Seminars in Fetal & Neonatal Medicine
Volume 12, Issue 1 , Pages 54-63 , February 2007

Iron in fetal and neonatal nutrition

  • Raghavendra Rao

      Affiliations

    • Division of Neonatology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA
    • Corresponding Author InformationCorresponding author. Mayo Medical Code 39, 420 Delaware Street SE, Minneapolis, MN 55455, USA. Tel.: +1 612 626 0644; fax: +1 612 624 8176.
    • ,
  • Michael K. Georgieff

      Affiliations

    • Institute of Child Development, Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN, USA
    • Institute of Child Development, Center for Neurobehavioral Development, University of Minnesota, Minneapolis, MN, USA

References 

  1. Panel on Micronutrients Subcommittee on Upper Reference Levels of Nutrients and of Interpretation and Uses of Dietary Reference Intakes, and the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food and Nutrition Board, Institute of Medicine . Iron. In: Dietary reference intakes for vitamin a, vitamin k, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium and zinc. Washington, DC: National Academy Press; 2001;p. 290–393
  2. Siimes AS, Siimes MA. Changes in the concentration of ferritin in the serum during fetal life in singletons and twins. Early Hum Dev. 1986;13:47–52
  3. Scholl TO. Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr. 2005;81:1218S–1222S
  4. Steer PJ. Maternal hemoglobin concentration and birth weight. Am J Clin Nutr. 2000;71:1285S–1287S
  5. Kilbride J, Baker TG, Parapia L, Khoury SA, Shugaidef SW, Jerwood D. Anaemia during pregnancy as a risk factor for iron-deficiency anaemia in infancy: a case-control study in Jordan. Int J Epidemiol. 1999;28:461–468
  6. Jaime-Perez JC, Herrera-Garza JL, Gomez-Almaguer D. Sub-optimal fetal iron acquisition under a maternal environment. Arch Med Res. 2005;36:598–602
  7. Kelly AM, MacDonald DJ, McDougall AN. Observations on maternal and fetal ferritin concentrations at term. Br J Obstet Gynaecol. 1978;85:338–343
  8. Singla PN, Tyagi M, Shankar R, Dash D, Kumar A. Fetal iron status in maternal anemia. Acta Paediatr. 1996;85:1327–1330
  9. Colomer J, Colomer C, Gutierrez D, Jubert A, Nolasco A, Donat J, et al. Anaemia during pregnancy as a risk factor for infant iron deficiency: report from the Valencia Infant Anaemia Cohort (VIAC) study. Paediatr Perinat Epidemiol. 1990;4:196–204
  10. Chockalingam UM, Murphy E, Ophoven JC, Weisdorf SA, Georgieff MK. Cord transferrin and ferritin values in newborn infants at risk for prenatal uteroplacental insufficiency and chronic hypoxia. J Pediatr. 1987;111:283–286
  11. Georgieff MK, Mills MM, Gordon K, Wobken JD. Reduced neonatal liver iron concentrations after uteroplacental insufficiency. J Pediatr. 1995;127:308–311
  12. Chelchowska M, Laskowska-Klita T. Effect of maternal smoking on some markers of iron status in umbilical cord blood. Rocz Akad Med Bialymst. 2002;47:235–240
  13. Sweet DG, Savage G, Tubman TR, Lappin TR, Halliday HL. Study of maternal influences on fetal iron status at term using cord blood transferrin receptors. Arch Dis Child. 2001;84:F40–F43
  14. Meberg A, Haga P, Sande H, Foss OP. Smoking during pregnancy–hematological observations in the newborn. Acta Paediatr Scand. 1979;68:731–734
  15. Georgieff MK, Petry CD, Mills MM, McKay H, Wobken JD. Increased n-glycosylation and reduced transferrin-binding capacity of transferrin receptor isolated from placentae of diabetic women. Placenta. 1997;18:563–568
