Hostname: page-component-cd9895bd7-8ctnn Total loading time: 0 Render date: 2024-12-26T18:39:14.594Z Has data issue: false hasContentIssue false
  • English
  • Français

Effect of iron supplementation on mental and motor development in children: systematic review of randomised controlled trials

Published online by Cambridge University Press:  02 January 2007

HPS Sachdev ,
Tarun Gera  and
Penelope Nestel
HPS Sachdev*
Affiliation:
Division of Clinical Epidemiology, Department of Pediatrics, Maulana Azad Medical College, New Delhi 110 002, India
Tarun Gera
Affiliation:
SL Jain Hospital, New Delhi 1 10 052, India
Penelope Nestel
Affiliation:
HarvestPlus, International Food Policy Research Institute, 2033 K Street NW, Washington, DC 20006-1002, USA
*
*Corresponding author: Email [email protected]
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Objective

To evaluate the effect of iron supplementation on mental and motor development in children through a systematic review of randomised controlled trials (RCTs).

Data sources

Electronic databases, personal files, hand search of reviews, bibliographies of books, abstracts and proceedings of international conferences.

Review methods

RCTs with interventions that included oral or parenteral iron supplementation, fortified formula milk or cereals were evaluated. The outcomes studied were mental and motor development scores and various individual development tests employed, including Bayley mental and psychomotor development indices and intelligence quotient.

Results

The pooled estimate (random effects model) of mental development score standardised mean difference (SMD) was 0.30 (95% confidence interval (CI) 0.15 to 0.46, P < 0.001; P < 0.001 for heterogeneity). Initial anaemia and iron-deficiency anaemia were significant explanatory variables for heterogeneity. The pooled estimate of Bayley Mental Development Index (weighted mean difference) in younger children (<27 months old) was 0.95 (95% CI −0.56 to 2.46, P = 0.22; P = 0.016 for heterogeneity). For intelligence quotient scores (≥8 years age), the pooled SMD was 0.41 (95% CI 0.20 to 0.62, P < 0.001; P = 0.07 for heterogeneity). There was no effect of iron supplementation on motor development score (SMD 0.09, 95% CI -0.08 to 0.26, P = 0.28; P = 0.028 for heterogeneity).

Conclusions

Iron supplementation improves mental development score modestly. This effect is particularly apparent for intelligence tests above 7 years of age and in initially anaemic or iron-deficient anaemic subjects. There is no convincing evidence that iron treatment has an effect on mental development in children below 27 months of age or on motor development.

Keywords

AnaemiaCognitionIrondeficiencyIron supplementationMental developmentMeta-analysisMotor developmentRandomised controlled trials
Type
Research Article
Information
Public Health Nutrition , Volume 8 , Issue 2 , April 2005 , pp. 117 - 132
Copyright
Copyright © The Authors 2005

