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Study flow diagram.
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Figure 1

Study flow diagram.

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'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included trials.
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Figure 2

'Risk of bias' graph: review authors' judgements about each 'Risk of bias' item presented as percentages across all included trials.

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'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included trial.
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Figure 3

'Risk of bias' summary: review authors' judgements about each 'Risk of bias' item for each included trial.

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Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.1 Incidence rate radiologically confirmed first or only episode of pneumonia.
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Figure 4

Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.1 Incidence rate radiologically confirmed first or only episode of pneumonia.

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Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.2 All‐cause mortality.
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Figure 5

Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.2 All‐cause mortality.

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Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.4 Mean serum vitamin D concentrations in ng/mL.
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Figure 6

Forest plot of comparison: 1 Vitamin D versus control, outcome: 1.4 Mean serum vitamin D concentrations in ng/mL.

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Comparison 1 Vitamin D versus control, Outcome 1 Incidence rate radiologically confirmed first or only episode of pneumonia.
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Analysis 1.1

Comparison 1 Vitamin D versus control, Outcome 1 Incidence rate radiologically confirmed first or only episode of pneumonia.

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Comparison 1 Vitamin D versus control, Outcome 2 All‐cause mortality.
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Analysis 1.2

Comparison 1 Vitamin D versus control, Outcome 2 All‐cause mortality.

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Comparison 1 Vitamin D versus control, Outcome 3 Any hospital admission.
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Analysis 1.3

Comparison 1 Vitamin D versus control, Outcome 3 Any hospital admission.

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Comparison 1 Vitamin D versus control, Outcome 4 End of supplementation mean serum vitamin D concentrations in ng/mL.
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Analysis 1.4

Comparison 1 Vitamin D versus control, Outcome 4 End of supplementation mean serum vitamin D concentrations in ng/mL.

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Comparison 1 Vitamin D versus control, Outcome 5 Baseline mean serum vitamin D concentrations in ng/mL.
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Analysis 1.5

Comparison 1 Vitamin D versus control, Outcome 5 Baseline mean serum vitamin D concentrations in ng/mL.

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Summary of findings for the main comparison. Vitamin D versus control for preventing infections in children under five years of age

Vitamin D versus control for preventing infections in children under five years of age

Patient or population: children under five years of age
Settings: hospitals, clinics, and community
Intervention: vitamin D supplementation (daily dose of 402 IU or quarterly supplementation of 100,000 IU)

Control: placebo or no supplementation

Outcomes

Illustrative comparative risks* (95% CI)

Relative/absolute effect
(95% CI)

Number of participants
(trials)

Quality of the evidence
(GRADE)

Assumed risk

Corresponding risk

Control

Vitamin D

All‐cause mortality

5 per 1000

7 per 1000
(3 to 19)

Risk ratio 1.43
(0.54 to 3.74)

3046

(1)

⊕⊕⊝⊝
low1,2

Cause‐specific mortality

3 per 1000

5 per 1000

(1 to 16)

Risk ratio 1.50
(0.42 to 5.30)

3046

(1)

⊕⊕⊝⊝
low1,2

Incidence rate radiologically confirmed first or only episode of pneumonia

157 episodes per 1000 person‐years

166 episodes per 1000 person years
(140 to 198)

Rate ratio 1.06
(0.89 to 1.26)

3134
(2)

⊕⊕⊕⊝
moderate2,3

Any hospital admission

9 per 100

8 per 100

(2 to 33`)

Risk ratio 0.86

(0.20 to 3.62)

88

(1)

⊕⊝⊝⊝
very low4,5,6

TB cases

‐

‐

‐

0 studies

‐

Diarrhoea cases

‐

‐

‐

2 studies7

‐

Malaria cases

‐

‐

‐

0 studies

‐

Febrile illness

‐

‐

‐

0 studies

‐

Mean serum vitamin D concentrations

141

125

Mean difference 7.72ng/mL higher (0.50 higher to 14.93 higher)

266

(4)

⊕⊕⊝⊝
low2,8

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
Abbreviations: CI: confidence interval; RR: risk ratio; GRADE: Grading of Recommendations Assessment, Development and Evaluation; TB: tuberculosis; HR: hazard ratio.

GRADE Working Group grades of evidence
High quality: further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: we are very uncertain about the estimate.

1Downgraded by 1 for imprecision: the estimate varies from 46% decrease to over 3‐fold increase for all‐cause mortality; and from 58% decrease to over 5‐fold increase for cause‐specific mortality.
2Downgraded by 1 for indirectness: data comes mainly from a single large trial conducted in Afghanistan with a high baseline prevalence of vitamin D deficiency limiting the generalizability of the estimate to developed countries. However, findings from this setting would be generalizable to majority of other developing countries.
3Imprecision: no serious imprecision as the Afghanistan trial was adequately powered to detect clinically important benefits with vitamin D. The 95% CI of the result is narrow and probably excludes clinically important benefits.
4Downgraded by 1 for high risk of bias in Alonso 2011 due to unblinding, high/differential loss to follow‐up and selective outcome reporting.
5Downgraded by 1 for indirectness: data comes mainly from one trial in developed country limiting the generalizability of the estimate to developing countries.
6The effect estimates are also imprecise with wide CIs.
7No effect however meta‐analysis could not be performed since Alonso 2011 reported the RR while Manaseki‐Holland 2012 reported the HR.
8Downgraded by 1 for imprecision: the estimate varies from 0.50 to over 14.00 ng/mL increase.

Figuras y tablas -
Summary of findings for the main comparison. Vitamin D versus control for preventing infections in children under five years of age
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Comparison 1. Vitamin D versus control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Incidence rate radiologically confirmed first or only episode of pneumonia Show forest plot

2

3134

Rate Ratio (Fixed, 95% CI)

1.06 [0.89, 1.26]

2 All‐cause mortality Show forest plot

1

Risk Ratio (M‐H, Fixed, 95% CI)

Subtotals only

3 Any hospital admission Show forest plot

1

88

Risk Ratio (M‐H, Fixed, 95% CI)

0.86 [0.20, 3.62]

4 End of supplementation mean serum vitamin D concentrations in ng/mL Show forest plot

4

266

Mean Difference (IV, Random, 95% CI)

7.72 [0.50, 14.93]

5 Baseline mean serum vitamin D concentrations in ng/mL Show forest plot

1

46

Mean Difference (IV, Fixed, 95% CI)

0.34 [‐3.30, 3.98]
Figuras y tablas -
Comparison 1. Vitamin D versus control
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