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Table of Contents
Vol. 92, No. 2, 2007
Issue release date: August 2007
Section title: Review
Free Access
Neonatology 2007;92:73–82
(DOI:10.1159/000100805)

The Assessment of Newborn Iron Stores at Birth: A Review of the Literature and Standards for Ferritin Concentrations

Siddappa A.M.a · Rao R.b · Long J.D.c · Widness J.A.d · Georgieff M.K.b
aDivision of Neonatology, Hennepin County Medical Center, and Department of Pediatrics, University of Minnesota School of Medicine, bDivision of Neonatology, Department of Pediatrics, University of Minnesota School of Medicine, and cDepartment of Educational Psychology, College of Education and Human Development, University of Minnesota, Minneapolis, Minn., dDivision of Neonatology, Department of Pediatrics, University of Iowa School of Medicine, Iowa City, Iowa, USA
email Corresponding Author

Abstract

Background: Serum ferritin measurements are used in clinical populations to estimate total body iron stores and the risk of subsequent iron deficiency or overload. The lack of normative newborn serum ferritin concentration data between 23 and 41 weeks has led to difficulty in establishing the incidence and degree of abnormal iron status in the neonatal period. Objectives: The primary objective of this review was to summarize the maternal and gestational factors that determine ferritin concentrations in full-term and pre-term newborn infants and to generate comprehensive reference values. The secondary objective was to assess serum ferritin concentrations in newborn infants at risk for abnormal fetal iron metabolism, including maternal diabetes mellitus, intrauterine growth restriction and maternal smoking during pregnancy. Methods: Serum ferritin and gestational age data at birth from 457 low-risk pre-term and term infants of 23–41 weeks gestation obtained from 35 published studies reviewed from a period of 25 years and from recently collected data from our centers were assessed by regression analysis. Slopes and intercepts of the high-risk groups were compared with the standard curve. Results: Umbilical cord serum ferritin concentrations increased with advancing gestational age, from a mean of 63 µg/l at 23 weeks to 171 µg/l at 41 weeks gestation (p < 0.001). The infants of diabetic mothers had a lower intercept than the control infants (p < 0.001). Conclusions: Iron deficiency and overload have been implicated in neurodevelopmental impairments. Normative cord serum ferritin data may permit a more precise assessment of infants who are at risk for abnormal iron status at birth.

© 2007 S. Karger AG, Basel


  

Key Words

  • Ferritin
  • Diabetic mother, infant
  • Iron
  • Iron deficiency

References

  1. Dallman PR: Biochemical basis for the manifestations of iron deficiency. Ann Rev Nutr 1986;6:13–40.
  2. Youdim MBH, Yehuda S: The neurochemical basis of cognitive deficits induced by brain iron deficiency: involvement of dopamine-opiate system. Cell Mol Biol 2000;46:491–500.
  3. Connor JR, Menzies SL: Altered cellular distribution of iron in the central nervous system of myelin deficient rats. Neuroscience 1990;34:265–271.
  4. Yu GSM, Steinkirchner TM, Rao GA, Larkin EC: Effect of prenatal iron deficiency on myelination in rat pups. Am J Pathol 1986;125:620–624.
  5. deUngria M, Rao R, Wobken JD, Luciana M, Georgieff MK: Perinatal iron deficiency decreases cytochrome c oxidase activity in selective regions of the brain. Pediatr Res 2000;48:169–176.
  6. Petry CD, Eaton MA, 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.
  7. Georgieff MK, Landon MB, Mills MM, Hedlund BE, Faassen AE, Schmidt RL, Ophoven JJ, Widness JA: Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990;117:455–461.
  8. 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.
  9. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW: Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000;105:e51
  10. Grantham-McGregor S, Ani C: A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:649S–668S.
  11. Fleming RE: Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: correlations and confounding variables. J Pediatr 2002;140:145–148.
  12. Tamura T, Goldenberg R, Hou J, Johnston K, Cliver SP, Ramsey SL, Nelson K: Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 2002;140:165–170.
  13. Siddappa AM, Georgieff MK, Wewerka S, Worwa C, Nelson CA, deRegnier R-A: Auditory recognition memory in iron-deficient infants of diabetic mothers. Pediatr Res 2004;55:1034–1041.
  14. 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.
  15. Beard J, deRegnier RA, Shaw M, Rao R, Georgieff M: Diagnosis of iron deficiency in infancy. Lab Med 2007;38:103–108.

