Temporal Trends in the Severity and Mortality of Neonatal Hypoxic-Ischemic Encephalopathy in the Era of Hypothermia

Abstract

<b><i>Introduction:</i></b> There is a paucity of studies examining temporal trends in the incidence and mortality of moderate-to-severe hypoxic-ischemic encephalopathy (HIE) during the last decade of therapeutic hypothermia (TH). <b><i>Methods:</i></b> Multicenter cross-sectional study of all infants ≥35 weeks gestational age diagnosed with moderate-to-severe HIE within 6 h of birth in an extensive region of Spain between 2011 and 2019, in order to detect trend changes over time in the (1) annual incidence, (2) severity of neurological and systemic organ involvement, and (3) neonatal death from HIE. <b><i>Results:</i></b> Annual incidence rate of moderate-to-severe HIE was 0.84 (95% confidence interval [CI] 0.7–0.97) per 1,000 births, without trend changes over time (<i>p</i> = 0.8), although the proportion of severe HIE infants showed an average annual decline of 0.86 points (95% CI 0.75–0.98). There were 102 (70%) infants diagnosed with moderate HIE and 44 (30%) with severe HIE. TH was offered to 139/146 (95%) infants. Infants with clinical and/or electrical seizures showed a decreasing trend from 56 to 28% (<i>p</i> = 0.006). Mortality showed a nonstatistically significant decline (<i>p</i> = 0.4), and the severity of systemic damage showed no changes (<i>p</i> = 0.3). Obstetric characteristics remained unchanged, while higher perinatal pH values (<i>p</i> = 0.03) and Apgar scores (<i>p</i> = 0.05), and less need for resuscitation (<i>p</i> = 0.07), were found over time. <b><i>Conclusion:</i></b> The annual incidence of moderate-to-severe HIE has stabilized at around 1 per 1,000 births, with a temporal trend toward a decrease in severe HIE infants and a slight decline of mortality. No association was found between temporal trends and changes in perinatal/obstetric characteristics over time.