Evaluating the safety and efficacy of Erythropoietin therapy for Neonatal Hypoxic Ischemic Encephalopathy: A systematic review and meta-analysis

Abstract

Background

Erythropoietin (EPO) is a proposed drug for the treatment of neonatal hypoxic ischemic encephalopathy (HIE). Multiple studies have linked its use, either as a monotherapy or in conjunction with therapeutic hypothermia (TH), with improved neonatal outcomes including death and neurodisability. However, there is also evidence in the literature that raises concerns about its efficacy and safety for the treatment of neonatal encephalopathy (NE).

Methods

We searched MEDLINE, Cochrane CENTRAL, and Embase for both observational studies and Randomised Control Trials (RCT) investigating the effectiveness of EPO in treating neonatal encephalopathy. Only studies in which at least 300U/kg of EPO was used and reported any one of the following outcomes: death, death or neurodisability, and cerebral palsy, were included.

Results

7 studies with 903 infants with the diagnosis of Neonatal Encephalopathy (NE) were included in our meta-analysis. EPO did not reduce the risk of death or neurodisability (risk ratio 0.68 [95% CI: 0.43-1.09]) (P=0.11). Similarly, the risk of cerebral palsy was not reduced by the administration of EPO (risk ratio 0.68 [95% CI: 0.33-1.40]) (P=0.30). The risk of death was also not reduced at any dose of EPO regardless of the use of TH.

Conclusion

The results of our meta-analysis do not support the use of EPO for the treatment of neonatal encephalopathy. However, future large-scale RCTs are needed to strengthen these findings.