Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0728731 (prematurity)
 7,134 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study. 137 52

Recent reports of neutropenia associated with the use of recombinant human erythropoietin (r-HuEpo) in preterm infants with the anaemia of prematurity have raised concern over the clinical use of this hormone. The present studies were undertaken to determine whether high-dose r-HuEpo has an effect on granulocyte production in vitro. The studies used a serum deprived, optimized semi-solid cell culture system to investigate the effect of lineage specific and non-specific granulocyte and erythroid colony stimulating factors on circulating peripheral blood granulocyte-macrophage colony forming units (CFU-GM), erythroid burst forming units (BFU-E) and multilineage colonies (CFU-Mix) from nine premature infants and seven healthy adults. CFU-GM were grown in the presence of interleukin 3 (IL3) 8 ng/ml, granulocyte-macrophage colony stimulating factor (GM-CSF) 20 ng/ml and granulocyte colony stimulating factor (G-CSF) 15 ng/ml alone and combinations of G-CSF with GM-CSF or IL3. The number, size and differentiation of CFU-GM colonies were then analysed in the presence and absence of high dose r-HuEpo (4 U/ml). High-dose r-HuEpo did not exert any significant modulatory effects on the number of CFU-GM colonies produced in the presence of IL3, GM-CSF and G-CSF alone or in combination. The number of cells within each CFU-GM colony did not change significantly, nor was there a significant change in the degree of differentiation. The combined number of BFU-E, CFU-GM and CFU-Mix colonies increased with r-HuEpo in both adults (1.8 x) and preterm infants (1.4 x), almost exclusively due to an increase in BFU-E derived colonies. Thus, no evidence was found for an r-HuEpo mediated redirection of multipotential haemopoietic stem cells into committed erythroid precursors at the expense of myeloid precursors.
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PMID:The in vitro effect of high-dose recombinant human erythropoietin on granulocyte-macrophage colony production in premature infants using a defined serum deprived cell culture system. 138 42

Recombinant human erythropoietin (rHuEPO) was administered subcutaneously three times a week to 18 infants with the anaemia of prematurity at doses of 75, 150, 300, or 600 units/kg per week for 4 weeks, starting at 3-4 weeks of postnatal age. A significant and dose-dependent increase in reticulocyte count was observed from a mean baseline value of 71 x 10(9)/l to 200 x 10(9)/l after 3 weeks of therapy, compared with a change from 69 to 97 x 10(9)/l in 66 historical controls. The haematocrit value remained unchanged during rHuEPO treatment, whereas it steadily declined until 9 weeks of postnatal age in the controls. These effects were accompanied by a marked reduction in serum iron concentration and transferrin saturation in patients receiving standard-dose iron supplements, but not in those given larger doses. Only 3 of 18 patients required a red blood cell transfusion. These infants were among the most anaemic at entry into the study and 2 of them were unable to complete rHuEPO therapy, while the third developed iron deficiency anaemia. These data indicate that rHuEPO with appropriate iron supplementation may accelerate the recovery from anaemia of prematurity. Larger scale placebo-controlled studies are now needed to confirm these findings and verify their impact on transfusion requirements of premature infants.
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PMID:Recombinant human erythropoietin in the treatment of infants with anaemia of prematurity. 139 27

A comparison was carried out between a series of neonates who weighed less than 1500 g at birth and received red cell transfusions for symptomatic anaemia of prematurity (group 1, n = 14) and controls of similar gestational age and weight, who remained well and were not transfused during their nursery stay (group 2, n = 10). Mean (SD) haemoglobin concentrations at birth were 163 (12) g/l and 183 (17) g/l (p = 0.004), respectively. Transfusion resulted in significantly better weight gain in six infants who had been growing poorly:mean (SE) 8.8 (2.8) g/day improved to 23.3 (2.1) g/day (p less than 0.002). Geometric mean (SD) serum immunoreactive erythropoietin (SiEp) concentrations (17.7 (1.3) U/l) for the whole group of infants were similar to those of normal adults (17.4 (4.7) U/l) despite considerably reduced haemoglobin values. There was a significant inverse correlation between haemoglobin and log SiEp concentrations in the infants requiring transfusion (r = -0.43; p less than 0.01), but this was not apparent in the untransfused babies. Moreover, at haemoglobin concentrations below 120 g/l the mean (SE) SiEp concentration of 20 (1.08) U/l in group 1 was significantly higher than in group 2 (14 (1.06) U/l; p = 0.002). These data suggest that an increased concentration of SiEp early in the course of the anaemia of prematurity helps to identify those infants who would benefit from red cell transfusions, but that clinical criteria, although ill defined, do so equally well.
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PMID:Serum erythropoietin concentrations in symptomatic infants during the anaemia of prematurity. 151 82

