Table 2.
Results of pairwise and dose–response meta-analysis
| Group | Study number; Patient number | Dose–response meta-analysis, RR (95% CI) | Pairwise Meta-analysis, RR (95% CI), NNT | ||
|---|---|---|---|---|---|
| 400 IU/d | 800 IU/d | 1200 IU/d | |||
| Main analysis | |||||
| All [28–70] | 43; 49,320 | 0.99 (0.98–1.01) | 0.99 (0.96–1.02) | 0.99 (0.96–1.02) | 0.99 (0.97–1.01) |
| Subgroup analysis | |||||
| Age group (years) | |||||
| < 7 [30, 32, 37, 39, 42, 51, 52, 54, 56, 60, 67, 69] | 12; 8826 | 0.95 (0.87–1.03) | 0.93 (0.83–1.04) | 0.93 (0.84–1.03) | 0.97 (0.91–1.13) |
| 7–17 [31, 33, 35, 44, 45, 55, 61, 64, 65] | 9; 11,525 | NA | NA | NA | 1.00 (0.96–1.04) |
| 18–65 [28, 29, 34, 38, 40, 41, 46, 47, 49, 50, 57, 59, 70] | 13; 3891 | 0.97 (0.91–1.03) | 0.95 (0.86–1.05) | 0.93 (0.84–1.04) | 0.94 (0.86–1.02) |
| > 65 [36, 43, 48, 53, 58, 62, 63, 66, 68] | 9; 25,078 | 0.99 (0.97–1.01) | 0.98 (0.95–1.01) | 0.98 (0.94–1.01) | 0.99 (0.98–1.01) |
| Gender proportion (%) | |||||
| Male > 60 [29, 33, 36, 41, 44, 45, 51, 67] | 8; 1930 | 0.92 (0.74–1.13) | 0.93 (0.77–1.13) | 0.95 (0.80–1.12) | 0.96 (0.82–1.13) |
| Male ≤ 60 [28, 30–32, 34, 35, 37–40, 42, 43, 46–50, 52–66, 68–70] | 35; 47,390 | 0.99 (0.99–1.00) | 0.99 (0.98–1.00) | 0.99 (0.98–1.00) | 0.99 (0.96–1.01) |
| Comorbidity | |||||
| General [28, 29, 31, 35, 37, 38, 41–45, 48, 49, 52–54, 56–58, 60–66, 68–70] | 29; 43,560 | 1.00 (0.99–1.01) | 0.99 (0.98–1.01) | 0.99 (0.98–1.01) | 0.99 (0.97–1.01) |
| Disease-specific [30, 32–34, 36, 39, 40, 46, 47, 50, 51, 55, 59, 67] | 14; 5610 | 0.94 (0.88–1.01) | 0.92 (0.83–1.01) | 0.91 (0.81–1.02) | 0.97 (0.91–1.03) |
| Baseline 25-hydroxyvitamin D levels (nmol/L) | |||||
| < 50 [35, 36, 43, 46–48, 50, 54, 55, 57, 64, 70] | 12; 11,588 | 0.99 (0.98–1.01) | 0.99 (0.96–1.02) | 0.99 (0.96–1.02) | 0.98 (0.94–1.03) |
| > 50 [28, 29, 33, 34, 38–40, 42, 45, 49, 52, 53, 56, 58–63, 65, 66] | 21; 13,995 | 0.99 (0.98–1.01) | 0.99 (0.96–1.02) | 0.99 (0.96–1.02) | 0.98 (0.95–1.02) |
| Dosing frequency | |||||
| Bolus [30, 51, 67] | 3; 1087 | NA | NA | NA | 0.96 (0.75–1.24) |
| Daily [28, 29, 31, 33–35, 39, 40, 42, 44, 45, 50, 52, 54, 56–60, 62, 65, 69, 70] | 23; 8788 | 0.94 (0.87–1.02) | 0.92 (0.82–1.02) | 0.92 (0.84–1.02) | 0.92 (0.85–0.99), 36 |
| Weekly [32, 41, 49, 61, 64] | 5; 12,864 | NA | NA | NA | 1.00 (0.98–1.02) |
| Monthly [36–38, 43, 46–48, 53, 55, 63, 66, 68] | 12; 26,581 | 0.99 (0.98–1.00) | 0.99 (0.97–1.00) | 0.98 (0.96–1.00) | 1.00 (0.99–1.01) |
