Two existing Cochrane systematic reviews assessing the effects and safety of vitamin A supplementation in children 6–59 months of age were updated for this guideline (4, 18). One review evaluated the effectiveness of vitamin A supplements in the prevention of morbidity and mortality in children 6–59 months of age (4). It showed that giving vitamin A supplements to children reduces the rates of mortality and some diseases. A meta-analysis of 17 trials (11 in Asia, 5 in Africa and 1 in Latin America) for all-cause mortality indicated that vitamin A reduces the overall risk of death by 24% (risk ratio (RR) 0.76; 95% confidence interval (CI) 0.69–0.83). When an unpublished cluster-randomized trial involving one million children in north India (the DEVTA trial) was considered, vitamin A supplementation reduced the effect size of all-cause mortality from 24% to 12% (RR 0.88; 95% CI 0.84–0.94). Due to limited availability of information on the DEVTA trial the quality of this trial could not be assessed.
Seven trials indicated that vitamin A supplementation significantly reduces diarrhoea-related mortality (RR 0.72; 95% CI 0.57–0.91), although mortality specifically due to measles (five trials: RR 0.80; 95% CI 0.51–1.24) or respiratory disease (seven trials: RR 0.78; 95% CI 0.54–1.14) was not reduced. The occurrence of new episodes of diarrhoea decreased (13 trials: RR 0.85; 95% CI 0.82–0.87). There was no significant effect on the incidence of respiratory disease (nine trials: RR 1.14; 95% CI 0.95–1.37), or hospitalizations due to diarrhoea or pneumonia.
There was a significantly increased risk of vomiting within the first 48 hours of supplementation with 100 000–200 000 IU of vitamin A (three trials: RR 2.75; 95% CI 1.81–4.19). Only one study reported data on bulging fontanelles as most studies included children over 1 year of age and thus would not have assessed this side-effect. There was no significant effect of vitamin A supplementation when the data were stratified by national child mortality rates (data from countries with low versus high child mortality rates) (4). It was not possible to perform subgroup analyses for dose and frequency of supplementation as the analyses were underpowered and any effects would have been attributed to chance.
The second review assessed whether micronutrient supplements, including vitamin A, are safe and effective in reducing morbidity and mortality in adults and children with human immunodeficiency virus (HIV) infection (18). It included five trials on vitamin A supplementation in children with a total of 1120 participants; only three trials (262 participants, all in Africa) contributed data on all-cause mortality. The data suggest that vitamin A reduces the overall risk of death (RR 0.55; 95% CI 0.37–0.82).
The overall quality of the evidence for all-cause mortality was high, whereas it was moderate to very low for the remaining critical outcomes (Annex 1). The quality of the available evidence for outcomes in HIV-positive children was moderate for all-cause mortality.
The effect of vitamin A supplementation on antibody response to measles vaccination has recently been evaluated in an additional review (19). A meta-analysis of seven trials indicated that vitamin A supplementation at 6 or 9 months of age did not affect the measles vaccine response (seroconversion rates). No study has prospectively assessed the impact of co-administration of vitamin A and measles vaccine on child mortality.
