Vitamin D Supplementation and Wheeze in Infants: One Size Does Not Fit All

William T. Basco, Jr, MD, MS


October 02, 2018

There are data to suggest that vitamin D may be important in reducing the risk for wheezing, particularly among either preterm or minority infants. A recent randomized, placebo-controlled clinical trial sought to determine whether supplementation of preterm black infants with vitamin D over an extended period postbirth could decrease the risk for recurrent wheezing.[1]

The infants were all born in US hospitals from 2013-2016 and were 28-36 weeks' gestational age (mean gestational age, 33 weeks). None had received more than 28 days of supplemental oxygen after birth. Infants already diagnosed with bronchopulmonary dysplasia were not included. The study also excluded children with documented chronic conditions that would predispose to wheezing.

The main outcome of interest was parental report of recurrent wheezing, defined as two or more episodes of wheezing before the children reached 12 months of adjusted age. The researchers also evaluated secondary outcomes, such as the number of lower respiratory tract infections, hospitalizations, and emergency department visits. A total of 300 babies were randomized, and equal numbers completed the trial (approximately 135 per group).

Just under one half (43%) of the sustained supplementation group received oxygen at any point, compared with over one third (36%) of the limited supplementation group. Otherwise, the groups were fairly similar.

Approximately 37% of the infants had a family history of food allergy, and over two thirds came from families with a history of eczema; in both groups, greater than 60% of infants had a family history of asthma.

One group of infants received 400 international units of cholecalciferol daily until they were 6 months adjusted age, in addition to any dietary vitamin D they might consume (the sustained supplementation group). The comparison group received 400 IU/day initially but discontinued the supplement when their dietary intake reached at least 200 IU/day of vitamin D (the limited supplementation group). The infants were evaluated every 3 months until 1 year of age. Follow-up at each visit was greater than 94%.

With regard to the primary outcome, the children who received sustained supplementation had a lower frequency of recurrent wheezing (31.1%) compared with the limited supplementation group (41.8%; relative risk, 0.66; 95% CI, 0.47-0.94; P =.02).

Some of the secondary outcomes were less common in the sustained supplementation group, such as a diagnosis of asthma and a diagnosis of eczema, but these differences did not reach statistical significance. Other secondary outcomes, such as emergency department visits for respiratory conditions, any pediatrician visit, or any sick visit to the pediatrician, were virtually identical between the two groups.

Adverse events were also not different between the two groups.

The authors concluded that among black infants who were born preterm, sustained supplementation with at least 400 IU/day of vitamin D through 6 months adjusted age reduced the risk for recurrent wheezing by 12 months of age.


An accompanying editorial reviewed some of the potential mechanisms by which vitamin D may improve lung health, including potential anti-inflammatory and proimmunogenicity effects.[2] The editorialist also reviewed some of the other recent randomized trials that examined the effect of maternal supplementation with vitamin D on the incidence of atopic illnesses in the offspring.

Although those trials generally did not show benefit, this trial suggests that there is a benefit to supplementing preterm infants of minority race and ethnicity. It is probably too early to apply this universally, but it suggests that continuing studies on the potential benefits of either maternal or postnatal infant supplementation with vitamin D may still be worth investigating.


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