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 - 24/12/18

Doi : 10.1016/j.jpeds.2018.11.022

Maxwell A. Barffour, PhD ^1,^2,^* , Guy-Marino Hinnouho, PhD ¹, Sengchanh Kounnavong, PhD ³, K. Ryan Wessells, PhD ¹, Kethmany Ratsavong, MD ³, Bangone Bounheuang, MD ³, Bigphone Chanhthavong, MD ³, Dalaphone Sitthideth, MD ³, Khanpaseuth Sengnam, MD ³, Charles D. Arnold, MS ¹, Kenneth H. Brown, MD ^1,⁴, Sonja Y. Hess, PhD ¹
¹ Program in International and Community Nutrition, Department of Nutrition, University of California, Davis, CA
² Public Health Program, College of Health and Human Services, Missouri State University, Springfield, MO
³ Lao Tropical and Public Health Institute (Lao TPHI), Vientiane, Laos
⁴ Nutrition and Global Development, Bill & Melinda Gates Foundation, Seattle, WA

^*Reprint requests: Maxwell A. Barffour, PhD, University of California Davis, Program in International & Community Nutrition, 3252 Meyer Hall, One Shields Ave, Davis, CA 95616.University of California DavisProgram in International & Community Nutrition3252 Meyer Hall, One Shields AveDavisCA95616

Sous presse. Épreuves corrigées par l'auteur. Disponible en ligne depuis le Monday 24 December 2018

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.gov NCT02428647.

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Abbreviations : AGP, CRP, LAZ, MUAC, ORS, RBP, sTfR, WAZ, WHO, WLZ

Plan

Methods

Ethical Approval

Study Design and Participants

Sample Size Considerations

Inclusion and Exclusion Criteria

Randomization

Study Interventions and Follow-Up

Study Procedures

Data Collection

Laboratory Analyses

Data Entry and Analyses

Supported by the Mathile Institute for the Advancement of Human Nutrition and Nutrition International (formerly the Micronutrient Initiative) (10-1347-UCALIF-07). Other aspects of the Lao Zinc Study were supported by the Bill & Melinda Gates Foundation (OPP1134272). K.B. and the spouse of S.H. work for the Bill & Melinda Gates Foundation, which provided part of the financial support. The sponsors had no involvement in the field implementation, data analyses, and manuscript writing. S.H. worked as a consultant for the Bill & Melinda Gates Foundation. The other authors declare no conflicts of interest.

Portions of this study were presented at the American Society for Nutrition Conference, June 12, 2018, Boston, Massachusetts, and at the International Congress on Nutrition, October 17, 2017, Buenos Aires, Argentina.