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

Moltu SJ, Sachse D, Blakstad EW, Strømmen K, Nakstad B, Almaas AN, Westerberg AC, Rønnestad A, Brække K, Veierød MB, Iversen PO, Rise F, Berg JP, Drevon CA - Nutrients (2014)

Bottom Line: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway. sissel.moltu@medisin.uio.no.

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.

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Related in: MedlinePlus

Selected regions of two NMR spectra (black for week 1 and red for week 1) of an SGA infant in the intervention group.
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nutrients-06-01913-f002: Selected regions of two NMR spectra (black for week 1 and red for week 1) of an SGA infant in the intervention group.

Mentions: Metabolite profiling in the present study largely followed a protocol described earlier [26]. Briefly, 150 μL of distilled water and 50 μL of a buffer at pH 7.4 containing D2O and trimethylsilylpropionate-d4 (TSP) were added to 350 μL of the samples, which were then centrifuged at 13,400× g for 5 min and transferred to 5 mm NMR tubes (Wilmad LabGlass, Vineland, NJ, USA). One-dimensional, water-suppressed proton NMR spectra were acquired at 300.0 K on a Bruker AVI-600 spectrometer (Bruker Biospin GmbH, Rheinstetten, Germany) equipped with a TCI cryoprobe and a BACS-60 automatic sample changer, under full automation of D2O locking, tuning and matching, and gradient shimming using TopSpin 2.1pl6 and iconNMR. Of each sample 32 scans and 4 dummy scans were collected into 64 k data points using the Bruker “noesygppr1d.comp” sequence with a spectral width of 20.6 ppm, 2.65 s acquisition time and a 25 Hz water presaturation during the 4 s relaxation delay. An exponential line broadening of 0.3 Hz was applied. The TSP signal achieved a full width at half maximum of less than 1 Hz after apodization and acted as spectral and concentration reference. The spectra were phase-corrected, a smooth baseline was removed, and the spectra were binned to a spectral width of 0.01 ppm. Signals were assigned to known metabolites using a reference database [27] and the software Chenomx NMR Suite 7.5 professional (Chenomx Inc., Edmonton AB, Canada). Two example spectra are shown in Figure 2. Pseudo-concentrations were extracted by integrating manually defined spectral regions corresponding to both known and unknown substances, and arranged in a table. Pseudo-concentrations are proportional to absolute concentrations and can be used as such in the statistical analysis. Both the spectra and the table of metabolite pseudo-concentrations were subsequently normalized to the total intensity of the respective spectra, and the metabolite table was log-transformed.


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

Moltu SJ, Sachse D, Blakstad EW, Strømmen K, Nakstad B, Almaas AN, Westerberg AC, Rønnestad A, Brække K, Veierød MB, Iversen PO, Rise F, Berg JP, Drevon CA - Nutrients (2014)

Selected regions of two NMR spectra (black for week 1 and red for week 1) of an SGA infant in the intervention group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4042575&req=5

nutrients-06-01913-f002: Selected regions of two NMR spectra (black for week 1 and red for week 1) of an SGA infant in the intervention group.
Mentions: Metabolite profiling in the present study largely followed a protocol described earlier [26]. Briefly, 150 μL of distilled water and 50 μL of a buffer at pH 7.4 containing D2O and trimethylsilylpropionate-d4 (TSP) were added to 350 μL of the samples, which were then centrifuged at 13,400× g for 5 min and transferred to 5 mm NMR tubes (Wilmad LabGlass, Vineland, NJ, USA). One-dimensional, water-suppressed proton NMR spectra were acquired at 300.0 K on a Bruker AVI-600 spectrometer (Bruker Biospin GmbH, Rheinstetten, Germany) equipped with a TCI cryoprobe and a BACS-60 automatic sample changer, under full automation of D2O locking, tuning and matching, and gradient shimming using TopSpin 2.1pl6 and iconNMR. Of each sample 32 scans and 4 dummy scans were collected into 64 k data points using the Bruker “noesygppr1d.comp” sequence with a spectral width of 20.6 ppm, 2.65 s acquisition time and a 25 Hz water presaturation during the 4 s relaxation delay. An exponential line broadening of 0.3 Hz was applied. The TSP signal achieved a full width at half maximum of less than 1 Hz after apodization and acted as spectral and concentration reference. The spectra were phase-corrected, a smooth baseline was removed, and the spectra were binned to a spectral width of 0.01 ppm. Signals were assigned to known metabolites using a reference database [27] and the software Chenomx NMR Suite 7.5 professional (Chenomx Inc., Edmonton AB, Canada). Two example spectra are shown in Figure 2. Pseudo-concentrations were extracted by integrating manually defined spectral regions corresponding to both known and unknown substances, and arranged in a table. Pseudo-concentrations are proportional to absolute concentrations and can be used as such in the statistical analysis. Both the spectra and the table of metabolite pseudo-concentrations were subsequently normalized to the total intensity of the respective spectra, and the metabolite table was log-transformed.

Bottom Line: The intervention group received significantly higher amounts of energy, protein, lipids, vitamin A, arachidonic acid and docosahexaenoic acid as compared to the control group.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Oslo University Hospital, P.O. Box 4950 Nydalen, Oslo 0424, Norway. sissel.moltu@medisin.uio.no.

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.

Show MeSH
Related in: MedlinePlus