Neuroprotective Effect of High Dose Erythropoietin in Very Preterm Infants

HYPOTHESIS Early administration of human erythropoietin (EPO) in very preterm infants reduces perinatal injury to the brain (retina), lung and gut and improves neurodevelopmental outcome at 24 months corrected age.

PRIMARY OBJECTIVE To determine whether cerebral outcome is improved if infants born between 26 0/7 and 31 6/7 gestational weeks at birth receive erythropoietin in high dose in the first three days after birth.

SECONDARY OBJECTIVES To determine whether early administration of EPO alters the incidence of complications typically associated with preterm birth, i.e. mortality, septicaemia, necrotising enterocolitis, bronchopulmonary dysplasia (oxygen dependency at 36 weeks postmenstrual age), retinopathy, intracranial haemorrhage, white matter disease (periventricular leucomalacia), growth failure, cerebral palsy and handicap at 5 years.

Biomarkers of encephalopathy of prematurity assessed on magnetic resonance imaging (MRI) at term equivalent age.

RATIONALE EPO has been shown to be protective against hypoxic-ischaemic and inflammatory injuries in a broad range of tissues and organs besides promoting red cell formation. It has been shown to have neuroprotective and neurotrophic activity in animals after acute brain damage as well as in adult stroke patients. Several mechanisms explaining this activity have been recognized: EPO inhibits glutamate release in the brain, modulates intracellular calcium metabolism, induces the generation of anti-apoptotic factors, reduces inflammation, decreases nitric oxide-mediated injury, and has direct antioxidant effects.