title: Non-invasive markers for early diagnosis and determination of the severity of necrotizing enterocolitis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Surgery, Maastricht University Medical Centre, and Nutrition and Toxicology Research Institute (NUTRIM), Maastricht, The Netherlands.
authors.forename: Geertje
authors.initials: G
authors.lastname: Thuijls
authors.forename: Joep P M
authors.initials: JP
authors.lastname: Derikx
authors.forename: Kim
authors.initials: K
authors.lastname: van Wijck
authors.forename: Luc J I
authors.initials: LJ
authors.lastname: Zimmermann
authors.forename: Pieter L
authors.initials: PL
authors.lastname: Degraeuwe
authors.forename: Twan L
authors.initials: TL
authors.lastname: Mulder
authors.forename: David C
authors.initials: DC
authors.lastname: Van der Zee
authors.forename: Hens A A
authors.initials: HA
authors.lastname: Brouwers
authors.forename: Bas H
authors.initials: BH
authors.lastname: Verhoeven
authors.forename: L W Ernest
authors.initials: LW
authors.lastname: van Heurn
authors.forename: Boris W
authors.initials: BW
authors.lastname: Kramer
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Erik
authors.initials: E
authors.lastname: Heineman
mesh_terms: D015415:Biomarkers / Q000032:analysis; D062465:Claudin-3; D020345:Enterocolitis, Necrotizing / Q000175:diagnosis* / Q000473:pathology; D050556:Fatty Acid-Binding Proteins / Q000652:urine*; D005243:Feces / Q000737:chemistry; D006801:Humans; D007231:Infant, Newborn; D039841:Leukocyte L1 Antigen Complex / Q000032:analysis*; D008565:Membrane Proteins / Q000652:urine*; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; C568122:CLDN3 protein, human; D062465:Claudin-3; D050556:Fatty Acid-Binding Proteins; D039841:Leukocyte L1 Antigen Complex; D008565:Membrane Proteins