References

1Yehuda, S, Youdim, MBH, Mostofsky, DI. Brain iron deficiency causes reduced learning capacity in rats. Pharmacology, Biochemistry, and Behavior 1986; 25 141–4.CrossRefGoogle ScholarPubMed
2Beard, JL, Connor, JR, Jones, BC. Brain iron: location and function. Progress in Food & Nutrition Science 1993; 17: 183–221Google ScholarPubMed
3Beard, JL, Connor, JR, Jones, BC. Iron in the brain. Nutrition Reviews 1993; 51: 157–70.CrossRefGoogle ScholarPubMed
4Connor, JR, Menzies, SL. Relationship of iron to oligodendrocytes and myelination. Glia 1996; 17: 83–93.3.0.CO;2-7>CrossRefGoogle ScholarPubMed
5Lansdown, R, Wharton, BA. Iron and mental and motor behaviour in children. In: Iron, Nutrition and Physiological Significance: Report of the British Nutrition Task Force. London: Chapman and Hall, 1995; 65–78.Google Scholar
6Grantham-McGregor, S, Ani, C. A review of studies on the effect of iron deficiency on cognitive development in children. Journal of Nutrition 2001; 131: 649S–68S.CrossRefGoogle ScholarPubMed
7Logan, S, Martins, S, Gilbert, R. Iron therapy for improving psychomotor development and cognitive function in children under the age of three with iron deficiency anaemia (Cochrane Review).In: The Cochrane Library, Issue 4. Oxford: Update Software, 2001.Google Scholar
8Juni, P, Altman, DG, Egger, M. Assessing the quality of randomised controlled trials. In: Egger, M, Smith, GD, Altman, DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. London: BMJ Publishing, 2001; 87–108.CrossRefGoogle Scholar
9Clarke, M, Oxman, AD, eds. Assessment of study quality. Cochrane Reviewers Handbook 4.1.1, updated December 2000. In: The Cochrane Library, Issue 1. Oxford: Update Software, 2001.Google Scholar
10Follmann, D, Elliott, P, Suh, I, Cutler, J. Variance imputation for overviews of clinical trials with continuous response. Journal of Clinical Epidemiology 1992; 45: 769–73.CrossRefGoogle ScholarPubMed
11Sterne, JAC, Egger, M, Smith, GD. Investigating and dealing with publication and other biases and other biases. In: Egger, M, Smith, GD, Altman, DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. London: BMJ Publishing, 2001; 189–208.CrossRefGoogle Scholar
12Sterne, JAC, Bradburn, MJ, Egger, M. Meta-analysis in STATATM. In: Egger, M, Smith, GD, Altman, DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. London: BMJ Publishing, 2001; 347–69.CrossRefGoogle Scholar
13Oski, FA, Honig, AS. The effects of therapy on the developmental scores of iron-deficient infants. Journal of Pediatrics 1978; 92: 21–5.CrossRefGoogle Scholar
14Dienard, AS, List, A, Lindgren, B, Hunt, JV, Chang, PN. Cognitive deficits in iron-deficient and iron deficient anemic children. Journal of Pediatrics 1986; 108: 681–9.CrossRefGoogle Scholar
15Pollitt, E, Hathirat, P, Kotchabhakdi, NJ, Missell, L, Valyasevi, A. Iron deficiency and educational achievement in Thailand. American Journal of Clinical Nutrition 1989; 50: 687–97.CrossRefGoogle ScholarPubMed
16Cantwell, RJ. The long-term neurological sequelae of anaemia in infancy. Pediatric Research 1974; 342: 68.Google Scholar
17Bruner, AB, Joffe, A, Duggan, AK, Casella, JF, Brandt, J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet 1996; 348: 992–6.CrossRefGoogle ScholarPubMed
18Oski, FA, Honig, AS, Helu, B, Howanitz, P. Effect of iron therapy on behavior performance in nonanemic, iron-deficient infants. Pediatrics 1983; 71: 877–80.CrossRefGoogle Scholar
19Pollitt, E, Soemantri, AG, Yunis, F, Scrimshaw, NS. Cognitive effects of iron deficiency anaemia. Lancet 1985; 1: 158.CrossRefGoogle ScholarPubMed
20Lozoff, B, Brittenham, GM, Wolf, AW, McClish, DK, Kuhnert, PM, Jimenez, R, et al. Iron deficiency anemia and iron therapy effects on infant developmental test performance. Pediatrics 1987; 79: 981–95.CrossRefGoogle ScholarPubMed
21Seshadri, S, Gopaldas, T. Impact of iron supplementation on cognitive functions in preschool and school-aged children: the Indian experience. American Journal of Clinical Nutrition 1989; 50(Suppl. 3): 675–84.CrossRefGoogle ScholarPubMed
22Heywood, A, Oppenheimer, S, Heywood, P, Jolley, D. Behavioral effects of iron supplementation in infants in Madang, Papua New Guinea. American Journal of Clinical Nutrition 1989; 50(Suppl. 3): 630–7.CrossRefGoogle ScholarPubMed
23Boivin, MJ, Giordani, B. Improvements in cognitive performance for school children in Zaire, Africa, following an iron supplement and treatment for intestinal parasites. Journal of Pediatric Psychology 1993; 18: 249–64.CrossRefGoogle ScholarPubMed
24Lozoff, B, Wolf, AW, Jimenez, E. Iron deficiency anemia and infant development: effects of extended oral iron therapy. Journal of Pediatrics 1996; 129: 382–9.CrossRefGoogle ScholarPubMed
25Lynn, R, Harland, P. A positive effect of iron supplementation on the IQs of iron deficient children. Personality and Individual Differences 1998; 24: 883–5.CrossRefGoogle Scholar
