title: Vasculitis as part of the fetal response to acute chorioamnionitis likely plays a role in the development of necrotizing enterocolitis and spontaneous intestinal perforation in premature neonates.
abstract: BACKGROUND
  Necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) are causes of bowel perforation in premature neonates. Studies have demonstrated that both are associated with acute chorioamnionitis (ACA) of the placenta.
  
  
  OBJECTIVE
  The aim of our study was to identify any histopathological links between placental histopathological abnormalities and the later development of NEC and/or SIP in premature patients presenting at our institution.
  
  
  METHODS
  Cases with a diagnosis of NEC/SIP were identified. Entry criteria were the diagnosis of NEC/SIP was confirmed clinically and/or histologically, had been made within the first 7 days of life, neonates were premature, and the placenta had been submitted for histological examination. In those cases with ACA, CD34 immunohistochemistry and Martius scarlet blue staining was performed. Medical records were reviewed for demographics, clinical variables, and clinical outcomes. Statistical analysis was performed using Fisher exact test.
  
  
  RESULTS
  In total, 21 cases met defined inclusion criteria (12 NEC, 8 SIP, and 1 clinically indeterminate). Mean gestational age was 27 weeks. Median age of presentation was 5 days. Placental histology showed ACA in 16 of 21 cases (76.2%). Of those with ACA, 13 of 16 (81.3%) had umbilical phlebitis, 12 of 16 (75.0%) had umbilical arteritis, 6 of 16 (37.5%) funisitis, and 12 of 16 (75.0%) had chorionic vasculitis. No differences (p > 0.05) were seen between ACA and diagnosis or clinical outcome (Fisher exact test). Of the 16 cases, 14 with ACA that later developed either NEC or SIP showed vasculitis in the umbilical cord and/or chorionic plate and/or stem villi vasculature. The association between ACA and vasculitis was highly significant (p < 0.01). Of those with ACA on placental histology, 12 of 16 (75.0%) cases were found to have intermediate-advanced stage fetal inflammatory response (FIR), whereas 13 of 16 (81.3%) had grade 2 (severe) FIR. Of the 16 cases, 8 (50.0%) had evidence of fibrin deposition/early thrombus formation within placental and/or umbilical vasculature. These were associated with vascular endothelial injury in vessels with prominent vasculitis.
  
  
  CONCLUSIONS
  NEC or SIP shows a significant association with ACA with presence of vasculitis as part of the FIR (p < 0.01). In a proportion of cases, the development of fibrin deposition in response to vasculitic endothelial damage of the placental vasculature may form part of the mechanism linking ACA and early postnatal development of NEC and/or SIP.
authors.affiliation: Sheffield Medical School, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ducey
authors.affiliation: Department of Paediatric Surgery, Sheffield Children's Hospital NHS Foundation Trust, Sheffield, United Kingdom.
authors.forename: Anthony
authors.initials: A
authors.lastname: Owen
authors.affiliation: Neonatal Unit, Sheffield Teaching Hospitals, Sheffield, United Kingdom.
authors.forename: Robert
authors.initials: R
authors.lastname: Coombs
authors.affiliation: Department of Histopathology, Sheffield Children's Hospital, Western Bank, Sheffield, United Kingdom.
authors.forename: Marta
authors.initials: M
authors.lastname: Cohen
mesh_terms: D000208:Acute Disease; D002821:Chorioamnionitis / Q000473:pathology*; D020345:Enterocolitis, Necrotizing / Q000150:complications / Q000473:pathology*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000473:pathology*; D007416:Intestinal Perforation / Q000150:complications / Q000473:pathology*; D010920:Placenta / Q000098:blood supply / Q000473:pathology*; D011247:Pregnancy; D012189:Retrospective Studies; D014657:Vasculitis / Q000150:complications / Q000473:pathology*