195 Prenatal Inflammation, Brain Damage and Two-Year Neurologic Outcome in Very Preterm Infants

Abstract

Background: Intrauterine inflammation has been associated with preterm birth and with fetal inflammatory response affecting various organs including immature brain. Prenatal etiology has been defined in a majority of term infants with later neurologic sequela but only in a minority of very preterm infants. Risk factors of cerebral white matter damage (WMD) may differ between term and preterm infants.Objective: To examine whether prenatal inflammation serves as a risk factor of WMD and poor neurologic and neurocognitive outcome in infants born before 32 weeks of gestation with birth weight under 1000 g.Design/Methods: A regional cohort of 61 infants born between 1998 and 2002 were enrolled in a prospective follow-up study. Medical records during hospitalization were observed. Placental pathology was examined. Sera from umbilical cord blood were analyzed for proinflammatory cytokines (IL-1 alpha, IL-1 beeta, IL-6, IL-8, TNF-alpha). Serial brain ultrasound examinations and magnetic resonance imaging were performed. Neurologic and neurocognitive outcome were assessed at two years of corrected age. The study was approved by the ethics committee of Oulu University Hospital.Results: Histologic chorioamnionitis (HCA) and high IL-6 predicted spontaneous preterm labor with high accuracy. High IL-6 and IL-8 associated with HCA. Intraventricular hemorrhage grade 2 to 3 was predicted by HCA (OR 8.1, 95%CI 1.6 - 42.5). Neither HCA or the cytokines directly associated with WMD, poor neurologic, or poor neurocognitive outcome. However, HCA and concomitant placental perfusion defect increased the risk of poor neurologic outcome (OR 15.2, 95%CI 1.3 - 181) and together with WMD additively predicted poor outcome. Several clinical factors describing cardiopulmonary instability after birth associated with WMD and with poor neurologic outcome.Conclusions: HCA and fetal cytokine response are not risk factors of WMD in very preterm extremely low birth weight infants. Present results support the theory of a complexity of pathogenetic mechanisms leading to poor neurologic outcome.