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: 8607636
• 负责人: A. CATHARINE ROSS
• 金额: $ 5.81万
• 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 2014-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8607636
• 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）的浓度比老年人低得多 儿童和吃得饱的成年人。新生儿的 VA 营养需求仅通过以下方式估算 确定母乳中消耗的 VA 量，但新生儿对 VA 的真实代谢需求 尚不清楚。 VA 补充试验正在进行中，其中在出生后立即给予大剂量推注 在 VA 缺乏被视为公共卫生问题的国家进行，以确定发病率是否 死亡率降低，但尚无 VA 代谢的生理模型来帮助指导公众健康 专业人士和政策制定者决定新生儿是否能够储存和保留大剂量的 VA。 假设是 VA 补充剂与安慰剂，以及 VA 及其活性代谢物的组合 与单独使用 VA 相比，视黄酸 (RA)、VARA 会改变新生儿全身视黄醇动力学。目标 利用数学模型来测试 VARA 是否比 VA 更有效地将视黄醇引导至 特定组织（肺和其他器官），以及母亲产后膳食 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 是否对炎症有有利影响 氧气治疗引起的肺部反应，这对于低出生体重婴儿来说通常是必需的。 这些研究将产生关于视黄醇的吸收、储存和利用的新知识，以及 新生儿的分子因素和功能结果。该研究对于理解具有重要意义 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；并有可能转化为改善新生儿重症监护。