| Trial duration (months) | |||||
| < 4 [28, 30, 35, 41, 44, 45, 57, 58, 69, 70] | 10; 2845 | 0.86 (0.69–1.07) | 0.80 (0.60–1.07) | 0.81 (0.63–1.04) | 0.81 (0.67–0.97), 16 |
| 4–12 [29, 31–33, 39, 42, 49–52, 59–61, 65, 67] | 15; 6698 | 0.92 (0.85–1.01) | 0.91 (0.81–1.02) | 0.93 (0.83–1.03) | 0.97 (0.89–1.05) |
| > 12 [34, 36–38, 40, 43, 46–48, 53–56, 62–64, 66, 68] | 18; 39,777 | NA | NA | NA | 1.00 (0.99–1.01) |
| Climatic zone | |||||
| Tropical or Subtropical [61, 65, 67, 69, 70] | 5; 2464 | 1.13 (1.00–1.29) | 1.06 (0.97–1.16) | 0.97 (0.82–1.15) | 0.97 (0.77–1.21) |
| Temperate [28–60, 62–64, 66, 68] | 38; 46,856 | 0.99 (0.99–1.00) | 0.99 (0.98–1.00) | 0.99 (0.97–1.00) | 0.99 (0.97–1.01) |
| Summer | |||||
| Summer-inclusive [32, 34, 36–38, 40, 42, 43, 46–49, 51, 52, 54–59, 62–70] | 29; 44,896 | 1.01 (0.99–1.02) | 1.01 (0.98–1.04) | 1.01 (0.98–1.03) | 1.00 (0.98–1.02) |
| Summer-sparing [28–31, 33, 35, 39, 41, 44, 45, 50, 53, 60, 61] | 14; 4424 | 0.83 (0.75–0.92) | 0.77 (0.67–0.88) | 0.79 (0.69–0.90) | 0.85 (0.74–0.98), 26 |
| Winter | |||||
| Winter-dominant [28–31, 35, 39, 44, 45, 60] | 9; 1961 | 0.72 (0.62–0.82) | 0.70 (0.61–0.81) | 0.80 (0.71–0.90) | 0.79 (0.71–0.89), 10 |
| Winter-non-dominant [32–34, 36–38, 40–43, 46–59, 61–70] | 34; 47,359 | 1.00 (0.99–1.02) | 1.01 (0.98–1.03) | 1.00 (0.98–1.03) | 1.00 (0.98–1.02) |
| Sensitivity analysis | |||||
| Type of ARIs | |||||
| Mixed upper and lower respiratory tract infections [29, 32–35, 42, 48, 49, 53–56, 60, 62–67] | 19; 21,974 | 1.00 (0.98–1.03) | 1.01 (0.97–1.05) | 1.01 (0.97–1.06) | 1.00 (0.97–1.03) |
| Upper respiratory tract infections [28, 38–41, 43, 45–47, 50, 52, 54, 57–59, 61, 68] | 17; 22,395 | 0.99 (0.94–1.00) | 0.99 (0.91–1.00) | 0.99 (0.92–1.00) | 0.98 (0.96–1.01) |
| Lower respiratory tract infections [30, 36, 37, 51, 54] | 5; 4305 | 0.98 (0.80–1.12) | 0.95 (0.82–1.09) | 0.95 (0.79–1.13) | 0.95 (0.83–1.08) |
| Influenza [31, 44, 52, 53, 55, 58, 59, 61, 69] | 9; 3594 | 0.98 (0.88–1.08) | 0.96 (0.80–1.13) | 0.96 (0.80–1.15) | 0.98 (0.89–1.07) |
The dose–response meta-analysis could not achieve convergence on age group: 7–17 years, dosing frequency: weekly, and trial duration: > 12 months. The sample size was too small for dosing frequency: bolus to perform dose–response analysis. NNT was calculated for those meta-analyses showing significant preventive results
ARI Acute respiratory infection, NA Not available, NNT Number needed to treat