society and the healthcare system is significant. Inpatient hospitalization costs associated with birth defects for children and adults with birth defects in the US in 2013 was $22.9 billion, which was 3% of all hospitalizations and 5% of total hospital costs. Children who survive infancy with a major birth defect have a high risk of other chronic short- and long-term health conditions and diminished quality of life. Although birth defects pose a significant public health challenge, public heath efforts to prevent most birth defects are limited. About 70% of cases of birth defects have unknown causes but are thought to arise from complex interactions between environmental and genetic factors. Thus, studies are needed to identify risk factors that can be modified to ultimately prevent birth defects. The long-term goal of our research is to determine the etiology birth defects and long-term health effects of teratogens and birth defects on maternal, and child health and development. The overall objective of this proposal is to elucidate the multifactorial etiology of structural birth defects. The rationale for this project is that the Centers for Disease Control and Prevention launched 2 multisite, population-based, case-control studies, the National Birth Defects Prevention Study (NBDPS), which ended in 2013 and the Birth Defects STudy to Evaluate Pregnancy exposureS (BD-STEPS) which began in 2014. The Arkansas Center for Birth Defects Research and Prevention, a site in the NBDPS for 16 years and a site in BD STEPS for 9 years, proposes to attain the objective through 4 specific aims: (1) identify and characterize pregnancies affected by specific birth defects and livebirths without major birth defects to participate as a Center in BD-STEPS; (2) conduct collaborative and local epidemiologic studies using NBDPS, BD-STEPS, and other data sources to identify potentially modifiable risk factors for specific birth defects; (3) conduct collaborative and local genetic and epigenetic studies using genetic data from the NBDPS, BD-STEPS, and other sources to identify genetic or gene-environment factors associated with birth defects; and (4) train and mentor the next generation of research scientists in birth defects epidemiology, implementation, conduct and analysis of population-based research. Our statewide population-based birth defects registry, sole academic health center, sole tertiary pediatric hospital, central health department and diverse high-risk population of reproductive age women, make Arkansas an ideal site for BD-STEPS. Through our continued participation in BD-STEPS, we will maintain a leading role in identifying modifiable risk factors that can be used to develop public health strategies to prevent birth defects.