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. 2016 Nov 9;11(11):CD008824.
doi: 10.1002/14651858.CD008824.pub2.

Vitamin D Supplementation for Preventing Infections in Children Under Five Years of Age

Free PMC article

Vitamin D Supplementation for Preventing Infections in Children Under Five Years of Age

Mohammad Y Yakoob et al. Cochrane Database Syst Rev. .
Free PMC article


Background: Vitamin D is a micronutrient important for bone growth and immune function. Deficiency can lead to rickets and has been linked to various infections, including respiratory infections. The evidence on the effects of supplementation on infections in children has not been assessed systematically.

Objectives: To evaluate the role of vitamin D supplementation in preventing pneumonia, tuberculosis (TB), diarrhoea, and malaria in children under five years of age. This includes high-, middle-, and low-income countries.

Search methods: We searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library, MEDLINE, EMBASE, LILACS, the WHO International Clinical Trials Registry Platform (ICTRP; , and the ISRCTN registry ( up to 16 June 2016.

Selection criteria: We included randomized controlled trials (RCTs) that evaluated preventive supplementation of vitamin D (versus placebo or no intervention) in children under five years of age.

Data collection and analysis: Two review authors independently screened the titles and abstracts, extracted the data, and assessed the risk of bias of included trials.

Main results: Four trials met the inclusion criteria, with a total of 3198 children under five years of age, and were conducted in Afghanistan, Spain, and the USA. Prevalence of vitamin D deficiency varied widely in these populations (range: 73.1% in Afghanistan, 10 to 12% in USA, and 6.2% in Spain). The included trials evaluated mortality (two trials), pneumonia incidence (two trials), diarrhoea incidence (two trials), hospitalization (two trials), and mean serum vitamin D concentrations (four trials).We do not know whether vitamin D supplementation impacts on all-cause mortality because this outcome was underpowered due to few events (risk ratio (RR) 1.43, 95% confidence interval (CI) 0.54 to 3.74; one trial, 3046 participants, low quality evidence).For pneumonia, episodes of 'radiologically confirmed' first or only episode of pneumonia were little different in the supplemented and unsupplemented group (Rate Ratio: 1.06, 95% confidence interval (CI) 0.89 to 1.26; two trials, 3134 participants, moderate quality evidence), and similarly for children with confirmed or unconfirmed pneumonia (RR 0.95, 95% CI 0.87 to 1.04; one trial, 3046 participants). In these two trials there were no obvious differences between supplemented and unsupplemented children regarding episodes of diarrhoea.In the single large trial from Afghanistan, the trial authors reported that vitamin D supplementation was associated with an increase in repeat episodes of pneumonia confirmed by chest radiograph (RR 1.69, 95% CI 1.28 to 2.21; one trial, 3046 participants), but not reflected in the outcome of confirmed or unconfirmed pneumonia (RR 1.06, 95% CI 1.00 to 1.13; one trial, 3046 participants).For hospital admission measured in one small trial, there was no difference detected (RR 0.86, 95% CI 0.20 to 3.62; one trial, 88 participants; very low quality evidence).The mean serum vitamin D concentrations were higher in supplemented compared to unsupplemented children at the end of supplementation (MD 7.72 ng/mL, 95% CI 0.50 to 14.93; four trials, 266 participants, low quality evidence). These results were driven primarily by two smaller trials with large magnitudes of effect. In the other two bigger trials, serum vitamin D concentrations were elevated in the intervention group for most of the trial duration but not at the end of supplementation. This may be due to time elapsed at measurement from the last dose, incomplete compliance, or increased need of vitamin D with infant age.We did not find any trial that reported on the incidence of TB, malaria or febrile illness, duration of pneumonia, duration of diarrhoea, severity of infection, and cause-specific mortality (due to TB, diarrhoea, or malaria).

Authors' conclusions: Evidence from one large trial did not demonstrate benefit of vitamin D supplementation on the incidence of pneumonia or diarrhoea in children under five years. To our knowledge, trials that evaluated supplementation for preventing other infections, including TB and malaria, have not been performed.

Conflict of interest statement

Dr. Zulfiqar Bhutta was a co‐investigator in the Manaseki‐Holland 2012 trial in Afghanistan, which we included in this Cochrane review.


Study flow diagram.
'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included trials.
'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included trial.
Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.1 Incidence rate radiologically confirmed first or only episode of pneumonia.
Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.2 All‐cause mortality.
Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.4 Mean serum vitamin D concentrations in ng/mL.
1.1. Analysis
Comparison 1 Vitamin D versus control, Outcome 1 Incidence rate radiologically confirmed first or only episode of pneumonia.
1.2. Analysis
Comparison 1 Vitamin D versus control, Outcome 2 All‐cause mortality.
1.3. Analysis
Comparison 1 Vitamin D versus control, Outcome 3 Any hospital admission.
1.4. Analysis
Comparison 1 Vitamin D versus control, Outcome 4 End of supplementation mean serum vitamin D concentrations in ng/mL.
1.5. Analysis
Comparison 1 Vitamin D versus control, Outcome 5 Baseline mean serum vitamin D concentrations in ng/mL.

Update of

  • Cochrane Database Syst Rev. doi: 10.1002/14651858.CD008824

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References to ongoing studies

ACTRN12616000659404 {unpublished data only}
    1. PREVARID ‐ PREVention of Acute Respiratory Infections with Vitamin D. Does vitamin D supplementation prevent acute respiratory infection health care visits among children under 2 years old? A randomized controlled trial. Ongoing study 1 July 2016.
NCT01229189 {unpublished data only}
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NCT01419821 {unpublished data only}
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