A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin

doi:10.1016/S0022-3476(96)70251-2

The Journal of Pediatrics

Volume 129, Issue 2, August 1996, Pages 258-263

https://doi.org/10.1016/S0022-3476(96)70251-2 Get rights and content

Abstract

OBJECTIVE: To determine whether intravenously administered iron supplements would improve the hematologic response to recombinant erythropoietin in stable preterm infants. METHODS: Forty-two preterm infants (<33 weeks' gestation, birth weight <1500 gm, hematocrit <38%) were treated with recombinant human erythropoietin (Eprex), 600 U/kg per week, and randomly assigned to receive either an oral preparation of ferrous lactate (elemental iron, 12 mg/kg per day) or an intravenous preparation of iron sucrose (6 mg/kg per week). RESULTS: Hematocrits, reticulocyte counts, and transfusions were similar in the oral group (OG) and the intravenous group (IVG). However, markedly higher serum ferritin concentrations were noted in the IVG (p <0.001), and by completion of the study the arithmetic mean values were 265 ± 127 μg/L versus 137 ± 65 μg/L in the IVG and the OG, respectively. The numbers of hypochromic erythrocytes increased in both groups during the study but were significantly higher in the OG (p = 0.04). Mean daily weight gain in the IVG (27 ± 6.4 gm/day) was greater than in the OG (22.9 ± 4.78 gm/day; p = 0.04). CONCLUSIONS: High doses of both orally administered iron and intravenously administered iron sucrose appear to supply sufficient iron for erythropoiesis in stable infants. Storage iron may become depleted after oral supplementation. The intravenous preparation appears to be safe and maintains serum ferritin concentrations, and it may be indicated for patients with low ferritin levels and for those not established on enteral feedings. (J PEDIATR 1996;129:258-63)

Section snippets

METHODS

The study was carried out in Cape Town in the Peninsula Maternal and Neonatal Service, where preterm infants requiring hospitalization are cared for in one of three nurseries. Forty-two premature infants (<33 weeks' gestation, <1500 gm at birth) were randomly assigned to receive either parenterally administered iron sucrose (elemental iron, 6 mg/kg per week) or ferrous lactate (elemental iron, 12 mg/kg per day), given orally. Both groups were given rHuEpo (Eprex, from Janssen-Cilag), 600 U/kg

Clinical features

There were no significant differences in the demographic characteristics of the preterm infants assigned to receive a supplemental oral or intravenous preparation of iron (Table I). The erythropoietin and intravenous infusions of iron were well tolerated, and there were no adverse effects. The duration of study for the “oral group” was 25.9 ± 10.8 days compared with 24.7 ± 10.1 for the “intravenous group” (p = 0.70); the combined mean was 25.3 days. The blood volume withdrawn during the study

DISCUSSION

Our study indicated that the hematologic response to rHuEpo in the orally and intravenously supplemented groups was similar. Both iron preparations appeared to be well tolerated and safe. The most striking finding was the difference in ferritin levels in the two groups. The intravenously supplemented group did not have a decline during rHuEpo therapy. To our knowledge, this has not been documented in other studies that have used oral iron. Carnielli et al.⁸ used intravenously administered iron

Acknowledgements

Financial support was received from Janssen-Cilag Pharmaceutica, Johannesburg, South Africa, who also provided the rHuEpo (Eprex). Supplies of iron sucrose were donated by Byk Gulden, Johannesburg, South Africa. We thank the Department of Chemical Pathology, Groote Schuur Hospital, for carrying out the iron studies and our nursing and medical colleagues (especially F. M. Harm, G. Moller, and A. Malan) for their assistance.

References (12)

RK 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
J Pediatr
(1995)
V Carnielli et al.
Effect of high doses of human recombinant erythropoietin on the need ior blood transfusions in preterm infants
J Pediatr
(1992)
MP Meyer et al.
Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study
Pediatrics
(1994)
KM Shannon et al.
Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants
Pediatrics
(1995)
MP Meyer et al.
Use of blood transfusion and recombinant human erythropoietin in anemia of prematurity: a comparison of costs [abstract]
Blood
(1994)
RF Maier et al.
The effect of epoietin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants
N Engl J Med
(1994)

There are more references available in the full text version of this article.

Cited by (76)

