Therapeutic hypothermia in severe hypoxic-ischemic encephalopathy: a cost-effectiveness analysis

Background: The incidence of hypoxic-ischemic encephalopathy (HIE) is 0.5 per 1,000 live births. Current standard treatment is therapeutic hypothermia (cooling) begun within 6 hours of life. In infants with severe HIE, this results in fewer deaths; however, more infants survive with major neurodevelopmental disability. Objective: We sought to determine whether cooling is cost-effective compared to no cooling in cases of severe HIE, and to compare it to the cost-effectiveness of cooling in cases of moderate HIE. Study design: A decision analytic model using TreeAge Pro (2020) software was designed comparing cooling to no cooling in a cohort of 5,800 term neonates with HIE. Model inputs were derived from the literature. Utilities were applied to life expectancy to generate quality-adjusted life years (QALYs). All costs and QALYs were discounted at an annual rate of 3%. The strategy was considered cost-effective if the incremental cost-effectiveness ratio (ICER) was below the willingness-to-pay threshold of $100,000 per QALY. Sensitivity analyses were conducted to assess the robustness of the results. Results: Cooling for the management of severe HIE resulted in increased costs and increased QALYs, with an ICER of 6,864. In our theoretical cohort, cooling resulted in 835 fewer neonatal deaths, but 52 additional cases of severe neurological disability with cooling due to increased survival. When varying the probability of a healthy child with cooling in univariate sensitivity analysis, cooling was found to be the cost-effective strategy across all ranges and the dominant (lower costs, higher QALYs) strategy above 68% (baseline estimate: 63%). Multivariate sensitivity analysis found cooling was the cost-effective strategy 99.7% of the time. Conclusion: Cooling is the cost-effective intervention with improved outcomes for neonates with severe perinatal hypoxic-ischemic encephalopathy over a wide range of assumptions. Despite the increased cost, more neonates survive morbidity free when compared with no cooling.