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Archives of Disease in Childhood. Fetal and Neonatal Edition logoLink to Archives of Disease in Childhood. Fetal and Neonatal Edition
. 1998 Jul;79(1):F44–F48. doi: 10.1136/fn.79.1.f44

Iron supplementation enhances response to high doses of recombinant human erythropoietin in preterm infants

V Carnielli, R Da Riol, G Montini
PMCID: PMC1720813  PMID: 9797624

Abstract

AIMS—To determine whether iron supplementation would enhance erythropoiesis in preterm infants treated with high doses of human recombinant erythropoietin (r-HuEPO).
METHODS—Sixty three preterm infants were randomly allocated at birth to one of three groups to receive: r-HuEPO alone, 1200 IU/kg/week (EPO); or r-HuEPO and iron, 1200 IU/kg/week of r-HuEPO plus 20mg/kg/week of intravenous iron (EPO+iron); or to serve as controls. All three groups received blood transfusions according to uniform guidelines.
RESULTS—Infants in the EPO+iron group needed fewer transfusions than controls—mean (95% CI) 1.0 (0.28-1.18) vs 2.9 (1.84-3.88) and received lower volumes of blood—mean (95% CI) 16.7 (4.9-28.6) vs 44.4 (29.0-59.7) ml/kg. The EPO group also needed lower volumes of blood than the controls—mean (95% CI) 20.1 (6.2-34.2) vs 44.4(29.0-59.7) ml/kg, but the same number of transfusions, 1.3 (0.54-2.06) vs 2.9 (1.84-3.88). Reticulocyte and haematocrit values from postnatal weeks 5 to 8 were higher in the EPO+iron than in the EPO group, and both groups had higher values than the controls. Mean (SEM) plasma ferritin was lower in the EPO group—65 (55) µg/l than in the EPO+iron group 780 (182) µg/l, and 561 (228) µg/l in the control infants.
CONCLUSIONS—Early administration of high doses of r-HuEPO with iron supplements significantly reduced the need for blood transfusion. Intravenous iron (20 mg/kg/week in conjunction with r-HuEPO yielded a higher reticulocyte count and haematocrit concentration after the forth week of life than r-HuEPO alone. Infants treated with r-HuEPO alone showed signs of reduced iron stores.



