Early Erythropoietin Administration does not Increase the Risk of Retinopathy in Preterm Infants

Chou, Hsin‐Hsu; Chung, Mei‐Ing; Zhou, Xiaoguang; Lin, Hung‐Chih

doi:10.1016/j.pedneo.2016.03.006

Cited by 19 publications

(22 citation statements)

References 39 publications

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“…Whether treatment with erythropoietin is preventative or a risk factor for ROP in preterm infants continues to be a matter of debate. Some researchers suggest that the timing of erythropoietin treatment might be an important factor in the pathogenesis of ROP .…”

Section: Discussionmentioning

confidence: 99%

“…Whether treatment with erythropoietin is preventative Figure 2 Comparisons between infants who did not develop ROP warranting treatment and infants who did warrant ROP treatment: (a) weekly mean number of blood transfusions during first seven (light grey bars = did not and dark grey bars = did); b) daily mean haemoglobin levels during the first 14 days of life (solid line = did not and dotted line = did); (c) weekly mean haemoglobin levels during the first seven weeks of life (solid line = did not and dotted line = did); (d) weekly mean haemoglobin levels from birth to a postmenstrual age 35 weeks (solid line = did not and dotted line = did), *p < 0.05, **p < 0.01, ***<0.001. or a risk factor for ROP in preterm infants continues to be a matter of debate. Some researchers suggest that the timing of erythropoietin treatment might be an important factor in the pathogenesis of ROP (30).…”

Section: Discussionmentioning

confidence: 99%

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Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity

et al. 2018

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Aim This study evaluated the correlation between retinopathy of prematurity (ROP), anaemia and blood transfusions in extremely preterm infants. Methods We included 227 infants born below 28 weeks of gestation at King Edward Memorial Hospital, Perth, Australia, from 2014–2016. Birth characteristics and risk factors for ROP were retrieved, and anaemia and severe anaemia were defined as a haemoglobins of <110 g/L and <80 g/L, respectively. Logistic regression was used for the analysis. Results Retinopathy of prematurity treatment was needed in 11% of cases and the mean number of blood transfusions (p < 0.01), and mean number of weeks of anaemia (p < 0.001) and of severe anaemia (p < 0.05), had positive associations with ROP cases warranting treatment. In the multivariate logistic regression analysis, the best-fit model of risk factors included anaemic days during first week of life, with an odds ratio (OR) of 1.46% and 95% confidence interval (CI) of 1.16–1.83 (p < 0.05), sepsis during the first 4 weeks of life (OR 3.14, 95% CI 1.10–9.00, p < 0.05) and days of ventilation (OR 1.03, 95% CI 1.01–1.06, p < 0.05). Conclusion The duration of anaemia during the first week of life was an independent risk factor for ROP warranting treatment and preventing early anaemia may decrease this risk.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity

et al. 2018

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“…A recent metaanalysis found that late EPO supplementation does not significantly reduce or increase any fatal adverse outcomes; there is only the increased risk of ROP (8). However, early injection of rEPO is not associated with the risk of retinopathy in premature infants (13,19). The development of ROP has been divided into 2 phases according to the alteration of vasculature.…”

Section: Discussionmentioning

confidence: 99%

“…Intravitreal injection of small interference RNA is effective in hindering the development of RNV (12). Moreover, a recent study indicated that early EPO administration did not raise the risk of ROP (13). A clinical analysis found that rEPO was an independent risk factor in the development of ROP (14).…”

