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Longitudinal Serum Metabolomics in Extremely Premature Infants : Relationships With Gestational Age, Nutrition, and Morbidities

Nilsson, Anders K. ; Tebani, Abdellah ; Malmodin, Daniel ; Pedersen, Anders ; Hellgren, Gunnel ; Löfqvist, Chatarina ; Hansen-Pupp, Ingrid LU orcid ; Uhlén, Mathias and Hellström, Ann LU (2022) In Frontiers in Neuroscience 16.
Abstract

An increasing number of extremely premature infants survive the neonatal period and beyond. Little is known about the maturation of the preterm infant’s metabolome and its relation to the development of morbidities. Using 1H-NMR, we investigated the serum metabolic profile of 87 infants born at a gestational age (GA) <28 weeks [mean GA (SD) 25.4 (1.4) weeks] in samples longitudinally collected from birth to term equivalent age. The infant metabolome was analyzed in relation to GA, postnatal age, nutrition, and preterm morbidities. At postnatal day 1, low GA correlated with high levels of 3-hydroxyisobutyrate, acetate, acetoacetate, acetone, formate, glucose, and valine. Nearly all quantified metabolites displayed postnatal... (More)

An increasing number of extremely premature infants survive the neonatal period and beyond. Little is known about the maturation of the preterm infant’s metabolome and its relation to the development of morbidities. Using 1H-NMR, we investigated the serum metabolic profile of 87 infants born at a gestational age (GA) <28 weeks [mean GA (SD) 25.4 (1.4) weeks] in samples longitudinally collected from birth to term equivalent age. The infant metabolome was analyzed in relation to GA, postnatal age, nutrition, and preterm morbidities. At postnatal day 1, low GA correlated with high levels of 3-hydroxyisobutyrate, acetate, acetoacetate, acetone, formate, glucose, and valine. Nearly all quantified metabolites displayed postnatal concentration changes. For example, the two phospholipid-related metabolites myo-inositol and ethanolamine displayed a similar decline from birth over the first weeks of life, irrespectively of GA. The proportion of enteral/parenteral energy intake in the first 28 days significantly correlated with mean levels of 52% of the analyzed metabolites. Low enteral energy intake was associated with high serum levels of 3-hydroxyisobutyrate, creatinine, glucose, glycerol, histidine, lactate, leucine, lysine, methionine, ornithine, phenylalanine, proline, threonine, and uridine. There were also significant correlations between high enteral intake and high serum levels of isoleucine and tyrosine. Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) outcomes were not significantly associated with metabolite levels in the neonatal period after correcting for multiple testing. In conclusion, the serum metabolome of extremely premature infants changes substantially in the neonatal period, largely driven by the gradual transfer from total parenteral nutrition to full enteral feeding. Further studies are needed to disentangle the intricate relationships between the metabolome, nutritional management, GA, and the development of preterm morbidities.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
bronchopulmonary dysplasia, enteral nutrition, ethanolamine, human milk, ketone bodies, one-carbon metabolism, parenteral nutrition, retinopathy of prematurity
in
Frontiers in Neuroscience
volume
16
article number
830884
publisher
Frontiers Media S. A.
external identifiers
  • scopus:85125746837
  • pmid:35250465
ISSN
1662-4548
DOI
10.3389/fnins.2022.830884
language
English
LU publication?
yes
id
8418267c-c084-4fee-8bf3-bc261e5ef992
date added to LUP
2022-05-02 11:22:24
date last changed
2024-02-17 22:21:50
@article{8418267c-c084-4fee-8bf3-bc261e5ef992,
  abstract     = {{<p>An increasing number of extremely premature infants survive the neonatal period and beyond. Little is known about the maturation of the preterm infant’s metabolome and its relation to the development of morbidities. Using 1H-NMR, we investigated the serum metabolic profile of 87 infants born at a gestational age (GA) &lt;28 weeks [mean GA (SD) 25.4 (1.4) weeks] in samples longitudinally collected from birth to term equivalent age. The infant metabolome was analyzed in relation to GA, postnatal age, nutrition, and preterm morbidities. At postnatal day 1, low GA correlated with high levels of 3-hydroxyisobutyrate, acetate, acetoacetate, acetone, formate, glucose, and valine. Nearly all quantified metabolites displayed postnatal concentration changes. For example, the two phospholipid-related metabolites myo-inositol and ethanolamine displayed a similar decline from birth over the first weeks of life, irrespectively of GA. The proportion of enteral/parenteral energy intake in the first 28 days significantly correlated with mean levels of 52% of the analyzed metabolites. Low enteral energy intake was associated with high serum levels of 3-hydroxyisobutyrate, creatinine, glucose, glycerol, histidine, lactate, leucine, lysine, methionine, ornithine, phenylalanine, proline, threonine, and uridine. There were also significant correlations between high enteral intake and high serum levels of isoleucine and tyrosine. Retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) outcomes were not significantly associated with metabolite levels in the neonatal period after correcting for multiple testing. In conclusion, the serum metabolome of extremely premature infants changes substantially in the neonatal period, largely driven by the gradual transfer from total parenteral nutrition to full enteral feeding. Further studies are needed to disentangle the intricate relationships between the metabolome, nutritional management, GA, and the development of preterm morbidities.</p>}},
  author       = {{Nilsson, Anders K. and Tebani, Abdellah and Malmodin, Daniel and Pedersen, Anders and Hellgren, Gunnel and Löfqvist, Chatarina and Hansen-Pupp, Ingrid and Uhlén, Mathias and Hellström, Ann}},
  issn         = {{1662-4548}},
  keywords     = {{bronchopulmonary dysplasia; enteral nutrition; ethanolamine; human milk; ketone bodies; one-carbon metabolism; parenteral nutrition; retinopathy of prematurity}},
  language     = {{eng}},
  publisher    = {{Frontiers Media S. A.}},
  series       = {{Frontiers in Neuroscience}},
  title        = {{Longitudinal Serum Metabolomics in Extremely Premature Infants : Relationships With Gestational Age, Nutrition, and Morbidities}},
  url          = {{http://dx.doi.org/10.3389/fnins.2022.830884}},
  doi          = {{10.3389/fnins.2022.830884}},
  volume       = {{16}},
  year         = {{2022}},
}