Recombinant human erythropoietin therapy for treatment of anemia of prematurity in very low birth weight infants: a randomized, double-blind, placebo-controlled trial. Effect of recombinant human erythropoietin administration on lipid peroxidation and antioxidant enzyme(s) activities in preterm infants. Recombinant human erythropoietin in the treatment of anemia of prematurity. Erythropoietin (rHuEPO) administration to premature infants for the treatment of their anemia. Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants. Effect of short-term erythropoietin therapy in anemic premature infants. Erythropoietin increases reticulocyte counts and maintains hematocrit in neonates requiring surgery. Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity. Does early erythropoietin therapy decrease transfusions in anemia of prematurity? Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity. Double blind trial of recombinant human erythropoietin in preterm infants. Randomised controlled double blind study of role of recombinant erythropoietin in the prevention of chronic lung disease. Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study. Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study. Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity. Enterally dosed recombinant human erythropoietin does not stimulate erythropoiesis in neonates. Recombinant human erythropoietin in anemia of prematurity. Effects of recombinant human erythropoietin in infants with very low birth weights. Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study. Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants. [Randomized multi-center trial of the administration of erythropoietin in anemia of prematurity]. Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions.
To evaluate the efficacy and safety of recombinant human erythropoietin (rHuEPO) in very low birth weight infants with anemia of prematurity.
                Thirty infants were randomly assigned to receive either rHuEPO (300 U/kg per dose) or placebo twice a week. Hematologic parameters, transfusion requirements, caloric intake, and growth were monitored.
                The number and volume of erythrocyte transfusions were significantly lower in infants treated with rHuEPO. Serum ferritin levels, similar in both groups at study entry, fell and were significantly lower in rHuEPO-group infants at the completion of the study. An inverse correlation was observed between reticulocyte count and absolute neutrophil count both at entry and at completion of the study.
                Twice-a-week administration of rHuEPO significantly reduces the need for erythrocyte transfusion in very low birth weight infants in stable condition. A significant decrease in serum ferritin levels in infants receiving rHuEPO suggests the need to determine the optimal dose of iron supplementation in these infants. In the present investigation, we studied the effect of recombinant human erythropoietin (r-HuEPO) on serum malondialdehyde (MDA) as an index of lipid peroxidation, related to iron-catalyzed free radical reaction and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities in very-low-birth weight (VLBW) infants. Forty premature infants, at gestational ages were less than 33 weeks and birthweights were less than 1,500 g, were enrolled in the study. The study population was randomly divided into 2 groups. Twenty infants in Group 1 (treatment group) were given r-HuEPO, and 20 infants in Group 2 served as the control. r-HuEPO treatment (750 U/kg a week) was initiated on the 10th day of life and continued for 6 weeks. Preterm infants given erythrocyte transfusions during the study were excluded from the results. Serum ferritin and MDA levels, and erythrocyte superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPX) activities were analyzed at the end of the first week of life (at the beginning of the study). Subsequently, serum ferritin, and MDA levels were measured at the end of the 3rd and the 6th week. SOD, CAT, and GPX activities in the hemolysate were analyzed at the end of the 4th week. Six infants in the control group and 1 infant in the r-HuEPO group received transfusions through the end of the study, and these infants were excluded from the results. Significantly decreased serum ferritin concentrations were found in the r-HuEPO group compared to those in the control group both at the end of the 3rd and the 6th week (P < 0.05, and P < 0.01, respectively). In addition, serum MDA levels were also significantly reduced in Group 1 compared to control both at the end of the 3rd and the 6th week (P < 0.01 and P < 