Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-599cfd5f84-9hh9z Total loading time: 0 Render date: 2025-01-07T07:27:43.103Z Has data issue: false hasContentIssue false

Chapter 8 - Anemia of Prematurity and Indications for Erythropoietin Therapy

from Section III - Erythrocyte Disorders

Published online by Cambridge University Press:  30 January 2021

By
Pamela J. Kling
Edited by
Pedro A. de Alarcón ,
Eric J. Werner ,
Robert D. Christensen  and
Martha C. Sola-Visner
Pedro A. de Alarcón
Affiliation:
University of Illinois College of Medicine
Eric J. Werner
Affiliation:
Children's Hospital of the King's Daughters
Robert D. Christensen
Affiliation:
University of Utah
Martha C. Sola-Visner
Affiliation:
Harvard University, Massachusetts
Get access

Summary

Anemia of prematurity is a multifactorial anemia, characterized by relatively low plasma erythropoietin (EPO) levels, iatrogenic blood loss, low circulating blood volumes and insufficient erythropoiesis. This anemia has been long characterized as nutritionally insensitive, but nutrition may influence its clinical course. Anemia of prematurity is treated with erythrocyte transfusions. However, delaying umbilical cord clamping may increase initial hematocrit percentages, improve infant iron status, prevent erythrocyte transfusions, decrease necrotizing enterocolitis (NEC), and decrease intraventricular hemorrhage (IVH). Many published studies have examined the potential of therapy with recombinant human EPO or other erythropoietic stimulating agent (ESA). Although EPO therapy is associated with statistically lower number of total erythrocyte transfusions, most early transfusions are not eliminated. However, early erythropoietic EPO dosing may also decrease NEC and IVH as well as improve neurocognitive outcomes. A recent systematic review refuted previous concerns that early administration of EPO was associated with increased retinopathy of prematurity (ROP). Early high dose EPO regimens are currently being studied for neuroprotection in premature infants. Iron deficiency in EPO treatment is also of potential concern, but long-term iron status of EPO treated premature infants is similar to controls.

Type
Chapter
Information
Neonatal Hematology
Pathogenesis, Diagnosis, and Management of Hematologic Problems
 , pp. 120 - 132
Publisher: Cambridge University Press
Print publication year: 2021

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Zanjani, ED, Ascensao, JL, McGlave, PB, Banisadre, M, Ash, RC. Studies in the liver to kidney switch of erythropoietin production. J Clin Invest 1981;67:1183–8.CrossRefGoogle ScholarPubMed
Eckardt, K-U, Ratcliffe, PJ, Tan, CC, Bauer, C, Kurtz, A. Age-dependent expression of the erythropoietin gene in rat liver and kidneys. J. Clin. Invest 1992;89:753–60.CrossRefGoogle ScholarPubMed
Kling, PJ, Schmidt, RL, Roberts, RA, Widness, JA. Serum erythropoietin levels during infancy: Associations with erythropoiesis. J Pediatr 1996;128:791–6.Google Scholar
Stockman, JA, III, Garcia, JF, Oski, FA. The anemia of prematurity: Factors governing the erythropoietin response. N Engl J Med 1977;296:647–50.Google Scholar
Ohls, RK. Evaluation and treatment of anemia in the neonate. In Christensen, RD, ed. Hematologic Problems of the Neonate (Philadelphia, PA: WB Saunders, 2000). pp. 137–69.Google Scholar
Lundstrom, U, Siimes, MA. At what age does iron supplementation become necessary in low-birth weight infants? J Pediatr 1977;91:878–83.Google Scholar
Ohls, RK. Erythropoietin to prevent and treat the anemia of prematurity. Curr Opin Pediatr 1999;11:108–14.Google Scholar
Maier, RF, Obladen, M, Messinger, D, Wardrop, CAJ. Factors related to transfusion in very low birthweight infants treated with erythropoietin. Arch Dis Child 1996;74:F182–F186.Google Scholar
