Erythropoietin serum levels, versus anaemia as risk factors for severe retinopathy of prematurity. Lundgren Pia,Hellgren Gunnel,Pivodic Aldina,Sävman Karin,Smith Lois E H,Hellström Ann Pediatric research BACKGROUND:Preterm infants with anaemia are treated with recombinant human erythropoietin (rhEPO). It is debated whether rhEPO treatment is a risk factor for retinopathy of prematurity (ROP). We evaluated longitudinal EPO and haemoglobin levels, blood transfusions and neonatal morbidities as risk factors for severe ROP. METHOD:This prospective study included 78 Swedish infants, born <28 weeks gestational age (GA), screened for ROP. We tested serum EPO levels on postnatal days 1, 7, 14 and 28 and at postmenstrual ages 32, 36 and 40 weeks. Haemoglobin levels and blood transfusions were recorded during postnatal weeks 1-4. Anaemia was defined as haemoglobin ≤110 g/L. RESULTS:During postnatal week 1, infants with severe ROP requiring treatment (28%) more frequently developed anaemia (42.9% versus 8.0%, P = 0.003) and had higher mean EPO levels (postnatal day 7: 14.2 versus 10.8 mIU/mL, P = 0.003) compared to infants with no or less severe ROP not requiring treatment. In multivariable analyses, GA and anaemia during week 1 remained significant risk factors, but elevated EPO level postnatal day 7 was no longer significant. CONCLUSIONS:Among infants born <28 weeks GA, anaemia during week 1 was a significant risk factor for severe ROP requiring treatment but not elevated EPO levels. 10.1038/s41390-018-0186-6

Reticulocyte hemoglobin content changes after treatment of anemia of prematurity. Pediatrics international : official journal of the Japan Pediatric Society BACKGROUND:Iron deficiency during infancy is associated with poor neurological development, but iron overload causes severe complications. Appropriate iron supplementation is therefore vital. Reticulocyte hemoglobin content (RET-He) provides a real-time assessment of iron status and chracterezes hemoglobin synthesis in preterm infants. However, the existing literature lacks detailed reports assessing chronological changes in RET-He. The aim of this study was to assess the chronological changes in RET-He during oral iron dietary supplementation, and concomitant therapy with recombinant human erythropoietin (rHuEPO) in preterm very low birthweight infants. METHODS:Very low birthweight infants, admitted to our neonatal intensive care unit were analyzed retrospectively. Hemoglobin (Hb), reticulocyte percentage (Ret), mean corpuscular volume, RET-He, serum iron (Fe), and serum ferritin were recorded. Data at birth (T0), the initial day of rHuEPO therapy (T1), the initial day of oral iron supplementation (T2), 1-2 weeks (T3), 3-4 weeks (T4), 5-6 weeks (T5), and 7-8 weeks (T6) from the initial day of oral iron supplementation were extracted, and their changes over time were examined. RESULTS:Reticulocyte hemoglobin content was highest at birth and declined rapidly thereafter, especially after starting rHuEPO therapy. There was no upward trend in RET-He after the initiation of oral iron supplementation, with a slower increase during 5-6 weeks after the initiation of iron therapy. CONCLUSIONS:During the treatment of anemia of prematurity, low RET-He levels may be prolonged. Anemia of prematurity should therefore be assessed and treated on a case-by-case basis, while considering the iron metabolic capacity of preterm infants. 10.1111/ped.15330

