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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.
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1 Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Department of Pediatric Gastroenterology, Amsterdam, The Netherlands
2 Amsterdam UMC, Vrije Universiteit, Department of Clinical Chemistry, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
3 Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit, Department of Epidemiology and Data Science, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
4 Amalia Children’s Hospital, Radboud UMC, Radboud Institute for Health Sciences, Department of Neonatology, Nijmegen, The Netherlands (GRID:grid.461578.9)
5 University Medical Center Groningen, Beatrix Children’s Hospital, University of Groningen, Division of Neonatology, Groningen, The Netherlands (GRID:grid.4494.d) (ISNI:0000 0000 9558 4598)
6 Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Department of Neonatology, Amsterdam, The Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262)
7 Maastricht UMC, Neonatal Intensive Care Unit, Department of Pediatrics, Maastricht, The Netherlands (GRID:grid.412966.e) (ISNI:0000 0004 0480 1382)
8 Amalia Children’s Center, Isala, Neonatal Intensive Care Unit, Zwolle, The Netherlands (GRID:grid.452600.5) (ISNI:0000 0001 0547 5927)
9 UMC Utrecht, Wilhelmina Children’s Hospital, Neonatal Intensive Care Unit, Utrecht, The Netherlands (GRID:grid.417100.3) (ISNI:0000 0004 0620 3132)
10 Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Amsterdam UMC, University of Amsterdam, Tytgat Institute for Liver and Intestinal Research, Amsterdam, The Netherlands (GRID:grid.7177.6) (ISNI:0000000084992262)
11 Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Department of Pediatric Gastroenterology, Amsterdam, The Netherlands (GRID:grid.7177.6)
12 Máxima Medical Center, Department of Neonatology, Veldhoven, The Netherlands (GRID:grid.414711.6) (ISNI:0000 0004 0477 4812)
13 Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam Gastroenterology Endocrinology Metabolism (AGEM) Research Institute, Department of Gastroenterology and Hepatology, Amsterdam, The Netherlands (GRID:grid.12380.38) (ISNI:0000 0004 1754 9227)
14 Emma Children’s Hospital, Amsterdam UMC, University of Amsterdam, Vrije Universiteit, Department of Pediatric Gastroenterology, Amsterdam, The Netherlands (GRID:grid.12380.38)