0.05, respectively). A good correlation was found between serum MDA and ferritin levels in Group 1. When the 2 groups were compared with respect to activities of SOD, CAT, and GPX at the end of the 4th week, no differences were observed. Our findings in this study show that administration of r-HuEPO significantly decreases lipid peroxidation, but does not affect erythrocyte antioxidant enzyme(s) activities in preterm infants. The mechanism responsible for the r-HuEPO-induced decrease in lipid peroxidation may concern inhibition to iron-catalyzed free radical reactions. Seventy premature infants (birthweight 1.75 kg or less, gestational age 33 weeks or less) with hemoglobin less than 10 g/dL and hematocrit less than 30% were studied and randomly divided into three groups. All of them received oral elemental iron 3 mg/kg/day and vitamin E 5 mg/kg/day during the study period. Recombinant human erythropoietin (rHuEPO) 150 U/kg was administered intravenously twice a week for 4 weeks in group A (26 infants). Infants in group A received a total of 4 erythrocyte transfusions because of frequent apnea. Infants in group B (25 infants) received erythrocyte transfusion when their hemoglobin levels was less than 10 g/dL with signs and symptoms (including tachycardia, tachypnea, poor feeding, apnea, poor weight gain) attributed to anemia or who had a hemoglobin less than 8 g/dL even if asymptomatic. Infants in group B received a total of 36 erythrocyte transfusions. Infants in group C (19 infants) were assigned to a non-rHuEPO and nontransfusion group. Three of the 19 premature infants in group C received erythrocyte transfusions later because of frequent and prolonged apneic episodes and were excluded from this study. Our data revealed that reticulocyte and serum erythropoietin values were higher (p < 0.01) in rHuEPO-treated group than transfusion group and hemoglobin and hematocrit values were lower in group C than the other two groups during the rHuEPO treatment period. No significant difference (p > 0.05) was found in neutrophil and platelet counts among these three groups. Serum ferritin values were found lower in the rHuEPO-treated group than the other two groups. Lower weight gain was found in infants in group C. We conclude that rHuEPO administration can reduce the need for blood transfusion. Poor weight gain can be found in infants with anemia of prematurity who do not receive rHuEPO or blood transfusion therapy. In an attempt to stimulate erythrocyte production and thereby decrease the requirement for red blood transfusions, recombinant human erythropoietin (rHuEPO) was administered to 16 premature infants with birth weights less than 1000 g and to 18 with birth weights of 1000-1300 g; two corresponding groups, who did not receive rHuEPO, were used as control groups. The rHuEPO was administered subcutaneously in a dose of 300 IU/kg three times a week for 6-8 weeks. The erythropoietin decreased the red blood requirement in both groups of infants, and the increment of hemoglobin following rHuEPO administration was not statistically significant. No correlation was observed between gestational age, number of transfusions, and reticulocyte percentage. The effect of rHuEPO was higher in the group of infants with birth weights of 1000-1300 g than in those of less than 1000 g. No significant side effects were observed during rHuEPO administration. The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8-7.2 mg/l to 10.5-11.3 mg/l.
                In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron. To determine the effectiveness of a 10-day subcutaneous erythropoietin (rHuEpo) course of 300 units per kg per dose plus oral iron compared to oral iron alone in anemic infants during their convalescent phase of illness.
                Prospective, randomized trial performed at a 40-bed, teaching, referral, level III, neonatal intensive care unit. Infants with a gestational age at birth of less than 32 weeks, hematocrit of less than or equal to 28% with a corrected reticulocyte count of less than or equal to 5%, postconceptual age of less than 48 weeks or 5 months chronological age, and a diagnosis of anemia of prematurity were considered for inclusion. Major outcome parameters included hematocrit, corrected reticulocyte count and red cell transfusion requirements.
                A total of 60 infants were enrolled (n=30 per group). Infants randomized to rHuEpo had a significantly higher post-treatment hematocrit and corrected reticulocyte count than infants in the iron only group (p<0.001). There was a trend towards fewer red cell requirements in the rHuEpo group.
