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Original Investigation
June 2018

Association of Histologic Chorioamnionitis With Perinatal Brain Injury and Early Childhood Neurodevelopmental Outcomes Among Preterm Neonates

Author Affiliations
  • 1Department of Paediatrics, The Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
  • 2Department of Paediatrics, Children’s Hospital of Eastern Ontario, Ottawa, Ontario, Canada
  • 3Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, the Netherlands
  • 4Department of Pediatrics, UCSF (University of California, San Francisco) Benioff Children’s Hospital, San Francisco
  • 5Department of Neurology, UCSF Benioff Children’s Hospital, San Francisco
  • 6Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada
  • 7Brain, Behaviour, and Development, BC Children’s Hospital Research Institute, Vancouver, British Columbia, Canada
  • 8Department of Epidemiology and Biostatistics, UCSF Benioff Children’s Hospital, San Francisco
  • 9Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  • 10Department of Anatomical Pathology, BC Women’s and Children’s Hospital and Health Centre, Vancouver, British Columbia, Canada
  • 11Department of Pathology and Laboratory Medicine, University of British Columbia, Vanouver, British Columbia, Canada
  • 12Department of Radiology, UCSF Benioff Children’s Hospital, San Francisco
JAMA Pediatr. 2018;172(6):534-541. doi:10.1001/jamapediatrics.2018.0102
Key Points

Question  Is histologic chorioamnionitis associated with perinatal brain injury and adverse neurodevelopmental outcomes among children born preterm?

Findings  In this multicenter cohort study of 350 children, histologic chorioamnionitis was not associated with perinatal intraventricular hemorrhage or punctate white matter injury nor with lower motor or cognitive scores at 18 to 24 months’ corrected age.

Meaning  Histologic chorioamnionitis is not associated with adverse early childhood neurodevelopmental outcomes among preterm neonates.


Importance  Understanding the role of chorioamnionitis, a major factor leading to preterm birth, in the pathogenesis of neonatal brain injury and adverse neurodevelopmental outcomes may help in identifying potentially modifiable perinatal variables affecting brain health and outcomes among children born preterm.

Objective  To evaluate whether histologic chorioamnionitis among neonates born very preterm is associated with intraventricular hemorrhage (IVH) and punctate white matter injury (WMI) or with adverse neurodevelopmental outcomes during early childhood.

Design, Setting, and Participants  Prospective cohort study conducted across 3 academic centers (from April 2006 to September 2013 in Canada, from March 2007 to March 2013 in the Netherlands, and from January 2004 to August 2011 in the United States). Children who were born preterm (24-32 weeks’ gestation) and who had undergone a placental pathologic evaluation, magnetic resonance imaging as soon as clinically stable, and Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III) assessments between 18 and 24 months’ corrected age (CA) were included. Magnetic resonance imaging scans were assessed for grade of IVH and volume of punctate WMI. Data analysis occurred between December 2016 and January 2018. Final multivariable analyses examining the association of chorioamnionitis with motor and cognitive outcomes accounted for academic center and perinatal and postnatal factors.

Main Outcomes and Measures  Punctate WMI volume and IVH detected on neonatal magnetic resonance imaging scans; motor and cognitive outcomes defined using Bayley-III assessments conducted among these children between 18 and 24 months’ CA.

Results  Of 350 neonates (182 male) in the final cohort, 145 (41.4%) had histologic chorioamnionitis. Gestational age was significantly lower among those with chorioamnionitis (median, 26.4 weeks; interquartile range [IQR], 25.6-27.7 weeks) than among those without chorioamnionitis (median, 28.0 weeks; IQR, 27.0-29.7 weeks). Chorioamnionitis was not associated with IVH or WMI, nor was it associated with worse motor outcomes in univariable or multivariable analyses (adjusted Bayley-III motor score, −2.2; 95% CI, −5.6 to 1.3). Cognitive scores were marginally yet statistically significantly lower among children with chorioamnionitis (median, 105; IQR, 95-110) than among those without chorioamnionitis (median, 105; IQR, 100-115) in the univariable model. This difference was attenuated in the multivariable model (adjusted Bayley-III cognitive score, −3.0; 95% CI, −6.4 to 0.4).

Conclusions and Relevance  Histologic chorioamnionitis was not associated with IVH or WMI near birth or with worse cognitive or motor outcomes from 18 to 24 months’ CA after accounting for perinatal factors. Postnatal factors attenuated the association between chorioamnionitis and neurodevelopmental outcomes, highlighting the importance of preventing postnatal illness, such as infection, to promote optimal outcomes among children born preterm.