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Monday 23 July 2018
Vitamin D and wheezing in childhood

The article WAidid suggests this week, "Prenatal vs Infant Vitamin D Supplementation and the Risk of Wheezing in Childhood", was published last month on JAMA and tackles the issue of vitamin D supplementation related benefits.

Although the association of vitamin D with respiratory disease has been observed for more than 100 years, the potential benefits of vitamin D for the prevention of respiratory tract disease, including wheezing disorders, continue to be investigated in many observational and epidemiologic studies. Most cell nuclei in the human body have a vitamin D receptor, through which vitamin D may affect gene transcription. 1,25-dihydroxyvitamin D3 (1,25[OH]2D3), the hormonal metabolite of vitamin D, regulates, directly or indirectly, approximately 2000 genes, such as the ones inhibiting cellular proliferation, differentiation, and angiogenesis, the ones inducing apoptosis, and the ones which upregulate antiinflammatory pathways and downregulate molecules, that activate immune and inflammatory cells. Although these known actions suggest potential pathways for the interaction of vitamin D and respiratory disease, a recent review concluded that there are few suitable clinical trials to support the beneficial effect of vitamin D supplementation on respiratory disease. The D-Wheeze study reported by Hibbs and colleagues is now one of these supporting studies, that attempts to fill this important evidence gap. D-Wheeze was a multicenter, double-blind, randomized clinical trial, that enrolled 300 black preterm infants, born between 28 weeks and less than 37 weeks’ gestation, who were randomized into 1 of 2 different postnatal vitamin D supplementation strategies. No attempt was made to standardize the feeding protocol within or across centers. An oral supplement of 400 IU/d of vitamin D was started after birth, when oral feedings were tolerated. When infants achieved a daily oral intake of 200 IU of vitamin D from the feedings of vitamin D–fortified human milk or infant formula, they were randomized to 1 of 2 groups. The sustained group continued the daily supplement of 400 IU of vitamin D, whereas the diet-limited group was maintained only on the vitamin D, that was present in the formula or human milk feedings. The protocol was continued until 6 months of age, adjusted for prematurity. The incidence of recurrent wheezing at 12 months occurred in 31.1% in the sustained group and 41.8% in the diet-limited group (absolute risk difference, −10.7%; relative risk, 0.66), a clinically significant difference. Regardless of feeding group, at 3 months, only a few of the 272 infants measured had a serum 25-hydroxyvitamin D (25[OH]D) level less than 20 ng/mL. No infant’s serum 25(OH)D level exceeded 80 ng/mL.
The authors underlined that the results of D-Wheeze should not be used to support vitamin D intakes that exceed 1000 IU/d in preterm infants, and that the vitamin D intakes studied are relevant also to infants who are not black or premature.
The results of this study complement and contrast with 2 previous studies in JAMA, that examined the effects of prenatal supplementation of vitamin D on recurrent wheezing or asthma among infants followed up until 3 years of age, which reported a slightly reduction in persistent or recurrent wheezing, without statistically significance.
In addition to the time of supplementation, the prenatal and postnatal supplementation trials differed in the populations enrolled. Therefore, the authors highlighted that the role of prenatal vs early-life supplementation, and in which populations, remains unclear, and that further follow-up studies of the infants in all 3 trials will be needed to determine whether the effects of prenatal or postnatal supplements of vitamin D on respiratory disease in infants are sustained.

AUTHOR: Frank R. Greer