1003 Erythropoietin (Epo) for moderate hypoxic-ischaemic encephalopathy (HIE)

Various summaries in this series have dealt with Epo as a neuroprotectant and its ability to protect against damage caused by a diversity of neuropathological conditions (see 0317, 0515, 0524). Erythropoietin decreases glutamate activity, induces the generation of neuronal anti-apoptotic factors, reduces inflammation, decreases nitric oxide-mediated injury and has direct anti-oxidant effects. Given this potential to protect, it was inevitable that researchers would turn to the possibility of a role for Epo in the management of HIE. A preliminary report/review appears in a recent article in Current Opinion in Pediatrics, with the authors being cautiously optimistic regarding the use of repeated, early, high-dose Epo as a neurotherapeutic agent for neonatal brain injury. The review begins by citing Epo’s safety in the many studies in which it has been used to prevent or treat anaemia. Most of the studies have used doses between 35 and 750U/kg/dose, but two recent studies have used much higher doses (up to 2500 and 3000U/kg/dose) without apparent Epo-related complications. The review proceeds with references to prospective and retrospective studies showing that Epo-exposed preterm infants have improved neurodevelopment when studied for up to two years, and then refers to the positive results obtained in a trial of Epo for moderate to severe HIE in term infants. 83 received Epo vs 84 controls, with 300 or 500U/kg given within the first 48 hours and then on alternate days for 2 weeks. Epo improved neurologic signs at 7, 14 and 28 days, reduced disability for moderate HIE, decreased the number of MDI scores below 70, and reduced the incidence of CP at 18 months of age. Death or disability occurred in 43.8% of controls vs 24.6% of Epo-treated. As has been found with hypothermic treatment, intervention was only effective for moderate injury. Combination trials are being contemplated (Epo plus hypothermia).

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Curr Opin Pediatr 19 Jan 2010; epub ahead of print
Lancet 2005; 365: 1890-2
Pediatrics 2009; 124: e218-226 and e681-7