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Selected References

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  1. Bechensteen A. G., Hågå P., Halvorsen S., Whitelaw A., Liestøl K., Lindemann R., Grøgaard J., Hellebostad M., Saugstad O. D., Grønn M. Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity. Arch Dis Child. 1993 Jul;69(1 Spec No):19–23. doi: 10.1136/adc.69.1_spec_no.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beck D., Masserey E., Meyer M., Calame A. Weekly intravenous administration of recombinant human erythropoietin in infants with the anaemia of prematurity. Eur J Pediatr. 1991 Sep;150(11):767–772. doi: 10.1007/BF02026707. [DOI] [PubMed] [Google Scholar]
  3. Beguin Y. The soluble transferrin receptor: biological aspects and clinical usefulness as quantitative measure of erythropoiesis. Haematologica. 1992 Jan-Feb;77(1):1–10. [PubMed] [Google Scholar]
  4. Brugnara C., Chambers L. A., Malynn E., Goldberg M. A., Kruskall M. S. Red blood cell regeneration induced by subcutaneous recombinant erythropoietin: iron-deficient erythropoiesis in iron-replete subjects. Blood. 1993 Feb 15;81(4):956–964. [PubMed] [Google Scholar]
  5. CONRAD M. E., CROSBY W. H. The natural history of iron deficiency induced by phlebotomy. Blood. 1962 Aug;20:173–185. [PubMed] [Google Scholar]
  6. Carnielli V. P., Da Riol R., Montini G. Recombinant erythropoietin in very-low-birth-weight infants. N Engl J Med. 1994 Sep 8;331(10):677–678. [PubMed] [Google Scholar]
  7. Carnielli V., Montini G., Da Riol R., Dall'Amico R., Cantarutti F. Effect of high doses of human recombinant erythropoietin on the need for blood transfusions in preterm infants. J Pediatr. 1992 Jul;121(1):98–102. doi: 10.1016/s0022-3476(05)82552-1. [DOI] [PubMed] [Google Scholar]
  8. Emmerson A. J., Coles H. J., Stern C. M., Pearson T. C. Double blind trial of recombinant human erythropoietin in preterm infants. Arch Dis Child. 1993 Mar;68(3 Spec No):291–296. doi: 10.1136/adc.68.3_spec_no.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Emmerson A. J. Role of erythropoietin in the newborn. Arch Dis Child. 1993 Sep;69(3 Spec No):273–275. doi: 10.1136/adc.69.3_spec_no.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. England J. M., Ward S. M., Down M. C. Microcytosis, anisocytosis and the red cell indices in iron deficiency. Br J Haematol. 1976 Dec;34(4):589–597. doi: 10.1111/j.1365-2141.1976.tb03605.x. [DOI] [PubMed] [Google Scholar]
  11. Finch C. A. Erythropoiesis, erythropoietin, and iron. Blood. 1982 Dec;60(6):1241–1246. [PubMed] [Google Scholar]
  12. Gallagher P. G., Ehrenkranz R. A. Erythropoietin therapy for anemia of prematurity. Clin Perinatol. 1993 Mar;20(1):169–191. [PubMed] [Google Scholar]
  13. Halpérin D. S., Félix M., Wacker P., Lacourt G., Babel J. F., Wyss M. Recombinant human erythropoietin in the treatment of infants with anaemia of prematurity. Eur J Pediatr. 1992 Sep;151(9):661–667. doi: 10.1007/BF01957568. [DOI] [PubMed] [Google Scholar]
  14. Halpérin D. S., Wacker P., Lacourt G., Félix M., Babel J. F., Aapro M., Wyss M. Effects of recombinant human erythropoietin in infants with the anemia of prematurity: a pilot study. J Pediatr. 1990 May;116(5):779–786. doi: 10.1016/s0022-3476(05)82671-x. [DOI] [PubMed] [Google Scholar]
  15. Kinmond S., Aitchison T. C., Holland B. M., Jones J. G., Turner T. L., Wardrop C. A. Umbilical cord clamping and preterm infants: a randomised trial. BMJ. 1993 Jan 16;306(6871):172–175. doi: 10.1136/bmj.306.6871.172. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kivivuori S. M., Heikinheimo M., Teppo A. M., Siimes M. A. Early rise in serum concentration of transferrin receptor induced by recombinant human erythropoietin in very-low-birth-weight infants. Pediatr Res. 1994 Jul;36(1 Pt 1):85–89. doi: 10.1203/00006450-199407001-00015. [DOI] [PubMed] [Google Scholar]
  17. Macdougall I. C., Cavill I., Hulme B., Bain B., McGregor E., McKay P., Sanders E., Coles G. A., Williams J. D. Detection of functional iron deficiency during erythropoietin treatment: a new approach. BMJ. 1992 Jan 25;304(6821):225–226. doi: 10.1136/bmj.304.6821.225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maier R. F., Obladen M., Messinger D., Wardrop C. A. Factors related to transfusion in very low birthweight infants treated with erythropoietin. Arch Dis Child Fetal Neonatal Ed. 1996 May;74(3):F182–F186. doi: 10.1136/fn.74.3.f182. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Maier R. F., Obladen M., Scigalla P., Linderkamp O., Duc G., Hieronimi G., Halliday H. L., Versmold H. T., Moriette G., Jorch G. The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. European Multicentre Erythropoietin Study Group. N Engl J Med. 1994 Apr 28;330(17):1173–1178. doi: 10.1056/NEJM199404283301701. [DOI] [PubMed] [Google Scholar]
