Zinc supplementation for preventing death and disease, and for growth, in children aged six months to 12 years of age

Review question

This review investigated the effectiveness of zinc supplementation for preventing illness and mortality, and for promoting growth, in children between six months and 12 years of age.

Background

Zinc is an essential micronutrient and zinc deficiency is an important public health problem in low- and middle-income countries. Zinc deficiency impairs growth and contributes to numerous child deaths per year due to diarrhoea, pneumonia, and malaria. This review aimed to determine if giving children zinc supplements would help prevent child death, disease, and growth deficits.

Study characteristics

We searched a wide range of electronic databases for studies that randomly assigned children aged six months to 12 years to either zinc supplementation or a control group that did not receive zinc. Eighty randomised studies with 205,401 eligible participants were included in this review. The evidence is current to December 2012.

Key results and the quality of the evidence

Giving children zinc supplements might reduce their risk of death in general, and their risk of death due to diarrhoea, lower respiratory tract infection (LRTI), or malaria. The quality of evidence for overall mortality was high, though evidence for other critical outcomes was only moderate. Children given zinc experience less diarrhoeal disease than children not given zinc; however, zinc does not seem to reduce children's risk of respiratory infection or malaria. Zinc supplementation may have a very small effect on growth, but eating more calories would probably have a larger effect for many malnourished children. Children who take zinc supplements may experience vomiting as a side effect.

Authors' conclusions: 

In our opinion, the benefits of preventive zinc supplementation outweigh the harms in areas where the risk of zinc deficiency is relatively high. Further research should determine optimal intervention characteristics such as supplement dose.

Read the full abstract...
Background: 

Zinc deficiency is prevalent in low- and middle-income countries, and contributes to significant diarrhoea-, pneumonia-, and malaria-related morbidity and mortality among young children. Zinc deficiency also impairs growth.

Objectives: 

To assess the effects of zinc supplementation for preventing mortality and morbidity, and for promoting growth, in children aged six months to 12 years of age.

Search strategy: 

Between December 2012 and January 2013, we searched CENTRAL, MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, Embase, African Index Medicus, Conference Proceedings Citation Index, Dissertation Abstracts, Global Health, IndMED, LILACS, WHOLIS, metaRegister of Controlled Trials, and WHO ICTRP.

Selection criteria: 

Randomised controlled trials of preventive zinc supplementation in children aged six months to 12 years compared with no intervention, a placebo, or a waiting list control. We excluded hospitalised children and children with chronic diseases or conditions. We excluded food fortification or intake, sprinkles, and therapeutic interventions.

Data collection and analysis: 

Two authors screened studies, extracted data, and assessed risk of bias. We contacted trial authors for missing information.

Main results: 

We included 80 randomised controlled trials with 205,401 eligible participants. We did not consider that the evidence for the key analyses of morbidity and mortality outcomes were affected by risk of bias. The risk ratio (RR) for all-cause mortality was compatible with a reduction and a small increased risk of death with zinc supplementation (RR 0.95, 95% confidence interval (CI) 0.86 to 1.05, 14 studies, high-quality evidence), and also for cause-specific mortality due to diarrhoea (RR 0.95, 95% CI 0.69 to 1.31, four studies, moderate-quality evidence), lower respiratory tract infection (LRTI) (RR 0.86, 95% CI 0.64 to 1.15, three studies, moderate-quality evidence), or malaria (RR 0.90, 95% CI 0.77 to 1.06, two studies, moderate-quality evidence).

Supplementation reduced diarrhoea morbidity, including the incidence of all-cause diarrhoea (RR 0.87, 95% CI 0.85 to 0.89, 26 studies, moderate-quality evidence), but the results for LRTI and malaria were imprecise: LRTI (RR 1, 95% CI 0.94 to 1.07, 12 studies, moderate-quality evidence); malaria (RR 1.05, 95% 0.95 to 1.15, four studies, moderate-quality evidence).

There was moderate-quality evidence of a very small improvement in height with supplementation (standardised mean difference (SMD) -0.09, 95% CI -0.13 to -0.06; 50 studies), but the size of this effect might not be clinically important. There was a medium to large positive effect on zinc status.

Supplementation was associated with an increase in the number of participants with at least one vomiting episode (RR 1.29, 95% CI 1.14 to 1.46, five studies, high-quality evidence). We found no clear evidence of benefit or harm of supplementation with regard to haemoglobin or iron status. Supplementation had a negative effect on copper status.

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