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

doi:10.1016/S0022-3476(95)70462-0

The Journal of Pediatrics

Volume 126, Issue 3, March 1995, Pages 421-426

https://doi.org/10.1016/S0022-3476(95)70462-0 Get rights and content

Abstract

Objective: 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. Methods: 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 care-givers were unaware of the treatment assignments, and erythrocyte transfusions were administered according to hematocrit and signs of anemia. Results: 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. Conclusions: We conclude that administration of Epo to VLBW infants during the first 2 weeks of life results in fewer transfusions and is cost-effective. (J Pediatr 1995;126:421-6)

Section snippets

METHODS

Infants were eligible for study if they required intensive care, were less than 48 hours of age, weighed between 750 and 1500 gm at birth, were born at ≥27 weeks of gestation, and had hematocrits between 0.40 and 0.60. Infants were ineligible for study if hemolytic or hemorrhagic disease was documented, or if, during mechanical ventilation, more than 80% oxygen was required for the preceding 4 hours. Infants were also ineligible if congenital heart disease or disease requiring immediate

RESULTS

After the interim analysis, the study was discontinued because of significant differences between groups in number of transfusions. Twenty patients were enrolled. There were no differences between groups in birth weight, gestational age, or age at the time of study entry (Table I). There were also no differences between groups in hematocrit, absolute reticulocyte count, or blood lactate concentration.

Changes in absolute reticulocyte count are shown in the upper panel of the Figure. Reticulocyte

DISCUSSION

After blood loss, adult subjects promptly increase production of endogenous erythropoietin, and the subsequent acceleration in erythropoiesis restores the erythroid mass.¹¹ A limited capacity to increase serum concentrations of erythropoietin during anemia appears to render VLBW infants less capable of compensating for blood loss.12, 13 The number of transfusions given to VLBW infants in the first few weeks of life remains a significant problem.¹ One recently studied alternative to transfusions

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Cited by (93)

