The Indian Journal of Pediatrics

, Volume 78, Issue 1, pp 65–72 | Cite as

Iron Deficiency: Beyond Anemia

Symposium On Nutritional Anemia - II
First Online:
Received:
Accepted:

Abstract

Iron deficiency is the most common nutritional disorder affecting at least one third of world’s population. Though anemia is common manifestation of iron deficiency, other effects of iron deficiency on various tissues, organs and systems are usually under recognized. Impaired brain development and cognitive, behavioural and psychomotor impairment are most worrisome manifestations of iron deficiency. Studies have demonstrated that some of these changes occurring during period of brain growth spurt (<2 years age) may be irreversible. Association of iron deficiency with febrile seizures, pica, breath holding spells, restless leg syndrome and thrombosis is increasingly being recognized. Impaired cell-mediated immunity and bactericidal function are generally noted in iron-deficient persons; however, the findings are inconsistent. Despite proven reversible functional immunological defects in vitro studies, a clinically important relationship between states of iron deficiency and susceptibility to infections remains controversial. Studies from malaria endemic regions have reported increased incidence of malaria in association with iron supplementation. These and some other aspects of iron deficiency are reviewed in this article.

Keywords

Iron deficiency anemia (IDA) Cognition Breath holding spells (BHS) Pica Febrile seizure Thrombosis Restless leg syndrome Infections 
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References

