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.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
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.
Panagiotou JP, Douros K. Clinicolaboratory findings and treatment of iron-deficiency anemia in childhood. Pediatr Hematol Oncol. 2004;21(6):519–32.
Saloojee H, Pettifor JM. Iron deficiency and impaired child development. BMJ. 2001;23:1377–8.
Ghosh K. Non-haematological effects of iron deficiency anemia—a persective. Indian J Med Sci. 2006;60(1):30–7.
Beard J. Iron deficiency alters brain development and functioning. J Nutr. 2003;133:1468–72.
Lozoff B. Perinatal iron deficiency and the developing brain. Pediatr Res. 2000;48:137–9.
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.
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.
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.
Sarici SU, Serdar MA, Dundaroz MR, et al. Brainstem auditory-evoked potentials in iron-deficiency anemia. Pediatr Neurol. 2001;24:205–8.
Oski FA, Honig AC. The effects of therapy on the developmental scores of iron deficient infants. J Pediatr. 1978;92:21–5.
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.
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.
Lozoff B, Wolf AW, Jimenez J. Iron deficiency anemia and infant development: effects of extended oral iron therapy. J Pediatr. 1996;129:328–9.
Deniard AS, List A, Lindgren B, et al. Xognitive deficient and iron deficient anemic children. J Pediatr. 1986;108:681–9.
Lozoff B, Jimenez J, Wolf AW. Long-term developmental outcome of infants with iron deficiency. N Engl J Med. 1991;325:687–94.
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.
Palti H, Pevsner B, Adler B. Does anemia in infancy affect achievment on development and intelligence tests. Hum Biol. 1983;55:189–94.
Winberg J, Levine S, Dollman PR. Long term consequences of iron deficiency in the rat. Pharmacol Biochem Behav. 1979;11:631–8.
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.
Williomson AM, Ng KT. Behavioral effects of iron deficiency in the adult rat. Physiol Behav. 1980;24:561–7.
Beard J, Erikson KM, Jones BC. Neonatal iron deficiency results in irreversible changes in dopamine function in rats. J Nutr. 2003;133:1174–9.
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.
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.
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.
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.
Pollitt E, Soemantri AG, Yunis F, et al. Cognitive effects of iron-deficiency anaemia. Lancet. 1985;19:158.
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.
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.
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.
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.
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.
Coltman CA. Pagophagia and iron lack. J Am Med Assoc. 1969;207:513.
Carlander. Aetiology of pica. Lancet. 1959;ii:569.
Reynolds RD, Binder HJ, Miller MB, et al. Pagophagia and iron deficiency anemia. Ann Intern Med. 1968;69(3):435–40.
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.
Brown WD, Dyment PG. Pagophagia and iron deficiency anemia in adolescent girls. Pediatrics. 1972;49:766–7.
Bridge EM, Livingston S, Tietze C. Breath-holding spells: their relationship to syncope, convulsions, and other phenomena. J Pediatr. 1943;23:539–61.
DiMario FJ. Breath-holding spells in childhood. Am J Dis Child. 1992;146:125–31.
Anil BG, Nedunchezian K, Jayanthini V. Breath holding spells: evaluation of autonomic nervous system function. Indian Pediatr. 2005;42:923–7.
Holowach J, Thurston DL. Breath-holding spells and anaemia. N Engl J Med. 1963;268:21–3.
Bhatia MS, Singhal PK, Dhar NK, et al. Breath-holding spells: an analysis of 50 cases. Indian J Pediatr. 1990;27:1073–9.
Colina KF, Abelson HT. Resolution of breath-holding spells with treatment of concomittant anaemia. J Pediatr. 1995;126:395–7.
Daoud AS, Batieha A, Al-Sheyyab M, et al. Effectiveness of iron therapy on breath-holding spells. J Pediatr. 1997;130:547–50.
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.
Mocan MC, Mocan H, Aslan Y, et al. Iron therapy in breath-holding spells and cerebral erythropoetin [letter]. J Pediatr. 1998;133:583–4.
Berg AT. Febrile seizures and epilepsy: the contribution of epidemiology. Paediatr Perinat Epidemiol. 1992;6:145–52.
Kobrinski N, Yager JY, Cheang MS, et al. Does iron deficiency raise the seizure threshold? J Child Neurol. 1995;10(2):105–9.
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.
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.
Naved-ur-Rehman, Billoo AG. Association between iron deficiency anemia and febrile seizures. J Coll Physicians Surg Pak. 2005;15(6):338–40.
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.
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.
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.
Hartfield DS, Lowry NJ, Keene DL, et al. Iron deficiency: a cause of stroke in infants and children. Pediatr Neurol. 1997;16:50–3.
Akins PT, Glenn S, Nemeth PM, et al. Carotid artery thrombus associated with severe iron-deficiency anemia and thrombocytosis. Stroke. 1996;27:1002–5.
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.
Maguire JL, deVeber G, Parkin PC. Association between iron-deficiency anemia and stroke in young children. Pediatr. 2007;120:1053–7.
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.
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.
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.
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.
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.
Earley CJ, Heckler D, Allen RP. The treatment of restless legs syndrome with intravenous iron dextran. Sleep Med. 2004;5:231–5.
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.
Trenkwalder C, Hogl B, Winkelmann J. Recent advances in diagnosis, genetics and treatment of Restless leg Syndrome. J Neurol. 2009;256:539–53.
Oppenheimer SJ. Iron and its relation to immunity and infectious disease. J Nutr. 2001;131:616S–35S.
Oppenheimer SJ, Hendrickse RG. The clinical effects of iron deficiency and iron supplementation. Nutr Abstr Rev. 1983;53:585–98.
Harju E. Empty iron stores as a significant risk factor in abdominal surgery. J Parenter Enteral Nutr. 1988;12:282–5.
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.
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.
MacKay HM. Anaemia in infancy; its prevalence and prevention. Arch Dis Child. 1928;3:117–47.
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.
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.
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.
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.
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.
National Family Health Survey-3, 2005–2006. International Institute of Population Sciences, Mumbai 2005.
About this article
Cite this article
Yadav, D., Chandra, J. Iron Deficiency: Beyond Anemia. Indian J Pediatr 78, 65–72 (2011). https://doi.org/10.1007/s12098-010-0129-7
- Iron deficiency anemia (IDA)
- Breath holding spells (BHS)
- Febrile seizure
- Restless leg syndrome