RESUMEN
OBJECTIVES: Infants of =1250 g birth weight receive multiple erythrocyte transfusions during their hospitalization. We hypothesized that early erythropoietin (Epo) and iron therapy would 1) decrease the number of transfusions received (infants 401-1000 g birth weight; trial 1) and 2) decrease the percentage of infants who received any transfusions (1001-1250 g birth weight; trial 2). METHODS: A total of 172 infants in trial 1 and 118 infants in trial 2 were randomized to treatment (Epo, 400 U/kg 3 times weekly) or placebo/control. Therapy was initiated by 4 days after birth and continued through the 35th postmenstrual week. All infants received supplemental parenteral and enteral iron. Complete blood and reticulocyte counts were measured weekly, and ferritin concentrations were measured monthly. Transfusions were administered according to protocol. Phlebotomy losses and transfusion data were recorded. RESULTS: Treated and placebo/control infants in trial 1 received a similar number of transfusions (4.3 +/- 3.6 vs 5.2 +/- 4.2, respectively). A similar percentage of treated and control infants in trial 2 received at least 1 transfusion (37% vs 46%). Reticulocyte counts were higher in treated infants during each week of the study in both trials. Hematocrits were higher among treated infants from week 2 on in both trials. Ferritin concentrations were higher in placebo/controls than in treated infants at weeks 4 and 8 in trial 1 and at week 4 in trial 2. No adverse effects of Epo or supplemental iron occurred. CONCLUSION: The combination of early Epo and iron as administered in this study stimulated erythropoiesis in infants who were =1250 g at birth. However, the lack of impact on transfusion requirements fails to support routine use of early Epo.neonate, intravenous iron, donor exposure.
Asunto(s)
Transfusión Sanguínea/estadística & datos numéricos , Eritropoyetina/uso terapéutico , Recién Nacido de Bajo Peso/sangre , Enfermedades del Prematuro/tratamiento farmacológico , Recien Nacido Prematuro/sangre , Anemia Neonatal/terapia , Desarrollo Infantil/efectos de los fármacos , Desarrollo Infantil/fisiología , Eritropoyesis/efectos de los fármacos , Eritropoyesis/fisiología , Eritropoyetina/farmacología , Femenino , Humanos , Recién Nacido de Bajo Peso/fisiología , Recién Nacido , Recien Nacido Prematuro/fisiología , Enfermedades del Prematuro/sangre , Hierro/farmacología , Hierro/uso terapéutico , Masculino , PlacebosRESUMEN
OBJECTIVES: To compare the pharmacokinetics and effectiveness of continuously administered recombinant erythropoietin (Epo) in total parenteral nutrition (TPN) solution with daily subcutaneously administered Epo. METHODS: Forty preterm infants in the first 72 hours of life were randomly assigned to receive Epo (200 units/kg per day for 10 consecutive days), either subcutaneously (20 infants, 1051 +/- 40 gm, 28.3 +/- 0.4 weeks of gestation; mean +/- SEM), or added daily to their TPN fluids (20 infants, 1028 +/- 36 gm, 27.9 +/- 0.4 weeks of gestation). Both groups received iron supplementation (1 mg/kg per day iron dextran in the TPN solution). Absolute reticulocyte counts and complete blood cell counts with differentials were measured, and transfusions and phlebotomy losses were recorded. Pharmacokinetics were determined in the first 16 infants. RESULTS: In the infants who received Epo subcutaneously, the elimination half-life was 17.6 +/- 4.4 hours on day 3 and 11.2 +/- 1.5 hours on day 10; the volume of distribution was 802 +/- 190 ml/kg on day 3 and 1330 +/- 243 m/kg on day 10. Serum Epo concentrations were higher on day 3 than on day 10 for both groups (subcutaneous: 400 +/- 64 mU/ml vs 177 +/- 29 mU/m, p <0.05; TPN: 395 +/- 64 vs 194 +/- 41 mU/ml, p <0.05). Clearance did not differ between the two groups with regard to route of administration and increased significantly from days 3 to 10 in both groups. Reticulocyte counts were similar in both groups. There were no differences between groups in the number of transfusions given, and the overall decline in hematocrit was similar. No adverse effects of Epo were noted in either group. CONCLUSIONS: Adding Epo to the TPN solution in this population results in similar Epo concentrations, clearance, and effectiveness as subcutaneous dosing.