The Role of Maternal Nutrition in the Teratogenesis of Alcohol in Humans

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DESCRIPTION (provided by applicant): This application for a K23 Mentored Patient-Oriented Research Career Development Award details a 5-year plan for training and research activities that will provide the skills and experience I need to achieve success as an independent investigator studying the roles of nutrition in fetal alcohol spectrum disorder (FASD). I am currently in my final academic year of a research fellowship in the Scholars in Clinical Science Program at Harvard Medical School and a clinical fellowship in Pediatric Emergency Medicine at Children's Hospital Boston, where I will begin a faculty position at the start of the proposed funding period. This K23 award will provide me with the support necessary to accomplish the following goals: (1) to assess the nutritional status of heavy drinking pregnant; (2) to examine the impact of maternal nutritional status on fetal alcohol-related growth restriction; (3) to gain expertise in nutritional physiology and alcohol-related teratology that will prepare me to conduct studies examining the roles of pre- and postnatal nutrition in FASD; and finally (4) to gain expertise in planning and executing pediatric patient-oriented research, and thereby develop an independent research career. To achieve these goals, I have assembled a mentoring team comprised of a primary mentor, Christopher Duggan, MD, Director of Clinical Research in the Division of Gastroenterology and Nutrition at Children's Hospital Boston, who conducts research in the fields of pediatric nutrition, gastroenterology, and global child health; and co-mentor Sandra Jacobson, PhD, Professor of Psychiatry and Behavioral Neurosciences at Wayne State University School of Medicine, who has expertise in examining the developmental effects of in utero exposure to neurotoxic agents, most notably alcohol and polychlorinated biphenyls (PCBs). Although it has been widely postulated that maternal nutritional status may interact with prenatal alcohol exposure in FASD, to our knowledge, there have been no published studies in humans examining the nutritional status of heavy drinking pregnant woman or the impact of their nutritional status on the teratogenesis of alcohol. The studies proposed here are designed to test the hypotheses that the nutritional status of heavy drinking pregnant women is poorer than that of women who abstain and that poor maternal nutritional status exacerbates alcohol-related prenatal growth restriction. I will use the resources available to me at Children's Hospital Boston, Harvard Medical School, the Harvard School of Public Health and the University of Cape Town to add these studies to a previously planned, NIH-funded prospective cohort study of heavy drinking pregnant women and abstainers/light-drinkers, focusing on 3 nutritional domains: 1) energy intake and gestational weight gain; 2) iron status; 3) methyl donor status (folate, vitamin B12, choline). These research activities in combination with structured coursework and didactics will give me the training, skills, and hands-on experience needed to develop into an independent investigator with an ongoing research program examining the potential roles of pre- and postnatal nutrition in FASD. PUBLIC HEALTH RELEVANCE: Prenatal alcohol exposure has been associated with intrauterine growth restriction and neurodevelopmental deficits that persist postnatally. Animal models of fetal alcohol spectrum disorder (FASD) have demonstrated important roles for maternal nutrition in the teratogenesis of alcohol, but the nutritional status of heavy drinking pregnant women and the impact of their nutritional status on FASD-related outcomes remain largely unstudied. Examination of specific nutritional indicators in heavy drinking pregnant women and how these measures of nutritional status affect alcohol-related reductions in birthweight will further our understanding of the role of maternal nutrition in FASD, which may ultimately contribute to the development and testing of nutritional interventions aimed at mitigating the teratogenic effects of alcohol.