Erythropoietin is a normal component of human milk. The excretion of exogenous epoetin alfa (recombinant human erythropoietin; EPO) in breastmilk has not been studied. Although some studies have shown an improve response of postpartum anemia when EPO was used with iron therapy, current consensus is that EPO has no clinically important effect on the increase in hemoglobin concentration over iron alone. No adverse reactions were reported in the breastfed infants of mothers who received EPO. No special precautions are required during breastfeeding if mothers receive EPO.
Some authors have hypothesized that erythropoietin in milk might help maintain the integrity of the lining of the mammary epithelium and the infant gastrointestinal tract, thereby reducing the risk of mother-to-child transmission of HIV infection (MTCT). A case-control study in Tanzania supports the protective role of erythropoietin in breastmilk against MTCT. Erythropoietin might also have a modest beneficial effect on the infant's red cell production. Holder pasteurization (62.5 degrees C for 30 minutes) decreases the concentration of endogenous erythropoietin by an average about 75%, with complete degradation in some samples.
Relevant published information on exogenous administration of epoetin alfa was not found as of the revision date. However, breastmilk normally contains erythropoietin. Erythropoietin concentrations in human milk are in the range of approximately 4 to 5 units/L in the first 1 to 2 months postpartum and increase to 20 to 40 units/L by the third month and to 100 to 150 units/L by 12 months. A study on pasteurization of breastmilk found that the erythropoietin concentration in breastmilk dropped from 1.9 international units/L before pasteurization to 0.5 international units/L after pasteurization.
Published information on absorption of epoetin alfa from breastmilk was not found as of the revision date. However, several studies in which oral doses of epoetin alfa and other recombinant forms of erythropoietin were given to preterm infants found that epoetin is absorbed to a small extent. Increases in hematocrit in infants treated with oral epoetin alfa have been small to negligible. However, one study found that hospitalized preterm infants taking enteral feedings and given 400 units daily of recombinant human erythropoietin by mouth with ferroussulfatehad higher reticulocyte counts and serum erythropoietin concentrations upon hospital discharge than control infants given only ferroussulfate.
Effects in Breastfed Infants:
Enhancement of gastrointestinal tract maturation has been proposed as a function of erythropoietin in breastmilk.
In a study of 40 women with postpartum anemia, 19 of 20 women who received iron and subcutaneous recombinant human erythropoietin (EPO; generic name and brand not specified) 200 IU/kg daily for 15 days were able to breastfeed their infants. This regimen is more aggressive than the approve three times/week regimen. In the control group that received only oral iron and folic acid, only 10 were able to breastfeed their infants. No adverse reactions were reported among the infants of women who receive EPO.
Possible Effects on Lactation:
In small studies, epoetin alfa administration decreased serum prolactin in patients with amylotrophic lateral sclerosis, but had no effect in normal subjects or in patients with renal failure undergoing chronic ambulatory peritoneal dialysis. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
1. Milman N. Postpartum anemia II: prevention and treatment. Ann Hematol. 2012;91:143-54. PMID:22160256 2. Makrydimas G, Lolis D, Lialios G et al. Recombinant human erythropoietin treatment of postpartum anemia. Preliminary results. Eur J Obstet Gynecol Reprod Biol. 1998;81:27-31. PMID:9846709 3. Semba RD, Juul SE. Erythropoietin in human milk: physiology and role in infant health. J Hum Lact. 2002;18:252-61. PMID:12192960 4. Arsenault JE, Webb AL, Koulinska IN et al. Association between breast milk erythropoietin and reduced risk of mother-to-child transmission of HIV. J Infect Dis. 2010;202:370-3. PMID:20557236 5. Pasha YZ, Ahmadpolir-Kacho M, Hajiahmadi M, Hosseini M. Enteral erythropoietin increases plasma erythropoietin level in preterm infants: a randomized controlled trial. Indian Pediatr. 2008;45:25-8. PMID:18250501 6. Untalan PB, Keeney SE, Palkowetz KH et al. Heat susceptibility of interleukin-10 and other cytokines in donor human milk. Breastfeed Med. 2009;4:137-44. PMID:19366315 7. Untalan PB, Keeney SE, Rivera A, Goldman AS. The effect of pasteurization on cytokines in human milk. J Invest Med. 2007;55 (Suppl S):S288. Abstract. 8. Calhoun DA, Christensen RD. Hematopoietic growth factors in neonatal medicine: the use of enterally administered hematopoietic growth factors in the neonatal intensive care unit. Clin Perinatol. 2004;31:169-82. PMID:15183665 9. Ballin A, Bilker-Reich A, Arbel E et al. Erythropoietin, given enterally, stimulates erythropoiesis in premature infants. Lancet. 1999;353:1849. Letter. PMID:10359412 10. Juul SE. Enterally doses recombinant human erythropoietin does not stimulate erythropoiesis in neonates. J Pediatr. 2003;143:321-6. PMID:14517513 11. Juul SE, Cristensen RD. Absorption of enteral recombinant human erythropoietin by neonates. Ann Pharmacother. 2003;37:782-6. PMID:12773061 12. Britton JR, Christensen RD. Enteral administration of recombinant erythropoietin to preterm infants. J Perinatol. 1995;15:281-3. PMID:8558334 13. Miller M, Iliff P, Stoltzfus RJ, Humphrey J. Breastmilk erythropoietin and mother-to-child HIV transmission through breastmilk. Lancet. 2002;360:1246-8. PMID:12401271 14. Tokgoz B, Utas C, Dogukan A et al. Influence of long term erythropoietin therapy on the hypothalamic-pituitary-thyroid axis in patients undergoing CAPD. Ren Fail. 2002;24:315-23. PMID:12166698 15. Bernini GP, Mariotti F, Brogi G et al. Effects of erythropoietin administration on prolactin secretion in normal subjects. Nephron. 1993;65:522-6. PMID:8302403 16. Markianos M, Kosmidis ML, Sfagos C. Reductions in plasma prolactin during acute erythropoietin administration. Neuro Endocrinol Lett. 2006;27:355-8. PMID:16816832
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Hematopoietic Cell Growth Factors
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