Vitamin A Supplementation and Retinol Metabolism in the Neonatal Period

描述（由申请人提供）：出生时，肝脏和血浆中维生素A （VA，视黄醇）的浓度远低于年龄较大的儿童和营养充足的成年人。新生儿对VA的营养需求只能通过确定母乳中VA的摄入量来估计，但新生儿对VA的真正代谢需求尚不清楚。VA补充试验,大剂量交付丸出生后不久,正在进行在弗吉尼亚州的国家缺乏被认为是一个公共卫生问题来确定发病率和死亡率减少,然而没有VA代谢的生理模型来指导公共卫生专业人员和决策者在决定如果新生儿能够存储和保留大剂量的丸。补充VA与安慰剂的假设是,与单独使用VA相比，VA及其活性代谢物维甲酸（RA）的组合，VARA将改变新生儿的全身视黄醇动力学。目的是利用数学模型来检验VARA是否比VA更有效地将视黄醇引导到特定组织（肺和其他器官），以及产妇产后饮食VA是否会改变新生儿视黄醇代谢。目的还测试VA和VARA是否有利地影响氧治疗引起的肺部炎症反应，这通常是低出生体重婴儿所必需的。这些研究将对视黄醇的吸收、储存和利用，以及新生儿的分子因素和功能结局产生新的认识。该研究对了解新生儿视黄醇生理有重要意义；VA营养需求；将其转化为国际和国家公共卫生政策决定；并有可能转化为改善新生儿重症监护。

DESCRIPTION (provided by applicant): At birth, the concentrations of vitamin A (VA, retinol) in liver and plasma are much lower than in older children and well-fed adults. The VA nutritional requirement of the neonate has only been estimated by determining the amount of VA consumed in breast milk, but the neonate's true metabolic requirement for VA is not known. VA supplementation trials in which a large bolus dose is delivered soon after birth are being conducted in countries where VA deficiency is considered a public health problem to determine if morbidity and mortality are reduced, yet there is no physiological model of VA metabolism to help guide public health professionals and policy makers in deciding if neonates are able to store and retain a large bolus dose of VA. The hypothesis is that VA supplementation vs. placebo, and a combination of VA and its active metabolite retinoic acid (RA), VARA, compared to VA alone, will alter whole-body retinol kinetics in neonates. The aims make use of mathematical modeling to test whether VARA is more effective than VA in directing retinol into specific tissues (lungs, and other organs), and whether maternal postpartum dietary VA alters retinol metabolism in the neonate. The aims also test whether VA and VARA favorably affects the inflammatory response of the lungs caused by oxygen treatment, as is frequently necessary for low birth weight infants. These studies will generate new knowledge on the absorption, storage and utilization of retinol, together with molecular factors and functional outcomes in neonates. The research will be significant for understanding neonatal retinol physiology; VA nutritional requirements; for translation to international and national public health policy decisions; and potentially for translation to improved neonatal intensive care. PUBLIC HEALTH RELEVANCE: Statement The physiological requirement of neonates for vitamin A (VA, retinol) is unknown and no model exists of whole-body retinol metabolism for this age group. We will use isotopic tracer analysis and mathematical modeling to establish a kinetic model of retinol metabolism in neonatal rats, and correlate the results with molecular and functional indicators of lung maturation. The evidence from these studies will help to inform U.S. dietary recommendations for infants, international VA supplementation policy, and clinical treatment of neonatal lung disease.