Zinc supplementation for preventing mortality, morbidity, and growth failure in children aged 6 months to 12 years of age.
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.


OBJECTIVE
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.


METHODS
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.


METHODS
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.


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


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.


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.
Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore MD, MD, USA, 21205.
Evan
E
Mayo-Wilson
Jean A
JA
Junior
Aamer
A
Imdad
Sohni
S
Dean
Xin Hui S
XH
Chan
Evelyn S
ES
Chan
Aneil
A
Jaswal
Zulfiqar A
ZA
Bhutta
D002423:Cause of Death; D002648:Child; D046688:Child Mortality; D002675:Child, Preschool; D003967:Diarrhea / Q000401:mortality; D005260:Female; D006130:Growth Disorders / Q000517:prevention & control*; D006801:Humans; D007223:Infant; D007226:Infant Mortality; D008288:Malaria / Q000401:mortality; D008297:Male; D009017:Morbidity; D016032:Randomized Controlled Trials as Topic; D012141:Respiratory Tract Infections / Q000401:mortality; D014131:Trace Elements / Q000008:administration & dosage* / Q000009:adverse effects; D015032:Zinc / Q000008:administration & dosage* / Q000009:adverse effects / Q000172:deficiency*
D014131:Trace Elements; D015032:Zinc