A randomized controlled trial on the effects of adding vitamin B 12 and folate

Objective: Premature infants, especially those with a birth weight less than 1500g, often suffer from anemia of prematurity and associated problems. Erythropoietin (Epo) therapy is a safe and effective way to prevent and treat anemia of prematurity. We hypothesized that combined administration of vitamin B12 and folate with Epo and iron may enhance Epo-induced erythropoiesis.

Design: In a randomized controlled trial, 64 premature infants (birth weight 801–1300g) receiving Epo and iron supplementation were randomized to either vitamin B12 (3µg/kg/d) and folate (100µg/kg/d) (treatment), or a lower dose of folate (60µg/kg/d) (control).

Results: During the 4-week observation period, vitamin B12 and folate significantly enhanced Epo-induced erythropoiesis as indicated by a 10% increase in RBC compared to folate alone (p=0.007). Hemoglobin (Hb) and hematocrit (Hct) remained stable in the treatment group, while they decreased in the control group (p=0.003 between groups). Vitamin B12 levels in the treatment increased over baseline and control values (p=0.003), whereas RBC folate levels were comparable between groups. Subsequent analysis showed slight, but non-significant differences in baseline values of RBC, Hb, Hct and mean corpuscular volume (MCV) which has to be addressed as limitation.

Conclusions: Under the aspect of the limitation of a slight imbalance in baseline data between study groups the combined therapy of vitamin B12 and folate with Epo, oral and intravenous iron appeared more effective in stimulating erythropoiesis in premature infants than Epo, iron and low-dose folate alone. Further trials are necessary to confirm these data.