                The rHuEpo regimen studied here was associated with an acute improvement in hematocrit and corrected reticulocyte counts. This study did not demonstrate a statistically significant decrease in transfusion therapy, in part related to increased subsequent use of rHuEpo in the control group. Taken together, these data demonstrate that this regimen can effectively treat anemia in convalescent premature infants. 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. Erythropoietin (rHuEPO) therapy has been shown to be beneficial in preventing and treating anaemia of prematurity and to decrease the need for blood transfusions. There is, however, only scanty data on the effect of rHuEPO therapy on iron metabolism. We studied 29 preterm infants (age 34 +/- 14 days) who were randomly assigned to receive either rHuEPO 900 U kg-1 week-1 with 6 mg kg-1 day-1 of iron for 4 weeks (n = 15) or no therapy. The following parameters were evaluated and compared between and within groups at the beginning, during and at the end of the study: Haematocrit (SI), reticulocytes (10(9) micrograms l-1), serum ferritin (microgram 1-1) and iron (mumol l-1). The results were as follows. At the baseline, erythropoietin levels were similar in both groups: 7.2 +/- 5.6 versus 6.2 +/- 3.2 mU ml-1 (NS). In the treated infants the haematocrit remained stable during the study and was significantly higher than in the control group by the end of the study: 0.34 +/- 0.03 versus 0.28 +/- 0.05 (p = 0.001). rHuEPO therapy increased the reticulocyte count from 130 +/- 70 to 430 +/- 200 (p = 0.0002). However, rHuEPO therapy depleted both serum ferritin and iron levels from 321 +/- 191 to 76 +/- 58 micrograms l-1 (p = 0.04) and from 18 +/- 5 to 13 +/- 4 mumol l-1 (p = 0.03), respectively. We conclude that rHuEPO therapy prevented anaemia and its sequelae; however, serum ferritin and iron levels were depleted. We suggest that the effect of rHuEPO may be further increased by higher iron supplementation. To investigate the effect of early erythropoietin treatment on induction of erythropoiesis and the need for transfusion in Very Low Birth Weight (VLBW) infants with acute neonatal problems.
                The study group consisted of 14 VLBW prematures with gestational ages less than 32 weeks who were given subcutaneous erythropoietin (600 U/kg per week) and oral iron (3 mg/kg per day) during the first 7-8 weeks of their life, while 13 other VLBW prematures that were given placebo constituted the control group. Weekly hematocrit, (Hct) reticulocyte (Ret) values and the volume of blood drawn and transfused were recorded in the both groups.
                The groups were comparable regarding with birth weights and gestational ages. The volume of the blood drawn (76.8 +/- 42.5 and 37.0 +/- 15.2) was higher and the volume of the transfusions (51.84 +/- 49.30 and 68.84 +/- 41.2) was lower in the study group but the differences between the groups were not significant (p>0.05). The hematocrit, the reticulocyte and the ferritin values were similar in both the groups at the end of the therapy.
                Under the neonatal intensive care circumstances of developing countries where blood volumes needed for laboratory analysis are still very high, phlebotomy losses can not be avoided. Thus early erythropoietin and iron therapy at these doses are not effective in decreasing the need for transfusion and induction of endogenous erythropoiesis. The effectiveness of recombinant human erythropoietin (r-HuEpo) in raising haemoglobin concentrations in very low birthweight infants was examined in a randomised multicentre study. Twenty nine 'healthy' appropriate for gestational age infants with birth weights 900-1400 g entered the study at 3 weeks of age. All infants received breast milk supplemented with 9 g/l human breast milk protein from 3 to 8 weeks of age. Eighteen mg iron was given daily from week 3 and was doubled if serum iron concentration fell below 16.0 mumol/l. Fourteen infants were randomised to receive 100 U/kg r-HuEpo subcutaneously three times a week from week 3 to week 7; 15 infants served as controls. After one week reticulocyte and haemoglobin concentrations were significantly higher in the r-HuEpo treated group and the haemoglobin values remained significantly higher throughout r-HuEpo treatment and at the concentrations observed in full term infants. No adverse effects were associated with the treatment. In stable very low birthweight infants with optimal iron and protein intakes, moderate dose r-HuEpo can produce significant gains in red cell production that may be clinically useful. Twenty four infants between 27 and 33 weeks' gestation were recruited into a double blind study to investigate the use of recombinant human erythropoietin (r-HuEpo) for the prevention of anaemia of prematurity. Between 50 and 150 U of r-HuEpo (n = 16) or placebo was administered subcutaneously twice a week from 7 days of age until discharge. There was a significant increase in the reticulocyte count in infants receiving r-HuEpo sustained from the second week of treatment until discharge compared with placebo. There was a reduction in the number of transfusions required in the r-HuEpo group with only 47% requiring a transfusion compared with 87% in the placebo group. During treatment with r-HuEpo there was a significant rise in the red cell folate concentration, a significant fall in the ferritin concentration, and a significantly higher percentage of haemoglobin F at discharge suggesting active erythropoiesis. The study provides strong evidence for the efficacy of r-HuEpo in stimulating erythropoiesis and reducing the requirement for transfusions for anaemia of prematurity. To evaluate the role of recombinant human erythropoietin (R-HuEpo) in reducing iron infusion, which may exacerbate free radical damage, leading to chronic lung disease.
