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Published on: January 7, 2018
Erythropoietin improves neurodevelopmental outcome of extremely preterm infants
Achim-Peter Neubauer1, Wolfgang Voss, Michael Wachtendorf
1Children's Hospital Auf der Bult, Hannover, Germany. neubauer-hannover@t-online.de
Insights
Recombinant human erythropoietin (rEpo) treatment improved school-age neurodevelopmental outcomes in extremely low birth weight (ELBW) infants, particularly those with intraventricular hemorrhage (IVH). This suggests rEpo is a promising therapy for high-risk infants.
Area of Science:
- Neonatal Medicine
- Neuroscience
- Developmental Pediatrics
Background:
- Erythropoietin (Epo) shows neuroprotective potential in animal models.
- Neurodevelopmental outcomes of extremely low birth weight (ELBW) infants are a significant clinical concern.
- Previous research has not evaluated the long-term neurodevelopmental effects of recombinant human erythropoietin (rEpo) in ELBW infants.
Purpose of the Study:
- To investigate the school-age neurodevelopmental and school outcomes of ELBW infants treated with rEpo.
- To determine if rEpo exhibits a neuroprotective effect in ELBW infants, especially those with intraventricular hemorrhage (IVH).
Main Methods:
- A cohort of 200 ELBW infants treated between 1993-1998 was followed up to 10-13 years of age.
- Neurodevelopmental outcomes of 89 rEpo-treated infants were compared to 57 untreated infants.
- Analyses of variance (ANOVAs) assessed the impact of rEpo treatment and IVH on intelligence quotient (IQ) scores.
Main Results:
- rEpo-treated infants showed significantly better overall development (55% vs 39%) and higher mean IQ scores (90.8 vs 81.3) compared to controls.
- These benefits were primarily observed in ELBW infants with IVH, who showed marked improvements in development (52% vs 6%) and IQ (90.3 vs 67.0) with rEpo treatment.
- ELBW infants without IVH did not show significant differences in outcomes between treated and untreated groups.
Conclusions:
- This observational study supports a neuroprotective role for rEpo in ELBW infants who experience IVH.
- rEpo represents a potential preventative therapeutic strategy for high-risk ELBW infants.
- Further research may elucidate the mechanisms underlying rEpo's neuroprotective effects in neonates.
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.
Interpretation:
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.
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