    External Resources

  16. Lott DG, Zimmerman MB, Labbe RF, Kling PJ, et al: Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia. Pediatrics 2005;116:414–422.
  17. Juul.SE, Zerzan JC, Strandiord TP, Woodrum DE: Zinc protoporphyrin/heme as an indicator of iron status in nicu patients. J Pediatr 2003;142:273–278.
  18. Siimes MA, Addiego JE, Dallman PR: Ferritin in serum: diagnosis of iron deficiency and iron overload in infants and children. Blood 1974;43:581–590.
  19. Rios E, Lipschitz DA, Cook JD, Smith NJ: Relationship of maternal and infant iron stores as assessed by determination of plasma ferritin. Pediatrics 1975;55:694.
  20. Lipschitz DA, Cook JD, Finch CA: A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med 1974;290:1213–1216.
  21. Walters GO, Miller FM, Worwood M: Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol 1973;26:770–772.
  22. Cook JD: Clinical evaluation of iron deficiency. Semin Hematol 1982;19:6–18.
  23. MacPhail AP, Charlton RW, Bothwell TH, Torrance JD: The relationship between maternal and infant iron status. Scand J Hematol 1980;25:141–150.
  24. Baynes RD: Assessment of iron status. Clin Chem 1996;29:209–215.
  25. Cook JD, Skikne BS: Iron deficiency: definition and diagnosis. J Intern Med 1989;226:349–355.
  26. Bothwell TH: Iron requirements during pregnancy and strategies to meet them. Am J Clin Nutr 2000;72:257S–264S.
  27. Oski FA: Iron deficiency in infancy and childhood. New Engl J Med 1993;329:190–193.
  28. Widdowsen EM, Sray CM: Chemical development in utero. Arch Dis Child 1951;26:205–214.
  29. Siimes ASI, 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.
  30. Messer RD, Russo AM, McWhirter WR, Spragemeyer D, Halliday JW: Serum ferritin in term and preterm infants. Aust Paediatr J 1980;16:185–188.
  31. Jansson L, Holmberg L, Ekman R: Variation of serum ferritin in low birth weight infants with maternal ferritin, birth weight and gestational age. Acta Haematol 1979;62:273–277.
  32. Sweet DG, Tubman TRJ, Lappin TRJ, Halliday HL: Study of maternal influences on fetal iron status at term using cord blood transferrin receptors. Arch Dis Child Fetal Neonatal Ed 2001;84:F40–F43.
  33. Carpani G, Marini F, Buscaglia M, Sinigaglia E, Moroni G: Red cell and plasma ferritin in normal fetuses at different ages of gestation. Eur J Haematol 1992;49:260–262.
  34. Haga P: Plasma ferritin concentrations in preterm infants in cord blood and during the early anemia of prematurity. Acta Pediatr Scand 1980;69:637–641.
  35. Hussain MAM, Gaafar TH, Laulight M, Hoffbrand AV: Relation of maternal and cord blood ferritin. Arch Dis Child 1977;52:782–784.
  36. Lao TT, Loong EPL, Chin RKH, Lam CWK, Lam YM: Relationship between newborn and maternal iron status and hematological indices. Biol Neonate 1991;60:303–307.
  37. Kelly AM, MacDonald DJ, Mc Dougall AN: Observations on maternal and fetal ferritin concentrations at term. Br J Obstet Gynaecol 1978;85:338–343.
  38. Agarwal RMD, Tripathi AM, Agarwal KN: Cord blood hemoglobin, iron and ferritin status in maternal anemia. Acta Paediatr Scand 1983;72:545–548.
  39. Erdem A, Erdem M, Arslan M, Yazici G, Eskandari R, Himmetoglu O: The effect of maternal anemia and iron deficiency on fetal erythropoiesis: comparison between serum erythropoietin, hemoglobin and ferritin levels in mothers and newborns. J Matern Fetal Neonatal Med 2002;11:329–332.
  40. Ziaei S, Hatefnia E, Togeh GH: Iron status in newborns born to iron-deficient mothers. Iran J Med Sci 2002;28:62–64.
  41. Puolakka J, Janne O, Vihko R: Evaluation by serum ferritin assay of the influence of maternal iron stores on the iron status of newborns and infants. Acta Obstet Gynecol Scand Suppl 1980;95:53–56.
  42. Ilyes I, Jezerniczky J, Kovacs J, Dvoracsek E, Csorba S: Relationship of maternal and newborn serum ferritin concentrations measured by immunoradiometry. Acta Paediatr Hung 1985;26:317–321.
  43. Fenton V, Cavill I, Fisher J: Iron stores in pregnancy. Br J Haematol 1977;37:145–149.
  44. O’Brien KO, Zavaleta N, Abrams SA, Caufield LE: Maternal iron status influences iron transfer to the fetus during the third trimester of pregnancy. Am J Clin Nutr 2003;77:924–930.
  45. Georgieff MK, Petry CD, Wobken JD: Liver and brain iron deficiency in newborn infants with bilateral renal agenesis (Potter’s syndrome). Pediatr Pathol Lab Med 1996;16:509–519.
  46. Georgieff MK, Landon MB, Mills MM, Hedlund BE, Faassen AE, Schmidt RL, Ophoven JJ, Widness JA: Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990;117:455–461.
  47. Sweet DG, Savage GA, Tubman R, Lappin TRJ, Halliday HL: Cord blood transferrin receptors to assess fetal iron status. Arch Dis Child Fetal Neonatal Ed 2001;85:F46–F48.
