title: Chorioamnionitis and early childhood outcomes among extremely low-gestational-age neonates.
abstract: OBJECTIVE
  Chorioamnionitis is strongly linked to preterm birth and neonatal infection. The association between histological and clinical chorioamnionitis and cognitive, behavioral, and neurodevelopmental outcomes among extremely preterm neonates is less clear. We evaluated the impact of chorioamnionitis on 18- to 22-month neurodevelopmental outcomes in a contemporary cohort of extremely preterm neonates.
  
  
  OBJECTIVE
  To compare the neonatal and neurodevelopmental outcomes of 3 groups of extremely low-gestational-age infants with increasing exposure to perinatal inflammation: no chorioamnionitis, histological chorioamnionitis alone, or histological plus clinical chorioamnionitis.
  
  
  METHODS
  Longitudinal observational study at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Two thousand three hundred ninety extremely preterm infants born at less than 27 weeks' gestational age (GA) between January 1, 2006, and December 31, 2008, with placental histopathology and 18 to 22 months' corrected age follow-up data were eligible.
  
  
  METHODS
  Chorioamnionitis.
  
  
  METHODS
  Outcomes included cerebral palsy, gross motor functional limitation, behavioral scores (according to the Brief Infant-Toddler Social and Emotional Assessment), cognitive and language scores (according to the Bayley Scales of Infant and Toddler Development, Third Edition), and composite measures of death/neurodevelopmental impairment. Multivariable logistic and linear regression models were developed to assess the association between chorioamnionitis and outcomes while controlling for important variables known at birth.
  
  
  RESULTS
  Neonates exposed to chorioamnionitis had a lower GA and higher rates of early-onset sepsis and severe periventricular-intraventricular hemorrhage as compared with unexposed neonates. In multivariable models evaluating death and neurodevelopmental outcomes, inclusion of GA in the model diminished the association between chorioamnionitis and adverse outcomes. Still, histological plus clinical chorioamnionitis was associated with increased risk of cognitive impairment as compared with no chorioamnionitis (adjusted odds ratio [OR], 2.38 [95% CI, 1.32 to 4.28] without GA; adjusted OR, 2.00 [95% CI, 1.10 to 3.64] with GA as a covariate). Histological chorioamnionitis alone was associated with lower odds of death/neurodevelopmental impairment as compared with histological plus clinical chorioamnionitis (adjusted OR, 0.68 [95% CI, 0.52 to 0.89] without GA; adjusted OR, 0.66 [95% CI, 0.49 to 0.89] with GA as a covariate). Risk of behavioral problems did not differ statistically between groups.
  
  
  CONCLUSIONS
  Antenatal exposure to chorioamnionitis is associated with altered odds of cognitive impairment and death/neurodevelopmental impairment in extremely preterm infants.
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, Michigan.
authors.forename: Athina
authors.initials: A
authors.lastname: Pappas
authors.affiliation: Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina.
authors.forename: Douglas E
authors.initials: DE
authors.lastname: Kendrick
authors.affiliation: Department of Pediatrics, Wayne State University, Detroit, Michigan.
authors.forename: Seetha
authors.initials: S
authors.lastname: Shankaran
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Stoll
authors.affiliation: Department of Pediatrics, University of Iowa, Iowa City.
authors.forename: Edward F
authors.initials: EF
authors.lastname: Bell
authors.affiliation: Department of Pediatrics, Women & Infants' Hospital, Brown University, Providence, Rhode Island.
authors.forename: Abbott R
authors.initials: AR
authors.lastname: Laptook
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Michele C
authors.initials: MC
authors.lastname: Walsh
authors.affiliation: Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland.
authors.forename: Abhik
authors.initials: A
authors.lastname: Das
authors.affiliation: Department of Pediatrics, Emory University School of Medicine, Children's Healthcare of Atlanta, Atlanta, Georgia.
authors.forename: Ellen C
authors.initials: EC
authors.lastname: Hale
authors.affiliation: Department of Pediatrics, Rainbow Babies & Children's Hospital, Case Western Reserve University, Cleveland, Ohio.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Newman
authors.affiliation: Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland.
authors.forename: Rosemary D
authors.initials: RD
authors.lastname: Higgins
mesh_terms: D002547:Cerebral Palsy / Q000453:epidemiology; D002653:Child Behavior Disorders / Q000453:epidemiology; D002821:Chorioamnionitis / Q000453:epidemiology*; D003072:Cognition Disorders / Q000453:epidemiology; D002658:Developmental Disabilities / Q000453:epidemiology; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D062071:Infant, Extremely Premature; D007235:Infant, Premature, Diseases / Q000453:epidemiology*; D016014:Linear Models; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D011247:Pregnancy; D012307:Risk Factors; D014481:United States / Q000453:epidemiology