Effects of early human recombinant erythropoietin therapy on the transfusion in healthy preterm infants. Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. Efficacy and cost analysis of treating very low birth weight infants with erythropoietin during their first two weeks of life: a randomized, placebo-controlled trial. A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country. Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery. [Early erythropoietin use for the prevention of anemia in infant premature]. The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 grams or less: a randomized, double-blind, placebo-controlled study. Effect of early versus late administration of human recombinant erythropoietin on transfusion requirements in premature infants: results of a randomized, placebo-controlled, multicenter trial. Follow-up of very low birth weight infants after erythropoietin treatment to prevent anemia of prematurity.
Early recombinant erythropoietin therapy and iron therapy would decrease the need for red blood cells transfusions and prevents anemia of prematurity.
                Fifty-eight preterm infants in newborn services at Ghaem Medical Center randomly were assigned, among them 18 patients were excluded. A total of 40 preterm infants with gestational age 28-34 weeks, birth weight 1000-1750 g followed the study: 20 infants in treatment group and 20 infants in control group were randomized to treatment (rhu EPO, 500u per kg, per week, 2 times weekly, subcutaneous) and control (no treatment). Therapy was initiated 4 days after birth and continued throughout the 4 weeks. All infants on enteral feeds received supplements: iron 3 mg/kg/d, vitamins and folat. Complete blood cells and reticulocyte counts were measured weekly. Transfusions and phlebotomy data were recorded. Statistical significance was determined by chi-square test, student t test and Mann-Whitney. A P value of < 0.05 was considered statistically significant.
                The reticulocyte counts were higher in treated infants during the study (p: 0.009). Final hematocrits were higher in treated infants (p: 0.02).The volume of packed red blood cells transfusions mililiter per infant significantly reduced (p: 0.05), the average number of transfusion per infant was also lower for treated infant than control [2 (10 % )vs 8 (40%) respectively]. No adverse effects of EPO or supplemental iron occurred.
                The combination of early rhu EPO and iron as administered in the present study stimulated erythropoiesis and decreased red blood cells transfusion in premature infants who were 1000-1750 g at birth. The enrollments of the larger and healthier preterm infants, who are at lower risk for transfusion, are limitation of the present study. 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).
                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.
                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.
                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. We hypothesized that using a higher dose of erythropoietin (Epo) and starting treatment on the first day of life would reduce the transfusion requirements of ventilator-dependent and non-ventilator-dependent very low birth weight (VLBW) infants. Moreover, we hypothesized that this treatment would be cost-effective.
                We randomly assigned 20 ill newborn VLBW infants to receive either Epo (200 units/kg per day) or placebo during their first 2 weeks of life. The caregivers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia.
                On day 1, reticulocyte counts and hematocrits were similar in the two groups. During the subsequent 2 weeks, reticulocyte counts of the placebo recipients fell significantly below those of the Epo recipients, but hematocrits in the two groups did not differ. More transfusions were received by the placebo recipients (mean = 1.4 per patient) than by the Epo recipients (mean = 0.2 per patient; p < 0.01). No adverse effects of Epo were noted, and the costs in the placebo group exceeded those in the Epo group.
                We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective. The purpose of this study was to evaluate the effectiveness of early treatment with erythropoietin (EPO) in two different treatment regimes (high vs. low dose) in comparison to the conventional treatment of packed red blood cell (PRBC) transfusions in the management of anaemia of prematurity in a country with limited resources. An open controlled trial was conducted on 93 preterm infants (7 days postnatal age, 900-1500 g birthweight). Patients were randomly assigned either to a low dose (250 IU/kg), a high dose (400 IU/kg), or a control group. EPO was administered subcutaneously three times a week and all infants received 6 mg/kg iron orally from study entry to endpoint of therapy. Haematological parameters were measured and compared. The success was defined as an absence of transfusions and a haematocrit that did not fall below 30 per cent during the time period that the infants were in the study. The three groups were statistically comparable at study entry with respect to gestational age, birthweight, Apgar scores, and haematological values. Over the period that the infants were in the study, 75 per cent of the low dose group and 71 per cent of the high dose group met the criteria for success compared with 40 per cent in the control group (p < 0.001). However, there was no significant difference in the number of transfusions when the low and high EPO dose groups (9.5 per cent) were combined and compared with the control group (26.7 per cent) p = 0.0587. It was concluded that in stable infants, 900-1500 g, where phlebotomy losses are minimized and stringent transfusion guidelines are adhered to, EPO does not significantly decrease the number of transfusions. A conservative approach in the management of anaemia of prematurity, is a viable alternative in areas with limited resources. Limited erythropoietin (Epo) production diminishes neonates' ability to regenerate blood removed by phlebotomy. Neonates requiring surgery are at risk to receive multiple transfusions. We sought to determine if recombinant Epo administration to neonates requiring surgery would stimulate erythropoiesis.