                A multicentre, randomised, placebo controlled, double blind study was carried out in four neonatal intensive care units in Yorkshire. Infants were randomly allocated and received either R-HuEpo (480 U/kg/wk) or placebo by twice weekly subcutaneous injection. The primary outcome measure was the number of days on respiratory support and a secondary outcome the number of blood transfusions required.
                Forty two very low birthweight (VLBW) infants were randomly allocated. There was little difference in the need for respiratory support one month after randomisation, but subsequently there was a trend towards a reduction in the proportion requiring respiratory support in the R-HuEpo group (difference at three months -0.50, 95% confidence interval -1.00, 0.17). During stay in hospital, the median number of blood transfusions was lower for infants in the R-HuEpo group (difference in medians -2, 95% CI -4, 0). The study was stopped early because of failure to recruit babies at the expected rate.
                R-HuEpo seems to reduce the number of days in oxygen for ill VLBW infants. These data could be used to construct a larger multicentre study to evaluate this effect further. We hypothesized that treatment with recombinant human erythropoietin (r-HuEPO) would stimulate erythropoiesis and would thereby reduce the need for erythrocyte transfusions in preterm infants. We treated 157 preterm infants born at 26.9 +/- 1.6 weeks of gestation who weighed 924 +/- 183 g at birth with either subcutaneous r-HuEPO (100 U/kg/d, 5 days per week) or placebo for 6 weeks in a randomized, double-blind, controlled clinical trial. All patients received oral iron and were managed according to uniform conservative transfusion guidelines.
                Treatment with r-HuEPO was associated with fewer erythrocyte transfusions (1.1 +/- 1.5 per infant in the r-HuEPO group versus 1.6 +/- 1.7 per infant in the placebo group; P = .046) and with a reduction in the volume of packed erythrocytes transfused (16.5 +/- 23.0 mL versus 23.9 +/- 25.7 mL per infant; P = .023). Overall, 43% of the infants in the r-HuEPO group and 31% of placebo-treated infants were transfusion-free during the study (P = .18). The volume of blood removed for laboratory tests and the need for respiratory support at the start of treatment had major effects on transfusion requirements independent of r-HuEPO. Reticulocyte counts were higher during treatment in the r-HuEPO group (P = .0001), and r-HuEPO-treated infants had higher hematocrit values at the end of the study (32% versus 27.3% in the placebo group; P = .0001). We found no differences in the incidence of major complications of prematurity between the treatment groups.
                We conclude that treatment with r-HuEPO at a weekly dose of 500 U/kg stimulates erythropoiesis, moderates the course of anemia, is associated with a reduction in erythrocyte transfusions, and appears safe in very low birth weight preterm infants who are receiving iron supplements. Conservative transfusion criteria, minimization of phlebotomy losses, and treatment with r-HuEPO are complementary strategies to reduce erythrocyte transfusions in these infants. We randomly assigned eight concurrently symptom-free premature infants (birth weight less than or equal to 1250 gm) at high risk of requiring erythrocyte transfusions for anemia of prematurity to 6 weeks of intensive treatment with either subcutaneous recombinant human erythropoietin (r-HuEPO group) or a placebo (control group). Treatment with r-HuEPO was initiated at a dose of 100 units/kg per day 5 days a week, and was increased to 200 units/kg per day after 2 or 3 weeks if target reticulocyte counts were not achieved. All patients were given supplemental oral iron therapy at a dose of 6 mg/kg per day, as tolerated. Mean reticulocyte counts in r-HuEPO-treated and control infants were 64,600 versus 67,500 cells/mm3 at entry; were 245,600 versus 78,000 cells/mm3 after 1 week; and averaged 262,600 versus 136,400 cells/mm3 during the study. Mean reticulocyte counts in r-HuEPO-treated infants were 251,200 cells/mm3 during the week when r-HuEPO, 100 units/kg per day, was given, and were 269,500 cells/mm3 after the dose was increased