Ohls, RK. Erythropoietin treatment in extremely low birth weight infants: Blood in versus blood out. J Pediatr 2002;141:3–6.Google Scholar
Kling, PJ, Sullivan, TM, Leftwich, ME, Roe, DJ. Score for neonatal acute physiology predicts erythrocyte transfusions in premature infants. Arch Dis Pediatr Adolesc Med 1997;151:27–31.CrossRefGoogle ScholarPubMed
Ekhaguere, OA, Morriss, FH, Jr., Bell, EF, Prakash, N, Widness, JA. Predictive factors and practice trends in red blood cell transfusions for very-low-birth-weight infants. Pediatr Res 2016;79:736–41.Google Scholar
Shannon, KM, Keith, JM, Mentzer, WC, et al. Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants. Pediatrics 1995;95:1–10.Google Scholar
Widness, JA, Seward, VJ, Kromer, IJ, et al. Changing patterns of red blood cell transfusion in very low birth weight infants. J Pediatr 1996;129:680–7.Google Scholar
Hume, H. Red blood cell transfusions for preterm infants: The role of evidence-based medicine. Sem Perinatol 1997;21:8–19.Google Scholar
Bednarek, FJ, Weisberger, S, Richardson, DK, et al. Variations in blood transfusions among newborn intensive care units. J Pediatr 1998;133:601–7.Google Scholar
Ringer, SA, Richardson, DK, Sacher, RA, Keszler, M, Churchill, WH. Variations in transfusion practice in neonatal intensive care. Pediatrics 1998;101:194–200.Google Scholar
Bell, EF, Strauss, RG, Widness, JA, et al. Randomized trial of liberal versus restrictive guidelines for red blood cell transfusion in preterm infants. Pediatrics 2005;115:1685–91.Google Scholar
Luban, NL. Management of anemia in the newborn. Early Hum Dev 2008;84:493–8.Google Scholar
Becquet, O, Guyot, D, Kuo, P, et al. Respective effects of phlebotomy losses and erythropoietin treatment on the need for blood transfusion in very premature infants. BMC Pediatr 2013;13:176.Google Scholar
Maier, RF, Sonntag, J, Walka, MM, et al. Changing practices of red blood cell transfusions in infants with birth weights less than 1000 g. J Pediatr 2000;136:220–4.Google Scholar
Donato, H, Vain, N, Rendo, P, 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. Pediatrics 2000;105:1066–1072.CrossRefGoogle ScholarPubMed
Widness, JA, Kulhavy, JC, Johnson, KJ, et al. Clinical performance of an in-line point-of-care monitor in neonates. Pediatrics 2000;106:497–504.Google Scholar
Moya, MP, Clark, RH, Nicks, J, Tanaka, DT. The effects of bedside blood gas monitoring on blood loss and ventilator management. Biol Neonate 2001;80:257–61.Google Scholar
Lin, JC, Strauss, RG, Kulhavy, JC, et al. Phlebotomy overdraw in the neonatal intensive care nursery. Pediatrics.2000;106:e19.Google Scholar
Bishara, N, Ohls, RK. Current controversies in the management of the anemia of prematurity. Semin Perinatol 2009;33:29–34.Google Scholar
Kinmond, S, Aitchison, TC, Holland, BM, et al. Umbilical cord clamping and preterm infants: A randomised trial. Brit Med J 1993;306:172–5.Google Scholar
Wardrop, CAJ, Holland, BM. The roles and vital importance of placental blood to the newborn infant. J Perinat Med 1995;23:139–43.Google Scholar
Ibrahim, HM, Krouskop, RW, Lewis, DF, Dhanireddy, R. Placental transfusion: Umbilical cord clamping and preterm infants. J Perinatol.2000;20:351–4.Google Scholar
Rabe, H, Diaz-Rossello, JL, Duley, L, Dowswell, T. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev 2012;8:CD003248.Google Scholar
Committee on Obstetric Practice. Committee opinion no. 684: Delayed umbilical cord clamping after birth. Obstet Gynecol 2017;129:e5–e10.Google Scholar
Strauss, RG. How I transfuse red blood cells and platelets to infants with the anemia and thrombocytopenia of prematurity. Transfusion 2008;48:209–17.Google Scholar
Aladangady, N, Aitchison, TC, Beckett, C, et al. Is it possible to predict the blood volume of a sick preterm infant? Arch Dis Child Fetal Neonatal Ed 2004;89:F344–7.Google Scholar
