Human recombinant erythropoietin in asphyxia neonatorum: pilot trial

Pediatrics. 2010 May;125(5):e1135-42. doi: 10.1542/peds.2009-2268. Epub 2010 Apr 12.

Abstract

Objective: The goal was to examine biochemical, neurophysiologic, anatomic, and clinical changes associated with erythropoietin administration to neonates with hypoxic-ischemic encephalopathy (HIE).

Methods: We conducted a prospective case-control study with 45 neonates in 3 groups, a normal healthy group (N = 15), a HIE-erythropoietin group (N = 15; infants with mild/moderate HIE who received human recombinant erythropoietin, 2500 IU/kg, subcutaneously, daily for 5 days), and a HIE-control group (N = 15; did not receive erythropoietin). Serum concentrations of nitric oxide (NO) were measured at enrollment for the normal healthy neonates and at enrollment and after 2 weeks for the 2 HIE groups. The 2 HIE groups underwent electroencephalography at enrollment and at 2 to 3 weeks. Brain MRI was performed at 3 weeks. Neurologic evaluations and Denver Developmental Screening Test II assessments were performed at 6 months.

Results: Compared with normal healthy neonates, the 2 HIE groups had greater blood NO concentrations (P < .001). At enrollment, the 2 HIE groups did not differ in clinical severity, seizure incidence, NO concentrations, or electroencephalographic findings. At 2 weeks of age, electroencephalographic backgrounds improved significantly (P = .01) and NO concentrations decreased (P < .001) in the HIE-erythropoietin group, compared with the HIE-control group; MRI findings did not differ between groups. At 6 months of age, infants in the HIE-erythropoietin group had fewer neurologic (P = .03) and developmental (P = .03) abnormalities.

Conclusion: This study demonstrates the feasibility of early administration of human recombinant erythropoietin to term neonates with HIE, to protect against encephalopathy.

Trial registration: ClinicalTrials.gov NCT00945789.

Publication types

  • Controlled Clinical Trial

MeSH terms

  • Asphyxia Neonatorum / drug therapy*
  • Brain / blood supply
  • Brain / drug effects
  • Brain / pathology
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Electroencephalography / drug effects
  • Erythropoietin / therapeutic use*
  • Female
  • Follow-Up Studies
  • Humans
  • Hypoxia-Ischemia, Brain / diagnosis
  • Hypoxia-Ischemia, Brain / drug therapy*
  • Infant
  • Infant, Newborn
  • Injections, Subcutaneous
  • Magnetic Resonance Imaging
  • Male
  • Neurologic Examination / drug effects
  • Nitric Oxide / blood
  • Prospective Studies
  • Recombinant Proteins

Substances

  • Recombinant Proteins
  • Erythropoietin
  • Nitric Oxide

Associated data

  • ClinicalTrials.gov/NCT00945789