Different Doses, Forms, and Frequencies of Zinc Supplementation for the Prevention of Diarrhea and Promotion of Linear Growth among Young Bangladeshi Children: A Six-Arm, Randomized, Community-Based Efficacy Trial.

BACKGROUND: Children in resource-limited settings remain vulnerable to zinc deficiency and its consequences. OBJECTIVES: To evaluate the effects of different doses, durations, and frequencies of zinc supplementation on the incidence of diarrhea and change in linear growth among young children. METHODS: We conducted a randomized, partially double-blind, controlled, 6-arm, community-based efficacy trial in Dhaka, Bangladesh. Children aged 9-11 mo were randomly assigned to receive 1 of the following interventions for 24 wk: 1) standard micronutrient powder (MNP) containing 4.1 mg zinc and 10 mg iron, daily; 2) high-zinc (10 mg), low-iron (6 mg) (HiZn LoFe) MNP, daily; 3) HiZn (10 mg) LoFe (6 mg)/HiZn (10 mg), no-iron MNPs on alternating days; 4) dispersible zinc tablet (10 mg), daily; 5) dispersible zinc tablet (10 mg), daily for 2 wk at enrollment and 12 wk; 6) placebo powder, daily. Primary outcomes were incidence of diarrhea and change in length-for-age z-score (LAZ) over the 24-wk intervention period. Home visits were conducted twice weekly to assess diarrhea and other morbidity. Incidence and prevalence outcomes were compared among groups with Poisson regression; continuous outcomes were compared using ANCOVA. RESULTS: A total of 2886 children were enrolled between February 2018 and July 2019. The mean incidence and prevalence of diarrhea among all participants was 1.21 episodes per 100 d and 3.76 d per 100 d, respectively. There were no differences in the incidence or prevalence of diarrhea across intervention groups. The decline in LAZ was slightly smaller among children in the daily HiZn LoFe MNP group compared with the placebo powder group (P < 0.05). CONCLUSIONS: The dose of zinc in MNPs as well as the duration and frequency of supplementation evaluated in this trial were not effective in reducing diarrhea; however, the daily HiZn LoFe MNP formulation offered modest improvements in linear growth among young children. This trial was registered at clinicaltrials.gov as NCT03406793.

Perspective: Putting the youngest among us into the nutrition "call for action" for food fortification strategies.

Adequate iron intake is essential for optimal child development, but iron deficiency and anemia among infants and young children are widespread in low- and middle-income countries. Large-scale food fortification strategies hold great promise for reducing micronutrient deficiencies; however, for children <2 y of age, the impact of such strategies is limited because their intake of staple foods is relatively low and fortification levels are targeted at the adult population. Iron supplementation, iron fortification of foods targeted to infants, and point-of-use fortification with iron-containing products such as multiple micronutrient powders (MNPs) and small-quantity lipid-based nutrient supplements are evidence-based approaches recommended to reduce anemia among infants and young children when used in the right context. Since 2003, the WHO, with support from UNICEF, has recommended the use of MNPs to control iron deficiency. However, the percentage of children with anemia has changed very little over the past 10 y. Five years ago the UN declared a decade of action on nutrition, including World Health Assembly (WHA) targets for maternal, infant, and young child nutrition, yet the WHA set no anemia targets for children. In July 2020 the leaders of 4 UN agencies issued a call for action to protect children's right to nutrition in the face of the COVID-19 pandemic and beyond. Given persistently high rates of anemia among young children, the negative developmental impact, the challenge of meeting iron needs from typical complementary food diets, and the availability of successful evidence-based fortification strategies for this age group, we encourage planners, speakers, and donors at this year's UN Food Systems Summit and the Tokyo Nutrition for Growth Summit to 1) call for the WHA to set anemia targets for infants and young children and 2) promote investment in evidence-based interventions to improve the iron status of young children.