In the U.S., major birth defects impact the morbidity and mortality of tens of thousands of children annually. An environmental exposure (broadly defined) or causal gene variant is estimated to explain only about one-third of all major defects that occur. Since 1996, the Iowa Center for Birth Defects Research and Prevention (CBDRP) has played a leadership role in surveillance and research of major birth defects. Our partnership with the Iowa Registry for Congenital and Inherited Disorders provides timely and comprehensive active surveillance of each in-state delivery. Our partnership with the Iowa Department of Public Health provides outreach to families in all 99 Iowa counties. These partnerships have also allowed us to successfully enroll mothers in the National Birth Defects Prevention Study (NBDPS) and related studies to collect environmental exposure and biological data. Using these data, we have made substantial contributions to birth defects epidemiology, ranging from methods development to identification of gene-environmental interaction effects. This work has provided critical insights into the etiology of several major birth defects and has been disseminated in high-impact journals. We propose to expand the work of the Iowa CBDRP through successful participation in the Birth Defects Study To Evaluate Pregnancy Exposures (BD-STEPS). Our overall goal is to identify modifiable maternal exposures in early pregnancy that may increase the risk for having a pregnancy affected by certain major, structural birth defects. We will conduct comprehensive and timely data collection and reporting for the BD-STEPS using our established and experienced surveillance and research infrastructure. We will also extend interdisciplinary collaborations to national and international scientists to increase dissemination of NBDPS and BD-STEPS findings in high-impact, peer-reviewed journals. Our proposed research activities will use a """"""""scaffold"""""""" approach for risk factor identification, by simultaneously examining environmental exposures and gene variants from """"""""discovery"""""""" to """"""""confirmation"""""""" to """"""""interaction."""""""" In particular, we will continue our high-impact etiological studie of orofacial clefts and craniosynostosis, and expand them to additional craniofacial and musculoskeletal defects. NBDPS and BD-STEPS data, along with those from independent populations provided by our collaborators, will offer rich resources for analyses of environmental exposures, genes, and gene-environmental interaction effects. Additionally, we will continue our leadership role and expand our training program to develop junior investigators in birth defects research. Along with pre-doctoral students, we will train clinical and research post- doctoral scholars in interdisciplinary team science for birth defects research. This research will encompass methodological, etiological, and translational studies. With our scientific expertise and highly experienced infrastructure, we are well-positioned to successfully complete our proposed research and training. Research findings generated will be used for family education, improvements in treatment, and application of prevention strategies and training activities will contribute to the next generation of birth defect researchers.

Public Health Relevance

The Iowa Center for Birth Defects Research and Prevention, in collaboration with premier scientists locally, nationally, and internationally, will extend and expand its leadership role in the investigation of environmental exposures, genes, and their potential interaction effects for major birth defects. This research will provide important insights into our understanding of modifiable factors to prevent or reduce the adverse consequences of major birth defects. Findings will be shared with other scientists and with professionals developing appropriate prevention interventions and resources for families affected by major birth defects.

National Institute of Health (NIH)
Centers for Disease Control and Prevention (NCBDD)
Research Project--Cooperative Agreements (U01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDD1-EEO (01))
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Iowa
Public Health & Prev Medicine
Schools of Public Health
Iowa City
United States
Zip Code
Carter, Tonia C; Sicko, Robert J; Kay, Denise M et al. (2017) Copy-number variants and candidate gene mutations in isolated split hand/foot malformation. J Hum Genet 62:877-884
Moreno Uribe, L M; Fomina, T; Munger, R G et al. (2017) A Population-Based Study of Effects of Genetic Loci on Orofacial Clefts. J Dent Res 96:1322-1329
Keppler-Noreuil, Kim M; Conway, Kristin M; Shen, Dereck et al. (2017) Clinical and risk factor analysis of cloacal defects in the National Birth Defects Prevention Study. Am J Med Genet A 173:2873-2885
Kummet, Colleen M; Moreno, Lina M; Wilcox, Allen J et al. (2016) Passive Smoke Exposure as a Risk Factor for Oral Clefts-A Large International Population-Based Study. Am J Epidemiol 183:834-41
DeRoo, Lisa A; Wilcox, Allen J; Lie, Rolv T et al. (2016) Maternal alcohol binge-drinking in the first trimester and the risk of orofacial clefts in offspring: a large population-based pooling study. Eur J Epidemiol 31:1021-1034
Rocheleau, Carissa M; Bertke, Stephen J; Lawson, Christina C et al. (2015) Maternal occupational pesticide exposure and risk of congenital heart defects in the National Birth Defects Prevention Study. Birth Defects Res A Clin Mol Teratol 103:823-33
Zhu, Yong; Romitti, Paul A; Caspers Conway, Kristin M et al. (2015) Maternal periconceptional alcohol consumption and congenital heart defects. Birth Defects Res A Clin Mol Teratol 103:617-29
Kancherla, Vijaya; Romitti, Paul A; Sun, Lixian et al. (2014) Descriptive and risk factor analysis for choanal atresia: The National Birth Defects Prevention Study, 1997-2007. Eur J Med Genet 57:220-9
Caspers Conway, Kristin M; Romitti, Paul A; Holmes, Lewis et al. (2014) Maternal periconceptional alcohol consumption and congenital limb deficiencies. Birth Defects Res A Clin Mol Teratol 100:863-76
Makelarski, Jennifer A; Romitti, Paul A; Rocheleau, Carissa M et al. (2014) Maternal periconceptional occupational pesticide exposure and neural tube defects. Birth Defects Res A Clin Mol Teratol 100:877-86