Vitamin A Supplementation and Retinol Metabolism in the Neonatal Period

新生儿期维生素A的补充和视黄醇的代谢

• 批准号: 8488455
• 负责人: A. CATHARINE ROSS
• 金额: $ 35.68万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-20 至 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8488455
• 关键词: Admixture; Adult; Affect; Africa; Air; All-Trans-Retinol; Alveolar; Area; Asia; Birth; Blood Vessels; Bolus Infusion; Bronchopulmonary Dysplasia; Cell Respiration; Child; Clinical Treatment; Country; Dexamethasone; Diet; Differentiation and Growth; Dose; Embryonic Development; Esterification; Esters; Failure; Family; Genes; Genetic Transcription; Health Policy; Health Professional; Hematopoiesis; Human; Human Milk; Immune response; Infant; Inflammation; Inflammatory Response; International; Kidney; Kinetics; Knowledge; Life; Ligands; Link; Liver; Low Birth Weight Infant; Lung; Lung diseases; Measures; Metabolic; Metabolism; Methods; Modeling; Molecular; Morbidity - disease rate; Mus; Neonatal; Neonatal Intensive Care; Newborn Infant; Nuclear; Nutrient; Nutritional Requirements; Organ; Outcome; Oxygen; Physiological; Physiology; Placebos; Plasma; Policies; Policy Maker; Postpartum Period; Public Health; Rattus; Recommendation; Recommended Dietary Allowance; Reporting; Research; Respiratory physiology; Retinal; Retinoid Receptor; Retinoids; Retinol Binding Proteins; Retinol Metabolism Pathway; Structure of parenchyma of lung; Supplementation; Surface; System; Testing; Tissue Differentiation; Tissues; Tracer; Translations; Tretinoin; Vitamin A; absorption; age group; cell type; feeding; functional outcomes; improved; lung maturation; mathematical model; mature animal; mortality; neonate; oxidation; postnatal; rapid growth; retinoic acid 4-hydroxylase; trafficking; uptake

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.

出生时，肝脏和血浆中维生素A（VA，视黄醇）的浓度远低于老年人， 儿童和营养良好的成年人。新生儿的VA营养需求仅通过以下方法估算： 确定母乳中VA的消耗量，但新生儿对VA的真正代谢需求 是未知的。VA补充试验中，一个大的推注剂量是交付后不久出生， 在VA缺乏症被认为是公共卫生问题的国家进行，以确定发病率是否 和死亡率降低，但没有VA代谢的生理模型来帮助指导公共卫生 专业人员和决策者在决定新生儿是否能够储存和保留大剂量的VA。 假设补充VA与安慰剂相比，以及VA及其活性代谢产物的组合 与单独VA相比，维甲酸（RA），VARA将改变新生儿全身视黄醇动力学。目标 利用数学建模来测试VARA是否比VA更有效地引导视黄醇进入 特定组织（肺和其他器官），以及母亲产后饮食中VA是否会改变视黄醇 新生儿的新陈代谢目的还测试VA和VARA是否有利地影响炎性 氧气治疗引起的肺部反应，通常是低出生体重婴儿所必需的。 这些研究将产生关于视黄醇的吸收、储存和利用的新知识， 新生儿的分子因素和功能结果。这一研究对于理解 新生儿视黄醇生理学; VA营养需求;翻译给国际和国内公众 卫生政策决定;并可能转化为改善新生儿重症监护。