title: Placental pathology is associated with severity of neonatal encephalopathy and adverse developmental outcomes following hypothermia.
abstract: OBJECTIVE
  Although neonatal encephalopathy (NE) due to perinatal asphyxia accounts for a notable proportion of brain injury, the causal pathway remains largely unexplained. We sought to determine the association of placental pathology with: (1) severity of NE in the first 6 hours postnatal, and (2) abnormal neurodevelopmental outcomes (NDO) in neonates requiring hypothermia therapy.
  
  
  METHODS
  This is a retrospective cohort study of neonates ≥36 weeks' gestation born at Parkland Hospital, Dallas, TX, from January 2006 through November 2011 with NE. Placental histology was reviewed and validated by a pediatric pathologist blinded to outcomes. Abnormal NDO was defined as death or Bayley-III score of <85 at 18-24 months of age.
  
  
  RESULTS
  Of 86,274 neonates ≥36 weeks' gestation, 120 had evidence of a combination of perinatal acidosis and NE. In all, 47 had mild NE and received no treatment, while 73 had moderate (n = 70) or severe (n = 3) NE and received systemic hypothermia. Nine neonates died and all survivors receiving hypothermia had a Bayley-III assessment at 22 ± 7 (SD) months of age. Chorioamnionitis with or without fetal response and patchy/diffuse chronic villitis were found to be independently associated with severity of NE (P < .001). Univariate logistic regression revealed an association with a diagnosis of major placental pathology (odds ratio, 3.5; 95% confidence interval, 1.1-11.4) and abnormal outcomes following cooling. Specifically, diffuse chronic villitis (odds ratio, 9.29; 95% confidence interval, 1.11-77.73) was the only individual predictor of abnormal NDO following hypothermia therapy.
  
  
  CONCLUSIONS
  Placental inflammatory villitis appears to be a harbinger of abnormal outcomes in neonates with NE, spanning to the 18-24 month NDO.
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
authors.forename: Imran N
authors.initials: IN
authors.lastname: Mir
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Johnson-Welch
authors.affiliation: Department of Obstetrics and Gynecology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
authors.forename: David B
authors.initials: DB
authors.lastname: Nelson
authors.affiliation: Department of Health System Research, Parkland Hospital at Dallas, Dallas, TX.
authors.forename: Larry S
authors.initials: LS
authors.lastname: Brown
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
authors.forename: Charles R
authors.initials: CR
authors.lastname: Rosenfeld
authors.affiliation: Department of Pediatrics, University of Texas Southwestern Medical Center at Dallas, Dallas, TX. Electronic address: lina.chalak@utsouthwestern.edu.
authors.forename: Lina F
authors.initials: LF
authors.lastname: Chalak
mesh_terms: D002675:Child, Preschool; D002821:Chorioamnionitis / Q000473:pathology; D002824:Chorionic Villi / Q000473:pathology*; D015331:Cohort Studies; D002658:Developmental Disabilities / Q000209:etiology* / Q000517:prevention & control; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000150:complications* / Q000628:therapy; D007223:Infant; D007231:Infant, Newborn; D010920:Placenta / Q000473:pathology*; D011237:Predictive Value of Tests; D011247:Pregnancy; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
keywords: hypothermia; hypoxic ischemic encephalopathy; neonatal encephalopathy; neurodevelopmental outcome