Public Health Nutrition (2006), 9:904-920 Cambridge University Press

Copyright © The Authors 2006

doi:10.1017/PHN2005918

Research Article

Effect of iron supplementation on physical growth in children: systematic review of randomised controlled trials

Abstract

Objective To evaluate the effect of iron supplementation on physical growth in children through a systematic review of randomised controlled trials (RCTs).

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

Review methods RCTs evaluating change in anthropometry with interventions that included oral or parenteral iron supplementation, or iron-fortified formula milk or cereals, were analysed.

Results Twenty-five trials (26 cohorts) had relevant information. There was no evidence of publication bias. The pooled estimates (random effects model) did not document a statistically significant (P<0.05) positive effect of iron supplementation on any anthropometric variable (weight-for-age, weight-for-height, height-for-age, mid upper-arm circumference, skinfold thickness, head circumference). Significant heterogeneity was evident, and its predictors included greater weight-for-age in supplemented children in malaria hyperendemic regions and greater weight-for-height for children above 5 years of age, but a negative effect on linear growth in developed countries and with supplementation for 6 months or longer.

Conclusions This review did not document a positive effect of iron supplementation on the physical growth of children. The identified predictors of heterogeneity should be considered as exploratory and requiring confirmation, not conclusive

(Received June 14 2005)

(Accepted November 21 2005)

Key Words: Anaemia; Anthropometry; Growth; Height-for-age; Iron deficiency; Iron supplementation; Meta-analysis; Randomised controlled trials; Weight-for-age; Weight-for-height

Correspondence:

^c1 corresponding author: Email hpssachdev@hotmail.com

^c2 Correspondence address: E-6/12 Vasant Vihar, New Delhi 110 057, India.

1 United Nations Administrative Committee on Coordination, Sub-Committee on Nutrition (ACC/SCN). Fourth Report on the World Nutrition Situation. Geneva: ACC/SCN in collaboration with International Food Policy Research Institute, 2000.

2 Nestel, P, ed. Iron Interventions for Child Survival. Proceedings of Workshop held in London17–18 May 1996Arlington, VAUSAID/OMNI and Institute of Child Health 1995.

3 Singh, P, Toteja, GS. Micronutrient profile of Indian children and women: summary of available data for iron and vitamin A. Indian Pediatrics 2003; 40: 477–9. [OpenURL Query Data]  [PubMed]  [Google Scholar]

4 Allen, L, Casterline-Sabel, J. Prevalence and causes of nutritional anemia. In: Ramakrishnan, U, ed. Nutritional Anemias. New York: CRC Press, 2001; 7–22.

5 Van den Broek, NR, Letsky, EA. Etiology of anaemia in pregnancy in south Malawi. American Journal of Clinical Nutrition 2000; 72: 247S–56S. [OpenURL Query Data]  [PubMed]  [Google Scholar]

6 Staubli Asobayire, F, Adou, P, Davidsson, L, Cook, JD, Hurrell, RF. Prevalence of iron deficiency with and without concurrent anaemia in population groups with high prevalence of malaria and other infections: a study in Côte d'Ivoire. American Journal of Clinical Nutrition 2001; 74: 776–82. [OpenURL Query Data]  [PubMed]  [Google Scholar]

7 Owen, GM, Lubin, AH, Garry, PJ. Preschool children in the United States: who has iron deficiency? Journal of Pediatrics 1971; 79: 563–8. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

8 Rao, KV, Radhiah, G, Raju, SV. Association of growth status and prevalence of anemia in preschool children. Indian Journal of Medical Research 1980; 71: 237–46. [OpenURL Query Data]  [PubMed]  [Google Scholar]

9 Lawless, JW, Latham, MC, Stephenson, LS, Kinoti, SN, Pertet, AM. Iron supplementation improves appetite and growth in anemic Kenyan preschool children. Journal of Nutrition 1994; 124: 645–54. [OpenURL Query Data]  [PubMed]  [Google Scholar]

10 Beard, J, Hass, JD, Hurtado, GL. The relationship of nutritional status to oxygen transport and growth in highland Bolivian children. Human Biology 1983; 55: 151–64. [OpenURL Query Data]  [Google Scholar]

