Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants

Objective. To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal i ron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants. Methods. A prospective, controlled, randomized, unmasked trial lasting 21 d ays was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions duri ng the study period. Mean (+/- standard error of the mean) age at study ent ry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all p articipants received oral supplements of 9 mg/kg/day of iron polymaltose co mplex (IPC), participants were randomized to receive 18 days of treatment w ith: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO 1 oral iron group); 3) 2 mg/kg/da y of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron 1 E PO group). To assess efficacy of the 3 treatments, serial blood samples wer e analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red b lood cell indices and plasma levels of transferrin, transferrin receptor (T fR), ferritin, and iron. Oxidant injury was assessed before and after treat ment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine. Results. At the end of treatment, Hb, Hct, reticulocyte count, and plasma T fR were markedly higher in both of the EPO-treated groups, compared with th e oral iron group. At study exit a trend toward increasing Hb and Hct level s and significantly higher reticulocyte counts were observed in the intrave nous iron 1 EPO group, compared with the EPO 1 oral iron group. During trea tment, plasma ferritin levels increased significantly in the intravenous ir on 1 EPO group and decreased significantly in the other 2 groups. By the en d of treatment, ferritin levels were significantly higher in the intravenou s iron 1 EPO group compared with the other 2 groups. Although plasma and ur ine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was sig nificantly greater in the subgroup of intravenous iron 1 EPO participants s ampled at the end of the 2-hour parenteral iron infusion, compared with val ues observed immediately before and after parenteral iron-dosing. Conclusions. In stable VLBW infants receiving EPO treatment, parenteral sup plementation with 2 mg/kg/day of iron sucrose results in a small, but signi ficant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral i ron alone. However, to reduce the potential adverse effects of parenteral i ron/kg/day on increasing plasma ferritin levels and on causing oxidative in jury, we suggest that the parenteral iron dose used should be reduced and/o r the time of infusion extended to maintain a serum iron concentration belo w the total iron-binding capacity.