Backes, CH, Rivera, BK, Haque, U, et al. Placental transfusion strategies in very preterm neonates: A systematic review and meta-analysis. Obstet Gynecol 2014;124:47–56.Google Scholar
Hutton, EK, Hassan, ES. Late vs early clamping of the umbilical cord in full-term neonates: Systematic review and meta-analysis of controlled trials. JAMA 2007;297:1241–52.Google Scholar
Chaparro, CM, Neufeld, LM, Alvarez, GT, Cedillo, RE-L, Dewey, KG. Effect of timing of umbilical cord clamping on iron status in Mexican infants: A randomised controlled trial. Lancet 2006;367:1997–2004.Google Scholar
Ohls, RK, Ehrenkranz, RA, Wright, LL, et al. The effects of early erythropoietin therapy on the transfusion requirements of preterm infants below 1250 grams birthweight: A multicenter, randomized controlled trial. Pediatrics 2001;108:934–42.CrossRefGoogle Scholar
Roseff, SD, Luban, NL, Manno, CS. Guidelines for assessing appropriateness of pediatric transfusion. Transfusion 2002;42:1398–413.CrossRefGoogle ScholarPubMed
Strauss, RG. Practical issues in neonatal transfusion practice. Am J Clin Path 1997;107:S57–S63.Google Scholar
Simon, TL, Alverson, DC, AuBuchon, J, et al. Practice parameter for the use of red blood cell transfusions. Arch Pathol Lab Med 1998;122:130–8.Google Scholar
Kirpalani, H, Whyte, RK, Andersen, C, et al. The Premature Infants in Need of Transfusion (PINT) study: A randomized, controlled trial of a restrictive (low) versus liberal (high) transfusion threshold for extremely low birth weight infants. J Pediatr 2006;149:301–7.Google Scholar
Whyte, R, Kirpalani, H. Low versus high haemoglobin concentration threshold for blood transfusion for preventing morbidity and mortality in very low birth weight infants. Cochrane Database Syst Rev 2011;11:CD000512.Google Scholar
Ibrahim, M, Ho, SK, Yeo, CL. Restrictive versus liberal red blood cell transfusion thresholds in very low birth weight infants: A systematic review and meta-analysis. J Paediatr Child Health 2014;50:122–30.Google Scholar
McCoy, TE, Conrad, AL, Richman, LC, et al. Neurocognitive profiles of preterm infants randomly assigned to lower or higher hematocrit thresholds for transfusion. Child Neuropsychol 2011;17:347–67.Google Scholar
McCoy, TE, Conrad, AL, Richman, LC, et al. The relationship between brain structure and cognition in transfused preterm children at school age. Dev Neuropsychol 2014;39:226–32.Google Scholar
Whyte, RK, Kirpalani, H, Asztalos, EV, et al. Neurodevelopmental outcome of extremely low birth weight infants randomly assigned to restrictive or liberal hemoglobin thresholds for blood transfusion. Pediatrics 2009;123:207–13.CrossRefGoogle ScholarPubMed
Warwood, TL, Ohls, RK, Lambert, DK, et al. Intravenous administration of darbepoetin to NICU patients. J Perinatol 2006;26:296–300.Google Scholar
Vamvakas, EC, Strauss, RG. Meta-analysis of controlled clinical trials studying the efficacy of rHuEPO in reducing blood transfusions in the anemia of prematurity. Transfusion 2001;41:406–15.Google Scholar
Ohlsson, A, Aher, SM. Early erythropoiesis-stimulating agents in preterm or low birth weight infants. Cochrane Database Syst Rev 2017;11:CD004863.Google Scholar
Aher, SM, Ohlsson, A. Late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2014;4:CD004868.Google Scholar
Aher, SM, Ohlsson, A. Early versus late erythropoietin for preventing red blood cell transfusion in preterm and/or low birth weight infants. Cochrane Database Syst Rev 2012;10:CD004865.Google Scholar
Maier, RF, Obladen, M, Kattner, E, et al. High- versus low-dose erythropoietin in extremely low birth weight infants. J Pediatr 1998;132:866–70.Google Scholar
Carnielli, VP, D Riol, R, Montini, G. Iron supplementation enhances response to high doses of recombinant human erythropoietin in preterm infants. Arch Dis Child 1998;79:F44–F48.Google Scholar
