Survival of premature infants has improved over the past decades, but neurodevelopmental outcome did not. One of the most consistent predictors of long-term developmental disabilities in preterm infants is brain injury, namely intraventricular haemorrhage (IVH) or periventricular haemorrhagic infarction (PVHI). Recombinant erythropoietin (rEPO) enhances repair in a variety of animal models with brain injury. Observational data suggest that rEPO improves long-term cognitive outcome in infants with IVH/PVHI. Recent magnetic resonance imaging (MRI) studies of our group revealed improved white matter (WM) development of high-dose rEPO given with a preventive strategy to preterm infants immediately after birth. Based on these findings we designed a new randomized control trial (RCT) following a therapeutic strategy to investigate rEPO in preterm infants with established IVH/PVHI. Working hypotheses: High dose rEPO treatment after IVH/PVHI compared with control treatment (placebo) leads to: (1) increased neuronal regeneration, restored neuronal integrity, and decreased brain injury; (2) improved short- and long-term neurodevelopment.Specific aims, objectives: (1) to determine the effect of rEPO on brain development in preterm infants with established brain damage, namely IVH/PVHI; (2) to understand the mechanisms of rEPO on brain development and neuronal integrity; (3) to improve cognitive abilities and motor function in those infants treated with rEPO.Experimental methods: (1) Execution of an investigator initiated, randomized, double blind, and multicentre trial of high-dose rEPO in very preterm infants suffering from IVH/PVHI (www.eporepair.ch). (2) Quantifying axonal injury in blood samples, sleep-wake-cycling by aEEG and brain MRI at term equivalent age (TEA) to assess brain growth and development, brain injury and functional network connectivity. (3) Standardized neurological and formal psychological examinations at various time points up to five years of age.Expected value of project: Since there is no specific treatment to ameliorate the neurodevelopmental sequelae of IVH/PVHI in preterm infants, this RCT is the first to test prospectively a promising drug in infants with IVH/PVHI. Recent MRI results showing improved WM development and less WM injuries in preterm infants who received prophylactic rEPO will be verified and MRI sequences, in order to assess functional connectivity, will be acquired.