Vitamin A supplements for preventing mortality, illness, and blindness in children aged under 5: systematic review and meta-analysis

Abstract

Objective: To determine if vitamin A supplementation is associated with reductions in mortality and morbidity in children aged 6 months to 5 years.

Design: Systematic review and meta-analysis. Two reviewers independently assessed studies for inclusion. Data were double extracted; discrepancies were resolved by discussion. Meta-analyses were performed for mortality, illness, vision, and side effects.

Data sources: Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, Medline, Embase, Global Health, Latin American and Caribbean Health Sciences, metaRegister of Controlled Trials, and African Index Medicus. Databases were searched to April 2010 without restriction by language or publication status.

Eligibility criteria for selecting studies: Randomised trials of synthetic oral vitamin A supplements in children aged 6 months to 5 years. Studies of children with current illness (such as diarrhoea, measles, and HIV), studies of children in hospital, and studies of food fortification or β carotene were excluded.

Results: 43 trials with about 215,633 children were included. Seventeen trials including 194,483 participants reported a 24% reduction in all cause mortality (rate ratio=0.76, 95% confidence interval 0.69 to 0.83). Seven trials reported a 28% reduction in mortality associated with diarrhoea (0.72, 0.57 to 0.91). Vitamin A supplementation was associated with a reduced incidence of diarrhoea (0.85, 0.82 to 0.87) and measles (0.50, 0.37 to 0.67) and a reduced prevalence of vision problems, including night blindness (0.32, 0.21 to 0.50) and xerophthalmia (0.31, 0.22 to 0.45). Three trials reported an increased risk of vomiting within the first 48 hours of supplementation (2.75, 1.81 to 4.19).

Conclusions: Vitamin A supplementation is associated with large reductions in mortality, morbidity, and vision problems in a range of settings, and these results cannot be explained by bias. Further placebo controlled trials of vitamin A supplementation in children between 6 and 59 months of age are not required. However, there is a need for further studies comparing different doses and delivery mechanisms (for example, fortification). Until other sources are available, vitamin A supplements should be given to all children at risk of deficiency, particularly in low and middle income countries.

Fig 1 Identification of studies to include in review of effect of vitamin A supplementation on mortality, illness, and blindness in children aged under 5

Fig 2 Assessment of risk of bias in studies on effect of vitamin A supplementation on mortality, illness, and blindness in children aged under 5

Fig 3 All cause mortality in studies on effect of vitamin A supplementation in children aged under 5

Fig 4 All cause mortality sensitivity analysis in studies on effect of vitamin A supplementation in children aged under 5, including deworming and vitamin A (DEVTA) trial

Fig 5 All cause mortality by dose in studies on effect of vitamin A supplementation in children aged under 5

Fig 6 Mortality funnel plot with trim and fill in studies on effect of vitamin A supplementation in children aged under 5. Observed=included studies. Imputed=observed effects trimmed to make funnel plot symmetrical, opposite effects imputed, trimmed studies and imputed effects replaced

Fig 7 Incidence of diarrhoea in studies on effect of vitamin A supplementation in children aged under 5

Fig 8 Incidence of measles in studies on effect of vitamin A supplementation in children aged under 5

Fig 9 All cause mortality cumulative meta-analysis in studies on effect of vitamin A supplementation in children aged under 5