Effect of Oral Erythropoietin in Prevention of Anemia of Prematurity

Introduction: Anemia of prematurity (AOP) is a common problem of very low birth weight babies. Blood transfusion is a necessity when it occurs in moderate to severe form putting the child in to the risk of transfusion related complications. Erythropoietin, a potent stimulator of hemopoesis is available in breast milk in good amount and absorbed intact under physiologic condition. In this background oral recombinant human erythropoietin (rhEPO) can be a useful alternative to its subcutaneous administration in prevention of AOP. Objective: To evaluate the efficacy of oral rhEPO in the prevention of AOP in very low birth weight (VLBW) neonates. Methods: This randomized controlled study conducted in the NICU of BSMMU over one year. Total 60 preterm (<34 weeks)VLBW (<1500g) infants were enrolled and randomly divided into Control (group-I), Oral (group-II) and Subcutaneous (group III). Experimental groups (group-II & group-III) received rhEPO 400 IU/Kg, 3 times weekly in oral and subcutaneous (S/C) route respectively and continued for 2 weeks (Total 6 doses). Therapy was initiated 14 days after birth when the baby achieved oral feeding of at least 50 ml/kg/day of breast milk. All infants received oral iron and folic acid supplementation up to 12 weeks of postnatal age. Transfusion data were recorded. Anthropometric and hematological assessments were done at 2, 4, 6 and 12 weeks of age. Results: Baseline clinical characteristics and hematological values were almost similar in all groups. Mean hemoglobin were 11.34±0.68gm/dl, 11.88±0.54gm/dl& 12.12±1.32 gm/dl, the mean hematocrit were 34.11±2.03%, 35.66±1.65% & 36.38±3.97% and the mean reticulocyte were 7.56±2.48%, 9.85±1.50% & 9.22±3.11% in the control, oral and subcutaneous group respectively and the differences are statistically significant (p<0.05).Weight gain was higher in the intervention group at 6 and 12 weeks follow up than the control group(p<0.05).Only 2 (5.25%) infants, one in each of the intervention groups required blood transfusion, compared to 6 (31.5%) infants in control group (p<0.01). Conclusion: Oral EPO is as good as subcutaneous use of EPO in stimulating erythropoesis, maintaining HCT and Hb at high level and is safe in preterm baby. Bangladesh J Child Health 2017; VOL 41 (2) :101-109

[1]  M. Hossain,et al.  Effect of short-term recombinant human erythropoietin therapy in the prevention of anemia of prematurity in very low birth weight neonates. , 2013, Bangladesh Medical Research Council bulletin.

[2]  Arne Ohlsson,et al.  Early erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. , 2012, The Cochrane database of systematic reviews.

[3]  W. Carlo Overview of Mortality and Morbidity , 2011 .

[4]  S. Khatami,et al.  Effects of early human recombinant erythropoietin therapy on the transfusion in healthy preterm infants , 2008, Indian journal of pediatrics.

[5]  B. Dvořák,et al.  Enteral Erythropoietin and Iron Stimulate Erythropoiesis in Suckling Rats , 2008, Journal of pediatric gastroenterology and nutrition.

[6]  Y. Pasha,et al.  The Effect of Human Recombinant Erythropoietin on Prevention of Anemia of Prematurity , 2007 .

[7]  R. Strauss Controversies in the management of the anemia of prematurity using single-donor red blood cell transfusions and/or recombinant human erythropoietin. , 2006, Transfusion medicine reviews.

[8]  N. Sarper,et al.  The effect of early recombinant erythropoietin and enteral iron supplementation on blood transfusion in preterm infants. , 2005, American journal of perinatology.

[9]  B. Arif,et al.  Recombinant human erythropoietin therapy in low‐birthweight preterm infants: A prospective controlled study , 2005, Pediatrics international : official journal of the Japan Pediatric Society.