Brown, MS, Jones, MA, Ohls, RK, Christensen, RD. Single-dose pharmacokinetics of recombinant human erythropoietin in preterm infants after intravenous and subcutaneous administration. J Pediatr 1993;122:655–7.Google Scholar
Widness, JA, Veng-Pedersen, P, Peters, C, et al. Erythropoietin pharmacokinetics in premature infants: Developmental, non-linearity, and treatment effects. J Appl Physiol 1996;80:140–8.Google Scholar
Ohls, RK, Veerman, MW, Christensen, RD. Pharmacokinetics and effectiveness of recombinant erythropoietin administered to preterm infants by continuous infusion in total parenteral nutrition solution. J Pediatr 1996;128:518–23.Google Scholar
Brown, MS, Keith, JF. Comparison between two and five doses a week of recombinant human erythropoietin for anemia of prematurity: A randomized trial. Pediatrics 1999;104:210–15.CrossRefGoogle ScholarPubMed
Bechensteen, AG, Håga, P, Halvorsen, S, et al. Erythropoietin, protein, and iron supplementation and the prevention of anaemia of prematurity. Arch Dis Child 1993;69:19–23.Google Scholar
Messer, J, Haddad, J, Donato, L, Astruc, D, Matis, J. Early treatment of premature infants with recombinant human erythropoietin. Pediatrics 1993;92:519–23.Google Scholar
Bechensteen, AG, Halvorsen, S, Haga, P, PM C, Liestøl, K. Erythropoietin (EPO), protein and iron supplementation and the prevention of anaemia of prematurity: Effects on serum immunoreactive Epo, growth and protein and iron metabolism. Acta Paediatr 1996;85:490–5.Google Scholar
Worthington-White, D, Behnke, M, Gross, S. Premature infants require additional folate and vitamin B-12 to reduce the severity of the anemia of prematurity. Am J Clin Nutr 1994;60:930–5.Google Scholar
Haiden, N, Schwindt, J, Cardona, F, et al. Effects of a combined therapy of erythropoietin, iron, folate, and vitamin B12 on the transfusion requirements of extremely low birth weight infants. Pediatrics 2006;118:2004–13.Google Scholar
Carnielli, VP, 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;121:98–102.CrossRefGoogle ScholarPubMed
Meyer, MP, Haworth, C, Meyer, JH, Commerford, A. A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin. J Pediatr 1996;129:258–63.Google Scholar
Kivivuori, SM, Virtanen, M, Raivio, KO, Viinikka, L, Siimes, MA. Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants. Eur J Pediatr 1999;158:147–51.Google Scholar
Pollak, A, Hayde, M, Hayn, M, et al. Effect of intravenous iron supplementation on erythropoiesis in erythropoietin-treated premature infants. Pediatrics 2001;107:78–85.CrossRefGoogle ScholarPubMed
Ohls, RK, Harcum, J, Schibler, KR, Christensen, RD. The effect of erythropoietin on the transfusion requirements of preterm infants weighing 750 grams or less: A randomized, double-blind, placebo-controlled study. J Pediatr 1997;131:661–5.Google Scholar
Kumar, P, Shankaran, S, Krishnan, RG. Recombinant human erythropoietin therapy for treatment of anemia of prematurity in very low birth weight infants: A randomized, double-blind, placebo-controlled trial. J Perinatol 1998;18:173–7.Google Scholar
Ohls, RK, Ehrenkranz, RA, Lemons, JA, et al. A multicenter randomized double-masked placebo-controlled trial of early erythropoietin and iron administration to preterm infants. Pediatr Res 1999;45:216A.Google Scholar
Zipursky, A. The risk of hematopoietic growth factor therapy in newborn infants. Pediatr Res 2002;51:549.CrossRefGoogle ScholarPubMed
Ohls, RK, Christensen, RD. Recombinant erythropoietin compared with erythrocyte transfusion in the treatment of anemia of prematurity. J Pediatr 1991;119:781–8.Google Scholar
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;150:767–72.Google Scholar
Halperin, DS, Wacker, P, Lacourt, G, et al. Effects of recombinant human erythropoietin in infants with anemia of prematurity: A pilot study. J Pediatr 1990;116:779–86.Google Scholar
