Erythropoietin improves neurodevelopmental outcome of extremely preterm infants.
OBJECTIVE
Erythropoietin has been reported to possess neuroprotective properties in animal studies. No previous studies have investigated the neurodevelopmental outcome of extremely low birth weight (ELBW) infants treated with recombinant human erythropoietin (rEpo) and evaluated it at school age.


METHODS
Of 200 ELBW infants treated from 1993 to 1998, 171 (86%) survived, and 148 (87%) were followed up to the age of 10 to 13 years. The neurodevelopmental and school outcome of the ELBW infants receiving rEpo treatment for stimulation of erythropoiesis in the first weeks of life (n = 89) was compared to that of untreated children (n = 57). To test for a neuroprotective effect of erythropoietin therapy, analyses of variance (ANOVAs) were conducted with erythropoietin treatment and intraventricular hemorrhage (IVH) as independent variables and Hamburg-Wechsler Intelligence Test for Children-III (HAWIK-III) intelligence quotient (IQ) scores as dependent variables.


RESULTS
The rEpo group scored significantly better than untreated children in the overall developmental assessment (55% vs 39% normally developed, p < 0.05) as well as in the psychological examination (mean composite HAWIK-III IQ score, 90.8 vs 81.3, p < 0.005). The results of ANOVAs show that these differences were ascribable to children with IVH. Whereas those children with IVH treated with rEpo scored significantly better than untreated children (52% vs 6% normally developed, composite HAWIK-III IQ score, 90.3 vs 67.0), treated and untreated children without IVH did not differ in their outcome. The treatment and control groups were comparable in perinatal parameters relevant to prognosis.


CONCLUSIONS
The results of our observational study confirm the hypothesis of a neuroprotective effect of rEpo in ELBW infants with IVH. This offers a promising preventative therapeutic option for the treatment of these high-risk infants.
Neubauer
Achim-Peter
AP
Children's Hospital Auf der Bult, Hannover, Germany. neubauer-hannover@t-online.de
Voss
Wolfgang
W
Wachtendorf
Michael
M
Jungmann
Tanja
T
D000293:Adolescent; D000367:Age Factors; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D002648:Child; D002658:Developmental Disabilities / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D004921:Erythropoietin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D052577:Infant, Extremely Low Birth Weight / Q000502:physiology*; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000401:mortality; D007361:Intelligence Tests; D008137:Longitudinal Studies; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009483:Neuropsychological Tests; D011994:Recombinant Proteins; D016896:Treatment Outcome; D014463:Ultrasonography / Q000379:methods
D011994:Recombinant Proteins; D004921:Erythropoietin