  1. 1.
    Xiaoxi Z, Wu T. Iron supplementation for iron deficiency anemia in children (Protocol). The Cochrane Database of Systemic Reviews 2007, Issue 2. Art no CD006465.Google Scholar
  2. 2.
    Panagiotou JP, Douros K. Clinicolaboratory findings and treatment of iron-deficiency anemia in childhood. Pediatr Hematol Oncol. 2004;21(6):519–32.CrossRefGoogle Scholar
  3. 3.
    Saloojee H, Pettifor JM. Iron deficiency and impaired child development. BMJ. 2001;23:1377–8.CrossRefGoogle Scholar
  4. 4.
    Ghosh K. Non-haematological effects of iron deficiency anemia—a persective. Indian J Med Sci. 2006;60(1):30–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003;133:1468–72.Google Scholar
  6. 6.
    Lozoff B. Perinatal iron deficiency and the developing brain. Pediatr Res. 2000;48:137–9.CrossRefPubMedGoogle Scholar
  7. 7.
    Roncagliolo M, Garrido M, Walter T, et al. Evidence of altered central nervous system development in infants with iron deficiency anemia at 6 month: delayed maturation of auditory brainstem responses. Am J Clin Nutr. 1998;68:683–90.PubMedGoogle Scholar
  8. 8.
    Algarin C, Peirano P, Garrido M, et al. Iron deficiency anemia in infancy: long-lasting effects on auditory and visual system functioning. Pediatr Res. 2003;53:217–23.CrossRefPubMedGoogle Scholar
  9. 9.
    Monga M, Walia V, Chandra J, et al. Effect of iron deficiency anemia on visual evoked potential of growing children. Brain and Development 2010;32(3):213–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Sarici SU, Serdar MA, Dundaroz MR, et al. Brainstem auditory-evoked potentials in iron-deficiency anemia. Pediatr Neurol. 2001;24:205–8.CrossRefPubMedGoogle Scholar
  11. 11.
    Oski FA, Honig AC. The effects of therapy on the developmental scores of iron deficient infants. J Pediatr. 1978;92:21–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Lozoff B, Viteri F, Urrutia J. The effects of short-term oral iron therapy on developmental deficits in iron deficient anemic infants. J Pediatr. 1982;100:351–7.CrossRefPubMedGoogle Scholar
  13. 13.
    Lozoff B, Brittenham GM, Wolf AW, et al. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics. 1987;79:981–95.PubMedGoogle Scholar
  14. 14.
    Lozoff B, Wolf AW, Jimenez J. Iron deficiency anemia and infant development: effects of extended oral iron therapy. J Pediatr. 1996;129:328–9.Google Scholar
  15. 15.
    Deniard AS, List A, Lindgren B, et al. Xognitive deficient and iron deficient anemic children. J Pediatr. 1986;108:681–9.CrossRefGoogle Scholar
  16. 16.
    Lozoff B, Jimenez J, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med. 1991;325:687–94.CrossRefPubMedGoogle Scholar
  17. 17.
    Lozoff B, Jimenez J, hagen J, et al. Poorer behavioral and developmental outcome more than 10 years after treatment for iron deficiency in infancy. Pediatrics. 2000;105:e51.CrossRefPubMedGoogle Scholar
  18. 18.
    Palti H, Pevsner B, Adler B. Does anemia in infancy affect achievment on development and intelligence tests. Hum Biol. 1983;55:189–94.Google Scholar
  19. 19.
    Winberg J, Levine S, Dollman PR. Long term consequences of iron deficiency in the rat. Pharmacol Biochem Behav. 1979;11:631–8.CrossRefGoogle Scholar
  20. 20.
    Winberg J, Dollman PR, Levine S. Iron deficiency during early development in the rat: behavioral and physiological consequences. Pharmacol Biochem Behav. 1980;12:493–502.CrossRefGoogle Scholar
  21. 21.
    Williomson AM, Ng KT. Behavioral effects of iron deficiency in the adult rat. Physiol Behav. 1980;24:561–7.CrossRefGoogle Scholar
  22. 22.
    Beard J, Erikson KM, Jones BC. Neonatal iron deficiency results in irreversible changes in dopamine function in rats. J Nutr. 2003;133:1174–9.PubMedGoogle Scholar
  23. 23.
    Unger EL, Paul T, Murray-Kolb LE, et al. Early iron deficiency alters sensorimotor development and brain monoamines in rats. J Nutr. 2007;137:118–24.PubMedGoogle Scholar
  24. 24.
    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–68S.PubMedGoogle Scholar
  25. 25.
    Sachdev HPS, Gera T, Nestel P. Effect of iron supplementation on mental and motor development in children: systematic review of randomized controlled trials. Public Health Nutr. 2005;8:117–32.CrossRefPubMedGoogle Scholar
  26. 26.
    McCann JC, Ames BN. An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioural function. Am J Clin Nutr. 2007;85:931–45.PubMedGoogle Scholar
  27. 27.
    Pollitt E, Soemantri AG, Yunis F, et al. Cognitive effects of iron-deficiency anaemia. Lancet. 1985;19:158.CrossRefGoogle Scholar
  28. 28.
    Seshadri S, Gopaldes T. Impact of iron supplementation on cognitive functions in pre-school and school-aged children: the Indian experience. Am J Clin Nutr. 1989;50:675–86.PubMedGoogle Scholar