  16. Georgieff MK, Landon MB, Mills MM, Hedlund BE, Faassen AE, Schmidt RL, et al. Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr. 1990;117:455–461
  17. Petry CD, Eaton MA, Wobken JD, Mills MM, Johnson DE, Georgieff MK. Iron deficiency of liver, heart, and brain in newborn infants of diabetic mothers. J Pediatr. 1992;121:109–114
  18. Rao R, Georgieff MK. Neonatal iron nutrition. Semin Neonatol. 2001;6:425–435
  19. Singla PN, Gupta VK, Agarwal KN. Storage iron in human foetal organs. Acta Paediatr Scand. 1985;74:701–706
  20. Lackmann GM, Schnieder C, Bohner J. Gestational age-dependent reference values for iron and selected proteins of iron metabolism in serum of premature human neonates. Biol Neonate. 1998;74:208–213
  21. Ehrenkranz RA. Iron, folic acid, and vitamin b12. In:  Tsang RC,  Luca A,  Uauy R,  Zlotkin S editor. Nutritional needs of the preterm infant. Scientific basis and practical guidelines. New York: Williams & Wilkins; 1993;p. 177–194
  22. Shaw JC. Iron absorption by the premature infant. The effect of transfusion and iron supplements on the serum ferritin levels. Acta Paediatr Scand Suppl. 1982;299:83–89
  23. Siddappa AM, Georgieff MK, Wewerka S, Worwa C, Nelson CA, Deregnier RA, et al. Iron deficiency alters auditory recognition memory in newborn infants of diabetic mothers. Pediatr Res. 2004;55:1034–1041
  24. Blayney L, Bailey-Wood R, Jacobs A, Henderson A, Muir J. The effects of iron deficiency on the respiratory function and cytochrome content or rat heart mitochondria. Circ Res. 1976;39:744–748
  25. Berant M, Khourie M, Menzies IS. Effect of iron deficiency on small intestinal permeability in infants and young children. J Pediatr Gastroenterol Nutr. 1992;14:17–20
  26. Guiang SF, Merchant JR, Eaton MA, Fandel KB, Georgieff MK. Intracardiac iron distribution in newborn guinea pigs following isolated and combined fetal hypoxemia and fetal iron deficiency. Can J Physiol Pharmacol. 1998;76:930–936
  27. Mackler B, Grace R, Finch CA. Iron deficiency in the rat: effects on oxidative metabolism in distinct types of skeletal muscle. Pediatr Res. 1984;18:499–500
  28. Aggett PJ. Trace elements of the micropremie. Clin Perinatol. 2000;27:119–129vi
  29. Lozoff B, Beard J, Connor J, Barbara F, Georgieff M, Schallert T. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr Rev. 2006;64:S34–S91
  30. Rao R, Tkac I, Townsend EL, Gruetter R, Georgieff MK. Perinatal iron deficiency alters the neurochemical profile of the developing rat hippocampus. J Nutr. 2003;133:3215–3221
  31. Jorgenson LA, Sun M, O'Connor M, Georgieff MK. Fetal iron deficiency disrupts the maturation of synaptic function and efficacy in area ca1 of the developing rat hippocampus. Hippocampus. 2005;15:1094–1102
  32. Jorgenson LA, Wobken JD, Georgieff MK. Perinatal iron deficiency alters apical dendritic growth in hippocampal ca1 pyramidal neurons. Dev Neurosci. 2003;25:412–420
  33. Wachs TD, Pollitt E, Cueto S, Jacoby E, Creed-Kanashiro H. Relation of neonatal iron status to individual variability in neonatal temperament. Dev Psychobiol. 2005;46:141–153
  34. Armony-Sivan R, Eidelman AI, Lanir A, Sredni D, Yehuda S. Iron status and neurobehavioral development of premature infants. J Perinatol. 2004;24:757–762
  35. DeBoer T, Wewerka S, Bauer PJ, Georgieff MK, Nelson CA. Explicit memory performance in infants of diabetic mothers at 1 year of age. Dev Med Child Neurol. 2005;47:525–531
  36. Georgieff MK, Wewerka SW, Nelson CA, Deregnier RA. Iron status at 9 months of infants with low iron stores at birth. J Pediatr. 2002;141:405–409
