Histological Characteristics of the Fetal Inflammatory Response Associated with Neurodevelopmental Impairment and Death in Extremely Preterm Infants

• Published in: The Journal of pediatrics Vol. 163; no. 3; pp. 652 - 657.e2
• Main Authors: Salas, Ariel A., MD, MSPH, Faye-Petersen, Ona M., MD, Sims, Brian, MD, PhD, Peralta-Carcelen, Myriam, MD, Reilly, Stephanie D., MD, McGwin, Gerald, MS, PhD, Carlo, Waldemar A., MD, Ambalavanan, Namasivayam, MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2013; Mosby, Inc
• Subjects: Adult; arteritis; Blindness - etiology; Cerebral Palsy - etiology; Chorioamnionitis - mortality; Chorioamnionitis - pathology; Chorioamnionitis - physiopathology; Cognition Disorders - etiology; death; Developmental Disabilities - diagnosis; Developmental Disabilities - etiology; Female; Follow-Up Studies; gestational age; Hearing Loss - etiology; Humans; Infant; Infant, Extremely Premature; Infant, Newborn; Infant, Premature, Diseases - diagnosis; Infant, Premature, Diseases - etiology; Infant, Premature, Diseases - mortality; infants; inflammation; Male; Nervous System Diseases - diagnosis; Nervous System Diseases - etiology; Nervous System Diseases - mortality; Neuromuscular Diseases - etiology; Neuropsychological Tests; Pediatrics; Poisson Distribution; Pregnancy; Regression Analysis; relative risk; Retrospective Studies; Severity of Illness Index; thrombosis; umbilical cord; vasculitis; aRR; RR; Risk ratio; Bayley Scales of Infant and Toddler Development, Third Edition; Fetal inflammatory response; BSID III; HCA; IVH; Intraventricular hemorrhage; Histological chorioamnionitis; FIR; Adjusted risk ratio
• ISSN: 0022-3476; 1097-6833
• DOI: 10.1016/j.jpeds.2013.03.081

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.