Unbiasing costs? An appraisal of economic assessment alongside randomized trials in neonatology
2021, Seminars in Perinatology
Economic evaluations performed alongside randomized controlled trials benefit from the protections against bias inherent in randomization. In this systematic review, we assessed the frequency and quality of economic assessments alongside randomized controlled trials of interventions in neonates published between 1990 and 2016. Over that period, 58 economic assessments were published, corresponding to approximately 2% of RCTs. We noted significant methodological limitations of these studies, including limitation of included costs to the health sector or payer rather than broader categories such as family or community expenditures (81%), short time horizon for cost measurement (less than one year in 60%), lack of reporting of uncertainty (26%), and infrequent analysis of costs and effects in a single metric (combined in 45%). Strategies for improving the quality and frequency of economic evaluations in neonatology are discussed, including selection of appropriate trials, funding, and peer review.
Metabolic Characteristics of Neonatal Erythrocytes
2017, Fetal and Neonatal Physiology, 2-Volume Set
Developmental Erythropoiesis
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Erythropoietin treatment for late anaemia after haemolytic disease of the newborn
2010, Anales de Pediatria
Tras varios años de empleo de eritropoyetina (EPO) en la profilaxis de la anemia del prematuro se empezó a utilizarla en algunos recién nacidos (RN) para tratar la anemia neonatal tardía posthemólisis y evitar la transfusión de hematíes.
Mostrar los resultados del tratamiento con EPO en la anemia neonatal tardía posthemólisis.
Estudio observacional en 13 RN con anemia tardía secundaria a enfermedad hemolítica por isoinmunización Rh (9 casos), ABO (2 casos), déficit de glucosa-6-P-deshidrogenasa (1 caso) e idiopática (1 caso). Los neonatos iniciaron el tratamiento con EPO cuando se encontraron en indicación de transfusión o próximo a ella.
Se empezó el tratamiento con EPO a la edad de 26±7 días (15–46), con un valor de hematocrito de 21,7±3% (18–27) y un recuento reticulocitario del 3,8±2,2%. En 11 niños se pudo evitar la transfusión (alcanzaron un hematocrito de 30,7±4,4% y reticulocitos del 5,9±1,4%) y sólo 2 debieron ingresar a tal efecto (con hematocrito 18±1,4% y reticulocitos del 0,6%). Tras la EPO se encuentra un aumento significativo de la hemoglobina (Hb) y de los reticulocitos
La EPO se ha mostrado útil para evitar la transfusión de hematíes en el 84% de los niños tratados. No se han observado efectos secundarios atribuibles a su uso.
After several years of erythropoietin (EPO) use in the prophylaxis of anaemia of prematurity, it also began to be administered to treat post-haemolytic disease anaemia of the newborn in order to avoid blood transfusions.
To show the results obtained with EPO treatment in post-haemolytic disease anemia of the newborn.
Observational study in 13 newborns with late anaemia due to an hemolytic disease caused by Rh isoimmunization (9 cases), AB0 isoimmunization (2 cases), glucose-6-P-dehydrogenase deficiency (1 case) or idiopathic (1 case). The newborns began EPO treatment when they reached the haematocrit level for a blood transfusion.
EPO treatment was started at 26±7 days of life (15–46), with a haematocrit value of 21.7±3% (18–27) and a reticulocyte count of 3.8±2.2%. Blood transfusion was not necessary in 11 newborns (haematocrit of 30.7±4.4% and reticulocytes of 5.9±1.4%), and only 2 newborns were admitted for a blood transfusion (haematocrit 18±4.4% and reticulocytes 0.6%). Significant increases in haemoglobin and reticulocyte figures were seen after EPO treatment.
EPO administration proved useful to avoid blood transfusion in 84% of treated newborns. No adverse events were detected which could be attributed to this treatment,.
Anemia in the Preterm Infant: Erythropoietin Versus Erythrocyte Transfusion-It's not that Simple
2009, Clinics in Perinatology
Citation Excerpt :
The results varied, and the relative benefit of r-EPO for AOP is related to the study design (early versus late treatment; liberal versus restrictive transfusion criteria), patient population, and value assigned to complex outcomes. Not all studies took into account the risk of infection transmission, exclusion of which would lower the cost of transfusion.32 Studies evaluating the cost of treating stable, growing premature infants with r-EPO are more likely to favor RBC transfusion over r-EPO than are studies focused on sicker premature infants at greater risk for RBC transfusion.72,74
Since the late 1980s recombinant human erythropoietin (r-EPO) has been studied as an alternative to packed red blood cell (RBC) transfusion for the treatment of anemia of prematurity in very low birth weight infants. Initial trials and reports focused on r-EPO's ability to prevent or treat anemia of prematurity with the goal of eliminating RBC transfusion but achieved limited success. New concerns about the safety of r-EPO administration have emerged. Past cost–benefit analyses of r-EPO administration versus transfusion for the treatment of anemia of prematurity have been nearly balanced. Autologous transfusion, blood-sparing technologies, changes in RBC transfusion technique and safety, and further elucidation of the risk–benefit ratio of r-EPO therapy may change the cost–benefit analysis.
Is there a role for erythropoietin in neonatal medicine?
2008, Early Human Development
Since it was first cloned in 1985, the therapeutic potential of recombinant human erythropoietin in the neonatal hyporegenerative anaemias has been studied—the anaemia of prematurity and haemolytic disease of the newborn. Between 60% and 100% of preterm infants are transfused before three weeks of age, a large proportion receiving more than one transfusion. Blood transfusions are currently also the mainstay of treatment for the hyporegenerative anaemia encountered in neonates with Rhesus disease. Sometimes the situation is complicated by the religious beliefs of the parents.
Blood transfusions are associated with numerous risks, from transmission of infection to local injury, and in an effort to minimize these risks Neonatologists have looked to recombinant erythropoietin. Despite an extensive number of studies, there is as yet no clear consensus as to whether the use of recombinant erythropoietin in Neonatal medicine minimizes the need for blood transfusions without risk to the neonate. In this article we review the evidence for and against the use of recombinant erythropoietin in Neonatal medicine.

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^☆: From the Division of Neonatology, University of Florida, Gainesville, and the Division of Human Development and Aging, University of Utah School of Medicine, Salt Lake City

^☆☆: Supported by grants HD-00988 and HL-44951 from the National Institutes of Health, grant RR-00064 from the National Center for Research Resources, and an award from the Children's Miracle Network Telethon.

^★: Reprint requests: Robin K. Ohls, MD, Division of Neonatology, University of Florida College of Medicine, P.O. Box 100296, JHMHC, Gainesville, FL 32610-0296.

^★★: 0022-3476/95/$3.00 + 0 9/20/60611

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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☆,☆☆,★,★★

Abstract

Section snippets

METHODS

RESULTS

DISCUSSION

Clin Perinatol

J PEDIATR

J PEDIATR

J PEDIATR

J PEDIATR

J PEDIATR

J PEDIATR

Erythropoietin and neonatal anemia

N Engl J Med

Recombinant erythropoietic growth factors as an alternative to erythrocyte transfusion for patients with "anemia of prematurity

Pediatrics

The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very low birth weight infants

N Engl J Med

Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study

Pediatrics

Recombinant human erythropoietin (r-HuEPO) stimulates erythropoiesis and reduces transfusions in preterm infants

Pediatr Res