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

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.

1H NMR-based urine metabolic profile of IUGR, LGA, and AGA newborns in the first week of life

“…The glycine, in particular, reached higher contents in neonates with fetal malnutrition. A similar difference in the levels of glycine has been recently observed between neonates small for gestational age (SGA) and controls [15]. Taurine belongs to the sulfur-containing amino acids; it is basic for neonates playing a key role in cell membrane stabilization, modulation of intracellular calcium levels, osmoregulation, and detoxification [16].…”

Preterm neonatal urinary renal developmental and acute kidney injury metabolomic profiling: an exploratory study

“…We also found that for infants without an AKI diagnosis, glycine was important to the correlation with gestational age. Both metabolites have been discussed previously in urinary metabolomics of neonates as markers of insufficient growth in utero [51, 52]. It has been suggested that because both of these amino acids are glucogenic; an increase of glycine would cause a reduction of amino acid oxidation or reduced glucogenesis as a means of conservation [53].…”

Metabolomics Reveals Dynamic Metabolic Changes Associated with Age in Early Childhood

“…The cross validation revealed a Q 2 value of greater than 0.5 is usually considered to be a good classification model [ 20 ]. The ratio Q 2 /R 2 is a measure of cross-validation reproducibility and Q 2 /R 2 above 0.5 are considered indicative of relevant associations [ 21 ]. A permutation test can evaluate whether the specific classification of the individuals in the two designed groups is significantly better than any other random classification in two arbitrary groups [ 22 ].…”