title: Bloodstream infections during the onset of necrotizing enterocolitis and their relation with the pro-inflammatory response, gut wall integrity and severity of disease in NEC.
abstract: BACKGROUND
  Bacterial involvement is believed to play a pivotal role in the development and disease outcome of NEC. However, whether a bloodstream infection (BSI) predisposes to NEC (e.g. by activating the pro-inflammatory response) or result from the loss of gut wall integrity during NEC development is a longstanding question.
  
  
  OBJECTIVE
  We hypothesize that the occurrence of a BSI plays a complementary role in the pathogenesis of NEC. The first aim of the study was to correlate the occurrence of a BSI during the early phase of NEC with intestinal fatty acid-binding protein (I-FABP) levels, as a marker for loss of gut wall integrity owing to mucosal damage, and Interleukin (IL)-8 levels, as a biomarker for the pro-inflammatory cascade in NEC. The second aim of the study was to investigate the relation between the occurrence of a BSI and disease outcome.
  
  
  METHODS
  We combined data from prospective trials from two large academic pediatric surgical centers. Thirty-eight neonates with NEC, 5 neonates with bacterial sepsis, and 14 controls were included.
  
  
  RESULTS
  BSIs occurred in 10/38 (26%) neonates at NEC onset. No association between the occurrence of BSIs and I-FABP levels in plasma (cohort 1: median 11ng/mL (range 0.8-298), cohort 2: median 6.8ng/mL (range 1.3-15)) was found in NEC patients (cohort 1: p=0.41; cohort 2: p=0.90). In addition, the occurrence of BSIs did not correlate with IL-8 (median 1562pg/mL (range 150-7,500); p=0.99). While the occurrence of a BSI was not correlated with Bell's stage (p=0.85), mortality was higher in patients with a BSI (p=0.005).
  
  
  CONCLUSIONS
  The low incidence of BSIs and the absent association of both the markers for loss of gut wall integrity and the pro-inflammatory response during the early phase of NEC, support the hypothesis that the presence of a BSI does not precede NEC.
authors.affiliation: Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands; Department of Medical Microbiology, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands. Electronic address: f.h.heida@umcg.nl.
authors.forename: F H
authors.initials: FH
authors.lastname: Heida
authors.affiliation: Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands.
authors.forename: J B F
authors.initials: JB
authors.lastname: Hulscher
authors.affiliation: Department of Pediatric Surgery, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Schurink
authors.affiliation: Department of Pediatrics, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands.
authors.forename: M J
authors.initials: MJ
authors.lastname: van Vliet
authors.affiliation: Department of Neonatology, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands.
authors.forename: E M W
authors.initials: EM
authors.lastname: Kooi
authors.affiliation: Department of Analytics, Medical University of Vienna, Austria.
authors.forename: D C
authors.initials: DC
authors.lastname: Kasper
authors.affiliation: Department of Pediatric Surgery, Research Core Unit for Pediatric Biochemistry, Medical University of Vienna, Austria.
authors.forename: M
authors.initials: M
authors.lastname: Pones
authors.affiliation: Department of Neonatology, Beatrix Children's Hospital, University Medical Center, Groningen, the Netherlands.
authors.forename: A F
authors.initials: AF
authors.lastname: Bos
authors.affiliation: Department of Pediatric Surgery, Research Core Unit for Pediatric Biochemistry, Medical University of Vienna, Austria.
authors.forename: T M
authors.initials: TM
authors.lastname: Benkoe
mesh_terms: D016470:Bacteremia / Q000097:blood / Q000150:complications* / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D020345:Enterocolitis, Necrotizing / Q000097:blood / Q000209:etiology*; D050556:Fatty Acid-Binding Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D016209:Interleukin-8 / Q000097:blood*; D008297:Male; D011446:Prospective Studies
chemical_list: D015415:Biomarkers; C508606:CXCL8 protein, human; C493404:FABP2 protein, human; D050556:Fatty Acid-Binding Proteins; D016209:Interleukin-8
keywords: Bloodstream infections; Gut wall integrity; Necrotizing enterocolitis; Pathophysiology; Proinflammatory cascade response