Human Recombinant Erythropoietin in Asphyxia Neonatorum: Pilot Trial

Abstract

WHAT'S KNOWN ON THIS SUBJECT:Neuronal apoptosis that follows hypoxia-ischemia is triggered by upregulation of NO synthase, with excessive accumulation of NO and release of excitatory amino acids such as glutamate. Animal studies demonstrated the ability of erythropoietin to attenuate these mechanisms. WHAT THIS STUDY ADDS:The administration of erythropoietin to infants with asphyxia with mild/moderate HIE was associated with favorable decreases in endogenous NO production, decreases in seizure activity, and improved neurodevelopmental outcomes to 6 months of age. 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 ϭ 15), a HIEerythropoietin group (N ϭ 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 ϭ 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 Ͻ .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 ϭ .01) and NO concentrations decreased (P Ͻ .001) in the HIEerythropoietin 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 ϭ .03) and developmental (P ϭ .03) abnormalities. CONCLUSION:This study demonstrates the feasibility of early administration of human recombinant erythropoietin to term neonates with HIE, to protect against encephalopathy.

The effect of erythropoietin on the severity of retinopathy of prematurity

“…Nevertheless, we believe that this finding is of importance as rHuEPO has a crucial role in the field of neonatal medicine. In recent years, both animal studies 24,25 and human clinical trials 16,26 have demonstrated that the use of rHuEPO reduces the severity of perinatal asphyxia, thus reducing the risk of disability in neonates. There is evidence to suggest that EPO has a protective effect on the developing kidney, 27 in the treatment of periventricular leukomalacia in neonates, 28 and in the reduction in ventilatory support time in preterm neonates.…”

High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial

“…[4][5][6]8 Two small trials in China and Egypt found that Epo therapy improved short-term neurologic outcomes after HIE. 18,19 However, these trials used alternative dosing regimens and did not include the use of hypothermia. In countries where therapeutic hypothermia has become a standard of care, [20][21][22] novel neuroprotective agents should be evaluated together with hypothermia.…”

Recombinant human erythropoietin improves neurological outcomes in very preterm infants

“…EPO produced in the central nervous system7 is upregulated after insult and plays a role in neuroprotection 8, 9, 10, 11. Experimental studies have reported that rhEPO possesses neuroprotective properties in different neonatal brain injury animal models,12, 13 and clinical studies have shown that rhEPO treatment reduces brain injury and the incidence of neurological disabilities in infants 8, 14, 15, 16, 17. In addition, improved neurodevelopmental outcomes have been observed in preterm infants with anemia after rhEPO treatment 17, 18, 19, 20.…”