to 200 units/kg per day. Mean hematocrit values at entry were 33.4% in babies who received r-HuEPO versus 33.6% in the control subjects, and were 31.4% in r-HuEPO-treated and 25.2% in the control subjects at the end of treatment. One r-HuEPO-treated and three control babies received transfusions during the study; the total volume of blood given was 17 ml in the r-HuEPO group and 101 ml in the control subjects. The percentage of hemoglobin F increased in infants not given transfusions. We conclude that r-HuEPO stimulates endogenous erythropoiesis in small premature babies who are receiving supplemental oral iron therapy. A controlled multicenter trial has been undertaken to confirm these promising preliminary observations. Experimental and clinical data implicate inadequate erythropoietin production as an important reason that infants acquire this anemia and suggest that recombinant human erythropoietin (r-HuEPO) might be used to treat or prevent it. We therefore randomly assigned 20 small premature infants (birth weight less than or equal to 1250 gm) who were highly likely to require erythrocyte transfusions for anemia of prematurity to receive 6 weeks of treatment with either intravenously administered r-HuEPO (at a dose of 100 units/kg twice each week) or a placebo. Hematologic measurements, transfusion requirements, and growth were followed during therapy and for 6 months thereafter. Treated (EPO) and control babies did not differ with respect to weight, hematocrit, overall mean absolute reticulocyte count, calculated erythrocyte mass, or rate of growth. However, reticulocyte counts increased earlier in patients given r-HuEPO. Six of ten babies in the EPO group, and 8 of 10 assigned to the control group, received at least one erythrocyte transfusion during treatment. For all infants the amount of blood sampled for laboratory tests was strongly predictive of the volume of packed erythrocytes transfused (r = 0.890; p = 0.0001). Of nine infants who had less than 20 ml packed erythrocytes removed for laboratory tests, none of four given r-HuEPO received a transfusion, whereas three of five infants assigned to the placebo group received one. No toxic effects were attributable to r-HuEPO, and no significant changes in leukocyte or platelet counts occurred during treatment. Reticulocyte counts were correlated with simultaneous platelet counts and were inversely related to absolute neutrophil counts in both study groups. We conclude that r-HuEPO administration is safe and feasible at the dose studied. Additional controlled trials utilizing higher doses of r-HuEPO and larger numbers of patients are justified. Twenty-four premature infants, < 32 weeks gestational age, were randomly assigned in a double-blind, placebo-controlled trial to 6 weeks of treatment with either recombinant human erythropoietin (rHuEpo) 150 U/kg three times per week given sc (n = 12) or placebo (n = 12). The infants were fed a diet rich in protein (3.2 g/kg/day) and energy (130 kcal/kg/day) based on their own mother's milk fortified with bovine protein together with moderate iron supplementation (4 mg/kg/day). During the treatment (rHuEpo versus placebo) significant differences in mean (+/- SD) reticulocyte count (4.8 +/- 1.2 versus 2.7 +/- 1.4%; p < 0.01), mean packed red cell volume (PCV) (0.38 +/- 0.03 versus 0.34 +/- 0.04, p < 0.05) and mean haemoglobin concentration (12.6 +/- 1.1 versus 11.5 +/- 1.2 g/100 ml; p < 0.05) were found. Within the rHuEpo group, PCV and haemoglobin concentration remained unaltered from entry to 1 week after cessation of treatment whereas a significant decline was observed in the placebo group. No indications of iron deficiency were seen. We conclude that moderate doses of rHuEpo given to infants fed a diet rich in protein and energy are effective in ameliorating anaemia of prematurity. High iron supplementation does not seem to be essential for a significant erythropoietic response. No adverse effect attributable to rHuEpo was observed. Human fetuses and neonates ingest erythropoietin (Epo) when they swallow amniotic fluid, colostrum, and human milk. This study was designed to determine whether enterally dosed recombinant Epo (rEpo) stimulates erythropoiesis in preterm neonates.
