Effect on the incidence of pneumonia of vitamin D supplementation by quarterly bolus dose to infants in Kabul: a randomised controlled superiority trial

Randomised, placebo-controlled, blinded superiority trial in Kabul, Afghanistan. Infants aged 1-11 months from inner-city Kabul; Exclusions: rickets or prior vitamin D treatment in the previous 3 months; Kwashiorkor or Marasmus. Randomised 3046 participants (1524 vitamin D3, 1522 placebo); follow-up through May 2009; intention-to-treat analysis; outcomes included radiographically confirmed pneumonia.

Vitamin D3 (cholecalciferol), 100000 IU per dose, oral in olive oil (0.5 mL), administered every 3 months for 18 months (6 doses total).

Quarterly 100,000 IU vitamin D3 did not reduce incidence or severity of pneumonia. Primary endpoint (first episode of radiographically confirmed pneumonia) showed no protective effect (IRR ≈ 1.07; 95% CI 0.89–1.27; P=0.48). No difference in hospital admissions or all-cause mortality. Serum calcifediol rose with vitamin D3 dosing, confirming biochemical response, but this did not translate into clinical benefit. Safety: two cases of calcifediol >375 nmol/L; deaths: 6 in vitamin D group vs 4 in placebo. Conclusion: quarterly bolus vitamin D3 is not an effective strategy to reduce pneumonia in this high-risk infant population.

Not generalizable to settings with different baseline vitamin D status; bolus dosing may differ in effectiveness from daily/weekly regimens; not powered for mortality differences; potential misclassification of pneumonia; follow-up limited to 18 months in a high-risk population.