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Background: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation for children aged 6 to 59 months. There are new data available from recently published randomised trials since the previous publication of this review in 2010, and this update incorporates this information and reviews the evidence., Objectives: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years., Search Methods: In March 2016 we searched CENTRAL, Ovid MEDLINE, Embase, six other databases, and two trials registers. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies., Selection Criteria: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation., Data Collection and Analysis: For this update, two reviewers independently assessed studies for inclusion and abstracted data, resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence., Main Results: We identified 47 studies (4 of which are new to this review), involving approximately 1,223,856 children. Studies took place in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most of the studies included equal numbers of girls and boys and lasted about a year. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for vitamin A compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-quality evidence). This result was sensitive to choice of model, and a random-effects meta-analysis showed a different summary estimate (24% reduction: RR 0.76, 95% CI 0.66 to 0.88); however, the confidence intervals overlapped with that of the fixed-effect model. Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 participants; high-quality evidence). There was no significant effect for VAS on mortality due to measles, respiratory disease, and meningitis. VAS reduced incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies; 77,946 participants; low-quality evidence) and measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies; 19,566 participants; moderate-quality evidence). However, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies; 10,541 participants; moderate-quality evidence)., Authors' Conclusions: Vitamin A supplementation is associated with a clinically meaningful reduction in morbidity and mortality in children. Therefore, we suggest maintaining the policy of universal supplementation for children under five years of age in populations at risk of VAD. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented vitamin A deficiency, it would be unethical to conduct placebo-controlled trials.

Background: Vitamin A deficiency is a significant public health problem in low and middle income countries. Vitamin A supplementation (VAS) provided to lactating postpartum mothers or to infants less than six months of age are two possible strategies to improve the nutrition of infants at high risk of vitamin A deficiency and thus potentially reduce their mortality and morbidity., Objectives: To evaluate the effect of:1. VAS in postpartum breast feeding mothers in low and middle income countries, irrespective of antenatal VAS status, on mortality, morbidity and adverse effects in their infants up until the age of one year.2. VAS initiated in the first half of infancy (< 6 months of age) in low and middle income countries, irrespective of maternal antenatal or postnatal VAS status, on mortality, morbidity and adverse effects up until the age of one year., Search Strategy: The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), EMBASE, MEDLINE, clinical trials websites, conference proceedings, donor agencies, 'experts' and researchers (up to October 15, 2010)., Selection Criteria: Randomized or quasi-randomised, individually or cluster randomised, placebo controlled trials involving synthetic VAS provided to the postpartum mothers or their infants up to the age of six months were eligible., Data Collection and Analysis: Two review authors assessed the studies for their risk of bias and collected data on outcomes., Main Results: Of the 18 included studies, eight provided information on maternal VAS and 15 on infant VAS.For maternal VAS, there was no evidence of a reduced risk of mortality of their babies during infancy (96,203 participants, seven studies, high quality evidence; random-effects model RR 1.00, 95% CI 0.94 to 1.06, P = 0.9; test of heterogeneity I(2) = 0%, P = 0.9) or in the neonatal period (moderate quality evidence); nor of morbidities (very low quality evidence).  For infant VAS, there was no evidence of a reduced risk of mortality during infancy (59,402 participants, nine studies, moderate quality evidence; random-effects model RR 0.97, 0.83 to 1.12, P = 0.65; test of heterogeneity I(2) = 49%, P = 0.05) or in the neonatal period, nor morbidities (low quality evidence), but an increased risk of bulging fontanelle (32,978 participants, 10 studies, low quality evidence; random-effects model RR 1.55, 1.05 to 2.28, P = 0.03; test of heterogeneity I(2) = 68%, P = 0.0009)., Authors' Conclusions: There is no convincing evidence that either maternal postpartum or infant vitamin A supplementation results in a reduction in infant mortality or morbidity in low and middle income countries.