Emmerson, A. Double blind trial of recombinant human erythropoietin in preterm infants: Comment. Archives Dis Child 1993;69:542.Google Scholar
Brown, MS, Baron, AE, France, EK, Hamman, RF. Association between higher cumulative doses of recombinant erythropoietin and risk for retinopathy of prematurity. J AAPOS 2006;10:143–9.Google Scholar
Ashley, RA, Dubuque, SH, Dvorak, B, et al. Erythropoietin stimulates vasculogenesis in neonatal rat mesenteric microvascular endothelial cells. Pediatr Res 2002;51:472–8.CrossRefGoogle ScholarPubMed
Rao, R, Georgieff, MK. Iron in fetal and neonatal nutrition. Semin Fetal Neonatal Med 2007;12:54–63.Google Scholar
Ledbetter, DJ, Juul, SE. Erthropoietin and the incidence of necrotizing enterocolitis in infants with very low birth weight. J Pediatr Surg 2000;35:178–82.Google Scholar
Ohls, RK, Osborne, KA, Chrstensen, RD. 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. J Pediatr 1995;126:421–6.Google Scholar
Bierer, R, Peceny, MC, Hartenberger, CH, Ohls, RK. Erythropoietin concentrations and neurodevelopmental outcome in preterm infants. Pediatrics. 2006;118:e635-640.Google Scholar
Ohls, RK, Cannon, DC, Phillips, J, et al. Preschool assessment of preterm infants treated with darbepoetin and erythropoietin. Pediatrics 2016;137:e20153859.Google Scholar
Neubauer, AP, Voss, W, Wachtendorf, M, Jungmann, T. Erythropoietin improves neurodevelopmental outcome of extremely preterm infants. Ann Neurol 2010;67:657–66.Google Scholar
Massaro, AN, Wu, YW, Bammler, TK, et al. Plasma biomarkers of brain injury in neonatal hypoxic-ischemic encephalopathy. J Pediatr 2018;194:67–75.CrossRefGoogle ScholarPubMed
Juul, SE, Comstock, BA, Heagerty, PJ, et al. High-dose erythropoietin for asphyxia and encephalopathy (HEAL): A randomized controlled trial – background, aims, and study protocol. Neonatology 2018;113:331–8.Google Scholar
Garg, B, Sharma, D, Bansal, A. Systematic review seeking erythropoietin role for neuroprotection in neonates with hypoxic ischemic encephalopathy: Presently where do we stand. J Matern Fetal Neonatal Med 2018;31:3214–24.Google Scholar
Fischer, HS, Reibel, NJ, Buhrer, C, Dame, C. Prophylactic early erythropoietin for neuroprotection in preterm infants: A meta-analysis. Pediatrics 2017;139:e20164317.CrossRefGoogle ScholarPubMed
Juul, SE, Mayock, DE, Comstock, BA, Heagerty, PJ. Neuroprotective potential of erythropoietin in neonates; design of a randomized trial. Matern Health Neonatol Perinatol 2015;1:27.Google Scholar
Fauchere, JC, Koller, BM, Tschopp, A, et al. Swiss erythropoietin neuroprotection trial g. safety of early high-dose recombinant erythropoietin for neuroprotection in very preterm infants. J Pediatr 2015;167:52–7 e53.CrossRefGoogle Scholar
Natalucci, G, Latal, B, Koller, B, et al. Swiss EPONTG. Effect of early prophylactic high-dose recombinant human erythropoietin in very preterm infants on neurodevelopmental outcome at 2 years: A randomized clinical trial. JAMA 2016;315:2079–85.Google Scholar
Shireman, TI, Hilsenrath, PE, Strauss, RG, Widness, JA, Mutnick, AH. Recombinant human erythropoietin vs transfusions in the treatment of anemia of prematurity. Arch Pediatr Adolesc Med 1994;148:582–8.Google Scholar
Maier, RF, Obladen, M, Scigalla, P, et al. The effect of epoetin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants. N Engl J Med 1994;330:1173–8.Google Scholar
Fain, J, Hilsenrath, P, Widness, JA, Strauss, RG, Mutnick, AH. A cost analysis comparing erythropoietin and red cell transfusions in the treatment of anemia of prematurity. Transfusion 1995;35:936–43.CrossRefGoogle ScholarPubMed
Yeo, CL, Choo, S, Ho, LY. Effect of recombinant human erythropoietin on transfusion needs in preterm infants. J Paediatr Child Health 2001;37:352–8.Google Scholar