  29. 29.
    Halterman JS, Kaczorowski JM, Aligne CA, et al. Iron deficiency and cognitive achievement among school aged children and adolescents in the United States. Pediatrics. 2001;107:1381–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Bruner AB, Joffe A, Duggan AK, et al. Randomized study of cognitive effects of iron supplementation in non-anemic iron deficient adolescent girls. Lancet. 1996;348:992–6.CrossRefPubMedGoogle Scholar
  31. 31.
    Friel JK, Aziz K, Andrews WL, et al. A double-masked, randomized control trial of iron supplementation in early infancy in healthy term breast-fed infants. J Pediatr. 2003;143:582–6.CrossRefPubMedGoogle Scholar
  32. 32.
    Lozoff B, De Andraca I, Castillo M, et al. Behavioral and developmental effects of preventing iron-deficiency anemia in healthy full-term infants. Pediatrics. 2003;112:846–54.PubMedGoogle Scholar
  33. 33.
    Coltman CA. Pagophagia and iron lack. J Am Med Assoc. 1969;207:513.CrossRefGoogle Scholar
  34. 34.
    Carlander. Aetiology of pica. Lancet. 1959;ii:569.CrossRefGoogle Scholar
  35. 35.
    Reynolds RD, Binder HJ, Miller MB, et al. Pagophagia and iron deficiency anemia. Ann Intern Med. 1968;69(3):435–40.PubMedGoogle Scholar
  36. 36.
    Kettaneh A, Eclache V, Fain O, et al. Pica and food craving in patients with iron deficiency anemia: a case control study in France. Am J Med. 2005;118:185–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Brown WD, Dyment PG. Pagophagia and iron deficiency anemia in adolescent girls. Pediatrics. 1972;49:766–7.PubMedGoogle Scholar
  38. 38.
    Bridge EM, Livingston S, Tietze C. Breath-holding spells: their relationship to syncope, convulsions, and other phenomena. J Pediatr. 1943;23:539–61.CrossRefGoogle Scholar
  39. 39.
    DiMario FJ. Breath-holding spells in childhood. Am J Dis Child. 1992;146:125–31.PubMedGoogle Scholar
  40. 40.
    Anil BG, Nedunchezian K, Jayanthini V. Breath holding spells: evaluation of autonomic nervous system function. Indian Pediatr. 2005;42:923–7.PubMedGoogle Scholar
  41. 41.
    Holowach J, Thurston DL. Breath-holding spells and anaemia. N Engl J Med. 1963;268:21–3.CrossRefPubMedGoogle Scholar
  42. 42.
    Bhatia MS, Singhal PK, Dhar NK, et al. Breath-holding spells: an analysis of 50 cases. Indian J Pediatr. 1990;27:1073–9.Google Scholar
  43. 43.
    Colina KF, Abelson HT. Resolution of breath-holding spells with treatment of concomittant anaemia. J Pediatr. 1995;126:395–7.CrossRefPubMedGoogle Scholar
  44. 44.
    Daoud AS, Batieha A, Al-Sheyyab M, et al. Effectiveness of iron therapy on breath-holding spells. J Pediatr. 1997;130:547–50.CrossRefPubMedGoogle Scholar
  45. 45.
    Mocan H, Yildiran A, Orhan F, et al. Breath holding spells in 91 children and response to treatment with iron. Arch Dis Child. 1999;81:261–2.CrossRefPubMedGoogle Scholar
  46. 46.
    Mocan MC, Mocan H, Aslan Y, et al. Iron therapy in breath-holding spells and cerebral erythropoetin [letter]. J Pediatr. 1998;133:583–4.PubMedGoogle Scholar
  47. 47.
    Berg AT. Febrile seizures and epilepsy: the contribution of epidemiology. Paediatr Perinat Epidemiol. 1992;6:145–52.CrossRefPubMedGoogle Scholar
  48. 48.
    Kobrinski N, Yager JY, Cheang MS, et al. Does iron deficiency raise the seizure threshold? J Child Neurol. 1995;10(2):105–9.CrossRefGoogle Scholar
  49. 49.
    Pisacane A, Sansor R, Impagliazzo N, et al. Iron deficiency anemia and febrile convulsion: case control study in children under 2 years. BMJ. 1996;313:343.PubMedGoogle Scholar
  50. 50.
    Daoud AS, Batieha A, Abu-Ekteish F, et al. Iron status: a possible risk factor for the first febrile seizure. Epilepsia. 2002;43(7):740–3.CrossRefPubMedGoogle Scholar
  51. 51.
    Naved-ur-Rehman, Billoo AG. Association between iron deficiency anemia and febrile seizures. J Coll Physicians Surg Pak. 2005;15(6):338–40.Google Scholar
  52. 52.
    Nagai T, Komatsu N, Sakata Y, et al. Iron deficiency anemia with marked thrombocytosis complicated by central retinal vein occlusion. Intern Med. 2005;44:1090–2.CrossRefPubMedGoogle Scholar
  53. 53.
    Kinoshita Y, Taniura S, Shishido H, et al. Cerebral venous sinus thrombosis associated with iron deficiency: two case reports. Neurol Med Chir (Tokyo). 2006;46:589–93.CrossRefGoogle Scholar
  54. 54.
    Benedict SL, Bonkowsky JL, Thompson JA, et al. Cerebral sinovenous thrombosis in children: another reason to treat iron deficiency anemia. J Child Neurol. 2004;19:526–31.CrossRefPubMedGoogle Scholar
  55. 55.
    Hartfield DS, Lowry NJ, Keene DL, et al. Iron deficiency: a cause of stroke in infants and children. Pediatr Neurol. 1997;16:50–3.CrossRefPubMedGoogle Scholar
