Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants

J Pediatr. 2013 Sep;163(3):652-7.e1-2. doi: 10.1016/j.jpeds.2013.03.081. Epub 2013 May 8.

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.

Study design: 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.

Conclusion: Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.

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.

MeSH terms

  • Adult
  • Blindness / etiology
  • Cerebral Palsy / etiology
  • Chorioamnionitis / mortality
  • Chorioamnionitis / pathology
  • Chorioamnionitis / physiopathology*
  • Cognition Disorders / etiology
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / etiology*
  • Female
  • Follow-Up Studies
  • Hearing Loss / etiology
  • Humans
  • Infant
  • Infant, Extremely Premature*
  • Infant, Newborn
  • Infant, Premature, Diseases / diagnosis
  • Infant, Premature, Diseases / etiology*
  • Infant, Premature, Diseases / mortality
  • Male
  • Nervous System Diseases / diagnosis
  • Nervous System Diseases / etiology*
  • Nervous System Diseases / mortality
  • Neuromuscular Diseases / etiology
  • Neuropsychological Tests
  • Poisson Distribution
  • Pregnancy
  • Regression Analysis
  • Retrospective Studies
  • Severity of Illness Index