11 Aukett, 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. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

12 Rosado, JL, Lopez, P, Munoz, E, Martinez, H, Allen, LH. Zinc supplementation reduced morbidity, but neither zinc nor iron supplementation affected growth or body composition of Mexican preschoolers. American Journal of Clinical Nutrition 1997; 65: 13–9. [OpenURL Query Data]  [PubMed]  [Google Scholar]

13 Idjradinata, P, Watkins, WE, Pollitt, E. Adverse effect of iron supplementation on weight gain of iron-replete young children. Lancet 1994; 343: 1252–4. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

14 Juni, 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 Books, 2001; 87–108.

15 Clarke, M, Oxman, AD, eds. Assessment of study quality. Cochrane Reviewers Handbook 4.1.1 [updated December 2000]. In: The Cochrane Library, Issue 1, 2001. Oxford: Update Software.

16 Follmann, 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. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

17 Sterne, JAC, Egger, M, Smith, GD. Investigating and dealing with publication and other biases. In: Egger, M, Smith, GD, Altman, DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. London: BMJ Books, 2001; 189–208.

18 Sterne, JAC, Bradburn, MJ, Egger, M. Meta-analysis in STATAe. In: Egger, M, Smith, GD, Altman, DG, eds. Systematic Reviews in Health Care: Meta-analysis in Context. London: BMJ Books, 2001; 347–69.

19 Fuerth, JH. Iron supplementation of the diet in full-term infants: a controlled study. Journal of Pediatrics 1972; 80: 974–9. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

20 Mejia, LA, Chew, F. Hematological effect of supplementing anemic children with vitamin A alone and in combination with iron. American Journal of Clinical Nutrition 1988; 48: 595–600. [OpenURL Query Data]  [PubMed]  [Google Scholar]

21 Haschke, F, Vanura, H, Male, C, Owen, G, Pietschnig, B, Schuster, E. Iron nutrition and growth of breast- and formula-fed infants during the first 9 months of life. Journal of Pediatric Gastroenterology and Nutrition 1993; 16: 151–6. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

22 Walter, T, Dallman, PR, Pizarro, F, Velozo, L, Pena, G, Bartholmey, SJ. Effectiveness of iron fortified infant cereal in prevention of iron deficiency anemia. Pediatrics 1993; 91: 976–82. [OpenURL Query Data]  [PubMed]  [Google Scholar]

23 Moffatt, 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 randomized clinical trial. Journal of Pediatrics 1994; 125: 527–34. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

24 Hyams, JS, Treem, WR, Etienne, NL, Weinerman, H, MacGilpin, D, Hine, P, et al. Effect of infant formula on stool characteristics of young infants. Pediatrics 1995; 95: 50–4. [OpenURL Query Data]  [PubMed]  [Google Scholar]

25 van den Hombergh, J, Dalderop, E, Smit, Y. Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani division, Tanzania. Journal of Tropical Pediatrics 1996; 42: 220–7. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

26 Daly, A, MacDonald, A, Aukett, A, Williams, J, Wolf, A, Davidson, J. Prevention of anaemia in inner city toddlers by an iron supplemented cows' milk formula. Archives of Disease in Childhood 1996; 75: 9–16. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

27 Beckett, C, Durnin, JV, Aitchison, TC, Pollitt, E. Effects of an energy and micronutrient supplement on anthropometry in undernourished children in Indonesia. European Journal of Clinical Nutrition 2000; 54(Suppl. 2): S52–9. [OpenURL Query Data]  [PubMed]  [Google Scholar]

28 Beasley, NMR, Tomkins, AM, Hall, A, Lorri, W, Kihamia, CM, Bundy, DAP. The impact of weekly iron supplementation on the iron status and growth of adolescent girls in Tanzania. Tropical Medicine & International Health 2000; 5: 794–9. [OpenURL Query Data]  [CrossRef]  [Google Scholar]

29 Kanani, SJ, Poojara, RH. Supplementation with iron and folic acid enhances growth in adolescent Indian girls. Journal of Nutrition 2000; 130(2S Suppl.): 452S–5S. [OpenURL Query Data]  [PubMed]  [Google Scholar]

