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.
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.
|Askenazi, David J; Koralkar, Rajesh; Patil, Neha et al. (2016) Acute Kidney Injury Urine Biomarkers in Very Low-Birth-Weight Infants. Clin J Am Soc Nephrol 11:1527-35|
|Tan, Libo; Babbs, Amanda E; Green, Michael H et al. (2016) Direct and indirect vitamin A supplementation strategies result in different plasma and tissue retinol kinetics in neonatal rats. J Lipid Res 57:1423-34|
|Panikkanvalappil, Sajanlal R; James, Masheika; Hira, Steven M et al. (2016) Hyperoxia Induces Intracellular Acidification in Neonatal Mouse Lung Fibroblasts: Real-Time Investigation Using Plasmonically Enhanced Raman Spectroscopy. J Am Chem Soc 138:3779-88|
|Owusu, Sarah A; Ross, A Catharine (2016) Retinoid Homeostatic Gene Expression in Liver, Lung and Kidney: Ontogeny and Response to Vitamin A-Retinoic Acid (VARA) Supplementation from Birth to Adult Age. PLoS One 11:e0145924|
|Askenazi, David; Saeidi, Behtash; Koralkar, Rajesh et al. (2016) Acute changes in fluid status affect the incidence, associative clinical outcomes, and urine biomarker performance in premature infants with acute kidney injury. Pediatr Nephrol 31:843-51|
|Saeidi, Behtash; Koralkar, Rajesh; Griffin, Russell L et al. (2015) Impact of gestational age, sex, and postnatal age on urine biomarkers in premature neonates. Pediatr Nephrol 30:2037-44|
|Lal, Charitharth Vivek; Ambalavanan, Namasivayam (2015) Biomarkers, Early Diagnosis, and Clinical Predictors of Bronchopulmonary Dysplasia. Clin Perinatol 42:739-54|
|Ramani, Manimaran; Bradley, Wayne E; Dell'Italia, Louis J et al. (2015) Early exposure to hyperoxia or hypoxia adversely impacts cardiopulmonary development. Am J Respir Cell Mol Biol 52:594-602|
|Lal, Charitharth Vivek; Ambalavanan, Namasivayam (2015) Genetic predisposition to bronchopulmonary dysplasia. Semin Perinatol 39:584-91|
|Tan, Libo; Wray, Amanda E; Green, Michael H et al. (2014) Compartmental modeling of whole-body vitamin A kinetics in unsupplemented and vitamin A-retinoic acid-supplemented neonatal rats. J Lipid Res 55:1738-49|
Showing the most recent 10 out of 22 publications