26Williams, J, Wolff, A, Daly, A, Macdonald, A, Aukett, A, Booth, AW. Iron supplemented formula milk related to reduction in psychomotor decline in infants from inner city areas: randomised study. British Medical Journal 1999; 318: 693–7.CrossRefGoogle ScholarPubMed
27Walka, H, Triana, N, Jahari, AB, Husaini, AM, Pollitt, E. Effects of an energy and micronutrient supplement on play behaviour in undernourished children in Indonesia. European Journal of Clinical Nutrition 2000; 54(Suppl. 2): S91–106.CrossRefGoogle ScholarPubMed
28Pollitt, E, Jahari, A, Walka, H. A developmental view of the effects of an energy and micronutrient supplement in undernourished children in Indonesia. European Journal of Clinical Nutrition 2000; 54(Suppl. 2): S107–13.CrossRefGoogle ScholarPubMed
29Lozoff, B, De Andraca, I, Castillo, M, Smith, JB, Walter, T, Pino, P. Behavioral and developmental effects of preventing iron deficiency anemia in healthy full-term infants. Pediatrics 2003; 112: 846–54.CrossRefGoogle ScholarPubMed
30Lozoff, B, Brittenham, GM, Viteri, FE, Wolf, AW, Urrutia, JJ. The effects of short-term oral iron therapy on developmental deficits in iron deficient anemic infants. Journal of Pediatrics 1982; 100: 351–7.CrossRefGoogle Scholar
31Driva, A, Kafatos, A, Salman, M. Iron deficiency and the cognitive and psychomotor development of children: a pilot study with institutionalised children. Early Child Development and Care 1985; 22: 73–82.CrossRefGoogle Scholar
32Soemantri, AG, Pollitt, E, Kim, I. Iron deficiency anemia and educational achievement. American Journal of Clinical Nutrition 1985; 42: 1221–8.CrossRefGoogle ScholarPubMed
33Aukett, MA, Parks, YA, Scott, PH, Wharton, BA. Treatment with iron increases weight gain and psychomotor development. Archives of Disease in Childhood 1986; 61: 849–57.CrossRefGoogle ScholarPubMed
34Soewondo, S, Husaini, M, Pollitt, E. Effects of iron deficiency on attention and learning processes in preschool children: Bandung, Indonesia. American Journal of Clinical Nutrition 1989; 50: 667–74.CrossRefGoogle ScholarPubMed
35Walter, T, De Andraca, I, Chadud, P, Perales, CG. Iron deficiency anemia: adverse effects on infant psychomotor development. Pediatrics 1989; 84: 7–17.CrossRefGoogle ScholarPubMed
36Soemantri, AG. Preliminary findings on iron supplementation and learning achievement of rural Indonesian children. American Journal of Clinical Nutrition 1989; 50: 698–702.CrossRefGoogle ScholarPubMed
37Idjradinata, P, Pollitt, E. Reversal of developmental delays in iron deficient anaemic infants treated with iron. Lancet 1993; 341: 1–4.CrossRefGoogle ScholarPubMed
38Moffatt, MEK, Longstaffe, S, Besant, J, Dureski, C. Prevention of iron deficiency and psychomotor decline in high risk infants through use of iron fortified infant formula: a randomised clinical trial. Journal of Pediatrics 1994; 125: 527–34.CrossRefGoogle Scholar
39Morley, R, Abbott, R, Fairweather-Tait, S, Macfayden, U, Stephenson, T, Lucas, A. Iron fortified follow on formula from 9 to 18 months improves iron status but not development or growth: a randomised trial. Archives of Disease in Childhood 1999; 81: 247–52.CrossRefGoogle ScholarPubMed
40Stoltzfus, RJ, Kvalsvig, JD, Chwaya, HM, Montresor, A, Albonico, M, Tielsch, JM, et al. Effects of iron supplementation and anthelminthic treatment on motor and language development of preschool children in Zanzibar: double blind, placebo controlled study. British Medical Journal 2001; 323: 1–8.CrossRefGoogle ScholarPubMed
41Stoltzfus, RJ, Dreyfuss, ML. Guidelines for the Use of Iron Supplements to Prevent and Treat Iron Deficiency Anemia. Washington, DC: ILSI Press, 1998.Google Scholar
42Nestel, P, Davidsson, L. Anemia, Iron Deficiency, and Iron Deficiency Anemia. Washington, DC: ILSI Press, 2002.Google Scholar
43Nokes, C, van den Bosch, C, Bundy, DAP. The Effects of Iron Deficiency and Anaemia on Mental and Motor Performance, Educational Achievement, and Behaviour in Children: An Annotated Bibliography. Report of the International Nutritional Anemia Consultative Group (INACG). Washington, DC: INACG, 1998.Google Scholar
44Symes, AL, Missala, K, Sourkes, TL. Iron and riboflavin dependent metabolism of a monoamine in the rat in vivo. Science 1971; 174: 153–5.CrossRefGoogle ScholarPubMed
45Dallman, PR, Siimes, M, Manies, EC. Brain iron: persistent deficiency following short-term iron deprivation in the young rat. British Journal of Haematology 1975; 31: 209–15.CrossRefGoogle ScholarPubMed
46Findlay, E, Reid, RL, Ng, KT, Armstrong, SM. The effect of iron deficiency during development on passive avoidance learning in the adult rat. Physiology & Behavior 1981; 27: 1089–96.CrossRefGoogle ScholarPubMed
47Weinberg, J, Levin, S, Dallman, PR. Long term consequences of early iron deficiency in rat. Pharmacology, Biochemistry, and Behavior 1979; 11: 631–8.CrossRefGoogle Scholar