[10]  M. Félix,et al.  Recombinant human erythropoietin in the treatment of infants with anaemia of prematurity , 1992, European Journal of Pediatrics.

[11]  T. Cole,et al.  Plasma folate levels in preterm infants, with and without a 1 mg daily folate supplement , 2005, European Journal of Pediatrics.

[12]  K. Maruyama,et al.  Oral iron supplementation in preterm infants treated with erythropoietin , 2004, Pediatrics international : official journal of the Japan Pediatric Society.

[13]  S. Juul,et al.  Absorption of Enteral Recombinant Human Erythropoietin by Neonates , 2003, The Annals of pharmacotherapy.

[14]  M. Meyer,et al.  Recombinant erythropoietin and blood transfusion in selected preterm infants , 2003, Archives of disease in childhood. Fetal and neonatal edition.

[15]  S. Bélisle,et al.  Recombinant Human Erythropoietin Use in Intensive Care , 2002, The Annals of pharmacotherapy.

[16]  A. Hutson,et al.  Effect of Recombinant Erythropoietin on “Late” Transfusions in the Neonatal Intensive Care Unit: A Meta-Analysis , 2002, Journal of Perinatology.

[17]  L. Wright,et al.  Effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birth weight: a multicenter, randomized, controlled trial. , 2001, Pediatrics.

[18]  F. Pohlandt,et al.  Red blood cell transfusions in very and extremely low birthweight infants under restrictive transfusion guidelines: is exogenous erythropoietin necessary? , 2001, Archives of disease in childhood. Fetal and neonatal edition.

[19]  J. Dame,et al.  Origin and Fate of Erythropoietin in Human Milk , 2000, Pediatric Research.

[20]  R. Ohls The use of erythropoietin in neonates. , 2000, Clinics in perinatology.

[21]  N. Vain,et al.  Effect of early versus late administration of human recombinant erythropoietin on transfusion requirements in premature infants: results of a randomized, placebo-controlled, multicenter trial. , 2000, Pediatrics.

[22]  A. Rosenberg,et al.  Factors Associated with Successful Epoetin Alfa Therapy in Premature Infants , 2000, The Annals of pharmacotherapy.

[23]  S. Juul,et al.  Why Is Erythropoietin Present in Human Milk? Studies of Erythropoietin Receptors on Enterocytes of Human and Rat Neonates , 1999, Pediatric Research.

[24]  R. Huch,et al.  Erythropoietic quality of maternal milk , 1999, The Lancet.

[25]  A. Ballin,et al.  Erythropoietin, given enterally, stimulates erythropoiesis in premature infants , 1999, The Lancet.

[26]  R. D. Da Riol,et al.  Iron supplementation enhances response to high doses of recombinant human erythropoietin in preterm infants , 1998, Archives of disease in childhood. Fetal and neonatal edition.

[27]  R. Roberts,et al.  Human Milk as a Potential Enteral Source of Erythropoietin , 1998, Pediatric Research.

[28]  J. Britton,et al.  Enteral administration of recombinant erythropoietin to preterm infants. , 1995, Journal of perinatology : official journal of the California Perinatal Association.

[29]  R. Ohls,et al.  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. , 1995, The Journal of pediatrics.

[30]  R. Ehrenkranz,et al.  Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. , 1995, Pediatrics.

[31]  G. Duc,et al.  The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants , 1994 .

[32]  D. Tsakiris,et al.  In Which Neonates Does Early Recombinant Human Erythropoietin Treatment Prevent Anemia of Prematurity? Results of a Randomized, Controlled Study , 1993, Pediatric Research.

[33]  K. Liestøl,et al.  Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity. , 1993, Archives of disease in childhood.

[34]  R. Ohls,et al.  Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity. , 1991, The Journal of pediatrics.

[35]  M. Aapro,et al.  Effects of recombinant human erythropoietin in infants with the anemia of prematurity: a pilot study. , 1990, The Journal of pediatrics.