Atasay, B, Gunlemez, A, Akar, N, Arsan, S. Does early erythropoietin therapy decrease transfusions in anemia of prematurity. Indian J Pediatr 2002;69:389–91.Google Scholar
Avent, M, Cory, BJ, Galpin, J, et al. A comparison of high versus low dose recombinant human erythropoietin versus blood transfusion in the management of anaemia of prematurity in a developing country. J Tropical Pediatr 2002;48:227–33.Google Scholar
Oski, FA. Iron deficiency in infancy and childhood. New Engl J Med 1993;329:190–3.Google Scholar
Oski, FA. Differential diagnosis of anemia. In Nathan, DG, Oski, FA, eds. 4th ed. Hematology of Infancy and Childhood (Philadelphia, PA: W.B. Saunders, 1993). pp. 346–53.Google Scholar
Dallman, PR. Iron deficiency in the weanling: A nutritional problem on the way to resolution. Acta Paediatr Scand Suppl 1986;323:59–67.CrossRefGoogle ScholarPubMed
Harthoorn-Lasthuizen, EJ, Lindemans, J, Langenhuijsen, MM. Does iron-deficient erythropoiesis in pregnancy influence fetal iron supply? Acta Obstet Gynecol Scand 2001;80:392–6.Google Scholar
McCarthy, PJ, Zundel, HR, Johnson, KR, Blohowiak, SE, Kling, PJ. Impact of growth restriction and other prenatal risk factors on cord blood iron status in prematurity. J Pediatr Hematol Oncol 2016;38(3):210–15.Google Scholar
Mukhopadhyay, K, Yadav, RK, Kishore, SS, et al. Iron status at birth and at 4 weeks in preterm-SGA infants in comparison with preterm and term-AGA infants. J Matern Fetal Neonatal Med 2012;25:1474–8.Google Scholar
McLimore, HM, Phillips, AK, Blohowiak, SE, et al. Impact of multiple prenatal risk factors on newborn iron status at delivery. J Pediatr Hematol Oncol 2013;35:473–77.Google Scholar
Jones, AD, Zhao, G, Jiang, YP, et al. Maternal obesity during pregnancy is negatively associated with maternal and neonatal iron status. Eur J Clin Nutr 2016;70(8):918–24.Google Scholar
MacQueen, BC, Christensen, RD, Ward, DM, et al. The iron status at birth of neonates with risk factors for developing iron deficiency: A pilot study. J Perinatol 2017;37:436–40.Google Scholar
McCarthy, EK, Kenny, LC, Hourihane, JOB, et al. Impact of maternal, antenatal and birth-associated factors on iron stores at birth: Data from a prospective maternal-infant birth cohort. Eur J Clin Nutr 2017;71:782–7.Google Scholar
Fomon, SJ. Iron. In Fomon, S, ed. Nutrition of Normal Infants (St. Louis, MO: Mosby, 1993). pp. 239–60.Google Scholar
Ehrenkranz, RA. Iron requirements of preterm infants. Nutrition 1994;10:77–8.Google Scholar
Fomon, SJ, Ziegler, EE, Nelson, SE, Serfass, RE, Frantz, JA. Erythrocyte incorporation of iron by 56-day-old infants fed a 58Fe-labeled supplement. Pediatr Res 1995;38:373–8.Google Scholar
Widness, JA, Lombard, KA, Ziegler, EE, et al. Erythroctye incorporation and absorption of 58Fe in premature infants treated with erythropoietin. Pediatr Res 1997;41:416–23.CrossRefGoogle Scholar
Georgieff, MK. Long-term brain and behavioral consequences of early iron deficiency. Nutr Rev 2011;69 Suppl 1:S43–48.Google Scholar
Saarinen, UM, Siimes, MA. Serum ferritin in assessment of iron nutrition in healthy infants. Acta Paediatr Scand 1978;67:745–51.Google Scholar
Al-Kharfy, T, Smyth, JA, Wadsworth, L, et al. Erythropoietin therapy in neonates at risk of having bronchopulmonary dysplasia and requiring multiple transfusions. J Pediatr 1996;129:89–96.Google Scholar
Bader, D, Blondheim, O, Jonas, R, et al. Decreased ferritin levels, despite iron supplementation, during erythropoietin therapy in anaemia of prematurity. Acta Paediatr 1996;85:496–501.Google Scholar
Bechensteen, AG, Halvorsen, S, Haga, P, Cotes, PM, Liestol, K. Erythropoietin, protein and iron supplementation and the prevention of anaemia of prematurity: Effects on serum immunoreactive Epo, growth and protein and iron metabolism. Acta Paediatr. 1996;85:490–5.Google Scholar
Emmerson, A. Role of erythropoietin in the newborn. Archives Dis Child 1993;69:273–5.Google Scholar
