Vitamin D Supplementation Reduced Recurrent Wheezing in Premature Black Infants

Infant in incubator
Infant in incubator
Vitamin D supplementation appears to reduce the recurrent wheezing by 12 months of age in black infants born prematurely.

In premature black infants, vitamin D supplementation reduces the incidence of recurrent wheezing by 12 months of age, according to the results of the D-Wheeze trial (Wheezing in Black Preterm Infants: Impact of Vitamin D Supplementation Strategy; Identifier: NCT01601847) published in the Journal of the American Medical Association.

Preterm birth is associated with wheeze. It is believed that early exposure to environmental and iatrogenic irritants may affect the development of the lungs, airways, or immune system, ultimately resulting in recurrent wheeze. Study results suggest that vitamin D plays a role in a number of pathways involved in wheeze. For example, vitamin D appears to be involved in regulating inflammation, response to pathogens, development of the lungs and airways, and the likelihood of allergic disease developing. Black infants have higher rates of preterm birth and wheezing associated with prematurity. Lower levels of vitamin D exposure are suspected as a potential cause.

Anna Maria Hibbs, MD, MSCE, of Case Western Reserve University in Cleveland, Ohio, and colleagues conducted a study involving 300 black infants born at 28 to 36 weeks’ gestation at 4 sites in the United States. The infants were born between January 2013 and January 2016 and followed through March 2017. The primary outcome was wheezing at 12 months’ adjusted age. Patients were randomly assigned to either sustained vitamin D supplementation or placebo (diet-limited supplementation). A total of 277 infants completed the trial. The infants had a mean gestational age of 33 weeks and a median birth weight of 1.9 kg.

For the primary outcome, 31.1% of those receiving vitamin D supplementation experienced recurrent wheezing compared with 41.8% of the placebo group (relative risk, 0.66; 95% CI, 0.47-0.94; P =.02). Analysis of secondary outcomes demonstrated no significant differences between the 2 groups for total medically attended illnesses or markers of allergy or bone health. Asthma Predictive Index was positive in 10.7% of the vitamin D group and 13.9% of the placebo group.

Similar percentages from each group (53.2% and 50.4% of the vitamin D and placebo groups, respectively) were seen in visits to the emergency department for respiratory causes, and there was no significant difference in hospitalizations for respiratory diseases or events. However, time point analyses demonstrated a significant decrease in the vitamin D group at some points for wheezing, use of respiratory medication, and hospitalization.

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The authors noted several study limitations, including the potential for misclassification of wheezing. Nonetheless, they maintained that the results of this study demonstrated a benefit for sustained vitamin D supplementation with no increase in allergy or eczema.


Hibbs AM, Ross K, Kerns LA, et al. Effect of vitamin D supplementation on recurrent wheezing in black infants who were born preterm. The D-Wheeze randomized clinical trial. JAMA. 2018;319:2086-2094.