Trends of neonatal hypoxic-ischemic encephalopathy prevalence and associated risk factors in the United States, 2010 to 2018


      Despite recent advances in perinatal care, neonatal hypoxic-ischemic encephalopathy remains one of the most common causes of neonatal morbidity and mortality. The trends for prevalence and mortality of neonatal hypoxic-ischemic encephalopathy have not been examined in the era of therapeutic hypothermia in the United States.


      This study aimed to determine (1) the overall and gestational age–specific (35–36, ≥37, and >42 weeks) trends of hypoxic-ischemic encephalopathy prevalence and use of therapeutic hypothermia, (2) the trends of mortality in association with hypoxic-ischemic encephalopathy, (3) the confounding variables associated with hypoxic-ischemic encephalopathy, and (4) the clinical outcomes of neonates with hypoxic-ischemic encephalopathy.

      Study Design

      This study used National Inpatient Sample datasets from 2010 to 2018. Moreover, the study included infants with a gestational age of ≥35 weeks with a documented hypoxic-ischemic encephalopathy diagnosis (mild, moderate, severe, or unspecified). We calculated trends in hypoxic-ischemic encephalopathy prevalence and the use of therapeutic hypothermia using chi-squared testing. Furthermore, this study used logistic regression models to control for confounders.


      A total of 32,180,617 infants were included, of which 31,249,100 were term (gestational age of ≥37 weeks) and 931,517 were late preterm (gestational age of 35–36 weeks). Hypoxic-ischemic encephalopathy prevalence slightly increased from 0.093% in 2010–2012 to 0.097% in 2016–2018 (P=.01) in term infants and did not significantly change in late preterm infants (P=.20). There were 6235 term infants (20.8%) and 449 late preterm infants (21.1%) with hypoxic-ischemic encephalopathy who were managed with therapeutic hypothermia. The use of therapeutic hypothermia in both term and late preterm infants has increased over the years (P<.01). The mortality rate with hypoxic-ischemic encephalopathy decreased over time from 11.5% to 12.3% between 2010 to 2012, and from 8.3% to 10.6% betweenn 2016 to 2018 (P<.01). The factors with the strongest association with hypoxic-ischemic encephalopathy were placental infarction or insufficiency (odds ratio, 144; 95% confidence interval, 134–157), placental abruption (odds ratio, 101; 95% confidence interval, 91–112), cord prolapse (odds ratio, 74; 95% confidence interval, 65–84), and maternal anemia (odds ratio, 26; 95% confidence interval, 20–37).


      Hypoxic-ischemic encephalopathy prevalence in neonates essentially remained the same at 1 per 1000 live births. The use of therapeutic hypothermia increased, and the mortality rate decreased in infants with hypoxic-ischemic encephalopathy. The identification of hypoxic-ischemic encephalopathy–associated factors should promote increased vigilance to optimize newborn outcomes.

      Key words

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