Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Vitamins and plant ingredients

The effect of folic acid supplementation with ferrous sulfate on the linear and ponderal growth of children aged 6–24 months: a randomized controlled trial

European Journal of Clinical Nutrition volume 69, pages 198–204 (2015)Cite this article

Subjects

Abstract

Background/Objectives:

Studies evaluating the effect of folic acid supplementation, either alone or in combination with iron, on the linear and ponderal growth of children are practically nonexistent. The aim of this study was to assess the effect of folic acid supplementation with ferrous sulfate on both linear growth and weight gain in anemic and nonanemic children attending Municipal Daycare Centers in Goiania, State of Goias, Brazil.

Subjects/Methods:

A double-blind, randomized, controlled trial was conducted on 188 children aged 6–24 months. The effects of ferrous sulfate and folic acid supplementation were evaluated using the analysis of variance procedure, based on a double factorial model with two factors of fixed effects (folic acid supplementation and ferrous sulfate supplementation), adjusted for initial weight. The level of significance was 0.05.

Results:

The children who received folic acid supplementation showed greater weight gain than the monthly average weight gain of those not given the supplement (P=0.026). This effect was independent of the dose of ferrous sulfate (P for interaction=0.693). Folic acid supplementation increased the gain of weight-for-age Z-score when compared with the placebo group (P=0.018), independent of the dose of ferrous sulfate.

Conclusion:

Folic acid had no effect on linear growth. The use of folic acid supplementation increased the monthly average weight gain and the gain in weight-for-age Z-score compared with the placebo group. This effect was independent of the dose of ferrous sulfate.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Stevens GA, Finucane MM, De-Regil LM, Paciorek CJ, Flaxman SR, Branca F et al. Global, regional, and national trends in hemoglobin concentration and prevalence of total and severe anaemia in children and pregnant and non-pregnant women for 1995-2011: a systematic analysis of population-representative data. Lancet 2013; 1: 16–25.

    Google Scholar 

  2. Black MM, Quigg AM, Hurley KM, Pepper MR . Iron deficiency and iron deficiency anemia in the first two years of life: strategies to prevent loss of developmental potential. Nutr Rev 2011; 69: 164–170.

    Article  Google Scholar 

  3. Brasil. Ministério da Saúde. Pesquisa Nacional de Demografia e Saúde da Criança e da Mulher – PNDS 2006: dimensões do processo reprodutivo e da saúde da criança/Ministério da Saúde, Centro Brasileiro de Análise e Planejamento. Ministério da Saúde: Brasília, 2009 300 pp.il. – (Série G. Estatística e Informação em Saúde).

  4. Jordão RE, Bernardi JLD, Barros Filho AA . Prevalência de anemia ferropriva no Brasil: uma revisão sistemática. Rev Paul Pediatr 2009; 27: 90–98.

    Article  Google Scholar 

  5. Vieira RCS, Ferreira HS . Prevalência de anemia em crianças brasileiras, segundo diferentes cenários epidemiológicos. Rev Nutr 2010; 23: 433–444.

    Article  Google Scholar 

  6. World Health Organization. Centers for Disease Control and Prevention. Worldwide prevalence of anaemia 1993–2005: WHO global database on anaemia. World Health Organization: Geneva, 2008.

  7. Gahagan S, YU S, Kaciroti N, Castillo M, Lozoff B . Linear and ponderal growth trajectories in well-nourished, iron-sufficient infants are unimpaired by iron supplementation. J Nutr 2009; 139: 2106–2112.

    Article  CAS  Google Scholar 

  8. Lozoff B, Armony-Sivan R, Kaciroti N, Jing Y, Golub M, Jacobson SW . Eye-blinking rates are slower in infants with iron-deficiency anemia that in no anemic iron-deficient or iron-sufficient infants. J Nutr 2010; 140: 1057–1061.

    Article  CAS  Google Scholar 

  9. Perng W, Mora-Plazas MM, Marin C, Villamor E . Iron status and linear growth: a prospective study in school-age children. Eur J Clin Nutr 2013; 67: 645–651.

    Article  Google Scholar 

  10. Hadler MC, Sigulem DM, Alves MF, Torres VM . Treatment and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial. Cad Saúde Pública 2008; 24: S259–S271.

    Article  Google Scholar 

  11. Bhutta Z, Klemm R, Shahid F, Rizvi A, Ray JH, Christian P . Treatment response to iron and folic and acid alone is the same as with multivitamins and/or arthelmintics in severely anemic 6- to 24- month-old children. J Nutr 2009; 139: 1568–1574.

    Article  CAS  Google Scholar 

  12. Rosado JL, González KE, Caamaño MC, García OP, Preciado R, Odio M . Efficacy of different strategies to treat anemia in children: a randomized clinical trial. Nutr J 2010; 9: 9–40.

    Article  Google Scholar 

  13. Matoth Y, Zehavi I, Topper E, Klein AT . Folate nutrition and growth in infancy. Arch Dis Child 1979; 54: 699–702.

    Article  CAS  Google Scholar 

  14. Ramakrishnam U, Neufeld LM, Flores R, River J, Martorell R . Multiple micronutrients supplementation during early childhood increases child size at 2 y of age only among high compliers. Am J Clin Nutr 2009; 89: 1125–1131.