30 Sharma, A, Prasad, K, Rao, KV. Identification of an appropriate strategy to control anemia in adolescent girls of poor communities. Indian Pediatrics 2000; 37: 261–7. [OpenURL Query Data]  [PubMed]  [Google Scholar]

31 Taylor, M, Jinabhai, CC, Couper, I, Klienschmidt, I, Jogessar, VB. The effect of different anthelminthic treatment regimens combined with iron supplementation on the nutritional status of schoolchildren in KwaZulu-Natal, South Africa: a randomized controlled trial. Transactions of the Royal Society of Tropical Medicine and Hygiene 2001; 95: 211–6. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

32 Sari, M, Bloem, MW, de Pee, S, Schultnik, WJ, Sastroamidjojo, S. Effect of iron fortified candies on the iron status of children aged 4–6 y in East Jakarta, Indonesia. American Journal of Clinical Nutrition 2001; 73: 1034–9. [OpenURL Query Data]  [PubMed]  [Google Scholar]

33 Pereira, SM, Begum, A, Baker, SJ. Studies in iron supplementation of preschool children. British Journal of Nutrition 1978; 39: 493–9. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

34 Pereira, SM, Begum, A, Mathan, VI, Baker, SJ. A preliminary simulated iron fortification trial in South Indian preschool children. British Journal of Nutrition 1979; 41: 413–7. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

35 Chwang, L, Soemantri, AG, Pollitt, E. Iron supplementation and physical growth of rural Indonesian children. American Journal of Clinical Nutrition 1988; 47: 496–501. [OpenURL Query Data]  [PubMed]  [Google Scholar]

36 Latham, MC, Stephenson, LS, Kinoti, SN, Zaman, MS, Kurz, KM. Improvements in growth following iron supplementation in young Kenyan school children. Nutrition 1990; 6: 159–65. [OpenURL Query Data]  [PubMed]  [Google Scholar]

37 Javaid, N, Haschke, F, Pietschnig, B, Schuster, E, Huemer, C, Shebaz, A, et al. Interactions between infections, malnutrition and iron nutritional status in Pakistani infants. Acta Paediatrica Scandinavica 1991; 374: 141–50. [OpenURL Query Data]  [CrossRef]  [Google Scholar]

38 Bhatia, D, Seshadri, S. Growth performance in anemia and following iron supplementation. Indian Pediatrics 1993; 30: 195–200. [OpenURL Query Data]  [PubMed]  [Google Scholar]

39 Brunser, O, Espinoza, J, Araya, M, Pacheco, I, Cruchet, S. Chronic iron intake and diarrheal disease in infants: a field study in a less-developed country. European Journal of Clinical Nutrition 1993; 47: 317–26. [OpenURL Query Data]  [PubMed]  [Google Scholar]

40 Angeles, IT, Schultink, WJ, Matulessi, P, Gross, R, Sastroamidjojo, S. Decreased rate of stunting among anemic Indonesian preschool children through iron supplementation. American Journal of Clinical Nutrition 1993; 58: 339–42. [OpenURL Query Data]  [PubMed]  [Google Scholar]

41 Hemminki, E, Nemet, K, Horvath, M, Malin, M, Schuler, D, Hollan, S. Impact of iron fortification of milk formulas on infants growth and health. Nutrition Research 1995; 4: 491–503. [OpenURL Query Data]  [CrossRef]  [Google Scholar]

42 Palupi, L, Schultnik, W, Achadi, E, Gross, R. Effective community intervention to improve hemoglobin status in preschoolers receiving once-weekly iron supplementation. American Journal of Clinical Nutrition 1997; 65: 1057–61. [OpenURL Query Data]  [PubMed]  [Google Scholar]

43 Gill, DG, Vincent, S, Segal, DS. Follow-on formula in the prevention of iron deficiency: a multicentre study. Acta Paediatrica 1997; 86: 683–9. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

44 Morley, 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 randomized trial. Archives of Disease in Childhood 1999; 81: 247–52. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