                Preterm infants (<1500 g birth weight) were randomly assigned to receive feedings supplemented with either rEpo (1000 U/kg per day) or placebo for 14 days (n=36). Reticulocyte counts, serum Epo concentrations, hematocrit, and zinc protoporphyrin to heme ratios were measured at baseline and after 7 and 14 days of study drug administration. Transfusion guidelines were followed. Transfusion requirements, medications, feeding tolerance, and clinical diagnoses were documented.
                Enteral rEpo was well tolerated. There were no differences in erythropoietic indexes based on treatment group. Serum Epo concentrations were not different in the treatment versus placebo group, nor were transfusion requirements.
                Enterally dosed rEpo (1000 U/kg/day) does not significantly influence erythropoiesis or iron utilization when given for a 2-week period, nor does it elevate the serum Epo concentration in preterm or term infants. Oral administration of rEpo is not an effective substitute for parenteral administration. To evaluate safety and efficacy of recombinant human erythropoietin (r-HuEPO)in reducing the need for red cell transfusions in anemia of prematurity.
                forty -two preterm infants (gestational age <32 weeks) were randomly assigned to a "treatment" group (r-HuEPO 400 units/kg every alternate day * 10 doses) or "no treatment" (control) group. All infants on enteral feeds received oral iron 3 mg/kg/day, graded up to 6 mg/kg/day.
                Higher reticulocyte counts in week 2 and 3 and higher hemoglobin levels in week 4 were noted after treatment with r-HuEPO. Despite stumulated erythropoiesis, the frequency of transfusions could not be reduced with r-HuEPO therapy.Overall, Phlebotomy losses, frequency and volume of redcell transfusions were significantly more in neonates with birthweight <1000 grams compared with those with birthweight >1000 grams (p<0.05). Associated side effects of r-HuEPO such as neutropenia,sepsis, hypertension or increased risk of late death did not occur.
                r-HuEPO therapy was safe without any side effects. Inability of r-HuEPO therapy to minimize red cell transfusions for anemia of prematurity may be explained by a relatively strict red-cell transfusion policy and the desired degree of treatment effect. Anaemia of prematurity, a postnatal fall in haemoglobin concentration and haematocrit, is particularly common in those born at less than 32 weeks of gestation. Experimental and clinical data implicate inadequate erythropoietin production as an important reason. In this study recombinant human erythropoietin (r-HuEpo) was used in an attempt to treat or prevent this anaemia and thereby provide an alternative to erythrocyte transfusions. Premature infants (birth weight < or = 1250 g and gestational age < or = 32 weeks), who were likely to need transfusions, were randomly assigned to receive 4 weeks of treatment with either subcutaneously administered r-HuEpo (200 U; n = 12) or placebo (n = 12), three times weekly. All patients had oral supplements of elemental iron at a dose of 3 mg/kg/day. Treatment was started in the third week of life. Reticulocyte counts were significantly raised (P < 0.05) in the group treated with r-HuEpo at the end of treatment. The neonates in the group treated with r-HuEpo needed fewer erythrocyte transfusions than those in the placebo group during treatment. There were no toxic effects attributable to r-HuEpo. The results indicate that treatment of infants with very low birth weights with r-HuEpo will reduce their need for erythrocyte transfusions. To investigate whether recombinant erythropoietin (rhEPO) reduces the need for transfusion in extremely low birth weight (ELBW) infants (birth weight 500-999 g) and to determine the optimal time for treatment.
                In a blinded multicenter trial, 219 ELBW infants were randomized on day 3 to one of 3 groups: early rhEPO group (rhEPO from the first week for 9 weeks, n = 74), late rhEPO group (rhEPO from the fourth week for 6 weeks, n = 74), or control group (no rhEPO, n = 71). All infants received enteral iron (3-9 mg/kg/day) from the first week. The rhEPO beta dose was 750 IU/kg/week. Success was defined as no transfusion and hematocrit levels never below 30%.
                Success rate was 13% in the early rhEPO group, 11% in the late rhEPO group, and 4% in the control group (P =.026 for early rhEPO versus control group). Median transfusion volume was 0.4 versus 0.5 versus 0.7 mL/kg/day (P =.02) and median donor exposure was 1.0 versus 1.0 versus 2.0 (P =.05) in the early rhEPO group, the late rhEPO group, and the control group, respectively. Infection risk was not increased and weight gain was not delayed with rhEPO beta.