    Article  Google Scholar 

  15. Fekete K, Berti C, Trovato M, Lohner S, Dullemeijer C, Souverein Ow et al. Effect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation. Nutr J 2012; 11: 2–8.

    Article  Google Scholar 

  16. Olney DK, Pollitt E, Kariger PK, Khalfan SS, Ali NS, Tielsch JM et al. Combined iron and folic acid supplementation with or without zinc reduce time to walking unassisted among Zanzibari infants 5-to 11-mo old. J Nutr 2006; 136: 2427–2434.

    Article  CAS  Google Scholar 

  17. Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R et al. Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial. Lancet 2006; 367: 144–152.

    Article  CAS  Google Scholar 

  18. Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A et al. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet 2006; 367: 133–143.

    Article  CAS  Google Scholar 

  19. Ramakrishnam U, Goldenberg T, Allen LH . Do multiple micronutrient interventions improve child health, growth and development? J Nutr 2011; 141: 2066–2075.

    Article  Google Scholar 

  20. Ramakrishnam U, Nguyen P, Martorell R . Effects of macronutrients on growth of children under 5y of age: meta-analyses of single and multiple nutrient interventions. Am J Clin Nutr 2009; 89: 191–203.

    Article  Google Scholar 

  21. Allen LH, Peerson JM, Olney DK . Provision of multiple rather that two or fewer micronutrients more effectively improves growth and other outcomes in micronutrient-deficient children and adults. J Nutr 2009; 139: 1022–1030.

    Article  CAS  Google Scholar 

  22. World Health Organization. Centers for Disease Control and Prevention. Iron deficiency anaemia: assessment, prevention and control. World Health Organization: Geneva, 2001.

  23. Stoltzfus RJ, Dreyfuss ML . Guidelines for the use of iron supplements to prevent and treat iron deficiency anemia (pp. 18-21). Ilsi Press: Washington DC, 1998.

    Google Scholar 

  24. Schulz KF, Altman DG, Moher D . CONSORT Group CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. BMC Med 2010; 8: 1–18.

    Article  Google Scholar 

  25. WHO Anthro for personal computers, version 3.2.2, 2011. Software for assessing growth and development of the world's children. WHO: Geneva, 2010 Available at: (http://www.who.int/childgrowth/software/en). Accessed: 10 October 2013.

  26. Silva DG, Franceschini SCC, Sigulem DM . Growth in non-anemic infant supplemented with different prophylactic iron doses. J Pediatr (Rio J) 2008; 84: 365–372.

    Article  Google Scholar 

  27. Dewey KG, Domellof M, Cohen RJ, Rivera LL, Hernell O, Lonnerdal B . Iron supplementation affects growth and morbidity of breast-fed infants: results on a randomized trial in Sweden and Honduras. J Nutr 2002; 132: 3249–3255.

    Article  CAS  Google Scholar 

  28. Majumdar I, Paul P, Talib VH, Ranga S . The effect of iron therapy on the growth of iron-replete and iron-deplete children. J Trop Pediatr 2003; 49: 84–88.

    Article  CAS  Google Scholar 

  29. Capozzi L, Russo R, Bertocco F, Ferrara D, Ferrara M . Effect on hematological and anthropometric parameters of iron supplementation in the first 2 years of life. Risks and benefits. Hematology 2011; 16: 261–264.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Dr Alexandre Coelho for his assistance in statistical analysis; the Department of Science and Technology/Department of Science, Technology and Strategic Inputs of the Ministry of Health and the Health Sector Fund, through Brazilian National Research Council (CNPq) (Project: CT-SAÚDE/MCT/MS/CNPq N. 30/2004, Case 506 193/2004-7); and the Goiania Municipal Health, Goiania Municipal Department of Education and the Clinic Hospital/UFG, Federal University of Goias.

Author Contributions

DAM and MCCMH designed research, analyzed data and wrote the article; AS wrote the article. VT prescribed the medication, conducted the clinical evaluation and revision of the article.

Author information

Authors and Affiliations

  1. Faculty of Nutrition Federal University of Goias - UFG, Goiânia, Goiás, Brazil

    D A Medeiros, M C C M Hadler & A Sugai

  2. School of Medicine, Pontifical Catholic University of Goias (PUC - Goiás), Goiânia, Goiás, Brazil

    V M Torres

Authors
  1. D A Medeiros
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M C C M Hadler
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A Sugai
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. V M Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to D A Medeiros.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Article from the dissertation of Daniela de Araújo Medeiros Dias entitled 'Effect of supplementation of ferrous sulfate, with and without folic acid, on the growth of infants: randomized controlled trial', presented to the Graduate Courses in Nutrition and Health, Federal University of Goias, 2014.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Medeiros, D., Hadler, M., Sugai, A. et al. The effect of folic acid supplementation with ferrous sulfate on the linear and ponderal growth of children aged 6–24 months: a randomized controlled trial. Eur J Clin Nutr 69, 198–204 (2015). https://doi.org/10.1038/ejcn.2014.220

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ejcn.2014.220

Search

Advanced search

Quick links