                Infants were randomized in double-masked fashion to receive Epo (200 units kg(-1) d(-1)) or placebo for 14 days. Complete blood count, absolute reticulocyte count (ARC), phlebotomy losses, and transfusions were measured during the study period. Infants were transfused using a strict transfusion protocol.
                In the Epo group (n = 10, 2034 +/- 308 g, 8 +/- 2 days old; mean +/- SEM), ARC increased significantly, whereas in the placebo group (n = 10, 2400 +/- 184 g, 7 +/- 2 days old), ARC remained low. Hematocrits in the Epo group trended upward from 34.4 1.7% to 37.3 1.9% (although not statistically significant) despite phlebotomy losses of 53 +/- 12 mL/kg. Hematocrits in the placebo group were 35.9 1.8% and 33.2 1.6% on days 1 and 15, respectively, with phlebotomy losses of 27 +/- 5 mL/kg. There were no differences in absolute neutrophil counts or platelet counts between groups at the end of the study. No adverse effects were noted.
                Infants randomized to Epo increased reticulocyte counts and hematocrits without adverse effects. Erythropoietin administration may provide an adjunct to present care in decreasing or eliminating erythrocyte transfusions in surgical neonates. Anemia is common among very low birth weight newborns and requires frequent blood transfusions. Erythropoietin was been reported to be useful in the prevention of this anemia.
                To assess the benefits of early (before the third week of life) Human recombinant Erythropoietin (r-EPO) administration to reduce the requirement of blood transfusions in very low birth weight newborns.
                Sixty newborns under 1500 g of birthweight were randomly assigned to receive r-EPO (n = 29) or placebo (n = 31) three times per week, during four weeks. Packed red cell volume and reticulocyte counts were measured weekly. Serum erythropoietin was measured prior to eighth dose. Transfusion requirements were recorded.
                r-EPO reduced transfusions from 1.41 +/- 1.1 to 0.69 +/- 1 transfusions/newborns (p < 0.001). At the fourth week of treatment, reticulocyte count was 14.8 +/- 7 and 6.4 +/- 4.9% in the active treatment group and placebo group respectively (p < 0.001).
                r-EPO reduces the requirement of transfusions in low birth weight infants. Clinical trials of erythropoietin (EPO) administration to preterm infants have not focused on infants weighing 750 gm or less, the population most likely to receive multiple transfusions because of large phlebotomy losses. It is unknown whether preterm infants weighing 750 gm or less will respond to EPO by accelerating erythropoiesis, or whether EPO administered to this population will decrease blood transfusions.
                We randomly assigned 28 extremely low birth weight preterm infants (mean +/- SEM: 24.7 +/- 0.3 weeks' gestation, 662 +/- 14 gm birth weight), in the first 72 hours of life, to receive either EPO (200 U/kg/day) or placebo for 14 days and administered transfusions only according to protocol over a 21-day study period. All infants received 1 mg/kg/day iron dextran in their total parenteral nutrition solution during the 14-day treatment period.
                During the 21-day study period, a lower number and volume of transfusions were received by the EPO recipients (4.7 +/- 0.7 transfusions per patient and 70 +/- 11 ml/kg per patient) than by the placebo recipients (7.5 +/- 1.1 transfusions per patient and 112 +/- 17 ml/kg per patient; p < 0.05, EPO vs placebo), whereas hematocrits remained similar in the two groups. Reticulocyte counts were similar in both groups on day 1 but were greater in the EPO recipients on day 14 (EPO day 1, 351 +/- 53; EPO day 14, 359 +/- 40 x 10(3)/microl; placebo day 1, 334 +/- 64; placebo day 14, 120 +/- 10 x 10(3)/microl; p < 0.01, EPO vs placebo). Serum ferritin concentrations were similar in both groups at the beginning of the study but were greater in the placebo recipients by day 14 (EPO, 262 +/- 44 microg/L; placebo, 593 +/- 92 microg/L; p < 0.01). No adverse effects of EPO or iron were noted.
