Vitamin D for preventing acute respiratory infections in children up to five years of age.

rationaleAcute respiratory infections (ARIs) are a leading cause of morbidity and mortality in children under five years of age and contribute to healthcare visits and hospitalisations globally. Vitamin D deficiency is common amongst pregnant women and young children. Given that vitamin D supplementation is safe, affordable, and easy to administer, its potential to reduce ARI-related healthcare visits holds substantial public health relevance. This review evaluates the benefit and harm of vitamin D supplementation in preventing ARI-related healthcare visits in young children, aiming to inform supplementation policies during pregnancy and early childhood.

objectivesTo determine the benefit and harm of vitamin D supplementation for preventing ARIs in children up to five years of age. SEARCH

methodsWe searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, Web of Science, WHO Global Index Medicus, and four clinical trial registries on 18 March 2025. ELIGIBILITY CRITERIA: We included randomised controlled trials (RCTs) comparing vitamin D to placebo, or a higher dose (≥ 1000 IU) versus a lower dose (≤ 1000 IU) administered from early pregnancy through to five years of age. We excluded studies involving children with chronic respiratory or systemic conditions. OUTCOMES: Critical outcomes: 1) healthcare visits made by children for an ARI: (a) the proportion of children with healthcare visits made for ARIs; (b) the mean number of healthcare visits made for ARIs per child; and 2) hypercalcaemia: the number of pregnant women and children with hypercalcaemia. RISK OF BIAS: We assessed risk of bias using the Cochrane risk of bias (RoB) 1 tool for outcomes reported in the summary of findings tables. SYNTHESIS

methodsWe synthesised outcome data using meta-analyses, calculating risk ratios (RR) for dichotomous, and mean differences (MD) for continuous outcomes, each with 95% confidence intervals (CI). Where meta-analysis was not feasible, we summarised the results narratively. We used GRADE to assess the certainty of the evidence for pre-specified outcomes. INCLUDED STUDIES: We included 107 RCTs involving 31,521 participants. Vitamin D supplementation was administered during pregnancy, early childhood, or both, and in some cases to both infants and lactating mothers. Interventions used vitamin D SYNTHESIS OF

resultsVitamin D supplementation may result in a slight reduction in the proportion of children who make ARI-related healthcare visits compared to placebo (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.91 to 1.00; P = 0.03; 10 studies, 2447 participants; low-certainty evidence), but probably does not reduce the mean number of ARI-related healthcare visits per child (mean difference (MD) 0.07, 95% CI -0.06 to 0.20; P = 0.32; 3 studies, 561 participants; moderate-certainty evidence). Comparisons between higher and lower doses of vitamin D probably do not reduce the proportion of children making ARI-related healthcare visits (RR 0.94, 95% CI 0.81 to 1.10; P = 0.46; 2 studies, 1382 participants; moderate-certainty evidence), and do not reduce the mean number of ARI-related healthcare visits per child (MD -0.10, 95% CI -0.59 to 0.39; P = 0.69; 1 study, 579 participants; low-certainty evidence). No cases of hypercalcaemia were reported among pregnant women in trials comparing vitamin D supplementation with placebo. In higher versus lower dose comparisons, supplementation may result in little to no difference in the risk of hypercalcaemia among pregnant women (RR 1.61, 95% CI 0.60 to 4.31; P = 0.34; 6 studies, 2379 participants; low-certainty evidence). Similarly, the evidence that vitamin D supplementation has little to no effect on the risk of hypercalcaemia in children, when compared with placebo, is very uncertain (RR 0.81, 95% CI 0.53 to 1.24; 7 studies, 1542 participants; very low-certainty evidence) and may result in little to no difference in the risk of hypercalcaemia in children when higher doses are compared to lower doses (RR 1.23, 95% CI 0.82 to 1.85; 7 studies, 1287 participants; low-certainty evidence). AUTHORS'

conclusionsWe found low-certainty evidence that vitamin D supplementation during pregnancy or early childhood may result in a slight reduction in the proportion of children under five years of age who make ARI-related healthcare visits, but probably does not reduce the mean number of healthcare visits for ARIs per child. This finding highlights the need for large, well-designed, placebo-controlled trials to confirm the potential benefit. We found moderate-certainty evidence that higher-dose vitamin D supplementation, compared with lower doses, probably does not reduce the proportion of children making healthcare visits for ARIs and does not reduce the mean number of ARI-related healthcare visits per child. Hypercalcaemia occurs infrequently in both pregnant women and children receiving vitamin D supplementation. Where hypercalcaemia could be measured, specifically in children receiving vitamin D versus placebo, vitamin D supplementation may have little to no effect on the risk of hypercalcaemia (very low-certainty evidence). In both children and pregnant women, a higher dose of vitamin D compared to a lower dose may result in little to no difference in the risk of hypercalcaemia (low-certainty evidence).

fundingThis Cochrane review had no dedicated funding. REGISTRATION: Protocol (2022) DOI: 10.1002/14651858.CD015111.