Erythropoietin is not a risk factor for severe retinopathy of prematurity among high risk preterm infants. Bui Kim Chi T,Ellenhorn Naomi,Abbasi Afshan,Villosis Maria Fe B,Nguyen Marielle,Truong Huy,Watson Tameka,Buchanan Joanna,Chen Qiaoling Early human development BACKGROUND:Retinopathy of prematurity (ROP) is a developmental retinal vaso-proliferative disease and a leading cause of blindness in children. Early gestational age, low birth weight and unregulated oxygen exposure are the main risk factors for the development of ROP. There are conflicting reports of a possible association between recombinant Erythropoietin (rhEPO) use and an increased risk for the development of ROP. OBJECTIVE:To determine whether rhEPO is an independent risk factor for the development of severe ROP among preterm infants with a gestational age of 23 to 32 weeks and a birth weight <1500 g. METHODS:We performed a retrospective study of risk factors for ROP on a cohort of 1762 premature infants born between 2009 and 2014, half of whom received rhEPO. To examine the association between treated ROP and rhEPO, a propensity score (PS) analysis was performed using the inverse probability of treatment weighted (IPTW) approach. RESULTS:The incidence of treated ROP was 7.3% (129/1762). PS analysis did not show an association between rhEPO and severe ROP needing treatment or ROP stage 2 or higher, in either the whole population or in the subgroup of babies born at 23 to 28 weeks gestation, in whom the incidence of severe ROP was the highest. Of 117 patients treated for Type 1 or worsening stage 3 ROP, 17 were first diagnosed after NICU discharge. CONCLUSION:Our study showed no association between Erythropoietin use and severe ROP and highlights the importance of Ophthalmology follow up after hospital discharge. 10.1016/j.earlhumdev.2021.105440

Effect of Early Erythropoietin on Retinopathy of Prematurity: A Stratified Meta-Analysis. Neonatology BACKGROUND:Recombinant human erythropoietin (rhEPO) lost its role in minimizing red blood cell transfusion in very preterm infants after it had been associated with severe retinopathy of prematurity (ROP). Previous systematic reviews did not stratify ROP by gestation and birth weight (BW). OBJECTIVES:The aim of this study was to investigate the effect of early prophylactic rhEPO on ROP in a stratified meta-analysis of randomized controlled trials (RCTs). METHODS:The databases EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched in January 2022 and complemented by citation searching. RCTs comparing early rhEPO treatment with no treatment or placebo were selected if they were published in a peer-reviewed journal and reported ROP outcomes. Previously unpublished data were requested from the study authors to allow stratified analyses by gestational age (GA) and BW. Data were extracted and analyzed using the standard methods of the Cochrane Neonatal Review Group. Pre-specified outcomes were "ROP stage ≥3" (primary outcome) and "any ROP." RESULTS:Fourteen RCTs, comprising 2,040 infants of &lt;29 weeks of GA, were included for meta-analysis. Data syntheses showed no effects of rhEPO on ROP stage ≥3 or on any ROP, neither in infants of &lt;29 weeks GA, nor in infants of &lt;1,000 g BW, nor in any GA strata. The risk ratio (95% confidence interval) for ROP stage ≥3 in infants of &lt;29 weeks of GA was 1.13 (0.84, 1.53), p = 0.41 (quality of evidence: moderate). CONCLUSIONS:The present meta-analysis detected no effects of early rhEPO on ROP in any comparison, but most stratified analyses were limited by low statistical power. 10.1159/000530126

Survey on clinical use and non-use of recombinant human erythropoietin in European neonatal units. Bolte Katharina,Maier Rolf F Journal of perinatal medicine Objectives Recombinant human erythropoietin (rhEPO) has been shown to effectively and safely prevent the anemia of prematurity and to reduce the transfusion need in very low birth weight (VLBW) infants and has been licensed for this indication in Europe in 1997. The objective of the study was to obtain information on the use or non-use of rhEPO in neonatal units in Germany and other European countries. Methods Anonymized 14-questions web-based questionnaire. Results Seventy-nine questionnaires from Germany and 63 questionnaires from other 15 European countries were completed. Of the responders, 39% indicated to use rhEPO routinely or occasionally in VLBW infants, whereas 61% responded to never use rhEPO in this population. The major reasons given for non-use were lack of recommendation in national guidelines (69%) and/or doubt about efficacy of rhEPO to reduce transfusion need (53%). Twenty-seven percent of the responders indicated to use rhEPO for neonates with birth weights above 1,500 g. Neuroprotection in VLBW infants (26%) and hypoxic ischemic encephalopathy in term neonates (27%) were given as indications for off label use of rhEPO. Conclusions This survey indicates that rhEPO is used for the anemia of prematurity as licensed in less than half of neonatal units in Germany and other European countries. On the other hand it seems to be used off label in neonates for neuroprotection in a considerable number of units although there is no final evidence on its neuroprotective effects. 10.1515/jpm-2020-0070