Clinical Question

Does zinc supplementation prevent mortality, morbidity, or growth failure in children six months to 12 years of age?

Evidence-Based Answer

Preventive zinc supplementation for children in low- and middle-income countries appears to reduce rates of diarrhea and may slightly reduce rates of growth failure. (Strength of Recommendation: A, based on consistent, good-quality patient-oriented evidence.)

Practice Pointers

Pneumonia and diarrhea cause approximately 15% and 10%, respectively, of deaths in children younger than five years around the world, and malaria accounts for 15% of deaths in this age group in sub-Saharan Africa.¹ Because approximately 17% of the world's population is at risk of inadequate zinc intake, and because the prevalence of inadequate zinc intake is correlated with the prevalence of growth stunting,² zinc supplementation has been proposed as a way to address targeted child health outcomes including infectious diseases, growth, and mortality in areas where diets are deficient in zinc. However, to date there are no standardized recommendations for dosing or duration of preventive zinc supplementation.

This Cochrane review incorporates data from 80 randomized controlled trials with a total of 205,923 participants specifically evaluating the use of zinc as a supplement for preventing death from diarrhea, lower respiratory tract infection, or malaria, as well as for reducing rates of all-cause mortality and growth failure. The authors did not include studies of food fortification with zinc or use of zinc as a therapeutic intervention. Seventy-three studies (91%) were from low- or middle-income countries, and seven (9%) were from North America or Europe. The included studies used a wide variety of zinc formulations, and the duration of preventive supplementation ranged from less than two months to 11 months or more.

Childhood mortality is not affected by zinc supplementation. The 13 included studies that addressed all-cause mortality did not find a statistically significant effect of zinc supplementation (relative risk [RR] = 0.95; 95% confidence interval [CI], 0.86 to 1.05), and there was no evidence from included studies that zinc supplementation reduced disease-specific mortality caused by diarrhea (RR = 0.95; 95% CI, 0.69 to 1.31), lower respiratory tract infection (RR = 0.86; 95% CI, 0.64 to 1.15), or malaria (RR = 0.90; 95% CI, 0.77 to 1.06).

The impact of preventive zinc supplementation on serious childhood infections is more ambiguous. Studies in the review demonstrated reductions in the incidence (RR = 0.87; 95% CI, 0.85 to 0.89) and prevalence (RR = 0.88; 95% CI, 0.86 to 0.90) of all-cause diarrhea, but there was no evidence of reductions in the incidence (RR = 1.05; 95% CI, 0.95 to 1.15) or prevalence (RR = 0.88; 95% CI, 0.47 to 1.64) of malaria. The studies also showed a possible increase in the prevalence of lower respiratory tract infection (RR = 1.20; 95% CI, 1.10 to 1.30).

There appears to be some benefit of zinc supplementation on growth-related outcomes. The included studies demonstrated small but statistically significant beneficial effects of zinc on height (standardized mean difference [SMD] = −0.09; 95% CI, −0.13 to −0.06), weight (SMD = −0.10; 95% CI, −0.14 to −0.07), and weight-to-height ratio (SMD = −0.05; 95% CI, –0.10 to –0.01), although zinc supplementation does not appear to reduce the prevalence of stunting.

Although the authors of this Cochrane review did not find a statistically significant reduction in all-cause or disease-specific mortality from preventive zinc supplementation, reductions in the risk of diarrhea and improvements in growth measures are encouraging. Childhood mortality is multifactorial, especially in low- and middle-income countries. Preventive zinc supplementation is not a panacea. However, particularly for physicians in public health or policy-making roles, zinc supplementation does appear to be at least one potentially beneficial piece of the puzzle for reducing rates of diarrhea and growth restriction among children with zinc-deficient diets.