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Black infant recurrent wheezing rate dropped from 42 percent to 31 percent with just 400 IU of vitamin D – RCT Dec 2018

Effect of Vitamin D Supplementation on Recurrent Wheezing in Black Infants Who Were Born Preterm: The D-Wheeze Randomized Clinical Trial

Pediatrics, December 2018, VOLUME 142 / ISSUE Supplement 4
Alan Goldsobel, AM Hibbs, K Ross, LA Kerns JAMA. 2018;319(20):2086–2094

VitaminDWiki

42% of black infants wheezed 2 or more times per year
Probably would have had far more reduction in wheezing if had used >1000 IU of vitamin D
Probably much increased rate of wheezing if premature birth
Dark-skinned pregnancies and infants assoicated with low levels of Vitamin D

Items in both categories Skin - Dark and Infant-Child are listed here:


PURPOSE OF THE STUDY.
To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing in African American infants who are prematurely born.

STUDY POPULATION.
The study population consisted of 300 African American infants born between 28 and 36 weeks’ gestation (mean gestational age: 33 weeks; median birth weight: 1.9 kg) at 4 sites in the United States over a 3-year period. The subjects were then managed for the first year of life for the development of parent-reported recurrent wheezing defined as ≥2 episodes of wheezing with or without an infection (primary outcome).

METHODS.
This was a multicenter, double-blind randomized clinical trial. Patients and families were enrolled before discharge from the NICU or newborn nursery. There was no standardization of the feeding protocol (formula or breast milk) in enrolled subjects. Initially, all infants received an open-label multivitamin providing 400 IU of vitamin D per day. When the infants achieved a daily intake of 200 IU of vitamin D from formula or fortified human milk, they were randomly assigned to either the sustained supplementation group (continuing to receive 400 IU/day of vitamin D) or the diet-limited supplementation group (cessation of supplementation [placebo supplement]). Both groups were supplemented with active treatment or placebo until 6 months of age adjusted for prematurity. A total of 153 infants were randomly assigned to the sustained group, and 147 were randomly assigned to the diet-limited group.

RESULTS.
A total of 277 infants (92.3%) completed the trial. Recurrent wheezing was reported in 31.1% of the infants in the sustained supplementation group and in 41.8% in the diet-limited group (risk difference = −10.7%; relative risk: 0.66; P = .02). Secondary outcomes included medically attended illnesses and markers of allergy, eczema, and bone health. No significant differences between the 2 groups were seen. Serum 25(OH)D levels were measured at baseline and 3 months. There were no statistical differences between treatment and placebo groups, and no levels exceeded 80 ng/mL (the upper limit was accepted as normal). No statistical differences were seen in any adverse event between the 2 groups.

CONCLUSIONS.
In this study, we found that in African American infants born prematurely, sustained supplementation with vitamin D resulted in a reduced risk of recurrent wheezing by 12 months adjusted age versus those infants with diet-limited supplementation.

REVIEWER COMMENTS.
In an accompanying editorial, it was noted that the authors of a 2011 Institute of Medicine report concluded that the available evidence was insufficient to establish a functional relationship between vitamin D and any health outcome other than the maintenance of bone health across the life span. Authors of a recent review also concluded that there are a few suitable clinical trials to support the beneficial effect of vitamin D supplementation on respiratory disease. In 2 previous studies published in the Journal of the American Medical Association, authors examined the effects of prenatal supplementation of vitamin D on recurrent wheezing or asthma among infants managed to 3 years of age (COPSAC2010 [Chawes BL, Bønnelykke K, Stokholm J, et al. Effect of vitamin D3 supplementation during pregnancy on risk of persistent wheeze in the offspring: a randomized clinical trial. JAMA. 2016;315(4):353–361] and VDAART [Litonjua AA, Carey VJ, Laranjo N, et al. Effect of prenatal supplementation with vitamin D on asthma or recurrent wheezing in offspring by age 3 years: the VDAART randomized clinical trial. JAMA. 2016;315(4):362–370]). Both revealed no statistical differences. In the D-Wheeze supplementation trial, a statistically significant decrease was shown in recurrent wheezing in those African American infants who were born prematurely and supplemented with vitamin D. Potential mechanisms for the positive effects of vitamin D include effects on the development of neonatal lung tissue and immune system. The author of the editorial notes that the vitamin D intakes studied in this trial are not relevant to infants who are not African American and premature.

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