NORTH CAROLINA BIRTH DEFECTS STUDY TO EVALUATE PREGNANCY EXPOSURES (NC BD-STEPS)

Project AbstractBirth defects are a leading cause of infant mortality, morbidity and healthcare costs in the United States, yetthe etiology of most birth defects remains unknown. Continued progress toward lessening the public healthimpact of birth defects can be facilitated by population-based epidemiologic research aimed at identifyingmodifiable lifestyle, environmental and genetic factors that contribute to the risk for specific birth defects. Since1996, the Centers for Birth Defects Research and Prevention (CBDRP) across the nation, funded by the CDC'sNational Center on Birth Defects and Developmental Disabilities, have collaborated on the National BirthDefects Prevention Study (NBDPS). The NBDPS was a population-based, multi-center case-control studywhich provided an unprecedented opportunity to assess the potential association between a variety ofmaternal exposures during early pregnancy and specific major, structural birth defects. Using the NBDPSresearch experience as a foundation from which to innovate, the new Birth Defects Study To EvaluatePregnancy exposureS (BD-STEPS) will delve further into several promising areas of birth defects researchthat have maximum potential for translation to birth defects prevention efforts. The North Carolina Center forBirth Defects Research and Prevention (NCCBDRP) was established in Fall 2002 and has been a majorcontributor to the collaborative data collection and research enterprise of the NBDPS. The NCCBDRP is acollaborative effort between the Department of Epidemiology at the University of North Carolina GillingsSchool of Global Public Health in Chapel Hill, NC (UNC), and the North Carolina Birth Defects MonitoringProgram (NCBDMP) at the North Carolina Division of Public Health in Raleigh, NC. The NCCBDRP hasestablished an outstanding and unique infrastructure to implement the BD-STEPS protocol and to conduct highquality epidemiologic and other research focused on the causes and prevention of birth defects. We haveassembled an impressive team of investigators and staff to contribute to the national study design, contributescientifically defensible and high quality data and specimen collection, and provide scientific oversight.Historically, the NCCBDRP has provided critical assistance and leadership to the NBDPS in many areasincluding epidemiology, biostatistics, method development and pilot design, genetics, study conduct, andquality control for interviewing and laboratory procedures. We are very well positioned to implement the newBD-STEPS protocol as well as to conduct innovative and collaborative research.The purpose of BD-STEPS is to identify modifiable maternal exposures in early pregnancy that mayincrease the risk for having a pregnancy affected by certain major, structural birth defects. The specificaims of the NCCBDRP are to (1) Implement the standardized BD-STEPS protocol as the NC BD-STEPS,including (a) use the NC birth defects surveillance system to identify 244 cases (among livebirths, stillbirthsand induced abortions) in the study area each year with one or more of the 17 birth defects included in thestudy protocol; (b) identify a random sample of 96 control infants per year using birth certificates; (c) conductclinical review for case classification and confirmation using abstracted medical records and otherinformation;(d) conduct all advance and follow-up mailings to potential participants including kits for self-collection of saliva, and provide contact information to the central interviewing agency; (e) obtain consent fromparticipants to abstract medical records; and (f) obtain residual newborn blood spots from the North CarolinaState Laboratory. (2) Provide substantive expertise for the innovative design of BD-STEPS interview questions,survey methods and novel study instruments including targeted online modules related to early pregnancyexposures such as diet, obesity, physical activity, infertility, occupation and chronic medical conditions; (3)Develop innovative study questions and proposals using BD-STEPS and NBDPS data to identify modifiablerisk factors for birth defects with maximum potential for public health impact, analyze genetic factors, conductrigorous analyses, present findings at national meetings, and publish at least 10 papers during the 5-yearaward period; (4) Provide expertise on epidemiologic and biostatistical methods such as bias analysis, missingdata, correlated exposures, pooled samples, approaches for the analysis of gene sets, multiple SNPs,haplotypes, GWAS and epigenetics; (5) Conduct innovative laboratory research to develop innovative methodsfor using dried blood spots to investigate potential risk factors for birth defects including toxic metals and otherexposures; (6) Participate in collaborative activities and research initiatives with other CBDRP and the CDC;and (7) Continue to train junior researchers in the field of birth defects epidemiology. By including multiplestudy sites, BD-STEPS will aim for a study population that is representative of the US population inracial/ethnic composition. The project period is anticipated to be 8/1/2013 - 7/31/2018.