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

描述(由申请人提供)：此K23指导患者导向研究职业发展奖的申请详细说明了一项为期5年的培训和研究活动计划，该计划将提供我作为一名独立研究人员取得成功所需的技能和经验，研究营养在胎儿酒精谱系障碍(FASD)中的作用。我目前是哈佛医学院临床科学学者项目研究奖学金的最后一个学年，以及波士顿儿童医院儿科急诊医学临床奖学金的最后一个学年，在那里我将在拟议的资助期开始时担任教职。这个K23奖项将为我提供必要的支持，以实现下列目标：(1)评估重度饮酒孕妇的营养状况；(2)检查母亲营养状况对胎儿酒精相关生长受限的影响；(3)获得营养生理学和酒精相关畸胎学方面的专业知识，以便进行研究探讨产前和产后营养在FASD中的作用；以及(4)获得计划和实施以患者为导向的儿科研究的专业知识，从而发展独立的研究事业。为了实现这些目标，我组建了一个辅导团队，成员包括：波士顿儿童医院胃肠病和营养科临床研究总监Christopher Duggan医学博士，他从事儿科营养、胃肠病学和全球儿童健康领域的研究；以及共同导师Sandra Jacobson博士，他是韦恩州立大学医学院精神病学和行为神经科学教授，他在研究子宫内暴露于神经有毒物质，主要是酒精和多氯联苯(PCbs)的发育影响方面具有专长。虽然人们普遍认为孕妇的营养状况可能与FASD的产前酒精暴露相互作用，但据我们所知，还没有发表过关于大量饮酒孕妇的营养状况或她们的营养状况对酒精致畸的影响的人体研究。这里提出的研究旨在检验这样的假设，即大量饮酒的孕妇的营养状况比戒酒的孕妇差，而糟糕的母亲营养状况加剧了与酒精相关的产前生长受限。我将利用波士顿儿童医院、哈佛医学院、哈佛公共卫生学院和开普敦大学现有的资源，将这些研究添加到先前计划的、由NIH资助的针对大量饮酒的孕妇和戒酒者/少量饮酒者的前瞻性队列研究中，重点关注3个营养领域：1)能量摄入和妊娠体重增加；2)铁状况；3)甲基捐赠者状况(叶酸、维生素B12、胆碱)。这些研究活动与结构化的课程和教学相结合，将为我提供所需的培训、技能和实践经验，使我能够发展成为一名独立调查员，并正在进行一项研究计划，探讨产前和产后营养在FASD中的潜在作用。

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.