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The Effect of Erythropoietin on Cerebral Palsy Prevention in Hypoxic Ischemic Encephalopathy (HIE): A Systemic Review and Meta-Analysis

A Systemic Review and Meta-Analysis

  • Fadhilah Tia Nur ,
  • Harsono Salimo ,
  • Hardiono D Pusponegoro ,
  • Ari Probandari ,
  • Bambang Purwanto ,
  • Soetrisno ,
  • Naili Nur Sa’adah Nuhriawangsa ,


Introduction: HIE plays a significant role in global disability, with 60% of newborns with severe HIE passing away or becoming severely disabled. Since there is still debate over the impact of EPO on HIE, we conducted a thorough analysis of the literature to determine whether erythropoietin may prevent cerebral palsy in HIE patients.

Methods: Database search included Cochrane Library, ProQuest, PubMed, ScienceDirect, and Scopus. RCTs reporting cerebral palsy, neurodevelopmental impairments, seizures, brain injury on MRI, or death were included. Qualitative studies were excluded. Critical appraisal was assessed using JBI while the I2, forest plot, and sensitivity analysis were performed on meta-analysis. The funnel plot and Egger’s test were used to assess bias. The GRADE method was used to assess the LOE independently.

Results: A total of 812 infants were included in 6 eligible articles. For the infant with HIE, EPO alone was statistically significant to prevent cerebral palsy in HIE patients (OR=0.90, p = 0.038, 95% confidence interval [95% CI] was 0.57-1.44). Erythropoietin administration also significantly reduced the risk of neurodevelopmental impairments (OR 0.50, p = 0.014, 95% CI 0.36-0.70) and risk of death (OR 0.81, p = 0.018, 95% CI 0.54-1.20). The event rate, which compared EPO vs. control, of cerebral palsy (13.03% vs. 13.43%, p <0.001), neurodevelopmental abnormalities (19.76% vs. 51.86%, p <0.001), seizures (26.75% vs. 37.52%, p <0.001), brain injury on MRI, which divided as white matter, subcortical, cortical, brainstem, and cerebellar (28.55% vs. 68.33%, 25.63% vs. 31.58%, 6.85% vs. 14.53%, 4.73% vs 29.01%, respectively, p <0.001), and death (14.31% vs 20.67%, p <0.001) was reduced.

Conclusion: With only 6 trials included, it is essential to do clinical trials with sufficient power to evaluate erythropoietin further. Researchers and clinicians must collaborate with specialists and form interest groups to define primary and secondary outcomes and acceptable guidelines for using erythropoietin in future trials.


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How to Cite

Nur, F. T. ., Salimo, H. ., Pusponegoro, H. D. ., Probandari, A. ., Purwanto, B. ., Soetrisno, & Nuhriawangsa, N. N. S. . (2024). The Effect of Erythropoietin on Cerebral Palsy Prevention in Hypoxic Ischemic Encephalopathy (HIE): A Systemic Review and Meta-Analysis: A Systemic Review and Meta-Analysis. Bali Medical Journal, 13(1), 635–646.




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Fadhilah Tia Nur
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Harsono Salimo
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Hardiono D Pusponegoro
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Ari Probandari
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Bambang Purwanto
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Naili Nur Sa’adah Nuhriawangsa
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