  48. Georgieff MK, Widness JA, Mills MM, Stonestreet BS: The effect of prolonged intrauterine hyperinsulinemia on iron utilization in fetal sheep. Pediatr Res 1989;26:467–469.
  49. Widness JA, Susa JB, Garcia JF, Singer DB, Seghal P, Oh W, Schwartz R, Schwartz HC: Increased erythropoiesis and elevated erythropoietin in infants born to diabetic mothers and in hyperinsulinemic rhesus fetuses. J Clin Invest 1981;67:637–642.
  50. Murata K, Toyoda N, Ichio T, Ida M, Sugiyama Y: Cord transferrin and ferritin values for erythropoiesis in newborn infants of diabetic mothers. Endocrinol Jpn 1989;36:827–832.
  51. Philipps AF, Porte PJ, Strabinsky S, Rosenkranz TS, Raye JR: Effects of chronic fetal hyperglycemia upon oxygen consumption in the ovine uterus and conceptus. J Clin Invest 1984;74:279–286.
  52. Milley JR, Papacostas JS, Tabata BK: Effect of insulin on uptake of metabolic substrates by the sheep fetus. Am J Physiol 1986;251:E349–E56.
  53. 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.
  54. Meberg A, Haga P, Sande H, Foss OP: Smoking during pregnancy – hematological observations in the newborn. Acta Pediatric Scand 1979;68:731–734.
  55. Gruslin A, Perkins SL, Manchanda R, Fleming N, Clinch JJ: Maternal smoking and fetal erythropoietin. Obstet Gynecol 2000;95:561–564.
  56. Morton RE, Nysenbaum A, Price K: Iron status in the first year of life. J Pediatr Gastroenterol Nutr 1998;1:707–712.
  57. Halliday HL, Lappin TRJ, McClure G: Iron status of the preterm infant during the first year of life. Biol Neonate 1984;45:228–235.
  58. Emery D, Barry D: Comparison of Maori and non-Maori maternal and fetal iron parameters. N Z Med J 2004;117:909–913.
  59. Zavaleta N, Caulfield LE, Garcia T: Changes in iron status during pregnancy in Peruvian women receiving prenatal iron and folic acid supplements with or without zinc. Am J Clin Nutr 2000;71:956–961.
  60. Celada A, Busset R, Gutierrez J, Herreros V: Maternal and cord blood ferritin. Helv Paediatr Acta 1982;37:239–244.
  61. Nemet K, Andrassy K, Bognar K, Czappan P, Stuber A, Simonovits I: Relationship between maternal and infant iron stores. 1. Fullterm infants. Haematologia (Budap) 1986;19:197–205.
  62. Milman N, Agger AO, Nielsen OJ: Iron status markers and serum erythropoietin in 120 mothers and newborn infants. Acta Obstet Gynecol Scand 1994;73:200–204.
  63. Gaspar MJ, Ortega MR, Moreiras O: Relationship between iron status in pregnant women and their newborn babies. Acta Obstet Gynecol Scand 1993;72:534–537.
  64. Wallenburg HCS, Van Eijk: Effect of oral iron supplementation during pregnancy on maternal and fetal iron status. J Perinat Med 1984;12:7–12.
  65. Singla PN, Tyagi M, Shankar R, Dash D, Kumar A: Fetal iron status in maternal anemia. Acta Pediatr 1996;85:1327–1330.
  66. Kurtoglu S, Atabek ME, Gunes T, Akcakus M, Keskin M, Kocaoglu C: Relationship between cord blood levels of IGF-I and ferritin in healthy term neonates. J Pediatr Endocrinol Metab 2004;17:737–742.
  67. Tamura T, Hou J, Goldenberg RL, Johnston KE, Cliver SP: Gender difference in cord serum ferritin concentrations. Biol Neonate 1999;75:343–349.
  68. Stacy DL, Han P: Serum ferritin measurements and the degree of agreement using four techniques. Am J Clin Pathol 1992;98:511–515.
  69. Cohen J, Cohen P, West SG, Aiken LS: Applied Multiple Regression/Correlation Analysis for the Behavioral Sciences, ed 3. Mahwah, Erlbaum, 2003, pp 303–320.
  70. Georgieff MK, Wewerka SW, Nelson CA, deRegnier R-A: Iron status at 9 months of infants with low iron stores at birth. J Pediatr 2002;141:405–409.
  71. Kilbride J, Baker TG, Parapia LA, et al: 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.
  72. American Academy of Pediatrics Committee on Nutrition: Nutritional needs of the preterm infants; in Kleinman RE (ed): Pediatric Nutrition Handbook, ed 5. Chapel Hill, NC American Academy of Pediatrics, 2004, pp 23–54.
  73. Georgieff MK: Iron; in Hay WH Jr, Thureen P (eds): Neonatal Nutrition and Metabolism, ed 2. Cambridge, Cambridge University Press, 2006, pp 291–298.
  74. Cooke RW, Drury JA, Yoxall CW, James C: Blood transfusion and chronic lung disease in preterm infants. Eur J Pediatr 1997;156:47–50.
  75. 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.
  76. Saarinen UM, Siimes MA: Iron absorption from breast milk, Cow’s milk and iron- supplemented formula: an opportunistic use of changes in total body iron determined by hemoglobin, ferritin and body weight in 132 infants. Pediatr Res 1979;13:143–147.
  77. Calvo EB, Galindo AC, Aspres NB: Iron status in exclusively breast fed infants. Pediatrics 1992;90:375–379.
  78. Griffin IJ, Reid MM, McCormick KP, Cooke RJ: Zinc protoporphyrin/haem ratio and plasma ferritin in preterm infants. Arch Dis Child Fetal Neonatal Ed 2002;87:F49–F51.

