Preventive zinc supplementation for children, and the effect of additional iron: a systematic review and meta-analysis

BMJ Open

Jun 2014

DOI: 10.1136/bmjopen-2013-004647

Citations:68

Influential Citations:3

Systematic Reviews / Meta-Analyses

Enhanced Details

Methods

Randomized controlled trials of preventive zinc supplementation in children aged 6 months to 12 years; hospitalised and chronically ill excluded; 80 trials, about 205,923 participants; multi-country settings (32 countries), many in low- and middle-income countries; included both stunted and non-stunted children; some trials included children over 5 years; two independent reviewers conducted study selection and data extraction; meta-analyses performed for mortality, illness and side effects.

Intervention

Zinc supplementation regimens (alone or with iron cosupplementation). Dosing varied: daily 0–5 mg, 5–10 mg, 10–15 mg, 15–20 mg, or ≥20 mg; most dosing daily (48 studies) with some weekly (11). Duration: <6 months (30 studies), 6–12 months (33), ≥12 months (16). Zinc salts included sulfate (most common), gluconate, acetate. Some trials included iron cosupplementation (zinc with iron).

Results

All-cause diarrhoea incidence reduced by about 13% (RR 0.87; 0.85–0.89). No clear effect on all-cause mortality (RR 0.95; 0.86–1.05) or on respiratory infections or malaria. Very small improvement in linear growth (SMD 0.09; 0.06–0.13). Vomiting increased (RR 1.29; 1.14–1.46). No effect on iron status. Among studies comparing zinc with iron versus zinc alone, mortality differences were inconclusive; diarrhoea reduction was not evident when iron cosupplementation was used. Effects may be larger in children over 1 year and in settings with higher zinc deficiency. In high-deficiency settings, benefits may outweigh harms; optimal dose, formulation and delivery strategies require further study.

Limitations

Evidence quality varies; potential reporting bias for diarrhoea; substantial heterogeneity across studies; unable to identify an optimal zinc regimen; limited data for certain outcomes (e.g., mortality by age subgroup); few trials with iron cosupplementation; most data come from low- and middle-income countries.

Abstract

Objective Zinc deficiency is widespread, and preventive supplementation may have benefits in young children. Effects for children over 5 years of age, and effects when coadministered with other micronutrients are uncertain. These are obstacles to scale-up. This review seeks to determine if preventive supplementation reduces mortality and morbidity for children aged 6 months to 12 years. Design Systematic review conducted with the Cochrane Developmental, Psychosocial and Learning Problems Group. Two reviewers independently assessed studies. Meta-analyses were performed for mortality, illness and side effects. Data sources We searched multiple databases, including CENTRAL and MEDLINE in January 2013. Authors were contacted for missing information. Eligibility criteria for selecting studies Randomised trials of preventive zinc supplementation. Hospitalised children and children with chronic diseases were excluded. Results 80 randomised trials with 205 401 participants were included. There was a small but non-significant effect on all-cause mortality (risk ratio (RR) 0.95 (95% CI 0.86 to 1.05)). Supplementation may reduce incidence of all-cause diarrhoea (RR 0.87 (0.85 to 0.89)), but there was evidence of reporting bias. There was no evidence of an effect of incidence or prevalence of respiratory infections or malaria. There was moderate quality evidence of a very small effect on linear growth (standardised mean difference 0.09 (0.06 to 0.13)) and an increase in vomiting (RR 1.29 (1.14 to 1.46)). There was no evidence of an effect on iron status. Comparing zinc with and without iron cosupplementation and direct comparisons of zinc plus iron versus zinc administered alone favoured cointervention for some outcomes and zinc alone for other outcomes. Effects may be larger for children over 1 year of age, but most differences were not significant. Conclusions Benefits of preventive zinc supplementation may outweigh any potentially adverse effects in areas where risk of zinc deficiency is high. Further research should determine optimal intervention characteristics and delivery strategies. show less