                Early rhEPO beta treatment effectively reduces the need for transfusion in ELBW infants. To assess the efficacy of recombinant human erythropoietin (rHuEpo) in the treatment of the anemia of prematurity.
                A double-blind, placebo-controlled study was conducted on 80 preterm infants (< or = 32 weeks; postnatal age, 2 to 8 weeks; central hematocrit < or = 35%). Patients were randomly assigned to receive subcutaneous rHuEpo (Eprex, 600 U/kg per week) or an equivalent volume of placebo, for up to 6 weeks. All patients received supplements of vitamin E (25 IU) and iron (3 mg/kg per day). The iron supplement was increased if declining serum ferritin measurements were noted.
                Treatment and placebo groups did not differ significantly with respect to mean gestational age, birth weight, hematocrit, or reticulocyte count at study entry. Fewer transfusions were administered to those receiving erythropoietin (7 compared with 21; P = .002). Compared with the placebo group, the infants receiving rHuEpo had a higher mean hematocrit (32.3 +/- 4% vs 29.3 +/- 6.2%; P = .014) and absolute reticulocyte count (223 +/- 73 vs 124.9 +/- 73 x 10(9)/L; P < .001) at the end of the study. The mean neutrophil count was not significantly reduced at study exit (P = .8), nor at any other period during the trial in the rHuEpo group. Intercurrent events (mostly infections) were not increased in the treatment group, although there was one case of sudden infant death syndrome at age 4 months.
                Using a dose of rHuEpo of 600 U/kg per week, this study has shown a clear reduction in the requirement for blood transfusion in preterm infants. To test the efficacy and safety of combining intravenous iron in amounts approximating the in utero iron accretion rate and the postnatal iron loss with erythropoietin (EPO) in very low birth weight (VLBW) infants.
                A prospective, controlled, randomized, unmasked trial lasting 21 days was performed in 29 clinically stable VLBW infants <31 weeks' gestation and <1300 g birth weight not treated with red blood cell transfusions during the study period. Mean (+/- standard error of the mean) age at study entry was 23 +/- 2.9 days. After a 3-day run-in baseline period in which all participants received oral supplements of 9 mg/kg/day of iron polymaltose complex (IPC), participants were randomized to receive 18 days of treatment with: 1) oral IPC alone (oral iron group); 2) 300 U of recombinant human EPO (r-HuEPO) kg/day and daily oral IPC (EPO + oral iron group); 3) 2 mg/kg/day of intravenous iron sucrose, r-HuEPO, and oral iron (intravenous iron + EPO group). To assess efficacy of the 3 treatments, serial blood samples were analyzed for hemoglobin (Hb), hematocrit (Hct), reticulocyte count, red blood cell indices and plasma levels of transferrin, transferrin receptor (TfR), ferritin, and iron. Oxidant injury was assessed before and after treatment by plasma and urine levels of malondialdehyde (MDA) and o-tyrosine.
                At the end of treatment, Hb, Hct, reticulocyte count, and plasma TfR were markedly higher in both of the EPO-treated groups, compared with the oral iron group. At study exit a trend toward increasing Hb and Hct levels and significantly higher reticulocyte counts were observed in the intravenous iron + EPO group, compared with the EPO + oral iron group. During treatment, plasma ferritin levels increased significantly in the intravenous iron + EPO group and decreased significantly in the other 2 groups. By the end of treatment, ferritin levels were significantly higher in the intravenous iron + EPO group compared with the other 2 groups. Although plasma and urine MDA or o-tyrosine did not differ among the 3 groups, plasma MDA was significantly greater in the subgroup of intravenous iron + EPO participants sampled at the end of the 2-hour parenteral iron infusion, compared with values observed immediately before and after parenteral iron-dosing.
                In stable VLBW infants receiving EPO treatment, parenteral supplementation with 2 mg/kg/day of iron sucrose results in a small, but significant, augmentation of erythropoiesis beyond that of r-HuEPO and enteral iron alone. However, to reduce the potential adverse effects of parenteral iron/kg/day on increasing plasma ferritin levels and on causing oxidative injury, we suggest that the parenteral iron dose used should be reduced and/or the time of infusion extended to maintain a serum iron concentration below the total iron-binding capacity. The purpose of this study was to test the therapeutic effect of human recombinant erythropoietin (rH-EPO) on anemia of prematurity.