There is a high level of erythropoiesis in the growing fetus. In utero relative hypoxia results in a relatively high haematocrit and predominant synthesis of haemoglobin F, with erythropoietin (EPO) produced in the liver regulating erythropoiesis. At birth after full-term pregnancy, fetal EPO concentrations are high, but decline progressively thereafter. In pre-term infants the expected postnatal decline in haemoglobin is more prolonged than in full-term infants and the premature infants may become anaemic. It has been shown in a randomized, double-blinded, placebo-controlled trial that recombinant human erythropoietin (r-HuEPO) at a dose of 100 U/kg given intravenously twice weekly for 6 weeks to infants with anaemia of prematurity produced an earlier increase in reticulocyte counts compared with placebo; however, the difference between treatments was not significant. r-HuEPO therapy did not suppress subsequent release of endogenous EPO. It is concluded that a higher dose of r-HuEPO may be required to treat anaemic premature infants.
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PMID:Potential for treatment of anaemia of prematurity with recombinant human erythropoietin: preliminary results. 157 65

In an attempt to stimulate endogenous erythrocyte production and thereby provide an alternative to erythrocyte transfusions, we administered recombinant human erythropoietin (rHuEpo) in doses of 75 to 300 units/kg/wk to seven infants with the anemia of prematurity. Treatment was started between 21 and 33 days of life, maintained for 4 weeks, and was well tolerated. All the patients had low baseline serum erythropoietin levels. After rHuEpo therapy, the number of reticulocytes increased from a mean baseline count of 75 x 10(9)/L to 95, 141, and 165 x 10(9)/L on days 7, 10, and 14 of therapy, respectively. Correction or stabilization of the anemia was observed in six of seven patients, whose estimated total erythrocyte volume increased by 49% during therapy (vs a predicted increment of 18% in the absence of rHuEpo). In one patient, however, the hematocrit declined during the treatment, and in three of the responders a secondary fall in hematocrit was noted either during therapy or after its discontinuation. Serum iron and ferritin levels rapidly decreased after the initiation of rHuEpo therapy, and in most patients transient early thrombocytosis and late neutropenia were observed. These data suggest that rHuEpo may correct or stabilize the anemia of prematurity. Its effects, however, may be limited by a variety of factors, among which iron availability probably plays an important role. Controlled studies will be needed to confirm these preliminary observations.
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PMID:Effects of recombinant human erythropoietin in infants with the anemia of prematurity: a pilot study. 169 80

Erythropoietin is a glycoprotein hormone that plays a vital role in erythropoiesis. It is mainly produced in the fetal liver till the third trimester of pregnancy. At that point, the kidney interstitium takes over this function and becomes the main source of erythropoietin. Hypoxia stimulates erythropoietin production by a mechanism that may require a heme protein as a second messenger. Erythropoietin stimulates the maturation of erythroid precursors (colony-forming unit-erythroid and burst-forming unit-erythroid) via at least two types of cell surface receptors. The higher-affinity receptors appear to be more important in modulating the effects of erythropoietin in vivo. Changes in intracellular calcium may ultimately mediate the action of erythropoietin on erythroid precursors. A specific and sensitive radioimmunoassay is now available for accurately measuring erythropoietin levels. All forms of erythrocytosis except polycythemia vera are associated with elevated erythropoietin levels. Levels are also high in cord blood obtained following fetal asphyxia. Reduced levels are seen in patients with anemia due to renal diseases. The response of erythropoietin to the degree of anemia appears to be attenuated in patients with cancer, chronic diseases, and human immunodeficiency virus (HIV) infection. Erythropoietin has been successfully used for treating patients with anemia due to renal failure. Its use has also been approved for the treatment of anemia patients receiving zidovudine for HIV infection. Encouraging results have been observed when erythropoietin was used to treat anemia due to rheumatoid arthritis, hematological malignancies, and prematurity. It has also been used to increase the yield of autologous blood collected prior to an elective surgical procedure. However, it has not proved to be useful in sickle cell anemia and myelodysplastic syndromes.
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PMID:Erythropoietin. Biology and clinical applications. 178 66

