Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity?

Romagnoli, C; Zecca, Enrico; Gallini, Francesca; Girlando, Pietro; Zuppa, Antonio Alberto

doi:10.1007/pl00008390

Cited by 85 publications

(83 citation statements)

References 4 publications

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“…The association between rEPO and ROP is based on the angiogenic action of rEPO. 13,14 Romagnoli et al 15 reported an increased risk of ROP when administered in week 1 of life. A recent meta-analysis by Ohlson and Aher 10 showed a greater risk for severe ROP in this subgroup, with a relative risk:1.7 (95% CI: 1.1-2.54) and a number needed to harm: 20 (95% CI: 11-100).…”

Section: Discussionmentioning

confidence: 99%

“…[10][11][12] Nevertheless, because of its demonstrated angiogenic activity, 13 several trials have associated the use of rEPO with retinopathy of prematurity (ROP). 14,15 Current meta-analyses have shown greater ROP incidence in VLBW infants who received rEPO before day 8 of life. [10][11][12] The most suitable dosage schedule, based on pharmacokinetic studies, remains unclear because of differences among studies.…”

Section: Introductionmentioning

confidence: 99%

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Comparison between one and three doses a week of recombinant erythropoietin in very low birth weight infants

et al. 2010

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Objective: To compare transfusion requirements and erythropoietic response in preterms between schedules of rEPO administration once or three times per week, using the same weekly dose.Study Design: Prospective, randomized trial including infants weighing <1500 g at birth and/or were p32 weeks' gestation: Group 1 (60 infants) received subcutaneous rEPO at 250 units kg À1 per dose, three times weekly for 6 weeks; Group 2 (59 infants), at 750 units kg À1 per dose, once weekly for 6 weeks. Efficacy was evaluated based on the transfusion requirement, hemoglobin changes, reticulocyte counts, serum transferrin receptor (sTfR) and serum ferritin. The frequency of adverse effects was registered in both groups.Result: A total of 13 infants were transfused in each group (relative risk: 0.98; 95% confidence interval: 0.4 to 2.3). Phlebotomy loss and red blood cell transfusion volumes received were similar in both groups. Hemoglobin levels were lower at end of study in Group 2 (10.6±1.5 g dl À1 versus 11.5±1.4 g dl À1 ; P<0.003). At end of study, reticulocyte counts and sTfR values increased and serum ferritin values decreased, without significant differences between the two groups. Incidence of complications was similar in both groups. Conclusion:The once-weekly rEPO schedule for very low birth weight infants proved as effective as the three-times-weekly schedule, in relation to erythropoietic stimulus and transfusion requirement.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Comparison between one and three doses a week of recombinant erythropoietin in very low birth weight infants

et al. 2010

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“…Although numerous randomized placebo-controlled studies have not reported significant differences in the incidence of ROP between Epo treated and placebo infants, retrospective reports have postulated that use of Epo may be associated with increased rates of ROP (32)(33)(34)(35). Brown and colleagues reported an association between cumulative doses of Epo and risk for ROP (33); however, the authors were unable to separate the relationship among extreme prematurity, Epo doses, and ROP.…”

Section: Discussionmentioning

confidence: 99%

Elevated Erythropoietin mRNA and Protein Concentrations in the Developing Human Eye

et al. 2008

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Erythropoietin (Epo) is an erythropoietic, neurotropic, and angiogenic factor, and may be involved in retinal development. Studies in adult diabetic retinopathy patients reveal significantly elevated vitreal Epo concentrations. It is unknown whether Epo plays a similar role in retinopathy of prematurity. We sought to determine whether Epo is present in the normally developing human eye. Fetal serum and vitreous samples were obtained from 12 to 24 wk gestation. RNA was extracted from isolated retina for Epo mRNA and hypoxia inducible factor-1␣ (HIF) mRNA determination by real-time polymerase chain reaction. Fetal serum was isolated from the umbilical cord. Serum and vitreous samples were analyzed for Epo protein by enzyme-linked immunosorbent serologic assay. In fetal retina, Epo mRNA increased with increasing gestational age, while HIF mRNA remained constant. Epo protein increased with increasing gestation in both vitreous and serum. At each gestational group measured (12-14, 15-17, 18 -20, and 21-24 wk), Epo concentrations were significantly greater in vitreous than in serum (p Ͻ 0.05). Epo mRNA and protein concentrations increase with increasing gestational age and are greater in the vitreous than serum. We speculate that changes in Epo production following preterm delivery might affect retinal vascular development.

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“…However, a meta analysis of these trials showed that neovascular ROP is increased in EPO-treated infants (Ohlsson and Aher, 2006). A few single center studies have linked EPO use to increased incidence of ROP Romagnoli et al, 2000). Collectively, these data suggest that EPO administration during the second phase of ROP may increase neovascularization.…”

Section: Erythropoietin (Epo)-epomentioning

confidence: 99%

Vascular endothelial growth factor in eye disease

Penn

Madan

Caldwell

et al. 2008

Progress in Retinal and Eye Research

615

527

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Collectively, angiogenic ocular conditions represent the leading cause of irreversible vision loss in developed countries. In the U.S., for example, retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration are the principal causes of blindness in the infant, working age and elderly populations, respectively. Evidence suggests that vascular endothelial growth factor (VEGF), a 40 kDa dimeric glycoprotein, promotes angiogenesis in each of these conditions, making it a highly significant therapeutic target. However, VEGF is pleiotropic, affecting a broad spectrum of endothelial, neuronal and glial behaviors, and confounding the validity of anti-VEGF strategies, particularly under chronic disease conditions. In fact, among other functions VEGF can influence cell proliferation, cell migration, proteolysis, cell survival and vessel permeability in a wide variety of biological contexts. This article will describe the roles played by VEGF in the pathogenesis of retinopathy of prematurity, diabetic retinopathy and age-related macular degeneration. The potential disadvantages of inhibiting VEGF will be discussed, as will the rationales for targeting other VEGF-related modulators of angiogenesis.

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Do recombinant human erythropoietin and iron supplementation increase the risk of retinopathy of prematurity?

Cited by 85 publications

References 4 publications

Comparison between one and three doses a week of recombinant erythropoietin in very low birth weight infants

Comparison between one and three doses a week of recombinant erythropoietin in very low birth weight infants

Elevated Erythropoietin mRNA and Protein Concentrations in the Developing Human Eye

Vascular endothelial growth factor in eye disease

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