Abstract 1559 Neonatal Immunology & Hematology Poster Symposium, Monday, 5/3

Objective: We previously reported that erythropoietin (Epo) is present in human cerebral spinal fluid (CSF). It is not known whether CSF Epo concentrations increase under conditions of central nervous system (CNS) injury, and if so, whether this is the result of loss of blood barrier integrity, or a net increase in CNS Epo production. We hypothesized that 1) Epo concentrations in the CSF are higher among neonates with brain injury (asphyxia, IVH, or meningitis) than in those without such injury, and 2) in neonates who have no evidence of brain injury, Epo does not cross the blood-brain barrier, but in neonates with asphyxia, IVH, or meningitis, Epo does so.

Study design: Paired CSF and blood samples (n=125) were obtained from 117 neonates and children categorized as follows: 20-asphyxia, 31-meningitis, 11-IVH, 20-neonatal controls, and 20-control children aged > one month. Twelve infants treated with recombinant (r)Epo, and eleven additional samples from children with miscellaneous neurological problems were also evaluated. Epo concentrations were measured by ELISA in paired CSF and plasma samples.

Results: CSF and plasma Epo concentrations were significantly higher in asphyxiated infants than in controls (170.8 ± 117.4 vs 4.5 ± 0.5 mU/mL; mean ± SEM, p< 0.05 respectively in CSF; 1,359.0 ± 949.0 vs 5.2 ± 0.46, p < 0.05 in plasma). Neonates with IVH had higher CSF Epo concentrations than controls (p < 0.01), but did not have higher plasma Epo concentrations than controls. Patients with meningitis did not have elevated CSF or plasma Epo concentrations. There was no correlation between CSF and plasma Epo concentrations in infants treated with rEpo.

Conclusions: Epo is selectively increased in the CSF by hypoxia, less so by IVH, and not at all by meningitis. rEpo treatment does not elevate CSF Epo in normal premature infants. These findings suggest that rEpo does not cross the blood brain barrier in normal infants, or in infants with CNS injury, and that systemic or local hypoxia induces increased CNS synthesis of Epo.