                Fifty-eight preterm infants less than 34 weeks of gestational age from three different hospitals were studied. Transfusional policies were similar in all three centers. Infants with ABO or Rh incompatibility were excluded. At 28 days after birth, 28 infants (48.3%) had hemoglobin levels under 10.5 g/dL and were randomized to receive rH-EPO or standard care. Those infants ascribed to the treatment group received 200 U/kg of body weight of rH-EPO subcutaneously once a day, three days a week for 4 weeks together with oral supplements of ferrous sulfate at a dosage of 4 mg/kg/day. Both groups received daily doses of 50 micrograms of folic acid and 5U of vitamin E per os. Erythropoietin and ferritin were determined at randomization and at 60 days of age. Hemoglobin, reticulocytes, leucocytes, granulocytes and platelets were measured once a week, from the beginning of the treatment until 60 days of age.
                At randomization into treatments, there were no significant differences between the groups with respect to weight, gestational age, hemoglobin (9.42 +/- 0.73 vs 9.26 +/- 0.68 g/dL), reticulocytes (61.7 +/- 32.2 vs 68.0 +/- 61.0 x 10(9)/L), ferritin, EPO1 leucocytes or platelets. At 60 days of age, the treatment group showed higher hemoglobin values (10.5 +/- 1.73 vs 9.1 +/- 1.0 g/dL, p < 0.05). There were no significant differences between reticulocyte counts (176.4 +/- 91.1 vs 112.6 +/- 85.0 x 10(9)/L), granulocytes (2,351 +/- 868 vs 2,075 +/- 856 x 10(9)/L), platelets (400 +/- 138 vs 316 +/- 164 x 10(9)/L) or ferritin (209 +/- 177 vs 393 +/- 328 micrograms/mL). Of the infants in the nontreated group, 13.3% received blood transfusions between 30 and 60 days of age, while only 6.7% of the treatment group did (p = 0.31).
                We have been able to find 11 controlled studies in the medical literature which deal with the clinical usage of rH-EPO in newborns. Six use the hormone in an early phase and 5 in a posterior one. Our study should be included in the later and, as happens in most of them, demonstrates the efficacy of rH-EPO in the treatment of late anemia of the preterm newborn as shown by an increment in the hemoglobin levels and a trend towards the diminution in the use of blood transfusions. We have not observed substantial adverse effects. To determine whether treatment with recombinant human erythropoietin (r-HuEPO) reduces transfusion requirements in premature neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions.
                A double-blind, randomized, controlled trial.
                Fifty-five infants appropriate in weight for gestational age (less than 1250 gm birth weight) who, at 10 days of age, were predicted to have a greater than 75% probability of having bronchopulmonary dysplasia. This criterion had previously been shown to identify infants requiring multiple transfusions. Twenty-seven infants were randomly assigned to receive r-HuEPO therapy and 28 to a control group. r-HuEPO was administered in a dosage of 20 U/kg body weight, subcutaneously, three times a week for 6 weeks. Control infants received sham treatment.
                Infants treated with r-HuEPO required significantly fewer transfusions than control infants during their entire hospital stay (mean 3.48 +/- 1.58 vs 5.68 +/- 2.30; p = 0.0001) and had a higher mean reticulocyte count (p < or = 0.0005) and a higher mean hemoglobin concentration (p < or = 0.005) during the treatment period. At follow-up, 4 months after term, there were no significant differences between the groups in mean reticulocyte count (p = 0.86) or mean hemoglobin concentration (p = 0.56). However, two infants in each group had low serum ferritin values indicative of depleted iron stores.
                Treatment with r-HuEPO effectively stimulated erythropoiesis in premature infants at high risk of having bronchopulmonary dysplasia and requiring multiple transfusions; the result was a reduction in transfusion requirements. This treatment, together with other strategies to reduce the need for transfusions, is appropriate in this population. Unrelated to r-HuEPO treatment, these infants may be at risk of having iron deficiency later in infancy.
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.