The Effects of Erythropoietin (EPO) on the Transfusion Requirements of Very Low Birth Weight Infants

Critically ill preterm infants experience in the first 1-2 weeks after birth daily blood
losses that may equal 5-10% of their total blood volume. Such losses and associated anemia
typically result in multiple erythrocyte transfusions. This iatrogenic anemia commonly is
followed by the anemia of prematurity, prompting additional transfusions.

This study tested the safety and efficacy of transfusing erythropoietin (Epo) and iron in
infants of <1,250g birth weight. For infants 401-1,000g birth weight (Trial 1), we tested
whether early erythropoietin (Epo) and iron therapy would decrease the number of transfusions
received. For infants 1,001-1,250g birth weight (Trial 2), we tested whether early
erythropoietin (Epo) and iron therapy would decrease the percentage of infants who received
any transfusions.

Therapy was initiated by day of life 4 and continued through the 35th postmenstrual week.
Infants were randomized to receive either Epo and iron therapy or a sham procedure. Treated
infants received 400 U/kg Epo 3 times weekly and a weekly intravenous infusion of 5 mg/kg
iron dextran until they had an enteral intake of 60 mL/kg/d. Infants in the placebo/control
group received sham subcutaneous injections when intravenous access was not available.
Complete blood and reticulocyte counts were measured weekly, and ferritin concentrations were
measured monthly.

Transfusions were administered according to protocol. Infants did not receive a transfusion
solely to replace blood lost through phlebotomy. Infants who met transfusion criteria
received a transfusion of 15 mL/kg packed red blood cells (PRBC) for a hematocrit of >25% or
20 mL/kg PRBC for a hematocrit of <=25%. Blood losses and transfusion data were recorded.

Trial 2 was terminated after enrollment of 118 infants after the Data and Safety Monitoring
Committee reviewed the final results of Trial 1 and preliminary results of Trial 2. On the
basis of these data, the Committee concluded that it was statistically unlikely that Trial 2
would demonstrate a significant decrease in the percentage of infants who would receive a
transfusion during the study.

Inclusion Criteria:

- Infants with a birth weight of 4010-1250g, <32 weeks' gestation, and 24-96 hours old
at the time of study entry

- Likely to survive >72 hours

- Informed consent from a parent or guardian.

Exclusion Criteria:

- Major congenital anomaly

- A positive direct antiglobulin test

- Evidence of coagulopathy

- Clinical seizures

- Systolic blood pressure >100 mm Hg (in the absence of pressor support)

- Absolute neutrophil count (ANC) of <=500/micro-L