45 Rahman, MM, Akramuzzaman, SM, Mitra, AK, Fuchs, GJ, Mahalanabis, D. Long-term supplementation with iron does not enhance growth in malnourished Bangladeshi children. Journal of Nutrition 1999; 129: 1319–22. [OpenURL Query Data]  [PubMed]  [Google Scholar]

46 Aguayo, VM. School administered weekly iron supplementation – effect on growth and hemoglobin status of non-anemic Bolivian school-age children: a randomized placebo-controlled trial. European Journal of Nutrition 2000; 39: 263–9. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

47 Mwanri, L, Worsley, A, Ryan, P, Masika, J. Supplemental vitamin A improves anemia and growth in anemic school children in Tanzania. Journal of Nutrition 2000; 130: 2691–6. [OpenURL Query Data]  [PubMed]  [Google Scholar]

48 Dossa, RAM, Ategbo, EAD, de Koning, FLHA, van Raaij, JMA, Hautvast, JGAJ. Impact of iron supplementation and deworming on growth performance in preschool Beninese children. European Journal of Clinical Nutrition 2001; 55: 223–8. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

49 Geltman, PL, Meyers, AF, Bauchner, H. Daily multivitamins with iron to prevent anemia in infancy: a randomized clinical trial. Clinical Pediatrics 2001; 40: 549–54. [OpenURL Query Data]  [PubMed]  [Google Scholar]

50 Dijkhuizen, MA, Wieringa, FT, West, CE, Martuti, S, Muhilal, . Effects of iron and zinc supplementation in Indonesian infants on micronutrient status and growth. Journal of Nutrition 2001; 131: 2860–5. [OpenURL Query Data]  [PubMed]  [Google Scholar]

51 Sungthong, R, Mo-uswan, L, Chongsuvivatwong, V, Geater, AF. Once weekly is superior to daily iron supplementation on height gain but not on hematological improvement among schoolchildren in Thailand. Journal of Nutrition 2002; 132: 418–22. [OpenURL Query Data]  [PubMed]  [Google Scholar]

52 Dewey, KG, Domellof, M, Cohen, RJ, Landa Rivera, L, Hernell, O, Lonnerdal, B. Iron supplementation affects growth and morbidity of breast-fed infants: results of a randomized trial in Sweden and Honduras. Journal of Nutrition 2002; 132: 3249–55. [OpenURL Query Data]  [PubMed]  [Google Scholar]

53 Ramakrishnan, U, Aburto, N, McCabe, G, Martorell, R. Multimicronutrient interventions but not vitamin A or iron interventions alone improve child growth: results of 3 meta-analyses. Journal of Nutrition 2004; 134: 2592–602. [OpenURL Query Data]  [PubMed]  [Google Scholar]

54 Sarker, SA, Davidsson, L, Mahmud, H, Walczyc, T, Hurrell, RF, Gyr, N, et al. Helicobacter pylori infection, iron absorption, and gastric acid secretion in Bangladeshi children. American Journal of Clinical Nutrition 2004; 80: 149–53. [OpenURL Query Data]  [PubMed]  [Google Scholar]

55 Perez-Exposito, AB, Villalpando, S, Rivera, JA, Griffin, IJ, Abrams, SA. Ferrous sulfate is more bioavailable among preschoolers than other forms of iron in a milk-based weaning food distributed by PROGRESA, a national program in Mexico. Journal of Nutrition 2005; 135: 64–9. [OpenURL Query Data]  [PubMed]  [Google Scholar]

56 Gera, T, Sachdev, HPS. Effect of iron supplementation on incidence of infectious illness in children: systematic review. British Medical Journal 2002; 325: 1142–4. [OpenURL Query Data]  [PubMed]  [CrossRef]  [Google Scholar]

57 Shah, D, Sachdev, HPS. Zinc availability and interactions with other micronutrients. Proceedings of Nutrition Society of India 2000; 48: 67–80. [OpenURL Query Data]  [Google Scholar]

58 Brown, KH, Peerson, JM, Rivera, J, Allen, LH. Effect of supplemental zinc on the growth and serum zinc concentrations of prepubertal children: a meta-analysis of randomized controlled trials. American Journal of Clinical Nutrition 2002; 75: 1062–71. [OpenURL Query Data]  [PubMed]  [Google Scholar]