Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis

Ann Surg. 2010 Jun;251(6):1174-80. doi: 10.1097/SLA.0b013e3181d778c4.

Abstract

Objectives: To improve diagnosis of necrotizing enterocolitis (NEC) by noninvasive markers representing gut wall integrity loss (I-FABP and claudin-3) and gut wall inflammation (calprotectin). Furthermore, the usefulness of I-FABP to predict NEC severity and to screen for NEC was evaluated.

Methods: Urinary I-FABP and claudin-3 concentrations and fecal calprotectin concentrations were measured in 35 consecutive neonates suspected of NEC at the moment of NEC suspicion. To investigate I-FABP as screening tool for NEC, daily urinary levels were determined in 6 neonates who developed NEC out of 226 neonates included before clinical suspicion of NEC.

Results: Of 35 neonates suspected of NEC, 14 developed NEC. Median I-FABP, claudin-3, and calprotectin levels were significantly higher in neonates with NEC than in neonates with other diagnoses. Cutoff values for I-FABP (2.20 pg/nmol creatinine), claudin-3 (800.8 INT), and calprotectin (286.2 microg/g feces) showed clinically relevant positive likelihood ratios (LRs) of 9.30, 3.74, 12.29, and negative LRs of 0.08, 0.36, 0.15, respectively. At suspicion of NEC, median urinary I-FABP levels of neonates with intestinal necrosis necessitating surgery or causing death were significantly higher than urinary I-FABP levels in conservatively treated neonates. Of the 226 neonates included before clinical suspicion of NEC, 6 developed NEC. In 4 of these 6 neonates I-FABP levels were not above the cutoff level to diagnose NEC before clinical suspicion.

Conclusions: Urinary I-FABP levels are not suitable as screening tool for NEC before clinical suspicion. However, urinary I-FABP and claudin-3 and fecal calprotectin are promising diagnostic markers for NEC. Furthermore, urinary I-FABP might also be used to predict disease severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / analysis
  • Claudin-3
  • Enterocolitis, Necrotizing / diagnosis*
  • Enterocolitis, Necrotizing / pathology
  • Fatty Acid-Binding Proteins / urine*
  • Feces / chemistry
  • Humans
  • Infant, Newborn
  • Leukocyte L1 Antigen Complex / analysis*
  • Membrane Proteins / urine*
  • Severity of Illness Index

Substances

  • Biomarkers
  • CLDN3 protein, human
  • Claudin-3
  • Fatty Acid-Binding Proteins
  • Leukocyte L1 Antigen Complex
  • Membrane Proteins