  56. 56.
    Akins PT, Glenn S, Nemeth PM, et al. Carotid artery thrombus associated with severe iron-deficiency anemia and thrombocytosis. Stroke. 1996;27:1002–5.PubMedGoogle Scholar
  57. 57.
    Belman AL, Roque CT, Ancona R, et al. Cerebral venous thrombosis in a child with iron deficiency anemia and thrombocytosis. Stroke. 1990;21:488–93.PubMedGoogle Scholar
  58. 58.
    Maguire JL, deVeber G, Parkin PC. Association between iron-deficiency anemia and stroke in young children. Pediatr. 2007;120:1053–7.CrossRefGoogle Scholar
  59. 59.
    Makhija S, Aneja S, Tripathi RP, et al. Etiological profile of stroke and its relation with prothrombotic states. Indian J Pediatr. 2008;75(6):579–84.CrossRefPubMedGoogle Scholar
  60. 60.
    Sebire G, Tabarki B, Saunders DE, Leroy I, Leisner R, Martin SC, et al. Cerebral venous sinus thrombosis in children: risk factors, presentation, diagnosis and outcome. Brain. 2005;128:477–89.CrossRefPubMedGoogle Scholar
  61. 61.
    Bilic E, Bilic E. Amino acid sequence homology of thrombopoietin and erythropoietin may explain thrombocytosis in children with iron deficiency anemia. J Pediatr Hematol Oncol. 2003;25:675–6.CrossRefPubMedGoogle Scholar
  62. 62.
    Tekin D, Yavuzer S, Tekin M, et al. Possible effects of antioxidant status on increased platelet aggregation in childhood iron-deficiency anemia. Pediatr Int. 2001;43:74–7.CrossRefPubMedGoogle Scholar
  63. 63.
    Balci K, Utku U, Asil T, et al. Deep cerebral vein thrombosis associated with iron deficiency anaemia in adults. J Clin Neurosci. 2007;14:181–4.CrossRefPubMedGoogle Scholar
  64. 64.
    Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med. 2004;5:231–5.CrossRefPubMedGoogle Scholar
  65. 65.
    Sloand JA, Shelly MA, Feigin A, et al. A doubleblind, placebo-controlled trial of intravenous iron dextran therapy in patients with ESRD and restless legs syndrome. Am J Kidney Dis. 2004;43:663–70.CrossRefPubMedGoogle Scholar
  66. 66.
    Trenkwalder C, Hogl B, Winkelmann J. Recent advances in diagnosis, genetics and treatment of Restless leg Syndrome. J Neurol. 2009;256:539–53.CrossRefPubMedGoogle Scholar
  67. 67.
    Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr. 2001;131:616S–35S.PubMedGoogle Scholar
  68. 68.
    Oppenheimer SJ, Hendrickse RG. The clinical effects of iron deficiency and iron supplementation. Nutr Abstr Rev. 1983;53:585–98.Google Scholar
  69. 69.
    Harju E. Empty iron stores as a significant risk factor in abdominal surgery. J Parenter Enteral Nutr. 1988;12:282–5.CrossRefGoogle Scholar
  70. 70.
    Oppenheimer SJ, Gibson FD, Macfarlane SBJ, et al. Iron supplementation increases prevalence and effects of malaria. Report on clinical studies in Papua New Guinea. Trans R Soc Trop Med Hyg. 1986;80:603–12.CrossRefPubMedGoogle Scholar
  71. 71.
    Oppenheimer SJ, Macfarlane SBJ, Moody JB, et al. Effect of iron prophylaxis on morbidity due to infectious disease. Report on clinical studies in Papua New Guinea. Trans R Soc Trop Med Hyg. 1986;80:596–602.CrossRefPubMedGoogle Scholar
  72. 72.
    MacKay HM. Anaemia in infancy; its prevalence and prevention. Arch Dis Child. 1928;3:117–47.CrossRefPubMedGoogle Scholar
  73. 73.
    Andelman MB, Sered BR. Utilization of dietary iron by term infants. A study of 1, 048 infants from a low socioeconomic population. Am J Dis Child. 1966;111:45–55.PubMedGoogle Scholar
  74. 74.
    Power HM, Heese HD, Beatty DW, et al. Iron fortification of infant formula: the effect on iron status and immune function. Ann Trop Paediatr. 1991;11:57–66.PubMedGoogle Scholar
  75. 75.
    Hemminki E, Nemet K, Horvath M, et al. Impact of iron fortification of milk formulas on infant’s growth and health. Nutr Res. 1995;15:491–503.CrossRefGoogle Scholar
  76. 76.
    Javaid N, Haschke F, Pietschnig B, et al. Interactions between infections, malnutrition and iron nutritional status in Pakistani infants. Acta Paediatr Scand Suppl. 1991;80:141–50.CrossRefGoogle Scholar
  77. 77.
    Mitra AK, Akramuzzaman SM, Fuchs GJ, et al. Long-term oral supplementation with iron is not harmful for young children in a poor community of Bangladesh. J Nutr. 1997;127:1451–5.PubMedGoogle Scholar
  78. 78.
    National Family Health Survey-3, 2005–2006. International Institute of Population Sciences, Mumbai 2005.Google Scholar

Copyright information

© Dr. K C Chaudhuri Foundation 2010

Authors and Affiliations

  1. 1.Department of PediatricsKalawati Saran Children’s Hospital and Lady Hardinge Medical CollegeNew DelhiIndia
  2. 2.Lady Hardinge Medical CollegeNew DelhiIndia

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