Vitamin A Supplementation and Retinol Metabolism in the Neonatal Period

描述(申请人提供)：出生时，肝脏和血浆中的维生素A(VA、视黄醇)浓度比年龄较大的儿童和喂养良好的成年人低得多。新生儿的VA营养需要量只能通过测定母乳中VA的消耗量来估计，但新生儿对VA的真实代谢需求尚不清楚。在VA缺乏被认为是公共健康问题的国家，正在进行VA补充试验，在这些国家，VA缺乏被认为是一个公共卫生问题，以确定是否降低了发病率和死亡率，但还没有VA代谢的生理模型来帮助指导公共卫生专业人员和政策制定者决定新生儿是否能够储存和保留大剂量VA。假设补充维生素A与安慰剂相比，与单独补充维生素A相比，维生素A及其活性代谢物维甲酸(RA)和VARA的组合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测试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)，以及母亲产后饮食VA是否改变了新生儿的视黄醇代谢。AIMS还测试VA和VARA是否有利地影响氧气治疗引起的肺部炎症反应，这是低出生体重婴儿经常需要的。这些研究将产生关于视黄醇的吸收、储存和利用的新知识，以及新生儿的分子因素和功能结果。这项研究将对了解新生儿视黄醇生理学；VA营养需求；转化为国际和国家公共卫生政策决策；以及潜在地转化为改善新生儿重症监护具有重要意义。 公共卫生相关性：声明新生儿对维生素A(VA、视黄醇)的生理需求尚不清楚，该年龄段的全身视黄醇代谢模型尚不存在。我们将使用同位素示踪分析和数学模型来建立新生大鼠视黄醇代谢的动力学模型，并将结果与肺成熟的分子和功能指标相关联。来自这些研究的证据将有助于为美国对婴儿的饮食建议、国际VA补充政策和新生儿肺部疾病的临床治疗提供参考。

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.