Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants: a prospective case–control study

N. Deianova; S. el Manouni el Hassani; E. A. Struijs; E. E. W. Jansen; A. Bakkali; M. A. van de Wiel; W. P. de Boode; C. V. Hulzebos; A. H. van Kaam; B. W. Kramer; E. d’Haens; D. C. Vijlbrief; M. M. van Weissenbruch; W. J. de Jonge; M. A. Benninga; H. J. Niemarkt; N. K. H. de Boer; T. G. J. de Meij

doi:10.1038/s41598-022-16351-8

Scientific Reports (Jul 2022)

Fecal amine metabolite analysis before onset of severe necrotizing enterocolitis in preterm infants: a prospective case–control study

N. Deianova,
S. el Manouni el Hassani,
E. A. Struijs,
E. E. W. Jansen,
A. Bakkali,
M. A. van de Wiel,
W. P. de Boode,
C. V. Hulzebos,
A. H. van Kaam,
B. W. Kramer,
E. d’Haens,
D. C. Vijlbrief,
M. M. van Weissenbruch,
W. J. de Jonge,
M. A. Benninga,
H. J. Niemarkt,
N. K. H. de Boer,
T. G. J. de Meij

Affiliations

N. Deianova: Department of Pediatric Gastroenterology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit
S. el Manouni el Hassani: Department of Pediatric Gastroenterology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit
E. A. Struijs: Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit
E. E. W. Jansen: Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit
A. Bakkali: Department of Clinical Chemistry, Amsterdam UMC, Vrije Universiteit
M. A. van de Wiel: Department of Epidemiology and Data Science, Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit
W. P. de Boode: Department of Neonatology, Amalia Children’s Hospital, Radboud UMC, Radboud Institute for Health Sciences
C. V. Hulzebos: Division of Neonatology, University Medical Center Groningen, Beatrix Children’s Hospital, University of Groningen
A. H. van Kaam: Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam
B. W. Kramer: Neonatal Intensive Care Unit, Department of Pediatrics, Maastricht UMC
E. d’Haens: Neonatal Intensive Care Unit, Amalia Children’s Center, Isala
D. C. Vijlbrief: Neonatal Intensive Care Unit, UMC Utrecht, Wilhelmina Children’s Hospital
M. M. van Weissenbruch: Department of Neonatology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam
W. J. de Jonge: Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research
M. A. Benninga: Department of Pediatric Gastroenterology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit
H. J. Niemarkt: Department of Neonatology, Máxima Medical Center
N. K. H. de Boer: Department of Gastroenterology and Hepatology, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute
T. G. J. de Meij: Department of Pediatric Gastroenterology, Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit

DOI: https://doi.org/10.1038/s41598-022-16351-8
Journal volume & issue: Vol. 12, no. 1
pp. 1 – 8

Abstract

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Abstract Infants developing necrotizing enterocolitis (NEC) have a different metabolomic profile compared to controls. The potential of specific metabolomics, i.e. amino acids and amino alcohols (AAA), as early diagnostic biomarkers for NEC is largely unexplored. In this multicenter prospective case–control study, longitudinally collected fecal samples from preterm infants (born <30 weeks of gestation) from 1–3 days before diagnosis of severe NEC (Bell’s stage IIIA/IIIB), were analyzed by targeted high-performance liquid chromatography (HPLC). Control samples were collected from gestational and postnatal age-matched infants. Thirty-one NEC cases (15 NEC IIIA;16 NEC IIIB) with 1:1 matched controls were included. Preclinical samples of infants with NEC were characterized by five increased essential amino acids—isoleucine, leucine, methionine, phenylalanine and valine. Lysine and ethanolamine ratios were lower prior to NEC, compared to control samples. A multivariate model was rendered based on isoleucine, lysine, ethanolamine, tryptophan and ornithine, modestly discriminating cases from controls (AUC 0.67; p < 0.001). Targeted HPLC pointed to several specific AAA alterations in samples collected 1–3 days before NEC onset, compared to controls. Whether this reflects metabolic alterations and has a role in early biomarker development for NEC, has yet to be elucidated.

Published in Scientific Reports

ISSN: 2045-2322 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Medicine; Science
Website: https://www.nature.com/srep/

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