Section: Introductionmentioning

confidence: 99%

Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

Yang¹,

Zhang²,

He³

et al. 2017

Turk J Med Sci

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About 10-16 mouse pups were used per group, and both eyes were removed for experimental Background/aim: Erythropoietin (EPO) has been proven recently to be a critical mediator in retinal neovascularization (RNV). Previous studies have indicated that the use of recombinant human EPO (rEPO) is a high risk factor in the development of retinopathy of prematurity. In this study, we aimed to investigate the effect of rEPO administration on RNV and its underlying mechanism in a mouse model of oxygen-induced retinopathy (OIR). Materials and methods:A murine model of OIR was used to generate RNV. After daily intraperitoneal injection of rEPO from postnatal day 12 (P12), mice were euthanized at P17. Whole-mount retina staining was used to indicate the nonperfused area and neovascularization tufts. Preretinal neovascular cells were calculated through hematoxylin and eosin staining. The expression levels of vascular endothelial growth factor (VEGF) and inducible nitric oxide synthase (iNOS) were detected via western blot analysis. Results:We found that injection of rEPO promoted the severity of RNV. The areas of neovascular tufts and preretinal neovascular cells were increased after administration of rEPO. When mice were injected with rEPO, a dose-dependent upregulation in VEGF and iNOS was observed. Conclusion:The study indicates the proangiogenic role of EPO, suggesting that rEPO contributes to the pathogenesis of RNV.

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“…Moreover, serum EPO level was elevated 14 days after birth in preterm infants who developed severe ROP [15,16], and was reduced 28 days after birth in preterm infants who developed any degree of ROP [17]. Consequently, it remains unclear whether rhEPO treatment is a risk factor for ROP development [1,[18][19][20][21]. Thus, we aimed to clarify the effect of rhEPO on ROP development in preterm infants by retrieving data from our previous prospective randomised rhEPO clinical trials in preterm infants (ClinicalTrials.gov: NCT02036073, NCT03919500).…”

mentioning

confidence: 99%

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants

et al. 2020

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Background Very preterm infants are at risk of developing retinopathy of prematurity (ROP). Recombinant human erythropoietin (rhEPO) is routinely used to prevent anemia in preterm infants; however, the effect of rhEPO on ROP development is still controversial. The purpose of this study was to evaluate the effect of early prophylactic low-dose rhEPO administration on ROP development in very preterm infants. Methods A total of 1898 preterm infants born before 32 weeks of gestation were included. Preterm infants received rhEPO (n = 950; 500 U/kg, rhEPO group) or saline (n = 948, control group) intravenously within 72 h of birth and then once every other day for 2 weeks. Results The total incidence of ROP was not significantly different between the two groups (10.2% vs. 13.2%, p = 0.055). Further analysis showed that rhEPO group had lower rates of type 2 ROP than the control group (2.2% vs. 4.1%, RR 0.98; 95% CI 0.96–1.00; p = 0.021). Subgroup analysis found that rhEPO treatment significantly decreased the incidence of type 2 ROP in infant boys (1.8% vs. 4.3%, p = 0.021) and in those with a gestational age of 28–296/7 weeks (1.1% vs. 4.9%, p = 0.002) and birth weight of 1000–1499 g (1.2% vs. 4.2%, p = 0.002). There was a small increasing tendency for the incidence of ROP in infants with a gestational age of < 28 weeks after rhEPO treatment. Conclusions Repeated low-dose rhEPO administration has no significant influence on the development of ROP; however, it may be effective for type 2 ROP in infant boys or in infants with gestational age > 28 weeks and birth weight > 1500 g. Trial registration The data of this study were retrieved from two clinical studies registered ClinicalTrials.gov (NCT 02036073) on January 14, 2014, https://clinicaltrials.gov/ct2/show/NCT02036073; and (NCT03919500) on April 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03919500.

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Early Erythropoietin Administration does not Increase the Risk of Retinopathy in Preterm Infants

Abstract: EPO administration did not significantly increase the risk of ROP of any stage reported or Stage ≥3. Further clinical trials investigating the impact of EPO on ROP in premature infants should include all confounding factors to clarify this important issue.

Cited by 19 publications

References 39 publications

Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity

Duration of anaemia during the first week of life is an independent risk factor for retinopathy of prematurity

Exogenous erythropoietin aggravates retinal neovascularizationin a murine model of proliferative retinopathy

Effect of early prophylactic low-dose recombinant human erythropoietin on retinopathy of prematurity in very preterm infants

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