Preventing URTI in Children: Does High-Dose Vitamin D Help or Harm?

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Nearly 350 children received either 2000 or 400 IU/day vitamin D over the course of 4 months.
Nearly 350 children received either 2000 or 400 IU/day vitamin D over the course of 4 months.

High-dose vitamin D supplements do not prevent wintertime viral upper respiratory tract infections in young healthy children, reports the Journal of the American Medical Association.1

Mary Aglipay, MSc, an epidemiologist from pediatric research at St Michael's Hospital, Toronto, Ontario, Canada, and colleagues examined the effects of high-dose vitamin D supplementation in preventing upper respiratory tract infections in children aged 1 to 5 years (Clinicaltrials.gov identifier: NCT01419262).

Previous trials of vitamin D supplementation in children suggested that it reduced influenza rates and other respiratory infections.2,3

In the vitamin D Outcomes and Invention in Toddlers trial (DO IT), 349 children (mean age, 2.7 years; 57.7% male) were randomly assigned to receive either 2000 IU/day of vitamin D drops or the standard 400 IU/day of vitamin D drops for at least 4 months between September 2011 and May 2015. The pragmatic trial had 5 parallel groups with a 1:1 ratio to account for variations in infections during 5 winter seasons.

The primary end point was the number of all-case laboratory-confirmed viral upper respiratory tract infections, as reported via parental-supplied nasal swabs. Parents did not have to bring their children for an office visit to confirm an infection.

Secondary end points included the time to the first laboratory-confirmed upper respiratory tract infection, laboratory-confirmed influenza, and noninfluenza upper respiratory tract infections and vitamin D levels. To enhance adherence to the study protocols, parents received monthly phone calls.

Children in the high-dose group had 1.05 laboratory-confirmed infections (95% CI, 0.91-1.19) vs 1.03 infections in children in the standard-dose group (95% CI, 0.90-1.16). The difference between the groups did not reach statistical significance (incidence rate ratio [IRR], 0.97; 95% CI, 0.80-1.16).

The secondary outcomes did not reach statistical significance, either. In the high-dose group, the median time to the first laboratory-confirmed infection was 3.95 months (95% CI, 3.02-5.95 months) compared with 3.29 months (95% CI, 2.66-4.14 months) in the standard-dose group. The number of parent-reported illnesses was 625 in the high-dose group vs 600 in the standard-dose group (IRR, 1.01; 95% CI, 0.88-1.16; P =.89).

The most prominent respiratory viruses in the study were enterovirus or rhinovirus, occurring in 63.2% of the patients in the high-dose group and in 59.8% of the control group.

“Our findings were that more vitamin D is not necessarily better.  Vitamin D has been thought to play a role in preventing or reducing colds in children, but there has been little clinical trial data available for clinicians to make decisions,” said Ms. Aglipay in an email interview with Pulmonology Advisor.

“Our findings do not support the routine use of high-dose vitamin D supplementation for the prevention of wintertime upper respiratory tract infections among healthy children.”

Summary and Clinical Applicability

Healthy young children may not need more than the standard 400 IU/day of vitamin D to prevent upper respiratory tract infections.

Study Limitations

  • Because the study relied on parents to take nasal swabs from their children, some swabs may not have been submitted when the children got an upper respiratory tract infection
  • Due to ethics board restrictions, the study could not compare the effects of vitamin D with placebo
  • The lack of effect in the high-dose vitamin D group may have been caused by already elevated levels of endogenous vitamin D at the end of summer when the study began
  • The study was powered to capture a reduction in 1 infection per month, but the children in the study had on average 1 infection per season

Disclosures: Muhammad Mamdani, MPH, PharmD, received fees from Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Hoffman La Roche, Novartis, Novo Nordisk, Pfizer, and AstraZeneca.

References

  1. Aglipay M, Birken CS, Parkin PC, et al. Effect of high-dose vs standard-dose wintertime vitamin D supplementation on viral upper respiratory tract infections in young healthy children. JAMA. 2017;318(3):245-254. doi:10.1001/jama.2017.8708
  2. Urashima M, Segawa T, Okazaki M, Kurihara M, Wada Y, Ida H. Randomized trial of vitamin D supplementation to prevent seasonal influenza A in school children. Am J Clin Nutr. 2010;91(5):1255-1260. doi:10.3945/ajcn.2009.29094
  3. Grant CC, Kaur S, Waymouth E, et al. Reduced primary care respiratory infection visits following pregnancy and infancy vitamin D supplementation: a randomised controlled trial. Acta Paediatr. 2015;104(4):396-404. doi:10.1111/apa.12819
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