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J Pediatr. 2014 Mar;164(3):607-12.e1-7. doi: 10.1016/j.jpeds.2013.10.091. Epub 2014 Jan 14.

Urine protein biomarkers for the diagnosis and prognosis of necrotizing enterocolitis in infants.

Author information

  • 1Division of Pediatric Surgery, Lucile Packard Children's Hospital, Palo Alto, CA; Department of Surgery, Stanford University School of Medicine, Stanford, CA. Electronic address: sylvester@stanford.edu.
  • 2Department of Surgery, Stanford University School of Medicine, Stanford, CA.
  • 3Department of Surgery, Stanford University School of Medicine, Stanford, CA; Pediatric Surgery, Department of Surgery, Johns Hopkins University, Baltimore, MD.
  • 4Division of Pediatric Surgery, Lucile Packard Children's Hospital, Palo Alto, CA; Department of Surgery, Stanford University School of Medicine, Stanford, CA.
  • 5Pediatric Surgery, Department of Surgery, Johns Hopkins University, Baltimore, MD.
  • 6Pediatric Surgery, Department of Surgery, Texas Children's Hospital, Houston, TX.
  • 7Department of Pediatrics, Division of Neonatology, Yale University School of Medicine, New Haven, CT.
  • 8Department of Pediatrics, Division of Neonatology, Children's Hospital of Philadelphia, Philadelphia, PA.
  • 9Pediatric Surgery, Department of Surgery, Nationwide Children's Hospital, Columbus, OH.

Abstract

OBJECTIVES:

To test the hypothesis that an exploratory proteomics analysis of urine proteins with subsequent development of validated urine biomarker panels would produce molecular classifiers for both the diagnosis and prognosis of infants with necrotizing enterocolitis (NEC).

STUDY DESIGN:

Urine samples were collected from 119 premature infants (85 NEC, 17 sepsis, 17 control) at the time of initial clinical concern for disease. The urine from 59 infants was used for candidate biomarker discovery by liquid chromatography/mass spectrometry. The remaining 60 samples were subject to enzyme-linked immunosorbent assay for quantitative biomarker validation.

RESULTS:

A panel of 7 biomarkers (alpha-2-macroglobulin-like protein 1, cluster of differentiation protein 14, cystatin 3, fibrinogen alpha chain, pigment epithelium-derived factor, retinol binding protein 4, and vasolin) was identified by liquid chromatography/mass spectrometry and subsequently validated by enzyme-linked immunosorbent assay. These proteins were consistently found to be either up- or down-regulated depending on the presence, absence, or severity of disease. Biomarker panel validation resulted in a receiver-operator characteristic area under the curve of 98.2% for NEC vs sepsis and an area under the curve of 98.4% for medical NEC vs surgical NEC.

CONCLUSIONS:

We identified 7 urine proteins capable of providing highly accurate diagnostic and prognostic information for infants with suspected NEC. This work represents a novel approach to improving the efficiency with which we diagnose early NEC and identify those at risk for developing severe, or surgical, disease.

Copyright © 2014 Mosby, Inc. All rights reserved.

PMID:
24433829
[PubMed - indexed for MEDLINE]
PMCID:
PMC4161235
Free PMC Article
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