  37. Tamura T, Goldenberg RL, Hou J, Johnston KE, Cliver SP, Ramey SL, et al. Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr. 2002;140:165–170
  38. Freeman VE, Mulder J, van't Hof MA, Hoey HM, Gibney MJ. A longitudinal study of iron status in children at 12, 24 and 36months. Public Health Nutr. 1998;1:93–100
  39. Whitington PF. Fetal and infantile hemochromatosis. Hepatology. 2006;43:654–660
  40. Kelly AL, Lunt PW, Rodrigues F, Berry PJ, Flynn DM, McKiernan PJ. Classification and genetic features of neonatal haemochromatosis: a study of 27 affected pedigrees and molecular analysis of genes implicated in iron metabolism. J Med Genet. 2001;38:599–610
  41. Flynn DM, Mohan N, McKiernan P, Beath S, Buckels J, Mayer D, et al. Progress in treatment and outcome for children with neonatal haemochromatosis. Arch Dis Child. 2003;88:F124–F127
  42. Cooke RW, Drury JA, Yoxall CW, James C. Blood transfusion and chronic lung disease in preterm infants. Eur J Pediatr. 1997;156:47–50
  43. Inder TE, Clemett RS, Austin NC, Graham P, Darlow BA. High iron status in very low birth weight infants is associated with an increased risk of retinopathy of prematurity. J Pediatr. 1997;131:541–544
  44. Ng PC, Lam CW, Lee CH, To KF, Fok TF, Chan IH, et al. Hepatic iron storage in very low birthweight infants after multiple blood transfusions. Arch Dis Child. 2001;84:F101–F105
  45. Kaur D, Peng J, Chinta SJ, Rajagopalan S, Di Monte DA, Cherny RA, et al. Increased murine neonatal iron intake results in Parkinson-like neurodegeneration with age. Neurobiol Aging. 2006, Jun 8;[Epub ahead of print]
  46. Hirano K, Morinobu T, Kim H, Hiroi M, Ban R, Ogawa S, et al. Blood transfusion increases radical promoting non-transferrin bound iron in preterm infants. Arch Dis Child. 2001;84:F188–F193
  47. Mumby S, Chaturvedi RR, Brierley J, Lincoln C, Petros A, Redington AN, et al. Iron overload in paediatrics undergoing cardiopulmonary bypass. Biochim Biophys Acta. 2000;1500:342–348
  48. Miller SM, McPherson RJ, Juul SE. Iron sulfate supplementation decreases zinc protoporphyrin to heme ratio in premature infants. J Pediatr. 2006;148:44–48
  49. Beard J, deRegnier RA, Shaw M, et al. Diagnosis of iron deficiency in infancy. Lab Med (in press).
  50. Juul SE, Zerzan JC, Strandjord TP, Woodrum DE. Zinc protoporphyrin/heme as an indicator of iron status in NICU patients. J Pediatr. 2003;142:273–278
  51. Lott DG, Zimmerman MB, Labbe RF, Kling PJ, Widness JA. Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia. Pediatrics. 2005;116:414–422
  52. Griffin IJ, Reid MM, McCormick KP, Cooke RJ. Zinc protoporphyrin/haem ratio and plasma ferritin in preterm infants. Arch Dis Child. 2002;87:F49–F51
  53. Rusia U, Flowers C, Madan N, Agarwal N, Sood SK, Sikka M. Serum transferrin receptor levels in the evaluation of iron deficiency in the neonate. Acta Paediatr Jpn. 1996;38:455–459
  54. Sweet DG, Savage GA, Tubman R, Lappin TR, Halliday HL. Cord blood transferrin receptors to assess fetal iron status. Arch Dis Child. 2001;85:F46–F48
  55. Kling PJ, Roberts RA, Widness JA. Plasma transferrin receptor levels and indices of erythropoiesis and iron status in healthy term infants. J Pediatr Hematol Oncol. 1998;20:309–314
  56. MacPhail AP, Charlton RW, Bothwell TH, Torrance JD. The relationship between maternal and infant iron status. Scand J Haematol. 1980;25:141–150
  57. Siddappa AJ, Rao R, Long JD, et al. The assessment of newborn iron stores at birth: a review of the literature and standards for ferritin concentrations. Biol Neonate (in press).
