Low Vitamin D Levels Associated with Increased Risk of Severe Flu in Children


Researchers from the University of Toronto evaluated 82 patients under 18 years of age from Toronto, Ottawa, Montreal, and Quebec.

Low levels of vitamin D (25[OH]D) and vitamin D-regulated antimicrobial peptide (AMP) human cathelicidin (LL-37) are associated with increased risk of severe influenza infections in pediatric patients, according to results from a preliminary study.

In research presented at the 2017 Annual Pediatric Academic Societies Meeting (PASM), a group of physicians headed by Eleanor Reid, MSc, from the Department of Nutritional Sciences at the University of Toronto in Toronto, Canada, evaluated 82 pediatric patients all less than 18 years of age. These patients were recruited from inpatient units from 4 Canadian pediatric referral centers in Toronto, Ottawa, Montreal, and Quebec. All of the patients were healthy with the exception of a lab-confirmed influenza A or B diagnosis.

“We wanted to examine the relationship between serum 25(OH)D levels and symptom severity in this population of otherwise-healthy children,” the team explained during an oral poster session at PASM. The group also investigated associations between LL-37 and two other AMPs, beta-defensin 3 (BD3) and beta-defensin 2 (BD2), and influenza severity in the study group.

In a 2015 study on vitamin D and influenza, published in the Canadian Family Physician, Gerry Schwalfenberg, MD, a physician at the University of Alberta in Edmonton, Canada, wrote that “there is a seasonality to influenza that correlates well with the seasonal drop in vitamin D.” He added in this article that vitamin D “as a prophylactic for influenza has shown promise in prevention of illness and reduction of secondary asthma in children” and speculated that falling vitamin D levels in wintertime, which would likely keep much of the Canadian population indoors, “would put the Canadian population at risk of a number of medical conditions.”

Dr. Reid’s team conducted follow-up assessments of their Canadian pediatric population at 48 hours, one week, two weeks, and four weeks after enrollment in the study to “obtain data on symptoms and influenza-related complications.” They also collected blood samples when the opportunity presented itself and used the Comprehensive Severity Index (CSI) score to quantify influenza severity. The study group of 82 patients were nearly two-thirds male (55) and had a median age of 5 years, with only 9 patients being 10 years old or older. Only 7 had received a flu vaccine; 9 were less than 6 months of age, so this measure was considered nonapplicable.

Of the 82 evaluated patients, 78 provided opportunity to assess vitamin D and AMP levels. Mean levels were 52.2 nmol/L for serum 25(OH)D, and patients with levels <50nmol/L “had significantly higher maxCSI scores than those with adequate serum levels,” the group noted. The team also found that of the 3 measured AMPs, “LL-37 levels were inversely associated with maxCSI scores.” BD2 levels were not associated with symptom severity, and 96% of patient samples contained BD3 levels too low to detect, so the team did not draw any conclusions on BD3 levels and symptom severity.

“Of course, we had a small sample size [for this study],” Dr. Reid said, also noting that the team only collected serum samples at one point during the study period. She added that other researchers “have postulated that serum 25(OH)D concentrations may vary over the course of an acute inflammatory response.”

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