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ABI Research Summaries - Charlotte A. Hobbs, MD, PhD Dr. Hobbs is the Director of the Arkansas Center for Birth Defects Research and Prevention, which was established in 1997, through a cooperative agreement with the Centers for Disease Control and Prevention. The mission of the Center is to reduce the prevalence and impact of birth defects on a state and national level. Activities include surveillance of birth defects in Arkansas, and participation in the National Birth Defects Prevention Study, the National Down Syndrome Study, and locally initiated genetic epidemiologic research studies. Dr. Hobbs' research focus areas include:
National Birth Defects Prevention Study. The primary goal of this case-control study, led by the Centers for Disease Control & Prevention, is to provide a collaborative database from which research studies on the causes and preventive factors of birth defects can be conducted. Eight birth defect Centers across the country contribute data from maternal interviews and clinical information from women with pregnancies affected by major structural birth defects, and control subjects with healthy pregnancies. Each year, 300 Arkansas women with pregnancies affected by 1 of 30 birth defects and 100 women with healthy pregnancies are enrolled in the National Birth Defects Prevention Study. Biological samples are obtained from each participant, infant and father, and maternal interviews are conducted. This unique study provides unprecedented power to test hypotheses posed by each Center regarding the etiology of birth defects. Genes, Micronutrients and Homeobox-related Malformations. Funded in 2000 by the National Institute of Child Health and Human Development, this project utilizes the infrastructure of the National Birth Defects Prevention Study, and is focused specifically on cases of neural tube defects and congenital heart defects. Experimental data support the hypothesis that disturbances in normal folate metabolism during critical phases of early embryogenesis promote errors in gene expression and cell differentiation that result in tissue-specific malformations. The aims of the study are to define: (a) the gene-nutrient interactions that may increase susceptibility to neural tube and congenital heart defects; (b) specific biochemical and molecular biomarkers of maternal micronutrients and their interactions with genetic polymorphisms involved in the folate metabolic pathway; and c) genetic alterations in homeobox genes associated with these defects and potential interaction with maternal genetic and micronutrient status. Trisomy 21: Risk Factors for Chromosome Nondisjunction-- Down Syndrome Study. The Arkansas Center is a collaborator in this multi-center project funded by the National Institute of Child Health and Human Development, and led by researchers at Emory University. The Arkansas Center collects buccal cell samples and pregnancy health and exposure data from families with and without Down syndrome-affected infants. The aims are to explore (1) the relationship of altered recombination and maternal age; (2) the importance of variations in genome-wide recombination; (3) the role of recombination in paternal nondisjunction; and (4) environmental and maternal risk factors for nondisjunction and for Down syndrome-associated birth defects. Preventive Health Behaviors of Reproductive-aged Women. This study assesses the impact of physician advice on women's regular intake of folic acid for prevention of neural tube defects. Many women report that they are aware of the benefits of folic acid, but they are hesitant to take folic acid supplements unless told to do so by a physician. This randomized trial tests the efficacy of a brief consultation by a physician or nurse about the benefits of folic acid. This study will assess whether a very brief amount of provider time can result in considerable reduction in the risk of a preventable birth defect. Data analyses for this study are complete and a manuscript is in preparation. Membrane Signaling Defects and Diabetic Embryopathy. Hyperglycemia-induced embryonic dysmorphogenesis has been studied for decades. However, no exact mechanism to explain this particular embryopathy has been published. Data from previous in vivo studies has shown that hyperglycemia insults yolk sac membranes during organogenesis. However, supplementation of inositol, safflower oil, or vitamin E to diabetic pregnant rats can reduce dysmorphogenesis to various degrees, acting through altered membrane signal transduction. Led by Dr. Reece, the goal of this study is to define the membrane signaling mechanisms involved in hyperglycemia-induced embryonic dysmorphogenesis. Selected Publications: Hobbs CA, Cleves MA, Simmons CJ. Genetic epidemiology and congenital malformations: From the chromosome to the crib. Archives of Pediatric and Adolescent Medicine Vol. 156(4):315-320; 2002. Hobbs CA, Cleves MA, Lauer RM, Burns TL, James SJ. Preferential Transmission of the MTHFR 677 T Allele to Infants with Down syndrome: Implications for a survival advantage. American Journal of Medical Genetics 113:9-14. 2002 Yoon PW, Rasmussen SA, Lynberg MC, Moore CA, Anderka M, Carmichael SL, Costa P, Druschel C, Hobbs CA, Romitti P, Langlois P, Edmonds LD, and The National Birth Defects Prevention Study. The National Birth Defects Prevention Study: Methods. Public Health Reports, 116 (Suppl. 1):32-40; 2001. Tilford JM, Robbins JM, Hobbs CA. Improving estimates of caregiver time cost and family burden associated with birth defects. Teratology, 64(S1):37-41; 2001. Hobbs CA, Sherman SL, Yi P, Hopkins SE, Torfs CP, Hine RJ, Pogribna M, Rozen R, James SJ. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. American Journal of Human Genetics, 67:623-630; 2000. Contact Information Charlotte A. Hobbs, MD, PhD Arkansas Center for Birth Defects Research and Prevention |