title: Effect of Prenatal Supplementation With Vitamin D on Asthma or Recurrent Wheezing in Offspring by Age 3 Years: The VDAART Randomized Clinical Trial.
abstract: OBJECTIVE
  Asthma and wheezing begin early in life, and prenatal vitamin D deficiency has been variably associated with these disorders in offspring.
  
  
  OBJECTIVE
  To determine whether prenatal vitamin D (cholecalciferol) supplementation can prevent asthma or recurrent wheeze in early childhood.
  
  
  METHODS
  The Vitamin D Antenatal Asthma Reduction Trial was a randomized, double-blind, placebo-controlled trial conducted in 3 centers across the United States. Enrollment began in October 2009 and completed follow-up in January 2015. Eight hundred eighty-one pregnant women between the ages of 18 and 39 years at high risk of having children with asthma were randomized at 10 to 18 weeks' gestation. Five participants were deemed ineligible shortly after randomization and were discontinued.
  
  
  METHODS
  Four hundred forty women were randomized to receive daily 4000 IU vitamin D plus a prenatal vitamin containing 400 IU vitamin D, and 436 women were randomized to receive a placebo plus a prenatal vitamin containing 400 IU vitamin D.
  
  
  METHODS
  Coprimary outcomes of (1) parental report of physician-diagnosed asthma or recurrent wheezing through 3 years of age and (2) third trimester maternal 25-hydroxyvitamin D levels.
  
  
  RESULTS
  Eight hundred ten infants were born in the study, and 806 were included in the analyses for the 3-year outcomes. Two hundred eighteen children developed asthma or recurrent wheeze: 98 of 405 (24.3%; 95% CI, 18.7%-28.5%) in the 4400-IU group vs 120 of 401 (30.4%, 95% CI, 25.7%-73.1%) in the 400-IU group (hazard ratio, 0.8; 95% CI, 0.6-1.0; P = .051). Of the women in the 4400-IU group whose blood levels were checked, 289 (74.9%) had 25-hydroxyvitamin D levels of 30 ng/mL or higher by the third trimester of pregnancy compared with 133 of 391 (34.0%) in the 400-IU group (difference, 40.9%; 95% CI, 34.2%-47.5%, P < .001).
  
  
  CONCLUSIONS
  In pregnant women at risk of having a child with asthma, supplementation with 4400 IU/d of vitamin D compared with 400 IU/d significantly increased vitamin D levels in the women. The incidence of asthma and recurrent wheezing in their children at age 3 years was lower by 6.1%, but this did not meet statistical significance; however, the study may have been underpowered. Longer follow-up of the children is ongoing to determine whether the difference is clinically important.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00920621.
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts.
authors.forename: Augusto A
authors.initials: AA
authors.lastname: Litonjua
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts.
authors.forename: Vincent J
authors.initials: VJ
authors.lastname: Carey
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Nancy
authors.initials: N
authors.lastname: Laranjo
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Harshfield
authors.affiliation: Harvard Medical School, Boston, Massachusetts3Department of Obstetrics and Gynecology, Brigham & Women's Hospital, Boston, Massachusetts.
authors.forename: Thomas F
authors.initials: TF
authors.lastname: McElrath
authors.affiliation: Pulmonary Center, Department of Medicine, Boston University School of Medicine, Boston, Massachusetts.
authors.forename: George T
authors.initials: GT
authors.lastname: O'Connor
authors.affiliation: Department of Pediatrics, Boston Medical Center, Boston, Massachusetts.
authors.forename: Megan
authors.initials: M
authors.lastname: Sandel
authors.affiliation: Department of Obstetrics and Gynecology, Boston Medical Center, Boston, Massachusetts.
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Iverson
authors.affiliation: Department of Obstetrics and Gynecology, Boston Medical Center, Boston, Massachusetts.
authors.forename: Aviva
authors.initials: A
authors.lastname: Lee-Paritz
authors.affiliation: Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri8St Louis Children's Hospital, St Louis, Missouri.
authors.forename: Robert C
authors.initials: RC
authors.lastname: Strunk
authors.affiliation: Division of Pediatric Allergy, Immunology and Pulmonary Medicine, Department of Pediatrics, Washington University School of Medicine, St Louis, Missouri8St Louis Children's Hospital, St Louis, Missouri.
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Bacharier
authors.affiliation: Department of Obstetrics and Gynecology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: George A
authors.initials: GA
authors.lastname: Macones
authors.affiliation: Kaiser Permanente Southern California, San Diego, California.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Zeiger
authors.affiliation: Kaiser Permanente Southern California, San Diego, California.
authors.forename: Michael
authors.initials: M
authors.lastname: Schatz
authors.affiliation: Department of Pediatrics, Medical University of South Carolina, Charleston.
authors.forename: Bruce W
authors.initials: BW
authors.lastname: Hollis
authors.affiliation: King's College London School of Medicine, Asthma, Allergy and Respiratory Science, Guy's Hospital Campus, London, United Kingdom.
authors.forename: Eve
authors.initials: E
authors.lastname: Hornsby
authors.affiliation: King's College London School of Medicine, Asthma, Allergy and Respiratory Science, Guy's Hospital Campus, London, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Hawrylowicz
authors.affiliation: Harvard Medical School, Boston, Massachusetts13Department of Population Medicine, Harvard Pilgrim Health Care Institute and Children's Hospital Boston, Boston, Massachusetts.
authors.forename: Ann Chen
authors.initials: AC
authors.lastname: Wu
authors.affiliation: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts2Harvard Medical School, Boston, Massachusetts.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Weiss
mesh_terms: D000328:Adult; D001249:Asthma / Q000453:epidemiology / Q000517:prevention & control*; D002675:Child, Preschool; D002762:Cholecalciferol / Q000008:administration & dosage* / Q000009:adverse effects; D019587:Dietary Supplements; D004311:Double-Blind Method; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D008297:Male; D011247:Pregnancy; D011263:Pregnancy Trimester, Third / Q000097:blood; D012008:Recurrence; D012135:Respiratory Sounds; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency; D014815:Vitamins / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D
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