  20. Messer J., Haddad J., Donato L., Astruc D., Matis J. Early treatment of premature infants with recombinant human erythropoietin. Pediatrics. 1993 Oct;92(4):519–523. [PubMed] [Google Scholar]
  21. Meyer M. P., Haworth C., Meyer J. H., Commerford A. A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin. J Pediatr. 1996 Aug;129(2):258–263. doi: 10.1016/s0022-3476(96)70251-2. [DOI] [PubMed] [Google Scholar]
  22. Meyer M. P., Meyer J. H., Commerford A., Hann F. M., Sive A. A., Moller G., Jacobs P., Malan A. F. Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study. Pediatrics. 1994 Jun;93(6 Pt 1):918–923. [PubMed] [Google Scholar]
  23. Montini G., Zacchello G., Perfumo F., Edefonti A., Bassi S., Cantaluppi A., Sarchi C., Cazzin M., Ferrari V., Boccazzi A. Pharmacokinetics and hematologic response to subcutaneous administration of recombinant human erythropoietin in children undergoing long-term peritoneal dialysis: a multicenter study. J Pediatr. 1993 Feb;122(2):297–302. doi: 10.1016/s0022-3476(06)80137-x. [DOI] [PubMed] [Google Scholar]
  24. Obladen M., Maier R., Segerer H., Grauel E. L., Holland B. M., Stewart G., Jorch G., Rabe H., Linderkamp O., Hoffmann H. G. Efficacy and safety of recombinant human erythropoietin to prevent the anaemias of prematurity. European Randomized Multicenter Trial. Contrib Nephrol. 1991;88:314–326. doi: 10.1159/000419541. [DOI] [PubMed] [Google Scholar]
  25. Ohls R. K., Veerman M. W., Christensen R. D. Pharmacokinetics and effectiveness of recombinant erythropoietin administered to preterm infants by continuous infusion in total parenteral nutrition solution. J Pediatr. 1996 Apr;128(4):518–523. doi: 10.1016/s0022-3476(96)70363-3. [DOI] [PubMed] [Google Scholar]
  26. Pisacane A. Neonatal prevention of iron deficiency. BMJ. 1996 Jan 20;312(7024):136–137. doi: 10.1136/bmj.312.7024.136. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Rhondeau S. M., Christensen R. D., Ross M. P., Rothstein G., Simmons M. A. Responsiveness to recombinant human erythropoietin of marrow erythroid progenitors from infants with the "anemia of prematurity". J Pediatr. 1988 Jun;112(6):935–940. doi: 10.1016/s0022-3476(88)80223-3. [DOI] [PubMed] [Google Scholar]
  28. Shannon K. M. Anemia of prematurity: progress and prospects. Am J Pediatr Hematol Oncol. 1990 Spring;12(1):14–20. doi: 10.1097/00043426-199021000-00004. [DOI] [PubMed] [Google Scholar]
  29. Shannon K. M., Keith J. F., 3rd, Mentzer W. C., Ehrenkranz R. A., Brown M. S., Widness J. A., Gleason C. A., Bifano E. M., Millard D. D., Davis C. B. Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. Pediatrics. 1995 Jan;95(1):1–8. [PubMed] [Google Scholar]
  30. Shannon K. M., Mentzer W. C., Abels R. I., Freeman P., Newton N., Thompson D., Sniderman S., Ballard R., Phibbs R. H. Recombinant human erythropoietin in the anemia of prematurity: results of a placebo-controlled pilot study. J Pediatr. 1991 Jun;118(6):949–955. doi: 10.1016/s0022-3476(05)82217-6. [DOI] [PubMed] [Google Scholar]
  31. Shannon K. M., Mentzer W. C., Abels R. I., Wertz M., Thayer-Moriyama J., Li W. Y., Thompson D., Decelle S., Phibbs R. H. Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: a pilot study. J Pediatr. 1992 Apr;120(4 Pt 1):586–592. doi: 10.1016/s0022-3476(05)82488-6. [DOI] [PubMed] [Google Scholar]
  32. Shannon K. Recombinant erythropoietin in anemia of prematurity: five years later. Pediatrics. 1993 Oct;92(4):614–617. [PubMed] [Google Scholar]
  33. Soubasi V., Kremenopoulos G., Diamandi E., Tsantali C., Tsakiris D. In which neonates does early recombinant human erythropoietin treatment prevent anemia of prematurity? Results of a randomized, controlled study. Pediatr Res. 1993 Nov;34(5):675–679. doi: 10.1203/00006450-199311000-00022. [DOI] [PubMed] [Google Scholar]
  34. Stockman J. A., 3rd, Garcia J. F., Oski F. A. The anemia of prematurity. Factors governing the erythropoietin response. N Engl J Med. 1977 Mar 24;296(12):647–650. doi: 10.1056/NEJM197703242961202. [DOI] [PubMed] [Google Scholar]
  35. Strauss R. G. Erythropoietin and neonatal anemia. N Engl J Med. 1994 Apr 28;330(17):1227–1228. doi: 10.1056/NEJM199404283301709. [DOI] [PubMed] [Google Scholar]
  36. Strauss R. G. Transfusion therapy in neonates. Am J Dis Child. 1991 Aug;145(8):904–911. doi: 10.1001/archpedi.1991.02160080082025. [DOI] [PubMed] [Google Scholar]
  37. Sullivan J. L. Iron, plasma antioxidants, and the 'oxygen radical disease of prematurity'. Am J Dis Child. 1988 Dec;142(12):1341–1344. doi: 10.1001/archpedi.1988.02150120095048. [DOI] [PubMed] [Google Scholar]

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