    External Resources

  79. 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.

  

Author Contacts

Michael K. Georgieff, MD
MMC 39, D-136 Mayo Building
420 Delaware St. SE
Minneapolis, MN 55455 (USA)
Tel. +1 612 626 2971, Fax +1 612 624 8176, E-Mail georg001@umn.edu

  

Article Information

Published online: March 14, 2007
Number of Print Pages : 10
Number of Figures : 2, Number of Tables : 2, Number of References : 79

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 92, No. 2, Year 2007 (Cover Date: August 2007)

Journal Editor: Halliday, H.L. (Belfast)
ISSN: 1661–7800 (print), 1661–7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Background: Serum ferritin measurements are used in clinical populations to estimate total body iron stores and the risk of subsequent iron deficiency or overload. The lack of normative newborn serum ferritin concentration data between 23 and 41 weeks has led to difficulty in establishing the incidence and degree of abnormal iron status in the neonatal period. Objectives: The primary objective of this review was to summarize the maternal and gestational factors that determine ferritin concentrations in full-term and pre-term newborn infants and to generate comprehensive reference values. The secondary objective was to assess serum ferritin concentrations in newborn infants at risk for abnormal fetal iron metabolism, including maternal diabetes mellitus, intrauterine growth restriction and maternal smoking during pregnancy. Methods: Serum ferritin and gestational age data at birth from 457 low-risk pre-term and term infants of 23–41 weeks gestation obtained from 35 published studies reviewed from a period of 25 years and from recently collected data from our centers were assessed by regression analysis. Slopes and intercepts of the high-risk groups were compared with the standard curve. Results: Umbilical cord serum ferritin concentrations increased with advancing gestational age, from a mean of 63 µg/l at 23 weeks to 171 µg/l at 41 weeks gestation (p < 0.001). The infants of diabetic mothers had a lower intercept than the control infants (p < 0.001). Conclusions: Iron deficiency and overload have been implicated in neurodevelopmental impairments. Normative cord serum ferritin data may permit a more precise assessment of infants who are at risk for abnormal iron status at birth.

