Chorioamnionitis and Two-Year Outcomes in Infants with Hypoxic-Ischemic Encephalopathy

Objective: To determine if chorioamnionitis is associated with an increased risk of adverse 2-year outcomes among infants with hypoxic-ischemic encephalopathy (HIE).

Study design: This cohort study included all infants with moderate to severe HIE treated with therapeutic hypothermia and enrolled on the High-dose Erythropoietin for Asphyxia and Encephalopathy Trial. Clinical chorioamnionitis (CC) was defined as a diagnosis made by a treating obstetrician and histologic chorioamnionitis (HC) was defined as placental inflammation observed on histology. We used proportional odds regression to determine the associations between CC, HC, and an ordinal 2-year neurodevelopmental outcome measure: no neurodevelopmental impairment (NDI), mild NDI, moderate NDI, severe NDI, or death.

Results: Of 500 infants, 65 (13%) were exposed to CC. Of 317 infants with placental data available, 125 (39%) were exposed to HC. Infants exposed to CC (odds ratio 0.57, 95% CI 0.34-0.95) and those exposed to HC (odds ratio 0.62, 95% CI 0.40-0.96) had a lower severity of primary outcome than unexposed infants. Infants exposed to chorioamnionitis also had lower frequencies of sentinel events (CC: P = .001; HC: P = .005), central pattern magnetic resonance imaging brain injury (CC: P = .02; HC: P = .02), and electroencephalogram background abnormalities (CC: P = .046; HC: P = .02), compared with unexposed infants.

Conclusions: Infants with HIE who were exposed to chorioamnionitis had lower severity of 2-year outcomes than unexposed infants. Our findings suggest that chorioamnionitis may lead to a lower severity of brain dysfunction than other pathophysiologic mechanisms of encephalopathy.