Effects of erythropoietin in neonates with hypoxic-ischemic encephalopathy receiving therapeutic hypothermia

Background: Minimizing multiple organ dysfunction-related mortality and morbidity is a critical issue for patients with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH). Although erythropoietin (EPO) has demonstrated protective effects on various hypoxic-ischemic organs in animal studies and clinical trials in adults, its effects on neonates with HIE require further investigation. Methods: This study retrospectively analyzed the medical records of neonates with HIE who received TH with or without EPO (TH+EPO vs TH groups) administration in a tertiary referral hospital from January 2016 to January 2021. Data regarding patient characteristics, medical treatment, and clinical (neurological, cardiac, respiratory, gastrointestinal, hepatic, and renal) function assessments were collected. To control for confounding factors and selection bias between the two groups, a 1: 1 propensity matching method was applied. Results: A total of 45 neonates with HIE received TH during the study period, with 24 patients (53%) in the TH+EPO group. After matching, each group enrolled 13 cases. No significant difference in mortality or hospital stay between the two groups was noted. During the first 3 days, the patients in the TH+EPO group showed significantly higher blood pressure (BP) than those in the TH group (p < 0.05 on day 1). The TH+EPO group showed trends of higher blood hemoglobin (p > 0.05) and creatinine (p > 0.05) levels and lower estimated glomerular filtration rate (p > 0.05) and urine output (p > 0.05) during the first 2 weeks than TH group. Conclusion: The use of EPO in addition to TH is safe for neonates with HIE. The neonates with moderate or severe HIE who received EPO may have a lesser risk of hypotension than those who received TH alone. Further clinical studies on renal and cardiac functions and long-term neurological effects of EPO are required.