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

Abstract

ObjectiveZinc 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.DesignSystematic 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 sourcesWe searched multiple databases, including CENTRAL and MEDLINE in January 2013. Authors were contacted for missing information.Eligibility criteria for selecting studiesRandomised trials of preventive zinc supplementation. Hospitalised children and children with chronic diseases were excluded.Results80 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.ConclusionsBenefits 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.

A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection

“…An analysis of mostly high-quality studies has demonstrated that the risk of RTI or pneumonia and diarrhea or dysentery may be reduced in children after zinc administration [207]. However, analysis of low-to-moderate quality studies found no protective effect of zinc (5 to ≥20 mg/day) against the risk of RTI or malaria in children, although there was a reduction in mortality associated with RTI, diarrhea, and malaria; the addition of iron to zinc conferred no additional benefits [208,209].…”

Zinc deficiency as risk factor for stunting among children aged 2-5 years

“…Iron and zinc play a role in the immune system. (23) The immune responses by T lymphocytes will be disturbed upon a decrease in the production of cells, which is caused by decreased DNA synthesis, so that iron and zinc deficiencies may cause disorders of the immune system. (26) Children with disorders of the immune system are more susceptible to infectious disease, thus affecting nutritional status.…”

“…(22) Underfives with iron deficiency are more suceptible to microorganisms, because iron deficiency is closely associated with damaged functional capacity of the immune defense mechanism that is important for the entry of infectious disease. (23) Iron plays a role in the immune system. The immune responses by the T lymphocytes will be disturbed upon decreased production of cells, which is caused by decreased DNA synthesis.…”

Iron deficiency anaemia: experiences and challenges

“…absorbed iron fraction) (21)(22)(23)(24) . Meta-analysis of trials involving nearly 10 000 young children in developing countries have consistently shown that conventional soluble oral iron supplementation used to treat IDA is associated with increased infection including bloody diarrhoea (22,(25)(26)(27) and detrimental changes to the gut microbiome and gut inflammation (27,28) , further increasing the burden from enteric infection and environmental enteropathy (i.e. persistent gut damage and inflammation that leads to malabsorption), which is a major cause of growth failure in children in resource-poor environments (29,30) .…”