title: Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants.
abstract: OBJECTIVE
  To test the hypothesis that increasing severity of the fetal inflammatory response (FIR) would have a dose-dependent relationship with severe neurodevelopmental impairment or death in extremely preterm infants.
  
  
  METHODS
  We report 347 infants of 23-28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or neurodevelopmental impairment at the 18- to 22-month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1, phlebitis; stage 2, arteritis with or without phlebitis; stage 3, subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis).
  
  
  RESULTS
  A FIR was detected in 110 placentas (32%). The rate of severe neurodevelopmental impairment/death was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs 35%; P < .05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with a higher rate of severe neurodevelopmental impairment/death (47% vs 23%; P < .05). After adjustment for confounding factors, only subacute necrotizing funisitis (risk ratio, 1.87; 95% CI, 1.04-3.35; P = .04) and chorionic plate vasculitis with thrombosis (risk ratio, 2.21; 95% CI, 1.10-4.46; P = .03) were associated with severe neurodevelopmental impairment/death.
  
  
  CONCLUSIONS
  Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, AL 35249, USA.
authors.forename: Ariel A
authors.initials: AA
authors.lastname: Salas
authors.forename: Ona M
authors.initials: OM
authors.lastname: Faye-Petersen
authors.forename: Brian
authors.initials: B
authors.lastname: Sims
authors.forename: Myriam
authors.initials: M
authors.lastname: Peralta-Carcelen
authors.forename: Stephanie D
authors.initials: SD
authors.lastname: Reilly
authors.forename: Gerald
authors.initials: G
authors.lastname: McGwin
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Carlo
authors.forename: Namasivayam
authors.initials: N
authors.lastname: Ambalavanan
mesh_terms: D000328:Adult; D001766:Blindness / Q000209:etiology; D002547:Cerebral Palsy / Q000209:etiology; D002821:Chorioamnionitis / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D003072:Cognition Disorders / Q000209:etiology; D002658:Developmental Disabilities / Q000175:diagnosis / Q000209:etiology*; D005260:Female; D005500:Follow-Up Studies; D034381:Hearing Loss / Q000209:etiology; D006801:Humans; D007223:Infant; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D008297:Male; D009422:Nervous System Diseases / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D009468:Neuromuscular Diseases / Q000209:etiology; D009483:Neuropsychological Tests; D016012:Poisson Distribution; D011247:Pregnancy; D012044:Regression Analysis; D012189:Retrospective Studies; D012720:Severity of Illness Index
keywords: Adjusted risk ratio; BSID III; Bayley Scales of Infant and Toddler Development, Third Edition; FIR; Fetal inflammatory response; HCA; Histological chorioamnionitis; IVH; Intraventricular hemorrhage; RR; Risk ratio; aRR