Background: Vitamin A deficiency (VAD) is a major public health problem in low and middle income countries affecting 190 million children under 5. VAD can lead to many adverse health consequences, including death., Objectives: To evaluate the effect of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged 6 months to 5 years., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2010 Issue 2),  MEDLINE (1950 to April Week 2 2010), EMBASE (1980 to 2010 Week 16), Global Health (1973 to March 2010), Latin American and Caribbean Health Sciences (LILACS), metaRegister of Controlled Trials and African Index Medicus (27 April 2010)., Selection Criteria: Randomised controlled trials (RCTs) and cluster RCTs evaluating the effect of synthetic VAS in children aged 6 months to 5 years living in the community. We excluded studies concerned with children in hospital and children with disease or infection. We excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods or beta-carotene supplementation., Data Collection and Analysis: Two review authors independently assessed studies for inclusion. Data were double abstracted and discrepancies were resolved by discussion. Meta-analyses were performed for outcomes including all-cause and cause-specific mortality, disease, vision, and side-effects., Main Results: 43 trials involving 215,633 children were included. A meta-analysis for all-cause mortality included 17 trials comprising 194,795 children with 3536 deaths in both groups. At follow-up, there was a 24% observed reduction in the risk of all-cause mortality for Vitamin A compared with Control (Relative risk (RR) = 0.76 [95% confidence interval (CI) 0.69, 0.83]). Seven trials reported diarrhoea mortality and a 28% overall reduction for VAS (RR = 0.72 [0.57, 0.91]). There was no significant effect of VAS on cause specific mortality of measles, respiratory disease and meningitis. VAS reduced incidence of diarrhoea (RR = 0.85 [0.82, 0.87]) and measles morbidity (RR = 0.50 [0.37, 0.67]); however, there was no significant effect on incidence of respiratory disease or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR = 2.75 [1.81, 4.19])., Authors' Conclusions: VAS is effective in reducing all-cause mortality by about 24% compared to no treatment. In our opinion, given the evidence that VAS causes considerable reduction in child mortality, further placebo-controlled trials of VAS in children between 6 months and 5 years of age are not required. There is a need for further studies comparing different doses and delivery mechanisms (for example, fortification).

Background: Measles is a major cause of childhood morbidity and mortality. Vitamin A deficiency is a recognized risk factor for severe measles infections. The World Health Organization (WHO) recommends administration of an oral dose of vitamin A (200,000 international units (IU), or 100,000 IU in infants) each day for two days to children with measles when they live in areas where vitamin A deficiency may be present., Objectives: To determine whether vitamin A therapy, commenced after measles has been diagnosed, is beneficial in preventing mortality, pneumonia and other secondary complications in children., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to March 2005), EMBASE (1980 to December 2004) and looked for unpublished studies., Selection Criteria: Only randomized controlled trials in which children with measles were given vitamin A or placebo along with standard treatment were considered., Data Collection and Analysis: Studies were assessed independently by two authors. The analysis of dichotomous outcomes was done using the StatXact software and results expressed as relative risk (RR) with 95% confidence interval (CI). Subgroup analyses were carried out for dose, formulation, age, hospitalization and pneumonia-specific mortality. Weighted mean differences (WMD) with 95% CI were calculated for continuous outcomes., Main Results: There was no significant reduction in the risk of mortality in the vitamin A group when all the studies were pooled using the random-effects model (RR 0.70; 95% CI 0.42 to 1.15). Using two doses of vitamin A (200,000 IU) on consecutive days was associated with a reduction in the risk of mortality in children under the age of two years (RR 0.18; 95% CI 0.03 to 0.61) and a reduction in the risk of pneumonia-specific mortality (RR 0.33; 95% CI 0.08 to 0.92). There was no evidence that vitamin A in a single dose was associated with a reduced risk of mortality among children with measles. There was a reduction in the incidence of croup (RR 0.53; 95% CI 0.29 to 0.89) but no significant reduction in the incidence of pneumonia (RR 0.92; 95% CI 0.69 to 1.22) or diarrhoea (RR 0.80; 95% CI 0.27 to 2.34) with two doses., Authors' Conclusions: Although we found no overall significant reduction in mortality with vitamin A therapy for children with measles there was evidence that two doses were associated with a reduced risk of mortality and pneumonia-specific mortality in children under the age of two years. There were no trials that directly compared a single dose with two doses.