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

Abstract

Background: Vitamin D has a role in regulating immune function, and its deficiency is a suggested risk factor for childhood pneumonia. Our aim was to assess whether oral supplementation of vitamin D(3) (cholecalciferol) will reduce the incidence and severity of pneumonia in a high-risk infant population.

Methods: We did a randomised placebo-controlled trial to compare oral 100,000 IU (2·5 mg) vitamin D(3) with placebo given to children aged 1-11 months in Kabul, Afghanistan. Randomisation was by use of a computer-generated list. Vitamin D or placebo was given by fieldworkers once every 3 months for 18 months. Children presenting at the study hospital with signs of pneumonia had their diagnosis confirmed radiographically. Our primary outcome was the first or only episode of radiologically confirmed pneumonia. Our analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00548379.

Findings: 1524 children were assigned to receive vitamin D(3) and 1522 placebo. There was no significant difference between the incidence of first or only pneumonia between the vitamin D (0·145 per child per year, 95% CI 0·129-0·164) and the placebo group (0.137, 0·121-0·155); the incidence rate ratio was 1·06 (95% CI 0·89-1·27). From 652 children during five separate periods of testing serum calcifediol, only one child in each of two testing periods had results greater than 375 nmol/L in the intervention group--a toxic level.

Interpretations: Quarterly bolus doses of oral vitamin D(3) supplementation to infants are not an effective intervention to reduce the incidence of pneumonia in infants in this setting.

Funding: Wellcome Trust and British Council.

Figure 1

Trial profile *One case was a severely malnourished child and another had received high-dose vitamin D within the past 3 months. †Did not want to be enrolled in the project for reasons such as did not want to go to Maiwand hospital, did not want the fieldworkers to come to their house, and other with no clear reasons. ‡The syringe with code number of 2706 was given to the child with study number of 2707, with 1070 to 1084, and with 2393 to 2939. §The syringe with code number of 1418 was given to the child with study number of 1814 and with 2335 to 2235. ¶The syringe with code number of 2215 was given to the child with study number of 2224.

Figure 2

Proportion of children with a first episode of pneumonia over time

Figure 3

Boxplot of serum calcifediol concentration Vertical lines represent the time of supplementation, and each placebo and vitamin D pair represent a sampling time. Boxes are medians with IQRs. Circles represent outliers. For November and December, 2008, p<0·001; for February, 2008, p=0·058; for May, 2008, p<0·001; and for July, 2009, p>1·0. One child in the vitamin D group in January, 2008, and one in May, 2008, had serum concentrations greater than 375 nmol/L (not shown).