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
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
- Dark skin pregnancies 2.6 times more likely to have low vitamin D – March 2017
- Dark skin births are much riskier due to lack of vitamin D
- Wheezing reduced 35 percent if vitamin D added during pregnancy – April 2015
- Recurrent wheeze 2X more likely if endotoxin (on some bacteria) and low vitamin D – May 2016
- 2X higher risk of wheezing and asthma if modified receptor genes, even if vitamin D levels OK – Sept 2015
- Children who wheezed were 2.7X more likely to have little vitamin D – April 2014
- Search VitaminDWiki for Wheeze 1150 items as of Dec 2018
- Children in India – 1 in 7 extremely low Vitamin D, 1 in 10 prediabetic – Sept 2019
- Pregnant while black increases chance of death – mothers 3X, infants 2X (low Vitamin D) – Feb 2019
- Black infant recurrent wheezing rate dropped from 42 percent to 31 percent with just 400 IU of vitamin D – RCT Dec 2018
- All preteen aged girls in India taking 2,000 IU of vitamin D got levels above 20 ng – RCT Nov 2018
- Low birth weight far more likely if African-American (low vitamin D) – 1997, Aug 2018
- Indoor pollution is a problem with obese black asthmatic children – May 2018
- Crohn's disease in black children is worse in 6 ways – Dec 2015
- Black infants far less likely to be breast-fed (wonder – culture or low Vitamin D) – Aug 2017
- Vitamin D needed to get children to just 20 ng in winter 800 IU white skin, 1100 IU dark (Sweden) – RCT June 2017
- Many US kids have less than 40 ng of Vitamin D – 99 out of 100 blacks, 91 out of 100 whites – Jan 2017
- Small for gestational age with low vitamin D – 3.6X higher for blacks than whites – April 2016
- Dark skinned children were vitamin D deficient in Italy (not infants) – Nov 2014
- Breastfed Infants in Iowa got very little vitamin D, especially if winter or dark skin – July 2013
- Black infants had far lower vitamin D levels which did not vary with season – Jan 2013
- 83 percent of children had less than 20 ng of vitamin D – 15 ng avg for hispanic – Aug 2012
- Rickets in 30 percent of infants in India who had low vitamin D – March 2011
- Large increase in dark skin children with vitamin D deficiency in Glasgow – June 2010
- Dark Skinned babies probably need vitamin D to prevent nutritional rickets - 2001
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.
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).
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.
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.
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.
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.