Developmental Erythropoiesis
2011, Fetal and Neonatal Physiology E-Book, Fourth Edition
Anemia in the Preterm Infant: Erythropoietin Versus Erythrocyte Transfusion-It's not that Simple
2009, Clinics in Perinatology
Citation Excerpt :
Infants receiving r-EPO have lower ferritin levels and hypochromic RBCs, necessitating supplementation with iron.31 Both intravenous and oral iron supplementation have been shown to maintain serum ferritin levels and to support erythropoiesis.33,35,37,50 Perhaps the most important finding of the first randomized, controlled trials of r-EPO was that implementing standard criteria for RBC transfusion alone safely reduced the number of transfusions administered, even for patients in the control group.20,29,32,33
Since the late 1980s recombinant human erythropoietin (r-EPO) has been studied as an alternative to packed red blood cell (RBC) transfusion for the treatment of anemia of prematurity in very low birth weight infants. Initial trials and reports focused on r-EPO's ability to prevent or treat anemia of prematurity with the goal of eliminating RBC transfusion but achieved limited success. New concerns about the safety of r-EPO administration have emerged. Past cost–benefit analyses of r-EPO administration versus transfusion for the treatment of anemia of prematurity have been nearly balanced. Autologous transfusion, blood-sparing technologies, changes in RBC transfusion technique and safety, and further elucidation of the risk–benefit ratio of r-EPO therapy may change the cost–benefit analysis.
Iron Therapy for Preterm Infants
2009, Clinics in Perinatology
Citation Excerpt :
Enteral doses as high as 18 to 36 mg/d (approximately 12–24 mg/kg d−1) have been used71 but do not seem to provide additional benefits and may cause hematochezia.66 Intravenous iron supplementation in a dose of 2 to 6 mg/kg or 20 mg/kg weekly may improve erythropoietic response and growth during rHuEPO therapy.70 Such therapy may be useful in infants who have low serum ferritin levels or in whom enteral nutrition has yet to be established.
Preterm infants are at risk for both iron deficiency and iron overload. The role of iron in multiple organ functions suggests that iron supplementation is essential for the preterm infant. Conversely, the potential for iron overload and the poorly developed antioxidant measures in the preterm infant argue against indiscriminate iron supplementation in this population. This article reviews the predisposing factors and consequences of iron deficiency and iron overload in the preterm infant, discusses the current recommendation for iron supplementation and its appropriateness, and describes potential management strategies that strike a balance between iron deficiency and iron toxicity.
Is there a role for erythropoietin in neonatal medicine?
2008, Early Human Development
Since it was first cloned in 1985, the therapeutic potential of recombinant human erythropoietin in the neonatal hyporegenerative anaemias has been studied—the anaemia of prematurity and haemolytic disease of the newborn. Between 60% and 100% of preterm infants are transfused before three weeks of age, a large proportion receiving more than one transfusion. Blood transfusions are currently also the mainstay of treatment for the hyporegenerative anaemia encountered in neonates with Rhesus disease. Sometimes the situation is complicated by the religious beliefs of the parents.
Blood transfusions are associated with numerous risks, from transmission of infection to local injury, and in an effort to minimize these risks Neonatologists have looked to recombinant erythropoietin. Despite an extensive number of studies, there is as yet no clear consensus as to whether the use of recombinant erythropoietin in Neonatal medicine minimizes the need for blood transfusions without risk to the neonate. In this article we review the evidence for and against the use of recombinant erythropoietin in Neonatal medicine.
Erythrocyte iron incorporation but not absorption is increased by intravenous iron administration in erythropoietin-treated premature infants
2006, Journal of Nutrition
Because critically ill premature infants experience significant iron loss due to phlebotomy and have high iron needs for growth, Fe absorption and incorporation studies are clinically important. A prospective, controlled, randomized, open 21-d study was conducted in infants with birth weight <1300 g and gestational age < 31 wk to assess the efficacy of combining intravenous (IV) sucrose iron (Fe) with erythropoietin (EPO) for increasing Fe absorption, RBC Fe incorporation, and erythropoiesis. Three clinically stable groups were enrolled at 3–4 wk of age: Control, EPO [2100 U EPO/(kg·wk)]; and IV Fe+EPO [2 mg IV sucrose Fe/(kg·d) plus 2100 U EPO/(kg·wk)]. All subjects received 9 mg/(kg·d) of oral Fe polymaltose. Subjects were not allowed RBC transfusions. Indicators of iron status and erythropoiesis were assessed before and 18 d after treatment. On d 4, tracer doses of oral polymaltose ⁵⁷Fe and IV sucrose ⁵⁸Fe were administered, and stool and blood samples were collected for Fe absorption and incorporation determinations. Compared with the Control group, the EPO group demonstrated greater hemoglobin (Hb) concentration and reticulocyte count, but no difference in Fe incorporation. In contrast, the IV Fe+EPO group demonstrated greater total Fe incorporation, Hb concentration, plasma ferritin, and reticulocyte count compared with the Control and EPO groups. Absorption of ⁵⁷Fe and nonisotopic polymaltose Fe did not differ among the groups (range: 48–58%, and 41–47%, respectively). We conclude that IV sucrose Fe administered in combination with EPO to very-low-birth weight premature infants significantly increases RBC Fe incorporation and erythropoiesis more than EPO alone, but without increasing iron absorption.
Reticulocyte hemoglobin content changes after treatment of anemia of prematurity
2022, Pediatrics International

View all citing articles on Scopus

^☆: From Neonatal Medicine, Department of Paediatrics and Department of Haematology, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

^☆☆: Supported by Janssen Pharmaceutica, suppliers of recombinant erythropoietin (Eprex).

^★: Reprints not available from authors.

^★★: 0022-3476/96/$5.00 + 0 9/21/74360

View full text

A comparison of oral and intravenous iron supplementation in preterm infants receiving recombinant erythropoietin☆,☆☆,★,★★

Abstract

Section snippets

METHODS

Clinical features

DISCUSSION

Acknowledgements

J Pediatr

J Pediatr

Recombinant human erythropoietin in the treatment of the anemia of prematurity: results of a double-blind, placebo-controlled study

Pediatrics

Recombinant human erythropoietin stimulates erythropoiesis and reduces erythrocyte transfusions in very low birth weight preterm infants

Pediatrics

Use of blood transfusion and recombinant human erythropoietin in anemia of prematurity: a comparison of costs [abstract]

Blood

The effect of epoietin beta (recombinant human erythropoietin) on the need for transfusion in very-low-birth-weight infants

N Engl J Med