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)

The purpose of this study was to determine whether an inappropriately low erythropoietin response in premature infants might be a basis for the anemia of prematurity. Erythropoietin was measured by radioimmunoassay in conjunction with hemoglobin and reticulocyte count in untransfused premature infants between birth and 60 days of age. The 27 infants had a mean gestational age of 31 weeks and a mean birth weight of 1378 gm. Between 2 and 30 days, mean erythropoietin concentration was 9.7 mU/ml, significantly and substantially lower than 15.2 mU/ml in 15 concurrently studied healthy adults (P less than 0.01). Subsequently, from 30 to 60 days, values rose gradually to a mean of 17.2 mU/ml, which did not differ significantly from the mean value in adults. Hemoglobin values fell from a mean of 12.9 gm/dl during the first month to 9.0 gm/dl between 30 and 60 days. Thus, during the second postnatal month, preterm infants had essentially the same erythropoietin values as in adults despite a mean hemoglobin concentration that averaged less than two thirds the adult value. This failure to mount a greater erythropoietin response may help to explain why hemoglobin declines to such low values at 2 months of age.
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PMID:Postnatal changes in erythropoietin levels in untransfused premature infants. 619 81

This study was undertaken to determine the factors that are important in determining the erythropoietin response in low-birth-weight infants during the period of so-called anemia of prematurity. In the first weeks of life oxygen consumption in a group of 21 infants gradually increased as hemoglobin level fell. The magnitude of the erythropoietin response inversely varied with the central venous oxygen tension (P-vO2) (r = -0.55, P less than 0.001). When the P-vO2 declined to less than 30 torr, erythropoietin values were uniformly increased above the "normal" range (defined as the values associated with P-vO2 greater than 38 torr). Erythropoietin values varied inversely with hemoglobin but in general did not exceed the values observed for normal adult men. The erythropoietin values in the infants were remarkably lower at any given hemoglobin level when compared with those of older children with anemia resulting from bone marrow failure. In general, elevations of erythropoietin were seen when the hemoglobin concentration declined to less than 10.0 gm/dl. Change in heart rate did not appear to be a reliable indicator of the presence of anemia; rather, it correlated best with oxygen consumption.
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PMID:Anemia of prematurity: determinants of the erythropoietin response. 650 12

Erythropoietin, hemoglobin, hematocrit, oxygen affinity (P50), and reticulocyte counts were measured weekly starting at 1 week of age in 10 very-low-birth-weight infants and on a single occasion in 15 healthy men. In the adults, "available oxygen" (derived from oxygen carrying capacity and P50) averaged 13.1 ml/dl blood and the mean erythropoietin level was 15.2 mU/ml. Erythropoietin levels in the infants were inversely related to concentration of hemoglobin, P50, and available oxygen. However, despite the much lower mean "available oxygen" of 9.3 ml/dl in the infants compared with that in adults (P less than 0.001), the mean erythropoietin value of 8.2 mU/ml in the infants was less than in adults (P less than 0.001). Furthermore, the erythropoietin response to decreased "available oxygen" was lowest in the least mature infants. VLBW infants often develop clinical evidence of hypoxia during the anemia of prematurity. The relatively low erythropoietin levels in relation to "available oxygen" are compatible with a decreased erythropoietin response to hypoxia compared with that in adults. Such a difference in response could be a contributing factor to the anemia of prematurity.
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PMID:Decreased response of plasma immunoreactive erythropoietin to "available oxygen" in anemia of prematurity. 650 13

Increased fetal Hb (HbF) synthesis has been shown to occur during fetal hypoxemia and severe anemia. To determine whether increased HbF synthesis occurs during anemia of prematurity, the levels of HbF synthesis were correlated with the degree of anemia and plasma erythropoietin levels. Thirteen newborn infants born at 29.2 +/- 1.7 wk of gestation were studied at a postconceptional age 36.0 +/- 1.1 wk. Hb levels ranged from 65 to 78 g/L. Blood samples were incubated in an amino acid mixture containing [3H]leucine and chromatographed allowing the separation and quantitation of the alpha, beta, and gamma (A gamma T, G gamma, and A gamma I) chains. Erythropoietin was determined by RIA. The mean HbF synthesis was 77.9 +/- 8.9% of total Hb synthesis (range: 61 to 91%). Plasma erythropoietin concentrations were 21.4 +/- 6.4 mU/mL. There was no correlation between the total Hb or HbF synthesis and the level of erythropoietin. There was, however, a significant inverse correlation between the Hb level and HbF synthesis (p < 0.01). Nine infants who had received transfusions during the first few days of life had a mean HbF that was 53.5 +/- 15.2% of total Hb, whereas their HbF synthesis was 78.4 +/- 7.6%. Four of the infants never received transfusions; the total circulating HbF and HbF synthesis in these infants were 87.7 +/- 7.7% and 76.8 +/- 12.7%, respectively. This study shows that there can be a reactivation of HbF synthesis during severe anemia of prematurity.
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PMID:The reactivation of fetal hemoglobin synthesis during anemia of prematurity. 752 26

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.
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PMID:Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother's milk during anaemia of prematurity. 754 3

