To assess the effects of therapeutic erythropoietin (EPO) compared to standard supportive treatment on death, long term neurodevelopmental disability and clinically important side effects in preterm infants (less than 35 weeks postmenstrual age (PMA)) with hypoxic ischaemic encephalopathy (HIE).
Secondary objectives include assessment of the adverse effects of EPO and effects on early prognostic indicators of adverse outcome (severity of electroencephalogram (EEG) abnormality; seizures (and number of anticonvulsants used); imaging appearance of areas of hyperintensity on diffusion weighted (DW) images; basal ganglia, posterior limb of internal capsule (PLIC) and/or white matter (WM) injury; parasagittal neuronal necrosis on late magnetic resonance imaging (MRI) (> 4 days)).
We plan subgroup analyses on the basis of:
- The dose of EPO:
- placebo or standard supportive treatment versus low doses of EPO (500 IU/kg/week to 1000 IU/kg/week);
- placebo or standard supportive treatment versus high doses of EPO (1001 IU/kg/week to 3000 IU/kg/week);
- placebo or standard supportive treatment versus very high doses of EPO (> 3000 IU/kg/week) .
- Severity of HIE (mild versus moderate versus severe) according to Sarnat staging (Sarnat 1976; Finer 1981):
- stage 1 (Mild): hyperalertness, hyper-reflexia, dilated pupils, tachycardia, absence of seizures;
- stage 2 (Moderate): lethargy, hyper-reflexia,miosis, bradycardia, seizures, hypotonia with weak suck and Moro;
- stage 3 (Severe): stupor, flaccidity, small to midposition pupils which react poorly to light, decreased stretch reflexes, hypothermia and absent Moro.
- Inclusion criteria: electrophysiological plus clinical criteria versus clinical criteria alone.
- Gestational age
- < 30 weeks PMA;
- ≥ 30 weeks PMA.
This is a protocol.