Trends of Neonatal Hypoxic-Ischemic Encephalopathy Prevalence and Associated Risk Factors in the United States, 2010 to 2018
Authors: Acun Ceyda , Karnati Sreenivas , Padiyar Swetha , Puthuraya Subhash , Aly Hany , Mohamed Mohamed 
Published: May 2023

Neonatal hypoxic ischemic encephalopathy (HIE) is one of the most common causes of neonatal morbidity and mortality worldwide. It has an overall mortality rate ranging from 15% to 25%, with up to 50% of survivors developing long-term neurological disabilities. Therapeutic hypothermia (TH) has been the only effective treatment for moderate to severe HIE in neonates ≥35 weeks of gestation. Infants with mild HIE previously had been excluded from studies, but a recent study reported approximately 16% developed a disability at 18 to 22 months of age. Despite treatment, up to 29% of neonates with HIE still develop adverse outcomes. To decrease the prevalence of neonatal HIE, prevention is key and a better understanding of associated maternal, perinatal, and neonatal risk factors is needed. The aim of this study was to assess trends of HIE prevalence and use of TH, mortality, and clinical neonatal outcomes.

This was a cross-sectional analysis using National Inpatient Sample data sets from 2010 to 2018. Included were newborn infants diagnosed with HIE or asphyxia, who were ≥35 weeks of gestation and had a birth weight ≥2500 g. Excluded were those with congenital heart disease, congenital central nervous system anomalies, congenital lung anomalies, congenital abdominal wall defects, gastroschisis or omphalocele, multiple congenital anomalies, common syndromes, and chromosomal disorders.

Of the 32,180,617 infants included in the analysis, 31,249,100 were term infants (>35 weeks). The prevalence of all degrees of HIE for term infants was approximately 0.1%. There was a modest increase from 0.093% during the years 2010 and 2012 up to 0.097% during 2016 and 2018. Approximately 21% of cases were managed with TH. More infants with moderate HIE received TH than those with severe HIE (29.9% vs 19.9%; P < 0.01). Fewer infants with mild or unspecified HIE received TH than those with severe HIE (17.7% and 17.3%, respectively; P < 0.01). From 2010 to 2018, the use of TH increased overall and within each grade of HIE (P < 0.01). The mortality rate was higher in term infants with all degrees of asphyxia than the general population (10.8% vs 0.06%; P < 0.01). Over time, the mortality rate in term infants decreased from 12.3% in 2010 to 8.3% in 2018 (P < 0.01).

The analysis included 931,517 were late preterm infants (35–36 weeks of gestation). The combined prevalence for all grades of HIE was 0.23% and did not change significantly over the years. Approximately 21% of late preterm infants were managed with TH. More infants with moderate HIE received TH than those with severe HIE (26.9% vs 20.1%). Fewer infants with mild HIE received TH (13.2%), and no significant difference was observed in infants with unspecified HIE compared with those with severe HIE (18.7% vs 20.1%). The use of TH increased has increased in late preterm infants over the years.

The strongest factors associated with HIE were placental infarction or insufficiency, placental abruption, and cord prolapse. Female infant sex, maternal Hispanic ethnicity, and maternal Asian race were associated with lower risk of HIE.

In conclusion, HIE prevalence remained essentially the same at 1 per 1000 live births. Use of TH increased, and mortality decreased over time. The strongest factors associated with HIE were placental factors.