Effect of zinc and multivitamin supplementation on the growth of Tanzanian children aged 6-84 wk: a randomized, placebo-controlled, double-blind trial

Abstract

Background: Poor child growth increases risks of mortality and morbidity. Micronutrient supplements have the potential to improve child growth.

Objective: We assessed the effect of daily zinc, multivitamin (vitamins C, E, and B-complex), and zinc and multivitamin (Zn+MV) supplementation on growth in infants in Tanzania.

Design: In this randomized, 2 × 2 factorial, double-blind trial, 2400 infants were randomly assigned to receive zinc, multivitamins, Zn+MVs, or a placebo at 6 wk of age and were followed up for 18 mo with monthly growth measurements. Mixed-effects models with restricted cubic splines for the mean change in anthropometric z scores were fit for each group. Likelihood ratio tests were used to compare the effect of supplements on growth trajectories. Cox proportional hazards models were used to compare incidences of stunting, wasting, and underweight.

Results: Children in all groups experienced growth faltering. At 19 mo of age, prevalences of stunting, wasting, and underweight were 19.8%, 6.0%, and 10.8%, respectively. Changes in weight-for-age z scores (WAZs) and weight-for-height z scores (WHZs) were significantly different across the 4 groups (P < 0.001 for both). The mean ± SE decline in the WAZ from baseline to the end of follow-up in the Zn+MV group was significantly less than in the placebo group (-0.36 ± 0.04 compared with -0.50 ± 0.04; P = 0.020), whereas the decline in the WHZ was significantly greater in the zinc-only group than in the placebo group (-0.57 ± 0.07 compared with -0.35 ± 0.07; P = 0.021). Supplements did not have a significant effect on mean change in the height-for-age z score or on rates of stunting, wasting, or underweight.

Conclusions: Although there were small but significant improvements in the WAZ in the Zn+MV group, daily zinc supplementation alone, multivitamin supplementation alone, and the combined Zn+MV did not reduce the incidences of underweight, stunting, or wasting in Tanzanian infants. Alternative approaches to prevent growth faltering should be pursued. This trial was registered at clinicaltrials.gov as NCT00421668.

Keywords: growth; infancy; multiple micronutrients; supplementation; zinc.

FIGURE 1

Study profile of the randomized trial of multivitamin and zinc supplementation to infants in Dar es Salaam, Tanzania. Zn+MV, zinc and multivitamin.

FIGURE 2

Changes (95% CIs) in HAZ, WAZ, and WHZ from 6 to 84 wk of age in 4 treatment arms. Curves were created with the use of mixed-effects models with restricted cubic splines with knots at 6 and 10 wk and 3, 6, 9, 12, 15, and 18 mo of age. n = 2336 for the HAZ analysis, n = 2347 for the WAZ analysis, and n = 2332 for the WHZ analysis. Bars represent 95% CIs for each of the 4 treatment groups at 6, 12, and 18 mo of follow-up. P-interaction values were derived from likelihood ratio tests that compared mixed-effects models with restricted cubic splines. The full model contained a Zn+MV interaction term as well as interaction terms between Zn+MVs and time and all time spline variables. The reduced model did not contain interaction terms for Zn+MVs and time or time spline variables. HAZ, height-for-age z score; MV, multivitamins; WAZ, weight-for-age z score; WHZ, weight-for-height z score; Zn+MV, zinc and multivitamin.