Original Investigation |

Chorioamnionitis and Early Childhood Outcomes Among Extremely Low-Gestational-Age Neonates

Athina Pappas, MD1; Douglas E. Kendrick, MStat2; Seetha Shankaran, MD1; Barbara J. Stoll, MD3; Edward F. Bell, MD4; Abbott R. Laptook, MD5; Michele C. Walsh, MD, MS3; Abhik Das, PhD6; Ellen C. Hale, RN, BS, CCRC3; Nancy S. Newman, BA, RN7; Rosemary D. Higgins, MD8; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network
[+] Author Affiliations
1Department of Pediatrics, Wayne State University, Detroit, Michigan
2Social, Statistical, and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina
3Department of Pediatrics, Emory University School of Medicine, Children’s Healthcare of Atlanta, Atlanta, Georgia
4Department of Pediatrics, University of Iowa, Iowa City
5Department of Pediatrics, Women & Infants’ Hospital, Brown University, Providence, Rhode Island
6Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland
7Department of Pediatrics, Rainbow Babies & Children’s Hospital, Case Western Reserve University, Cleveland, Ohio
8Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland
JAMA Pediatr. 2014;168(2):137-147. doi:10.1001/jamapediatrics.2013.4248.
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Importance  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.

Design, Setting, and Participants  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.

Main Exposure  Chorioamnionitis.

Main Outcomes and Measures  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 and Relevance  Antenatal exposure to chorioamnionitis is associated with altered odds of cognitive impairment and death/neurodevelopmental impairment in extremely preterm infants.

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