© 2007 S. Karger AG, Basel


  

Author Contacts

Michael K. Georgieff, MD
MMC 39, D-136 Mayo Building
420 Delaware St. SE
Minneapolis, MN 55455 (USA)
Tel. +1 612 626 2971, Fax +1 612 624 8176, E-Mail georg001@umn.edu

  

Article Information

Published online: March 14, 2007
Number of Print Pages : 10
Number of Figures : 2, Number of Tables : 2, Number of References : 79

  

Publication Details

Neonatology (Fetal and Neonatal Research)

Vol. 92, No. 2, Year 2007 (Cover Date: August 2007)

Journal Editor: Halliday, H.L. (Belfast)
ISSN: 1661–7800 (print), 1661–7819 (Online)

For additional information: http://www.karger.com/NEO


Article / Publication Details

First-Page Preview
Abstract of Review

Received: 7/11/2006
Accepted: 12/17/2006
Published online: 3/14/2007
Issue release date: August 2007

Number of Print Pages: 10
Number of Figures: 2
Number of Tables: 2

ISSN: 1661-7800 (Print)
eISSN: 1661-7819 (Online)

For additional information: http://www.karger.com/NEO


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Dallman PR: Biochemical basis for the manifestations of iron deficiency. Ann Rev Nutr 1986;6:13–40.
  2. Youdim MBH, Yehuda S: The neurochemical basis of cognitive deficits induced by brain iron deficiency: involvement of dopamine-opiate system. Cell Mol Biol 2000;46:491–500.
  3. Connor JR, Menzies SL: Altered cellular distribution of iron in the central nervous system of myelin deficient rats. Neuroscience 1990;34:265–271.
  4. Yu GSM, Steinkirchner TM, Rao GA, Larkin EC: Effect of prenatal iron deficiency on myelination in rat pups. Am J Pathol 1986;125:620–624.
  5. deUngria M, Rao R, Wobken JD, Luciana M, Georgieff MK: Perinatal iron deficiency decreases cytochrome c oxidase activity in selective regions of the brain. Pediatr Res 2000;48:169–176.
  6. Petry CD, Eaton MA, 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.
  7. Georgieff MK, Landon MB, Mills MM, Hedlund BE, Faassen AE, Schmidt RL, Ophoven JJ, Widness JA: Abnormal iron distribution in infants of diabetic mothers: spectrum and maternal antecedents. J Pediatr 1990;117:455–461.
  8. 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.
  9. Lozoff B, Jimenez E, Hagen J, Mollen E, Wolf AW: Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics 2000;105:e51
  10. Grantham-McGregor S, Ani C: A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:649S–668S.
  11. Fleming RE: Cord serum ferritin levels, fetal iron status, and neurodevelopmental outcomes: correlations and confounding variables. J Pediatr 2002;140:145–148.
  12. Tamura T, Goldenberg R, Hou J, Johnston K, Cliver SP, Ramsey SL, Nelson K: Cord serum ferritin concentrations and mental and psychomotor development of children at five years of age. J Pediatr 2002;140:165–170.
  13. Siddappa AM, Georgieff MK, Wewerka S, Worwa C, Nelson CA, deRegnier R-A: Auditory recognition memory in iron-deficient infants of diabetic mothers. Pediatr Res 2004;55:1034–1041.
  14. 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.
  15. Beard J, deRegnier RA, Shaw M, Rao R, Georgieff M: Diagnosis of iron deficiency in infancy. Lab Med 2007;38:103–108.