Meyer, MP, Meyer, JH, Commerford, A, et al. Recombinant human erythropoietin in the treatment of the anemia of prematurity: Results of a double-blind, placebo-controlled study. Pediatrics 1994;93:918–23.Google Scholar
Morris, KP, Watson, S, Reid, MM, Hamilton, PJ, Coulthard, MG. Assessing iron status in children with chronic renal failure on erythropoietin: Which measurements should we use? Pediatr Nephrol 1994;8:51–6.Google Scholar
Goodnough, LT, Skikne, B, Brugnara, C. Erythropoietin, iron and erythropoiesis. Blood 2000;96:823–33.Google Scholar
Akkermans, MD, Uijterschout, L, Abbink, M, et al. Predictive factors of iron depletion in late preterm infants at the postnatal age of 6 weeks. Eur J Clin Nutr 2016;70:941–6.Google Scholar
Taetle, R. The role of transferrin receptors in hemopoietic cell growth. Exp Hematol 1990;18:360–5.Google Scholar
Kivivuori, SM, Heikinheimo, M, Teppo, A-M, Siimes, MA. Early rise in serum concentration of transferrin receptor induced by recombinant human erythropoietin in very-low-birth-weight infants Pediatr Res. 1994;36:85–9.CrossRefGoogle ScholarPubMed
Bechensteen, AG, Haga, P, Halvorsen, S, et al. Effect of low and moderate doses of recombinant human erythropoietin on the haematological response in premature infants on a high protein and iron intake. Eur J Pediatr 1997;156:56–61.Google Scholar
Kohgo, Y, Niitsu, Y, Kondo, H, et al. Serum transferrin receptor as a new index of erythropoiesis. Blood 1987;70:1955–8.Google Scholar
Beguin, Y, Clemons, GK, Pootrakul, P, Fillet, G. Quantitative assessment of erythropoiesis and functional classification of anemia based on measurements of serum transferrin receptor and erythropoietin. Blood 1993;81:1067–76.Google Scholar
Beguin, Y, Loo, M, S. RZ, et al. Early prediction of response to recombinant human erythropoietin in patients with the anemia of renal failure by serum transferrin receptor and fibrinogen. Blood 1993;82:2010–16.Google Scholar
Rusia, U, Flowers, C, Madan, N, Agarwal, N, Sood, SK. Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate. Acta Paediatr Japon 1995;38:455–9.Google Scholar
Kling, PJ, Widness, JA. Transfusions, (RBC Tx) and erythropoiesis indicators influence serum transferrin receptors (TfR) levels in premature infants. Pediatr Res 1995;37:282A.Google Scholar
Kling, PJ, Roberts, RA, Widness, JA. Plasma transferrin receptor levels and indices of erythropoiesis and iron status in healthy term infants. Am J Pediatr Hem/Onc 1997;20:309–14.Google Scholar
Krallis, N, Cholevas, V, Mavridis, A, et al. Effect of recombinant human erythropoietin in preterm infants. Eur J Haematol 1999;63:71–6.Google Scholar
Kasper, DC, Widness, JA, Haiden, N, Berger, A, et al. Characterization and differentiation of iron status in anemic very low birth weight infants using a diagnostic nomogram. Neonatology 2009;95:164–71.CrossRefGoogle ScholarPubMed
Braun, J, Lindner, K, Schreiber, M, Heidler, RA, Horl, WH. Percentage of hypochromic red blood cells as predictor of erythropoietic and iron response after i.v. iron supplementation in maintenance haemodialysis patients. Nephrol Dial Transplan 1997;12:1173–81.Google Scholar
Rettmer, RL, Carlson, TH, Origenes, ML, Jack, RM, Labbe, RF. Zinc protoporphyrin/heme ratio for diagnosis of preanemic iron deficiency. Pediatrics 1999;104:e37.Google Scholar
Kaltwasser, JP, Gottschalk, R. Erythropoietin and iron. Kidney Int 1999;55:S49–S56.Google Scholar
National Kidney Foundation. Clinical Practice Guidelines for the Treatment of Anemia of Chronic Renal Failure (New York: National Kidney Foundation; 1999), available online at https://bit.ly/33S1B23.Google Scholar
Lott, DG, Zimmerman, MB, Labbe’, RF, Kling, PJ, Widness, JA. Erythrocyte zinc protoporphyrin ratios are elevated with prematurity and with fetal hypoxia. Pediatrics 2005;116:414–22.Google Scholar