In order to prevent or to treat anemia of prematurity, more than 800 preterm infants were enrolled into controlled studies with recombinant erythropoietin (rhEPO) during the past five years. The effective dosage seems to be within the range of 300 to 1200 IU/kg per week, markedly higher than in adults or children with anemia due to renal failure. No adverse events nor impairment of granulopoiesis or platelet formation could be attributed to erythropoietin. Statistical metaanalysis of eight controlled trials revealed an 18% reduction of transfused infants. The preventive effect was scarce in very small and very sick preterm infants, and during the first two weeks of life, when hemorrhagic anemia due to diagnostic blood loss is predominant. rhEPO treatment is one step in the concept to prevent anemia of prematurity. This concept should also include placental transfusion, minimizing of diagnostic sampling, miniaturized laboratory tests, adequate iron supplementation, and optimal nutritive protein administration.
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PMID:Recombinant erythropoietin for prevention of anemia in preterm infants. 765 11

It has been well established that erythropoietin (EPO) in the dosage range of 500 units/kilo/week and perhaps slightly lower doses will produce a brisk reticulocyte response in infants with anemia of prematurity. Controlled clinical trials to demonstrate that this therapy can result in significant reductions in transfusion in these babies face several complex issues of experimental design. 1. Should the study population be relatively bigger, healthier babies (< 1500 grams birth weight, not on ventilatory support) who have lower transfusion requirements, or smaller sicker infants (< 1250 grams birth weight and on ventilators) who have higher transfusion requirements? These infants will need adequate nutrition and liberal supplementation with iron if they are to respond adequately, but the sicker smaller infants will take longer to meet these nutritional goals. 2. Timing is important because spontaneous recovery occurs at about 35 to 36 weeks of corrected gestational age, so to be effective, therapy must start before 33 weeks of gestational age and preferably earlier than that. 3. Since the end point is transfusion, the criteria used for transfusions become a critical issue. If liberal transfusion criteria are used, the study will be doubly biased in favor of EPO efficacy. There will be an increased number of transfusion events in the control population and spontaneous recovery from the anemia of prematurity will be overly suppressed in the control population. It's likely that the current transfusion criteria are too liberal thus introducing these biases to experimental design.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Erythropoietin therapy for extremely premature infants. 765 12

All forms of oxygen deprivation act as a stimulus for the production of the hormone erythropoietin. The main sites of production are specialized renal fibroblasts in adult mammals and hepatic cells in mammalian fetuses and neonates. The hormone's name is a succint description of its main effect: erythropoietin stimulates red cell production from bone marrow precursors and hence controls the O2-carrying capacity of the blood. The peripheral red cell count is kept constant by a closely controlled feedback mechanism involving O2 supply, erythropoietin secretion and erythropoiesis; the system may become unbalanced in conditions such as chronic renal disease, chronic inflammation and prematurity. Recombinant human erythropoietin is used as hormonal replacement therapy to correct various types of anemia and replenish the red cell count following hemorrhage or blood donation for autologous transfusion.
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PMID:Erythropoietin--from gene structure to therapeutic applications. 765 25

Epoetin alfa is a recombinant form of the principal hormone responsible for erythrogenesis, erythropoietin. Already an established treatment for anaemia associated with renal failure, epoetin alfa may also be used to correct anaemia in other patient groups. The drug increases the capacity for autologous blood donation in patients scheduled to undergo surgery and attenuates the decrease in haematocrit often seen in untreated autologous donors. However, transfusion requirements did not significantly decrease in many trials. Epoetin alfa also accelerates red blood cell recovery after allogeneic--but not autologous--bone marrow transplant. Limited data in patients with adult rheumatoid arthritis suggest that while epoetin alfa increases haematocrit/haemoglobin levels, overall clinical rheumatological status may not improve. However, the drug did improve quality of life in a small cohort of children with juvenile rheumatoid arthritis in addition to correcting anaemia. Response rates to treatment with epoetin alfa in patients with anaemia associated with cancer range between 32 and 85%. Anaemia associated with cancer chemotherapy also responds well to treatment with the drug as does anaemia associated with zidovudine therapy in patients with acquired immune deficiency syndrome (AIDS). Studies evaluating the use of epoetin alfa as treatment for anaemia of prematurity have used different methodologies and dosages, making overall analysis difficult. Nevertheless, it appears that high dosages are necessary for response. Results from 1 study suggest that treatment with epoetin alfa appears to be more costly than transfusional support in this application; the relevance of this finding is questionable, however, given that the aim of treatment with epoetin alfa is elimination of transfusion requirements. The incidence of many adverse events associated with epoetin alfa treatment in patients with renal failure (hypertension, seizures and thromboembolic events) has been minimal in patients without renal failure. Adverse events occurred at a similar rate in placebo and epoetin alfa recipients in placebo-controlled trials evaluating the use of the drug as treatment for anaemia in patients with cancer receiving chemotherapy or patients with AIDS receiving zidovudine. In summary, epoetin alfa is an effective alternative to blood transfusion, reducing anaemia and producing consequent improvements in quality of life in many nonrenal applications. It was more effective than placebo in a number of double-blind trials and may be particularly useful as treatment for anaemia associated with other drugs such as cisplatin and zidovudine.
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PMID:Epoetin alfa. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in nonrenal applications. 772 31

Increased understanding of the pathophysiology of anemia of prematurity (AOP) has emerged over the past years. It is apparent that low levels of endogenous erythropoietin (Epo) is the basis for this phenomenon. This has resulted in an effective therapeutic approach for this condition. Administration of Epo can ameliorate the signs and symptoms of AOP and lessen, and in many cases avoid, the necessity for blood transfusion.
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PMID:Pathophysiology and treatment of the anemia of prematurity. 774 31


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