Background
Acute upper respiratory tract infections (URTIs) are the most common acute infectious diseases in children, especially in preschool children. Vitamin A has a positive role in the immune system and may improve the host's defences against infections. Studies show that children with vitamin deficiency are more likely to suffer from respiratory tract infections. Therefore, we assessed the role of vitamin A supplementation in the prevention of acute upper respiratory tract infections in preschool children (up to seven years of age).
Review question
What is the role of vitamin A supplementation in the prevention of acute URTIs in preschool children (up to seven years of age), compared to no supplementation?
Search date
We searched for evidence up to 8 June 2023.
Study characteristics
All included studies were conducted in lower- and middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas more likely to experience malnutrition and dry eye. In two studies, vitamin E was a co-treatment administered in addition to vitamin A.
Key results
We included six studies involving 27,351 participants. We have very low to low confidence in the evidence provided by the studies.
Five studies reported the number of acute URTIs over a period of time. The included studies varied by population and the results were presented in different forms, so we could only combine three studies together (meta-analysis). We are uncertain if vitamin A supplementation lowers the number of acute URTIs over a two-week period (three studies, 22,668 participants). Two studies reported the proportion of participants with acute URTI. The effect of vitamin A supplementation on the proportion of participants with acute URTI is uncertain (two studies, 15,535 participants). Only one study (116 participants) reported adverse events and none occurred in infants in the placebo or vitamin A groups.
Two studies (296 participants) reported the severity of subjective symptoms, presented by the average duration of acute URTIs. Vitamin A may have little to no effect on the average duration of acute URTIs.
Authors' conclusions
From evidence in which we have very low to low confidence, we found that there may be no benefit in using vitamin A supplementation to prevent acute URTIs in children up to seven years of age. High-quality studies focusing on preschool children with vitamin A deficiency are needed to identify whether vitamin A supplementation may be effective.
The evidence for the use of vitamin A supplementation to prevent acute URTI is uncertain, because population, dose and duration of interventions, and outcomes vary between studies. From generally very low- to low-certainty evidence, we found that there may be no benefit in the use of vitamin A supplementation to prevent acute URTI in children up to seven years of age. More RCTs are needed to strengthen the current evidence. Future research should report over longer time frames using validated tools and consistent reporting, and ensure adequate power calculations, to allow for easier synthesis of data. Finally, it is important to assess vitamin A supplementation for preschool children with vitamin A deficiency.
According to global prevalence analysis studies, acute upper respiratory tract infections (URTIs) are the most common acute infectious disease in children, especially in preschool children. Acute URTIs lead to an economic burden on families and society. Vitamin A refers to the fat-soluble compound all-trans-retinol and also represents retinol and its active metabolites. Vitamin A interacts with both the innate immune system and the adaptive immune system and improves the host's defences against infections. Correlation studies show that serum retinol deficiency was associated with a higher risk of respiratory tract infections. Therefore, vitamin A supplementation may be important in preventing acute URTIs.
To assess the effectiveness and safety of vitamin A supplements for preventing acute upper respiratory tract infections in children up to seven years of age.
We searched CENTRAL, MEDLINE, Embase, the Chinese Biomedical Literature Database, and two trial registration platforms to 8 June 2023. We also checked the reference lists of all primary studies and reviewed relevant systematic reviews and trials for additional references. We imposed no language or publication restrictions.
We included randomised controlled trials (RCTs), which evaluated the role of vitamin A supplementation in the prevention of acute URTIs in children up to seven years of age.
We used the standard methodological procedures expected by Cochrane.
We included six studies (27,351 participants). Four studies were RCTs and two were cluster-RCTs. The included studies were all conducted in lower-middle-income countries (two in India, two in South Africa, one in Ecuador, and one in Haiti). Three studies included healthy children who had no vitamin A deficiency, one study included children born to HIV-infected women, one study included low-birthweight neonates, and one study included children in areas with a high local prevalence of malnutrition and xerophthalmia. In two studies, vitamin E was a co-treatment administered in addition to vitamin A. We judged the included studies to be at either a high or unclear risk of bias for random sequence generation, incomplete outcome data, and blinding.
Primary outcomes
Six studies reported the incidence of acute URTIs during the study period. Five studies reported the number of acute URTIs over a period of time, but there was population heterogeneity and the results were presented in different forms, therefore only three studies were meta-analysed. We are uncertain of the effect of vitamin A supplementation on the number of acute URTIs over two weeks (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.09; I2 = 44%; 3 studies, 22,668 participants; low-certainty evidence). Two studies reported the proportion of participants with an acute URTI. We are uncertain of the effect of vitamin A supplementation on the proportion of participants with an acute URTI (2 studies, 15,535 participants; low-certainty evidence). Only one study (116 participants) reported adverse events. No infant in either the placebo or vitamin A group was found to have feeding difficulties (failure to feed or vomiting), a bulging fontanelle, or neurological signs before or after vitamin A administration (very low-certainty evidence).
Secondary outcomes
Two studies (296 participants) reported the severity of subjective symptoms, presented by the mean duration of acute URTI. Vitamin A may have little to no effect on the mean duration of acute URTI (very low-certainty evidence).