High-dose oral vitamin D supplementation for prevention of infections in children aged 0 to 59 months: a systematic review and meta-analysis

Abstract

Context: Vitamin D plays an important role in immune function, and the deficiency thereof has been associated with several infections, most notably respiratory tract infections. However, data from intervention studies investigating the effect of high-dose vitamin D supplementation on infections have been inconclusive.

Objective: The aim of this study was to evaluate the level of evidence regarding the efficacy of vitamin D supplementation above the standard dose (400 IU) in preventing infections in apparently healthy children < 5 years of age.

Data sources: PubMed, Scopus, Science Direct, Web of Science, Google Scholar, CINAHL, and MEDLINE electronic databases were searched between August 2022 and November 2022. Seven studies met the inclusion criteria.

Data extraction: Meta-analyses of outcomes in more than one study were performed using Review Manager software. Heterogeneity was evaluated using the I2 statistic. Randomized controlled trials in which vitamin D was supplemented at > 400 IU compared with placebo, no treatment, or standard dose were included.

Data analysis: Seven trials that enrolled a total of 5748 children were included. Odds ratios (ORs) with 95%CIs were calculated using random- and fixed-effects models. There was no significant effect of high-dose vitamin D supplementation on the incidence of upper respiratory tract infection (OR, 0.83; 95%CI, 0.62-1.10). There was a 57% (95%CI, 0.30-0.61), 56% (95%CI, 0.27-0.07), and 59% (95%CI, 0.26-0.65) reduction in the odds of influenza/cold, cough, and fever incidence, respectively, with daily supplementation of vitamin D > 1000 IU. No effect was found on bronchitis, otitis media, diarrhea/gastroenteritis, primary care visits for infections, hospitalizations, or mortality.

Conclusion: High-dose vitamin D supplementation provided no benefit in preventing upper respiratory tract infections (moderate certainty of evidence) but reduced the incidence influenza/cold (moderate certainty of evidence), cough, and fever (low certainty of evidence). These findings are based on a limited number of trials and should be interpreted with caution. Further research is needed.

Systematic review registration: PROSPERO registration number CRD42022355206.

Keywords: children; infections; pneumonia; upper respiratory tract infection; vitamin D supplementation.

Figure 1

Flow diagram of the literature search process.

Figure 2

Summary of the risk of bias of studies included in the systematic review.

Figure 3

Forest plot of the meta-analysis of the effect of vitamin D supplementation on the incidence of upper respiratory tract infection. Abbreviation: M-H, Mantel-Haenszel.

Figure 4

Forest plot of the meta-analysis of the effect of vitamin D supplementation on the incidence of pneumonia. Abbreviation: M-H, Mantel-Haenszel.

Figure 5

Subgroup analysis of the effect of supplementation with > 1000 IU of vitamin D per day on the incidence of cold/influenza. Abbreviation: M-H, Mantel-Haenszel.

Figure 6

Forest plot of the effect of vitamin D supplementation on the incidence of cough. Abbreviation: M-H, Mantel-Haenszel.

Figure 7

Forest plot of the effect of vitamin D supplementation on the incidence of fever. Abbreviation: M-H, Mantel-Haenszel.