Treament and prevention of anemia with ferrous sulfate plus folic acid in children attending daycare centers in Goiânia, Goiás State, Brazil: a randomized controlled trial

The objective of this study was to assess the prevalence of anemia and the therapeutic and prophylactic response to ferrous sulfate and folic acid. A double-blind, randomized, controlled clinical trial was conducted with 196 children 6 to 24 months of age enrolled in municipal daycare centers in Goiânia, Goiás State, Brazil. The children were assigned to two treatment groups that received a daily dose (5 times a week) of either 4.2mg/kg/day of ferrous sulfate + folic acid (50μg) or 4.2mg/kg/day of ferrous sulfate + folic acid placebo. One of the prevention groups received 1.4mg/kg/day of ferrous sulfate + folic acid (50μg/day) and the other 1.4mg/kg/day of ferrous sulfate + folic acid placebo. Supplementation lasted approximately three months. Baseline anemia prevalence was 56.1% (95%CI: 48.963.1). After treatment, anemia prevalence in the folic acid group (14%) was lower than in the placebo group (34.9%) (p = 0.02). After prophylaxis in the non-anemic children, the incidence of anemia did not differ between the groups, but there was an increase in hemoglobin level in the folic acid group (p = 0.003). Iron plus folic acid was effective for the treatment of anemia and improvement of hemoglobin level in non-anemic children. Nutritional Epidemiology; Anemia; Ferrous Sulfate; Folic Acid; Child Day Care Centers Introduction Nutritional anemia can be due to iron, folic acid, or vitamin B12 deficiency 1. Iron is the main nutrient involved in nutritional anemia, followed by folic acid 2. Deoxyribonucleic acid (DNA) synthesis depends on the coenzyme folate for the biosynthesis of the nucleotide pyrimidine, which is required for cell division 3, and folate is thus one of the necessary nutrients for hematopoiesis 4. Iron deficiency anemia is the most common nutritional problem in the world 5, with a negative impact on mental, motor, cognitive, and immune development 6,7,8. An anemia prevalence greater than or equal to 40% is considered a serious public health problem 4, and in Brazil children 6 to 24 months of age constitute one of the most vulnerable groups 9,10. The World Health Organization and the Brazilian Ministry of Health recommend that infants receive exclusive breastfeeding until six months of life 11. It has been shown that absorption of iron from breast milk is reduced by the consumption of other foods or beverages, particularly before or after breatfeeding 12. With the introduction of supplementary feeding, infants require an additional source of iron to prevent iron deficiency anemia 4. Various studies have used various intermittent doses at different weekly frequencies for anemia prevention and treatment 13,14,15,16. Although the use of iron supplements is recommended for infants in areas with high prevalence ARTIGO ARTICLE Hadler MCCM et al. S260 Cad. Saúde Pública, Rio de Janeiro, 24 Sup 2:S259-S271, 2008 of anemia, their efficacy has not been totally elucidated 17. Some studies have suggested that other factors besides iron can limit the hemoglobin response and control of anemia, like vitamin A and other micronutrients or non-nutritional factors 13. A study of Mexican children showed that iron, vitamin A, vitamin B12, vitamin E, and riboflavin deficiencies were common at baseline. The authors observed that many children receiving iron supplements remained anemic (30%) after six months of treatment and at 12 months (31%), despite the eradication of iron deficiency 18. Thus, supplementation with one or more nutrients is one of the strategies to fight borderline micronutrient deficiency, since it can increase the effectiveness of programs to fight anemia. However, there is still limited information on interactions between micronutrients (when supplemented), based on pharmacological studies 19. It is important to assess the efficacy and effectiveness of iron supplementation compared to the combination of iron and folic acid in children younger than 24 months 20. In addition, the possibility of meeting the multiple needs for these micronutrients makes this an interesting strategy 21. The objectives of this study were to evaluate the prevalence of anemia in children from 6 to 24 months of age and the therapeutic and prophylactic response to ferrous sulfate plus folic acid on hemoglobin levels, in municipal daycare centers in Goiânia, Goiás State, Brazil.