  58. American Academy of Pediatrics, C o N . Iron deficiency. In:  Kleinman RE editors. Pediatric nutrition handbook. Elk Grove Village: American Academy of Pediatrics; 1998;p. 299–312
  59. Olivares M, Llaguno S, Marin V, Hertrampf E, Mena P, Milad M. Iron status in low-birth-weight infants, small and appropriate for gestational age. A follow-up study. Acta Paediatr. 1992;81:824–828
  60. Lundstrom U, Siimes MA, Dallman PR. At what age does iron supplementation become necessary in low-birth-weight infants. J Pediatr. 1977;91:878–883
  61. Milman N, Bergholt T, Eriksen L, Byg KE, Graudal N, Pederson P. Iron prophylaxis during pregnancy – how much iron is needed? A randomized dose- response study of 20–80mg ferrous iron daily in pregnant women. Acta Obstet Gynecol Scand. 2005;84:238–247
  62. Preziosi P, Prual A, Galan P, Daouda H, Boureima H, Hercberg S. Effect of iron supplementation on the iron status of pregnant women: consequences for newborns. Am J Clin Nutr. 1997;66:1178–1182
  63. Friel JK, Aziz K, Andrews WL, Harding SV, Courage ML, Adams RJ. A double-masked, randomized control trial of iron supplementation in early infancy in healthy term breast-fed infants. J Pediatr. 2003;143:582–586
  64. Dauncey MJ, Davies CG, Shaw JC, Urman J. The effect of iron supplements and blood transfusion on iron absorption by low birthweight infants fed pasteurized human breast milk. Pediatr Res. 1978;12:899–904
  65. Fomon SJ, Nelson SE, Ziegler EE. Retention of iron by infants. Annu Rev Nutr. 2000;20:273–290
  66. Rao R, Georgieff MK. Microminerals. In:  Tsang RC,  Uauy R,  Koletzko B,  Zlotkin SH editor. Nutrition of the preterm infant. Scientific basis and practical guidelines. Cincinnati: Digital Educational Publishing, Inc; 2005;p. 277–310
  67. O'Brien KO, Zavaleta N, Abrams SA, Caulfield LE. Maternal iron status influences iron transfer to the fetus during the third trimester of pregnancy. Am J Clin Nutr. 2003;77:924–930
  68. van Rheenen P, Brabin BJ. Late umbilical cord-clamping as an intervention for reducing iron deficiency anaemia in term infants in developing and industrialised countries: a systematic review. Ann Trop Paediatr. 2004;24:3–16
  69. Chaparro CM, Neufeld LM, Tena Alavez G, Equia-Liz Cedillo R, Dewey KG. Effect of timing of umbilical cord clamping on iron status in mexican infants: a randomised controlled trial. Lancet. 2006;367:1997–2004
  70. Franz AR, Mihatsch WA, Sander S, Kron M, Pohlandt F, et al. Prospective randomized trial of early versus late enteral iron supplementation in infants with a birth weight of less than 1301 grams. Pediatrics. 2000;106:700–706
  71. Pollak A, Hayde M, Hayn M, Herkner K, Lombard KA, Lubec G, et al. Effect of intravenous iron supplementation on erythropoiesis in erythropoietin treated premature infants. Pediatrics. 2001;107:78–85
  72. Hall RT, Wheeler RE, Benson J, Harris G, Rippetoe L. Feeding iron-fortified premature formula during initial hospitalization to infants less than 1800grams birth weight. Pediatrics. 1993;92:409–414
  73. Whitington PF, Hibbard JU. High-dose immunoglobulin during pregnancy for recurrent neonatal haemochromatosis. Lancet. 2004;364:1690–1698
  74. Palmer C, Roberts RL, Bero C. Deferoxamine posttreatment reduces ischemic brain injury in neonatal rats. Stroke. 1994;25:1039–1045

PII: S1744-165X(06)00102-8

doi: 10.1016/j.siny.2006.10.007

Seminars in Fetal & Neonatal Medicine
Volume 12, Issue 1 , Pages 54-63 , February 2007

Article Tools