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

描述（由申请人提供）：K23指导患者导向研究职业发展奖的申请详细说明了培训和研究活动的5年计划，这将提供我作为一名独立研究者成功研究营养在胎儿酒精谱系障碍（FASD）中的作用所需的技能和经验。目前是我在哈佛医学院临床科学项目的研究奖学金的最后一个学年，也是波士顿儿童医院儿科急诊医学的临床奖学金的最后一个学年，我将在拟议的资助期开始时开始担任教职。这个K23奖将为我实现以下目标提供必要的支持：(1)评估重度饮酒孕妇的营养状况；(2)探讨母体营养状况对胎儿酒精相关性生长受限的影响；(3)获得营养生理学和酒精相关致畸学方面的专业知识，这将为我进行产前和产后营养在FASD中的作用的研究做准备；最后(4)获得规划和执行儿科患者导向研究的专业知识，从而发展独立的研究事业。为了实现这些目标，我组建了一个指导团队，其中包括一位主要导师Christopher Duggan，医学博士，波士顿儿童医院胃肠病学和营养科临床研究主任，他在儿科营养、胃肠病学和全球儿童健康领域进行研究；和共同导师桑德拉·雅各布森博士，韦恩州立大学医学院精神病学和行为神经科学教授，她在检查子宫内暴露于神经毒性物质（尤其是酒精和多氯联苯）对发育的影响方面具有专业知识。尽管人们普遍认为，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，还没有发表过关于重度饮酒孕妇的营养状况或营养状况对酒精致畸的影响的人类研究。本文提出的研究旨在验证以下假设：重度饮酒孕妇的营养状况比不饮酒孕妇差，孕妇营养状况差加剧了与酒精相关的产前生长限制。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提供给我的资源，将这些研究添加到先前计划的、由美国国立卫生研究院资助的、针对重度饮酒孕妇和戒酒者/轻度饮酒者的前瞻性队列研究中，重点关注3个营养领域：1)能量摄入和妊娠期体重增加；2)铁态；3)甲基供体状态（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，将为我提供培训、技能和实践经验，使我成为一名独立的研究者，并开展一项正在进行的研究项目，研究产前和产后营养在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.