Urinary metabolite profiles in premature infants show early postnatal metabolic adaptation and maturation.
OBJECTIVE
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.


CONCLUSIONS
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.
Department of Pediatrics, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway. sissel.moltu@medisin.uio.no.
Sissel J
SJ
Moltu
Department of Medical Biochemistry, University of Oslo, P.O.Box 4950 Nydalen, Oslo 0424, Norway. sissel.moltu@medisin.uio.no.
Daniel
D
Sachse
Department of Child and Adolescents Medicine, Akershus University Hospital, Lørenskog 1478, Norway. e.w.blakstad@medisin.uio.no.
Elin W
EW
Blakstad
Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, Oslo 0317, Norway. kestro@ous-hf.no.
Kenneth
K
Strømmen
Department of Child and Adolescents Medicine, Akershus University Hospital, Lørenskog 1478, Norway. britt.nakstad@medisin.uio.no.
Britt
B
Nakstad
Department of Child and Adolescents Medicine, Akershus University Hospital, Lørenskog 1478, Norway. a.n.almaas@gmail.com.
Astrid N
AN
Almaas
Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, Oslo 0317, Norway. a.c.westerberg@medisin.uio.no.
Ane C
AC
Westerberg
Department of Neonatal Intensive Care, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway. aronnest@ous-hf.no.
Arild
A
Rønnestad
Department of Neonatal Intensive Care, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway. uxkbre@ous-hf.no.
Kristin
K
Brække
Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, Oslo 0317, Norway. m.b.veierod@medisin.uio.no.
Marit B
MB
Veierød
Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, Oslo 0317, Norway. p.o.iversen@medisin.uio.no.
Per O
PO
Iversen
Department of Chemistry, University of Oslo, P.O. Box 1033 Blindern, Oslo 0315, Norway. frode.rise@kjemi.uio.no.
Frode
F
Rise
Department of Medical Biochemistry, University of Oslo, P.O.Box 4950 Nydalen, Oslo 0424, Norway. j.p.berg@medisin.uio.no.
Jens P
JP
Berg
Department of Nutrition, University of Oslo, P.O. Box 1046 Blindern, Oslo 0317, Norway. c.a.drevon@medisin.uio.no.
Christian A
CA
Drevon
D000222:Adaptation, Physiological; D015415:Biomarkers / Q000652:urine; D001942:Breast Feeding; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D007234:Infant, Premature / Q000254:growth & development* / Q000378:metabolism*; D007236:Infant, Small for Gestational Age / Q000254:growth & development; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D015596:Nutrition Assessment; D025341:Principal Component Analysis
D015415:Biomarkers