The anemia of prematurity is defined by a progressive decline in hemoglobin level occurring over the first 2 months of life. Unlike term newborns whose "physiologic anemia" rarely if ever necessitates any treatment, preterm infants may become anemic enough to have clinical symptoms that indicate a need for red blood cell transfusions. Various factors contribute to the development of this anemia. Some of these factors, such as the short life span of erythrocytes in preterm infants, increased sensitivity of the erythrocytes to oxidative injury, and the blood losses caused by repeated phlebotomies, would normally be expected to induce corrective reticulocytosis. Characteristically, however, this anemia is hyporegenerative. Thus, it is associated with relative reticulocytopenia, low serum erythropoietin levels, and bone marrow erythroid hypoplasia. The recent availability of recombinant human erythropoietin has opened new perspectives in the management of a variety of anemias. Based on current knowledge of the regulation and pathophysiology of fetal and neonatal erythropoiesis, recombinant erythropoietin may represent a logical and efficient alternative to giving red blood cell transfusions in the treatment of the anemia of prematurity. Clinical trials have been initiated in several countries using different approaches and methodology. At this early stage these trials do not yet fully affirm that recombinant erythropoietin can be used as the first-line therapy in infants with the anemia of prematurity. Our own observations, however, suggest that this agent is well tolerated by preterm infants and may exert a corrective effect on the anemia of prematurity.
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PMID:Use of recombinant erythropoietin in treatment of the anemia of prematurity. 179 63

Circulating erythroid progenitors (BFU-E) in five anaemic preterm infants (haemoglobin less than 100 g/l) were about 2 and 4.4 times as abundant as in 10 preterm infants who were not anaemic and five healthy adults, respectively, and were significantly more responsive to low concentrations of recombinant human erythropoietin (rHuEpo) than those from healthy adults. These results encourage further studies in the use of rHuEpo for the treatment of the anaemia of prematurity.
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PMID:Erythropoietin responsive progenitors in anaemia of prematurity. 186 30

Extensive clinical studies have documented the effectiveness of recombinant human erythropoietin (rHuEPO) in correcting the anemia of adult dialysis patients, but the safety and efficacy of rHuEPO in children with renal anemia cannot yet be confirmed, due to the relative deficiency of reported studies involving pediatric subjects. To date, published experience with rHuEPO therapy in children has totaled 257 patients, although the majority of these reports have appeared only as abstracts. Overall experience has been favorable, with renal anemia and transfusion dependency successfully resolved in almost all pediatric patients reported. However, controlled clinical trials have not been performed, so it is not yet possible to clearly define the risks associated with rHuEPO therapy in children. Hypertension appears to occur or become worse in up to one third of treated children, but it is unclear to what extent rHuEPO therapy is accompanied by an increased risk of seizures, thrombosis of vascular access, hyperkalemia, hyperphosphatemia, or peritonitis (when administered via the intraperitoneal route). Only preliminary and somewhat conjectural recommendations can be offered regarding pediatric rHuEPO dosing, route of administration, special precautions, and adjunctive monitoring and therapy. Fortunately, a multicenter controlled clinical trial is underway that is designed to address these issues. Because the harmful effects of renal anemia are typically more profound for children than they are for adults, the benefits of rHuEPO promise to be even greater among pediatric patients. Whether rHuEPO therapy will substantially improve growth and neurologic and psychosocial development remains to be seen, but the potential is there for rHuEPO to dramatically improve the lives of children who suffer from the effects of the anemia of chronic renal failure. Other non-renal anemias that afflict pediatric patients, such as the anemia of prematurity, also may be amenable to rHuEPO therapy.
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PMID:Pediatric uses of recombinant human erythropoietin: the outlook in 1991. 192 79


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