Miller, SM, McPherson, RJ, Juul, SE. Iron sulfate supplementation decreases zinc protoporphyrin to heme ratio in premature infants. J Pediatr 2006;148:44–8.Google Scholar
Winzerling, JJ, Kling, PJ. Iron deficient erythropoiesis in premature infants measured by blood zinc protoporphyrin/heme. J Pediatr 2001;139:134–6.Google Scholar
Blohowiak, SE, Chen, ME, Repyak, KS, et al. Reticulocyte enrichment of zinc protoporphyrin/heme discriminates impaired iron supply during early development. Pediatr Res 2008;64:63–7.Google Scholar
Shaw, JCL. Iron absorption by the premature infant: The effect of transfusion and iron supplements on the serum ferritin levels. Acta Paediatr Scand Suppl 1982;299:83–9.Google Scholar
Arad, I, Konijn, AM, Linder, N, Goldstein, MDM, Kaufmann, NA. Serum ferritin levels in preterm infants after multiple blood transfusions. Am J Perinatol 1988;5:40–3.Google Scholar
Brown, MS. Effect of transfusion and phlebotomy on serum ferritin levels in low birth weight infants. J Perinatol 1996;16:39–42.Google ScholarPubMed
Soubasi, V, Kremenopoulos, G, Diamanti, E, et al. Follow-up of very low birth weight infants after erythrpoietin treatment to prevent anemia of prematurity. J Pediatr 1995;127:291–7.Google Scholar
Sullivan, JL. Iron, plasma antioxidants and the ‘oxygen radical disease of prematurity’. Am J Dis Child 1988;142:1341–4.Google Scholar
Evans, PJ, Evans, R, Kovar, IZ, Holton, AF, Halliwell, B. Bleomycin-detectable iron in the plasma of premature and full-term neonates. FEBS Letters 1992;303:210–12.Google Scholar
Miller, NJ, Rice-Evans, C, Davies, MJ, Gopinathan, V, Milner, A. A novel method for measuring antioxidant capacity and its application to monitoring the antioxidant status in premature neonates. Clin Sci 1993;84:407–12.Google Scholar
Humphrey, MJ, Harrell-Bean, HA, Eskelson, C, Corrigan, JJ. Blood transfusion in the neonate: Effects of dilution and age of blood on hemolysis. J Pediatr 1982;101:605–7.Google Scholar
Kling, PJ, Reichard, RD, Roberts, RA, Winzerling, JJ, Woodward, SS. The effects of transfusions on oxidative stress and plasma erythropoietin levels in premature infants. Ann Hematol 2000;79:B13.Google Scholar
Obladen, M, Maier, R, Grauel, L, et al. Recombinant human erythropoietin (rhEPO) for prevention of anaemia of prematurity: A randomized multicentre trial. Pediatr Res 1990;28:287A(Abstr).Google Scholar
Shannon, KM, Mentzer, WC, Abels, RI, et al. Recombinant human erythropoietin in anemia of prematurity: Preliminary results of a double-blind placebo controlled pilot study. J Pediatr 1991;118:949–55.Google Scholar
Shannon, KM, Mentzer, WC, Abels, RI, et al. Enhancement of erythropoiesis by recombinant human erythropoietin in low birth weight infants: A pilot study. J Pediatr 1992;120:586–92.Google Scholar
Soubasi, V, Kremenpoulos, 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;34:675–9.Google Scholar
Ronnestad, A, Moe, PJ, Breivik, N. Enhancement of erythropoiesis by erythropoietin, bovine protein and energy fortified mother’s milk during anaemia of prematurity. Acta Paediatrica 1995;84:809–11.Google Scholar
Samanci, N, Ovali, F, Dagoglu, T. Effects of recombinant human erythropoietin in infants with very low birth weights. J Int Med Res 1996;24:190–8.Google Scholar
Giannakopoulou, C, Bolonaki, I, Stiakaki, E, et al. Erythropoietin (rHuEPO) administration to premature infants for the treatment of their anemia. Pediatr Hematol Oncol 1998;15:37–43.Google Scholar
Maier, RF, Obladen, M, Mueller-Hansen, I, et al. Early treatment with erythropoietin beta ameliorates anemia and reduces transfusion requirements in infants with birth weights below 1000 g. J Pediatr 2002;141:8–15.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure [email protected] is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

Available formats
×