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

• Published in: JAMA : the journal of the American Medical Association Vol. 319; no. 20; pp. 2086 - 2094
• Main Authors: Hibbs, Anna Maria, Ross, Kristie, Kerns, Leigh Ann, Wagner, Carol, Fuloria, Mamta, Groh-Wargo, Sharon, Zimmerman, Teresa, Minich, Nori, Tatsuoka, Curtis
• Format: Journal Article
• Language: English
• Published: United States American Medical Association 22.05.2018
• Subjects: African Americans; Age; Babies; Birth weight; Black people; Breast milk; Calcifediol - blood; Children; Cholecalciferol - administration & dosage; Clinical trials; Diet; Dietary Supplements; Female; Gestation; Gestational age; Humans; Immune system; Infant, Newborn; Infant, Premature; Infants; Infections; Male; Neonates; Original Investigation; Patients; Premature birth; Respiratory diseases; Respiratory Sounds - drug effects; Respiratory tract; Respiratory tract diseases; Risk reduction; Secondary Prevention; System effectiveness; Vitamin D; Vitamins - administration & dosage; Wheezing
• ISSN: 0098-7484; 1538-3598
• DOI: 10.1001/jama.2018.5729

IMPORTANCE: Black infants born preterm face high rates of recurrent wheezing throughout infancy. Vitamin D supplementation has the potential to positively or negatively affect wheezing through modulation of the pulmonary and immune systems. OBJECTIVE: To assess the effectiveness of 2 vitamin D dosing strategies in preventing recurrent wheezing. DESIGN, SETTING, AND PARTICIPANTS: A randomized clinical trial enrolled 300 black infants born at 28 to 36 weeks’ gestation between January 2013 and January 2016 at 4 sites in the United States, and followed them up through March 2017. Randomization was stratified by site and maternal milk exposure. INTERVENTIONS: Patients were enrolled prior to discharge from the neonatal intensive care unit or newborn nursery and received open-label multivitamin until they were consuming 200 IU/d of cholecalciferol from formula or fortifier added to human milk, after which they received either 400 IU/d of cholecalciferol until 6 months of age adjusted for prematurity (sustained supplementation) or placebo (diet-limited supplementation). One-hundred fifty three infants were randomized to the sustained group, and 147 were randomized to the diet-limited group. MAIN OUTCOMES AND MEASURES: Recurrent wheezing by 12 months’ adjusted age was the primary outcome. RESULTS: Among 300 patients who were randomized (mean gestational age, 33 weeks; median birth weight, 1.9 kg), 277 (92.3%) completed the trial. Recurrent wheezing was experienced by 31.1% of infants in the sustained supplementation group and 41.8% of infants in the diet-limited supplementation group (difference, −10.7% [95% CI, −27.4% to −2.9%]; relative risk, 0.66 [95% CI, 0.47 to 0.94]). Upper and lower respiratory tract infections were among the most commonly reported adverse events. Upper respiratory infections were experienced by 84 of 153 infants (54.9%) in the sustained group and 83 of 147 infants (56.5%) in the diet-limited group (difference, −1.6% [95% CI, −17.1% to 7.0%]). Lower respiratory infections were experienced by 33 of 153 infants (21.6%) in the sustained group and 37 of 147 infants (25.2%) in the diet-limited group (difference, −3.6% [95% CI, −16.4% to 4.4%]). CONCLUSIONS AND RELEVANCE: Among black infants born preterm, sustained supplementation with vitamin D, compared with diet-limited supplementation, resulted in a reduced risk of recurrent wheezing by 12 months’ adjusted age. Future research is needed to better understand the mechanisms and longer-term effects of vitamin D supplementation on wheezing in children born preterm. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01601847