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

Systematic review and meta-analysis of randomized trials in children under five years of age in hospital, clinic, and community settings. Included studies enrolled healthy term infants and infants aged 1 to 11 months from Afghanistan, Spain, and the USA, with varying baseline vitamin D deficiency.

Included vitamin D supplementation regimens were heterogeneous across trials. Two infant studies used vitamin D 400 IU/day for 12 weeks to 6 months, one trial used vitamin D 402 IU/day for 12 months, and the largest trial used oral vitamin D3 100,000 IU quarterly for 18 months. Comparators were placebo or usual care.

Vitamin D supplementation did not show a clear benefit for preventing infections in young children. The largest trial found no reduction in the first or only episode of radiologically confirmed pneumonia (RR 1.06, 95% CI 0.89 to 1.26) or all-cause mortality (RR 1.43, 95% CI 0.54 to 3.74), but repeat episodes of radiologically confirmed pneumonia were higher (RR 1.69, 95% CI 1.28 to 2.21). Mean serum vitamin D concentrations increased by 7.72 ng/mL (0.50 higher to 14.93 higher) across four trials (266 participants). Trials evaluating vitamin D for prevention of TB or malaria were not performed, and available evidence did not demonstrate benefit for diarrhoea.

The evidence base was sparse and heterogeneous, with only one large trial providing infection outcomes and several smaller trials mainly reporting serum vitamin D levels rather than clinical infections. Doses, durations, ages, and baseline deficiency status varied across studies, some infection data were unpublished or incompletely reported, and there was no direct trial evidence for TB or malaria prevention. Two children in the largest trial had toxic vitamin D concentrations, which raises safety monitoring concerns.