    External Resources

  16. Lott DG, Zimmerman MB, Labbe RF, Kling PJ, et al: Erythrocyte zinc protoporphyrin is elevated with prematurity and fetal hypoxemia. Pediatrics 2005;116:414–422.
  17. Juul.SE, Zerzan JC, Strandiord TP, Woodrum DE: Zinc protoporphyrin/heme as an indicator of iron status in nicu patients. J Pediatr 2003;142:273–278.
  18. Siimes MA, Addiego JE, Dallman PR: Ferritin in serum: diagnosis of iron deficiency and iron overload in infants and children. Blood 1974;43:581–590.
  19. Rios E, Lipschitz DA, Cook JD, Smith NJ: Relationship of maternal and infant iron stores as assessed by determination of plasma ferritin. Pediatrics 1975;55:694.
  20. Lipschitz DA, Cook JD, Finch CA: A clinical evaluation of serum ferritin as an index of iron stores. N Engl J Med 1974;290:1213–1216.
  21. Walters GO, Miller FM, Worwood M: Serum ferritin concentration and iron stores in normal subjects. J Clin Pathol 1973;26:770–772.
  22. Cook JD: Clinical evaluation of iron deficiency. Semin Hematol 1982;19:6–18.
  23. MacPhail AP, Charlton RW, Bothwell TH, Torrance JD: The relationship between maternal and infant iron status. Scand J Hematol 1980;25:141–150.
  24. Baynes RD: Assessment of iron status. Clin Chem 1996;29:209–215.
  25. Cook JD, Skikne BS: Iron deficiency: definition and diagnosis. J Intern Med 1989;226:349–355.
  26. Bothwell TH: Iron requirements during pregnancy and strategies to meet them. Am J Clin Nutr 2000;72:257S–264S.
  27. Oski FA: Iron deficiency in infancy and childhood. New Engl J Med 1993;329:190–193.
  28. Widdowsen EM, Sray CM: Chemical development in utero. Arch Dis Child 1951;26:205–214.
  29. Siimes ASI, 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.
  30. Messer RD, Russo AM, McWhirter WR, Spragemeyer D, Halliday JW: Serum ferritin in term and preterm infants. Aust Paediatr J 1980;16:185–188.
  31. Jansson L, Holmberg L, Ekman R: Variation of serum ferritin in low birth weight infants with maternal ferritin, birth weight and gestational age. Acta Haematol 1979;62:273–277.
  32. Sweet DG, Tubman TRJ, Lappin TRJ, Halliday HL: Study of maternal influences on fetal iron status at term using cord blood transferrin receptors. Arch Dis Child Fetal Neonatal Ed 2001;84:F40–F43.
  33. Carpani G, Marini F, Buscaglia M, Sinigaglia E, Moroni G: Red cell and plasma ferritin in normal fetuses at different ages of gestation. Eur J Haematol 1992;49:260–262.
  34. Haga P: Plasma ferritin concentrations in preterm infants in cord blood and during the early anemia of prematurity. Acta Pediatr Scand 1980;69:637–641.
  35. Hussain MAM, Gaafar TH, Laulight M, Hoffbrand AV: Relation of maternal and cord blood ferritin. Arch Dis Child 1977;52:782–784.
  36. Lao TT, Loong EPL, Chin RKH, Lam CWK, Lam YM: Relationship between newborn and maternal iron status and hematological indices. Biol Neonate 1991;60:303–307.
  37. Kelly AM, MacDonald DJ, Mc Dougall AN: Observations on maternal and fetal ferritin concentrations at term. Br J Obstet Gynaecol 1978;85:338–343.
  38. Agarwal RMD, Tripathi AM, Agarwal KN: Cord blood hemoglobin, iron and ferritin status in maternal anemia. Acta Paediatr Scand 1983;72:545–548.
  39. Erdem A, Erdem M, Arslan M, Yazici G, Eskandari R, Himmetoglu O: The effect of maternal anemia and iron deficiency on fetal erythropoiesis: comparison between serum erythropoietin, hemoglobin and ferritin levels in mothers and newborns. J Matern Fetal Neonatal Med 2002;11:329–332.
  40. Ziaei S, Hatefnia E, Togeh GH: Iron status in newborns born to iron-deficient mothers. Iran J Med Sci 2002;28:62–64.
  41. Puolakka J, Janne O, Vihko R: Evaluation by serum ferritin assay of the influence of maternal iron stores on the iron status of newborns and infants. Acta Obstet Gynecol Scand Suppl 1980;95:53–56.
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    External Resources

  79. 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.