Effects of Daily Zinc, Daily Multiple Micronutrient Powder, or Therapeutic Zinc Supplementation for Diarrhea Prevention on Physical Growth, Anemia, and Micronutrient Status in Rural Laotian Children: A Randomized Controlled Trial

Abstract

Objectives: To evaluate the optimal zinc supplementation strategy for improving growth and hematologic and micronutrient status in young Laotian children.

Study design: In total, 3407 children aged 6-23 months were randomized to receive either daily preventive zinc tablets (7 mg/d), high-zinc, low-iron micronutrient powder (10 mg/d zinc, 6 mg/d iron, and 13 other micronutrients), therapeutic zinc supplementation for diarrhea (20 mg/d for 10 days per episode), or daily placebo powder; all were followed for ~9 months. Anthropometry, hemoglobin, zinc, and iron status were assessed at baseline and endline. Analyses were by intention-to-treat, using linear and modified Poisson regression.

Results: At baseline, mean (±SD) age was 14.2 ± 5.1 months and stunting and anemia prevalence were 37.9% and 55.6%, respectively. At endline, zinc deficiency in the preventive zinc (50.7%) and micronutrient powder (59.1%) groups were significantly lower than in the therapeutic zinc (79.2%) and control groups (78.6%; P < .001), with no impact on stunting (37.1%-41.3% across the groups, P = .37). The micronutrient powder reduced iron deficiency by 44%-55% compared with other groups (P < .001), with no overall impact on anemia (P = .14). Micronutrient powder tended to reduce anemia by 11%-16% among children who were anemic at baseline (P = .06).

Conclusions: Despite improving zinc status, preventive zinc and micronutrient powder had no impact on growth. The micronutrient powder improved iron status and tended to reduce anemia among the subset of previously anemic children.

Trial registration: ClinicalTrials.govNCT02428647.

Figure 2

Effects of 32-40 weeks of supplementation with daily preventive zinc supplements, micronutrient powder, or therapeutic zinc supplements for diarrhea on anemia prevalence among rural Laotian children, stratified by baseline hemoglobin concentrations. *Models adjusted for age, sex, district, and baseline hemoglobin. No effects of micronutrient powder on anemia in previously nonanemic children (baseline Hb ≥110; P > .05 for all pairwise comparisons); in previously anemic children (baseline Hb <110), the micronutrient powder reduced the prevalence of anemia by 9 percentage points (vs preventive zinc; P = .008), by 7 percentage points (vs therapeutic zinc; P = .041) and by 6 percentage points (vs control, P = .08). MNP, micronutrient powder; PZ, preventive zinc; TZ, therapeutic zinc.

Figure 1

Consort diagram of study participant progression through the growth and biochemical assessments in the Lao Zinc Study. The micronutrient powder group received 1 micronutrient powder sachet daily (vitamin A [400 µg of retinol equivalents], thiamin [0.5 mg], riboflavin [0.5 mg], niacin [6 mg], vitamin B6 [0.5 mg], folic acid [150 µg of dietary folate equivalents], cyanocobalamin [0.9 µg], ascorbic acid [30 mg], cholecalciferol [5 mg], dl-α-tocopheryl acetate [5 mg of tocopherol equivalents], copper sulfate anhydrous [to provide 0.56 mg copper], potassium iodate [to provide 90 µg iodine], ferrous fumarate [to provide 6 mg of iron], selenium selenite [to provide 17 µg of selenium], zinc gluconate [to provide 10 mg of zinc]) and placebo tablet (1 per day for 10 days) during diarrhea episodes. The preventive zinc group (preventive zinc supplements) received 1 zinc tablet (7 mg/d) daily and placebo tablet (1 per day for 10 days) during diarrhea episodes. The therapeutic zinc group (therapeutic zinc supplements) received 1 placebo tablet daily and a 20-mg zinc tablet (1 per day for 10 days) during diarrhea episodes. Controls received 1 placebo powder sachet daily and placebo tablet (1 per day for 10 days) during diarrhea episodes. All children received ORS during diarrhea episodes, regardless of group allocation.