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Nutrients 2014, 6(5), 1913-1930; doi:10.3390/nu6051913
Article

Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation

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1 Department of Pediatrics, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway 2 Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, Oslo 0317, Norway 3 Department of Medical Biochemistry, University of Oslo, P.O.Box 4950 Nydalen, Oslo 0424, Norway 4 Department of Medical Biochemistry, Oslo University Hospital, P.O. Box 4956 Nydalen, Oslo 0424, Norway 5 Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, Oslo 0315, Norway 6 Department of Child and Adolescents Medicine, Akershus University Hospital, Lørenskog 1478, Norway 7 Institute of Clinical Medicine, University of Oslo, P.O. Box 1171 Blindern, Oslo 0318, Norway 8 Department of Neonatal Intensive Care, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway 9 Atlantis Medical University College, P.O. Box 4290 Nydalen, Oslo 0402, Norway 10 Department of Biostatistics, University of Oslo, P.O. Box 1122 Blindern, Oslo 0317, Norway 11 Department of Hematology, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway These authors contributed equally to this work.
* Author to whom correspondence should be addressed.
Received: 30 January 2014 / Revised: 14 April 2014 / Accepted: 30 April 2014 / Published: 12 May 2014
(This article belongs to the Special Issue Paediatric Nutrition)
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Abstract

Objectives: Early nutrition influences metabolic programming and long-term health. We explored the urinary metabolite profiles of 48 premature infants (birth weight < 1500 g) randomized to an enhanced or a standard diet during neonatal hospitalization. Methods: Metabolomics using nuclear magnetic resonance spectroscopy (NMR) was conducted on urine samples obtained during the first week of life and thereafter fortnightly. Results: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group. Enhanced nutrition did not appear to affect the urine profiles to an extent exceeding individual variation. However, in all infants the glucogenic amino acids glycine, threonine, hydroxyproline and tyrosine increased substantially during the early postnatal period, along with metabolites of the tricarboxylic acid cycle (succinate, oxoglutarate, fumarate and citrate). The metabolite changes correlated with postmenstrual age. Moreover, we observed elevated threonine and glycine levels in first-week urine samples of the small for gestational age (SGA; birth weight < 10th percentile for gestational age) as compared to the appropriate for gestational age infants. Conclusion: This first nutri-metabolomics study in premature infants demonstrates that the physiological adaptation during the fetal-postnatal transition as well as maturation influences metabolism during the breastfeeding period. Elevated glycine and threonine levels were found in the first week urine samples of the SGA infants and emerged as potential biomarkers of an altered metabolic phenotype.
Keywords: prematurity; very low birth weight; pediatric nutrition; intervention study; metabolomics; urine; nuclear magnetic resonance spectroscopy; glycine; threonine prematurity; very low birth weight; pediatric nutrition; intervention study; metabolomics; urine; nuclear magnetic resonance spectroscopy; glycine; threonine
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Moltu, S.J.; Sachse, D.; Blakstad, E.W.; Strømmen, K.; Nakstad, B.; Almaas, A.N.; Westerberg, A.C.; Rønnestad, A.; Brække, K.; Veierød, M.B.; Iversen, P.O.; Rise, F.; Berg, J.P.; Drevon, C.A. Urinary Metabolite Profiles in Premature Infants Show Early Postnatal Metabolic Adaptation and Maturation. Nutrients 2014, 6, 1913-1930.

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