Abstract
Background
Wheeze is a common condition affecting nearly one in three preschool children with few effective preventive interventions. Observational studies have suggested that vitamin D may improve lung function in children and adults, though no trial has examined whether a high dose of vitamin D supplementation can prevent wheezing in healthy preschool children.
Objectives
This study aimed to determine whether high dose vitamin D supplementation could reduce wheezing in young healthy children compared to a standard dose of vitamin D supplementation.
Design/Methods
This study was a prespecified secondary analysis of a 1:1 parallel, multicenter, superiority randomized clinical trial. The trial was conducted through a large primary care research network in Toronto, ON. Children with health conditions affecting growth, chronic condition(s) except for asthma, severe developmental delays, and children with gestational age < 32 weeks were excluded.
Healthy children age 1 to 5 years were randomized to either ‘standard-dose’ (400IU/day) or ‘high-dose’ (2000IU/day) orally supplemented vitamin D. Parents administered 1 drop/day of the assigned formulation (Kids Ddrops containing vitamin D3) to their child between time of enrolment (September-November) until follow-up (April-June). The outcome for this prespecified secondary analysis was one or more wheezing episode ascertained monthly by telephone. A binomial regression model was used to obtain the relative risk of one or more wheezing episodes in the high-dose group compared to the standard-dose group with 95% confidence intervals.
Results
Between September 2011 and June 2015, 703 children were recruited of which 631 (89.6%) provided data on wheezing. Mean age was 2.03 years and 57% were male. At baseline, 17 % of children in the high-dose group and 15 % of children in the standard-dose group had serum 25-hydroxyvitamin D levels below 75 nmol/L. Wheezing in the past was reported at baseline by 22% in the high-dose group and 20% in the standard-dose group. One or more wheezing episodes occurred in 16% of participants in the high-dose group and 12% of participants in the standard-dose group over the winter season which was not statistically different (RR=1.38, 95% CI: 0.93, 2.07, p=0.12).
Conclusion
In this randomized clinical trial of healthy young children, the risk of wheezing was not reduced by high-dose vitamin D compared to standard-dose supplementation. These results are consistent with several observational studies of vitamin D supplementation and wheeze in childhood. The trial was conducted across multiple sites, enhancing the generalizability of results. This study was limited by parent-reported outcomes, though gold standard tests for wheeze (e.g. spirometry) are challenging to perform in young children.