Ohls 2001A.

Methods	Double‐blind randomised controlled trial Study location: multi‐centre trial, USA Trial period not stated The study was performed concurrently, as 2 parallel trials based on birth weight, because different primary outcomes were evaluated in each trial. We report under Ohls 2001A on infants with birth weight 401 to 100 grams, and under Ohls 2001B on infants with birth weight 1001 to 1250 grams.
Participants	172 infants with birth weight between 401 grams and 1000 grams, PMA < 32 weeks, and between 24 and 96 hours old at the time of study entry, who were likely to survive > 72 hours
Interventions	87 infants in the EPO group received 400 U/kg EPO (unnamed product) 3 times weekly (1200 IU/kg/week, high dose) IV, or SC when IV access was not available. 85 infants in the placebo/control group received sham SC injections when IV access was not available. An adhesive bandage covered the true and sham injection sites. Treatment was continued until discharge, transfer, death, or 35 completed weeks' corrected GA. Treated infants received a weekly IV infusion of 5 mg/kg iron dextran (high dose) until they had an enteral intake of 60 mL/kg/d. Iron dextran was added to the TPN solution and was administered over 24 hours or was diluted in 10% dextrose in water or normal saline and was administered over 4 to 6 hours. Placebo/control infants received 1 mg/kg iron dextran once a week, administered in a similar manner. Once infants in both groups had enteral intake of 60 mg/kg/d, they were given iron a dose of 3 mg/kg/d. The dose was gradually increased to 6 mg/kg/d, depending on enteral intake. Study infants received enteral vitamin E 15 to 25 IU/d, and enteral folate supplements 25 to 50 mcg/d were provided according to centre practice.
Outcomes	Use of 1 or more red blood cell transfusions Mean number of erythrocyte transfusions per infant (primary outcome) Number of donors the infant was exposed to Total volume of blood transfused per infant Late‐onset sepsis Mortality Chronic lung disease (at 36 weeks' postmenstrual age) ROP Severe IVH (stage ≥ 3) NEC BPD Neutropenia Hypertension Hospital stay At follow‐up (see notes), growth, development, rehospitalization, transfusions
Notes	It is not stated whether infants who had received blood transfusions before study entry were included. Strict protocol was used to administer transfusions during the study period. Of 72 EPO‐treated and 70 placebo‐control infants surviving to discharge, follow‐up data at 18 to 22 months' corrected age were collected on 51 of 72 EPO‐treated infants (71%) and 51 of 70 placebo/controls (73%). Study was supported by grants from Ortho‐Biotech and Schein Pharmaceuticals.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	No information provided
Allocation concealment (selection bias)	Low risk	Blinding of randomisation: yes. All caregivers and investigators (except research nurses) were masked to treatment assignment.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	All caregivers and investigators (except research nurses) were masked to treatment assignment.
Blinding of outcome assessment (detection bias) All outcomes	Low risk	All caregivers and investigators (except research nurses) were masked to treatment assignment.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	All infants were followed through their hospital stay up to 120 days. Of 72 EPO‐treated and 70 placebo‐control infants surviving to discharge, follow‐up data at 18 to 22 months' corrected age were collected on 51 of 72 EPO‐treated infants (71%) and 51 of 70 placebo/controls (73%). Follow‐up rates were low.
Selective reporting (reporting bias)	Unclear risk	The protocol for the study was not available to us; therefore we cannot ascertain whether deviations from the protocol occurred.
Other bias	Low risk	Appears free of other bias. Study was supported by grants from Ortho‐Biotech and Schein Pharmaceuticals.