Vitamin A Supplementation and Retinol Metabolism in the Neonatal Period

新生儿期维生素 A 补充和视黄醇代谢

• 批准号: 8008598
• 负责人: A. CATHARINE ROSS
• 金额: $ 32.87万
• 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/8008598
• 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; Hydrolysis; 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; RalDH1; 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; public health relevance; rapid growth; trafficking; uptake

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.

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养成良好的成年人。 Neonate的VA营养需求仅通过确定母乳中消耗的VA量来估算，但是新生儿对VA的真正代谢需求尚不清楚。 VA补充试验在出生后不久就进行了大量大通剂量，在VA缺乏症被认为是公共卫生问题的国家中，可以确定发病率和死亡率是否降低，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确定Neononates可以决定是否能够储存大型Bolus bolus dose and Bolus dose va va。假设是，与单独的VA相比，VA及其活性代谢物视网膜酸（RA）（RA）的组合将改变新生儿的全身视黄醇动力学。目的利用数学建模来测试VARA在将视黄醇引导到特定组织（肺部和其他器官）中是否比VA更有效，以及母体产后饮食VA是否改变了新生儿中视黄醇代谢。目的还测试了VA和Vara是否有利地影响氧气治疗引起的肺的炎症反应，这对于低出生体重婴儿通常是必需的。这些研究将产生有关视黄醇的吸收，储存和利用的新知识，以及分子因素和新生儿的功能结果。这项研究对于理解新生儿视网膜生理学非常重要。 VA营养要求；转化为国际和国家公共卫生政策决策；并有可能翻译以改善新生儿重症监护。 公共卫生相关性：陈述新生儿对维生素A（VA，视黄醇）的生理要求是未知的，并且对于这个年龄段，不存在全身视网膜代谢的模型。我们将使用同位素示踪剂分析和数学模型来建立新生大鼠中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。这些研究的证据将有助于为婴儿提供有关婴儿的饮食建议，国际弗吉尼亚州补充政策以及对新生儿肺部疾病的临床治疗。