title: Intestinal fatty acid-binding protein as a diagnostic marker for complicated and uncomplicated necrotizing enterocolitis: a prospective cohort study.
abstract: BACKGROUND
  Early NEC symptoms are non-specific and diagnostic tests lack discriminative power. Intestinal fatty acid-binding protein (I-FABP), mainly located in small bowel enterocytes, is released into the blood following NEC-associated enterocyte disruption. Aim of this prospective cohort trial was to determine the diagnostic value of I-FABP measured in plasma (I-FABPp) and urine (I-FABPu) for the presence of NEC, to evaluate I-FABP levels during NEC development, and to assess its prognostic value for the progression from suspected to complicated disease.
  
  
  METHODS
  Between 2010 and 2012 we prospectively enrolled neonates with suspected NEC. We measured I-FABP levels eight-hourly from onset of suspected NEC for at least 48 hours, or until surgery. NEC diagnosis was confirmed radiologically or during operation. We defined NEC as complicated if it resulted in surgery and/or death. We determined disease course and diagnostic I-FABP cut-off points.
  
  
  RESULTS
  The study comprised 37 neonates (24M, 13F), gestational age 28 (24-36) weeks, birth weight 1190 (570-2,400) grams. We found significantly higher I-FABPp and I-FABPu levels in NEC patients (n = 22) than in patients with other diagnoses (n = 15). Cut-off values for diagnosing NEC were 9 ng/mL I-FABPp and 218 ng/mL I-FABPu, with corresponding likelihood ratios (LRs) of 5.6 (95% CI 0.89-35) and 5.1 (95% CI 0.73-36), respectively. I-FABP levels were highest in the first eight hours after symptom onset and gradually decreased over time. Cut-off values for complicated disease were 19 ng/mL I-FABPp and 232 ng/mL I-FABPu, with LRs of 10 (95% CI 1.6-70) and 11 (95% CI 1.6-81), respectively.
  
  
  CONCLUSIONS
  Both plasma and urinary I-FABP levels specifically identify NEC in preterm infants prior to appearance of diagnostic radiological signs suggestive for NEC. Moreover, serial I-FABP measurements accurately predict development of complicated disease.
authors: Department of Paediatric Surgery, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Maarten
authors: M
authors: Schurink
authors: Department of Neonatology, University of Groningen, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Elisabeth M W
authors: EM
authors: Kooi
authors: Department of Neonatology, University of Groningen, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Christian V
authors: CV
authors: Hulzebos
authors: Surgical Research Laboratory, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Rozemarijn G
authors: RG
authors: Kox
authors: Department of Epidemiology, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Henk
authors: H
authors: Groen
authors: Department of Paediatric Surgery, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Erik
authors: E
authors: Heineman
authors: Department of Neonatology, University of Groningen, Beatrix Children's Hospital, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Arend F
authors: AF
authors: Bos
authors: Department of Paediatric Surgery, University of Groningen, University Medical Centre Groningen, Groningen, the Netherlands.
authors: Jan B F
authors: JB
authors: Hulscher
mesh_terms: D015415:Biomarkers / Q000097:blood / Q000652:urine; D018450:Disease Progression; D020345:Enterocolitis, Necrotizing / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D050556:Fatty Acid-Binding Proteins / Q000097:blood / Q000378:metabolism* / Q000652:urine; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D016013:Likelihood Functions; D008297:Male; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins