Efeito da fortificação e suplementação de ácido fólico nos níveis séricos e indicadores antropométricos de crianças: Ensaio clínico randomizado

Abstract

Folic acid is a water-soluble B-complex vitamin (vitamin B9) that plays an essential role in DNA synthesis and repair, cell division, and blood cell formation, making it a key nutrient in food fortification and supplementation policies. Fortification with multiple micronutrients has been widely adopted in several countries as a public health strategy to prevent nutritional deficiencies, especially among young children. Objective: To assess the impact of folic acid fortification and supplementation on serum folate levels, average monthly weight gain (Article 1), and changes in the distribution of serum folate categories (Article 2) in Brazilian children aged 6 to 42 months. Methods: This was an open-label, randomized, controlled, parallel-group clinical trial using a cluster design. Data collection was conducted from March 2018 to March 2019 in 10 Municipal Early Childhood Education Centers (CMEIs) in Goiânia (GO), Brazil. Clinical, socioeconomic, anthropometric, dietary, and biochemical variables were evaluated. Statistical tests included Kolmogorov–Smirnov (normality), KruskalWallis (weight gain comparisons by folate category), Student’s t-test (mean differences between intervention groups), multiple linear regression (weight gain), and in Article 2, McNemar’s test and multinomial logistic regression to analyze serum folate categories before and after the intervention. Results: In Article 1, involving 167 children, participants were allocated based on anemia diagnosis and received either powdered multiple micronutrient fortification or liquid supplementation with iron and folic acid. At baseline, 4.8% had folate deficiency, 43.1% normal levels, and 52.1% elevated levels. A significant association was found between higher baseline folate levels and greater monthly weight gain (p = 0.001), as well as better z-scores for weight-for-age (p = 0.042), weight-for-height (p = 0.029), and BMIfor-age (p = 0.027), especially among non-anemic children. After the intervention, significant differences remained for weight-for-age (p = 0.002) and height/length-for-age (p = 0.001), according to folate levels, with no differences between intervention types (p = 0.877). The effect of fortification with 150 μg of folic acid via powdered micronutrients was also evaluated against 50 μg via liquid supplementation across four intervention groups. After 15 weeks, there was no significant change in the proportions of folate deficiency or normal status, but a reduction in the prevalence of folate excess was observed in the group receiving ferrous sulfate and folic acid (from 51.8% to 40.5%; p = 0.057). Furthermore, female sex (OR = 2.236; p = 0.049) and younger age (OR = 0.887; p < 0.001) were associated with higher folate levels. These findings suggest a differential metabolic response according to sex and age, even though short-term interventions did not significantly alter the overall classification of folate status. Conclusion: The findings suggest that higher folate levels are associated with improved child growth, although short-term interventions did not lead to significant changes in anthropometric parameters. The lower prevalence of folate excess with reduced doses suggests a possible metabolic adjustment, highlighting the need for individualized supplementation. Long-term and comprehensive strategies are recommended to enhance the benefits and ensure the safety of folic acid use in pediatric populations.