                The combination of EPO and parenteral iron stimulates erythropoiesis in preterm infants weighing 750 gm or less and results in fewer transfusions during their first 3 weeks of life. The administration of recombinant human erythropoietin (rHuEPO), started after the first 2 weeks of life, reduces the transfusion requirement in premature infants. However, its use throughout the first 2 weeks of life, when anemia results predominantly from phlebotomy losses, remains controversial. We investigated whether early use of rHuEPO would reduce the total transfusion requirement and/or the number of transfusions throughout the first 2 weeks of life.
                We randomized 114 infants with birth weight (BW) <1250 g to receive rHuEPO (1250 units/kg/week; IV; early group: n = 57) or placebo (late group: n = 57) from day 2 to day 14 of life; subsequently, all the patients received rHuEPO (750 units/kg/week, subcutaneously) for 6 additional weeks. All infants were given oral iron (6 mg/kg/day) and folic acid (2 mg/day).
                The early group showed higher hematocrit and reticulocyte counts than the late group in the first 3 weeks of life, but there was no difference in the total number of transfusions (early: 1.8 +/- 2.3 vs late: 1.8 +/- 2.5 transfusion/patient) or the transfusion requirement throughout the first 2 weeks of life (early:.8 +/- 1.1 vs late:.9 +/- 1.3) could be demonstrated. In infants with BW <800 g and total phlebotomy losses >30 mL/kg (n = 29), a lower number of transfusions was received by infants in the early group, compared with late group, from the second week to the end of the treatment (early: 3.4 +/- 1.1 vs late: 5.4 +/- 3.7 transfusion/patient). No clinical adverse effects were observed. Thrombocytosis was detected during the treatment with rHuEPO in 31% of the infants.
                In the whole population, the early administration of rHuEPO induced a rise of reticulocyte counts, but not enough to reduce the transfusion requirement. The most severely ill infants (BW <800 g and phlebotomy losses >30 mL/kg) seemed to benefit from early use of rHuEPO, and this deserves additional study. Treatment with recombinant human erythropoietin (rHuEPO) stimulates erythropoiesis and reduces the need for transfusions in hospitalized preterm infants. The aim of our study was to follow very low birth weight infants after the initial 6 weeks of rHuEPO treatment.
                We randomly assigned 97 very low birth weight infants with a gestational age of 31 weeks or less and birth weight of 1500 gm or less to receive rHuEPO, 300 units/kg per week (erythropoietin (EPO) 300, n = 33), rHuEPO, 750 units/kg per week (EPO 750; n = 28), or no treatment (control, n = 36). The rHuEPO was administered from the first week of life for 6 weeks. After EPO therapy was discontinued, 75 neonates were followed weekly until discharge and at 3, 6, and 12 months of age.
                Mean numbers (+/- SD) of packed erythrocyte transfusions per patient from the time rHuEPO therapy was discontinued until discharge were 0.38 +/- 0.64 (EPO 300), 0.23 +/- 0.52 (EPO 750), 0.9 +/- 1.1 (control) (p < 0.05 in both EPO groups vs control). Mean reticulocyte counts at the sixth week were 6% +/- 2.2% (EPO 300), 6.9% +/- 2.2% (EPO 750), and 3.1% +/- 2.6% (control) in the three groups (p < 0.01 in both EPO groups vs control), and at the eighth week were 4.7% +/- 2.8% (EPO 300), 5.4% +/- 2.7% (EPO 750), and 2.6% +/- 2.2% (control) (p < 0.01 in both EPO groups vs control). Serum ferritin levels were significantly higher at the sixth week, and the percentage of hemoglobin F was significantly lower at 6, 8, and 10 weeks in the control group versus EPO groups. At 3, 6, and 12 months of age, there were no differences in reticulocytes, ferritin, HbF, and growth among groups.
                Preterm infants who received rHuEPO had a normal pattern of erythropoiesis after the drug was discontinued. These data provide strong evidence that the anemia of prematurity is the result of a transient developmental abnormality in EPO production.
Late administration of EPO reduces the use of one or more RBC transfusions, the number of RBC transfusions per infant but not the total volume of RBCs transfused per infant. Any donor exposure is likely not avoided as most studies included infants who had received RBC transfusions prior to trial entry. Late EPO does not significantly reduce or increase any clinically important adverse outcomes. Further research of the use of late EPO treatment to prevent donor exposure is not indicated. Research efforts should focus on limiting donor exposure during the first few days of life in sick neonates, when RBC requirements are most likely to be required and cannot be prevented by late EPO treatment.