Project Abstract Component A: BD-STEPS Core at the NC Center for Birth Defects Research and Prevention Birth defects are a leading cause of infant mortality and childhood morbidity, yet the etiology of most cases is unknown. Established in 2002 with funding from the CDC, the North Carolina Center for Birth Defects Research and Prevention (NCCBDRP) has been a major contributor to the National Birth Defects Prevention Study (NBDPS) and Birth Defects Study To Evaluate Pregnancy exposureS (BD-STEPS). The next phase of BD-STEPS will continue to build on these important multi-site, population-based case-control studies to identify novel epidemiologic and genetic risk factors for major structural birth defects that can be translated into prevention strategies. The NCCBDRP's Specific Aims are to (1) Implement the BD-STEPS Core protocol in North Carolina including: (a) Utilize the existing state-wide, population-based birth defects surveillance system in NC to actively ascertain at least 150 cases per year among livebirths, stillbirths and elective abortions with a study-eligible birth defect in the demographically diverse 33-county study area; (b) Utilize birth certificates to identify an eligible population-based sample of approximately 100 control infants per year born in the same study area; (c) Conduct clinical case review and classification by clinical geneticist and pediatric cardiologist using abstracted medical records; (d) Partner with CDC's central interviewing contractor to facilitate NC participation in the core interview and online occupational survey; (e) Conduct supplemental data collection about reportable infections before and during pregnancy; (f) Conduct supplemental biospecimen collection of residual newborn blood spots; (2) Establish a unique data resource for investigating prescription medication use during pregnancy and birth defects by linking BD-STEPS and NBDPS participants in NC with health insurance claims records from NC Medicaid and Blue Cross Blue Shield NC; (3) Establish a unique biospecimen resource for investigating prenatal environmental exposures and birth defects by collecting shed deciduous teeth from BD-STEPS and NBDPS participants in NC; (4) Leverage the NCCBDRP's well- established group of investigators and collaborators to develop innovative, high-impact studies with BD-STEPS and NBDPS data on genetics, epigenetics, and gene-exposure interactions associated with birth defects, and epidemiologic risk factors for birth defects including medication use during pregnancy, maternal chronic and infectious disease, and key social determinants of health such as individual- and neighborhood-level socioeconomic factors, acculturation, employment and workplace conditions, and environmental factors; (5) Produce at least seven NC-led manuscripts for publication in high-impact journals using pooled data from BD- STEPS and/or NBDPS during the 3.5-year award period; and (6) Continue our long-standing, successful training program i...