title: Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial.
abstract: OBJECTIVE
  Observational studies have suggested that increased dietary vitamin D intake during pregnancy may protect against wheezing in the offspring, but the preventive effect of vitamin D supplementation to pregnant women is unknown.
  
  
  OBJECTIVE
  To determine whether supplementation of vitamin D3 during the third trimester of pregnancy reduces the risk of persistent wheeze in the offspring.
  
  
  METHODS
  A double-blind, single-center, randomized clinical trial conducted within the Copenhagen Prospective Studies on Asthma in Childhood 2010 cohort. Enrollment began March 2009 with a goal of 708 participants, but due to delayed ethical approval, only 623 women were recruited at 24 weeks of pregnancy. Follow-up of the children (N = 581) was completed when the youngest child reached age 3 years in March 2014.
  
  
  METHODS
  Vitamin D3 (2400 IU/d; n = 315) or matching placebo tablets (n = 308) from pregnancy week 24 to 1 week postpartum. All women received 400 IU/d of vitamin D3 as part of usual pregnancy care.
  
  
  METHODS
  Age at onset of persistent wheeze in the first 3 years of life. Secondary outcomes included number of episodes of troublesome lung symptoms, asthma, respiratory tract infections, and neonatal airway immunology. Adverse events were assessed.
  
  
  RESULTS
  Of the 581 children, persistent wheeze was diagnosed during the first 3 years of life in 47 children (16%) in the vitamin D3 group and 57 children (20%) in the control group. Vitamin D3 supplementation was not associated with the risk of persistent wheeze, but the number of episodes of troublesome lung symptoms was reduced, and the airway immune profile was up-regulated (principal component analysis, P = .04). There was no effect on additional end points. Intrauterine death was observed in 1 fetus (<1%) in the vitamin D3 group vs 3 fetuses (1%) in the control group and congenital malformations in 17 neonates (5%) in the vitamin D3 group vs 23 neonates (8%) in the control group. [table: see text].
  
  
  CONCLUSIONS
  The use of 2800 IU/d of vitamin D3 during the third trimester of pregnancy compared with 400 IU/d did not result in a statistically significant reduced risk of persistent wheeze in the offspring through age 3 years. However, interpretation of the study is limited by a wide CI that includes a clinically important protective effect.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT00856947.
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bo L
authors.initials: BL
authors.lastname: Chawes
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark2Department of Pediatrics, Naestved Hospital, Naestved, Denmark.
authors.forename: Jakob
authors.initials: J
authors.lastname: Stokholm
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Nadja H
authors.initials: NH
authors.lastname: Vissing
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark2Department of Pediatrics, Naestved Hospital, Naestved, Denmark.
authors.forename: Elín
authors.initials: E
authors.lastname: Bjarnadóttir
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Ann-Marie M
authors.initials: AM
authors.lastname: Schoos
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Helene M
authors.initials: HM
authors.lastname: Wolsk
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark2Department of Pediatrics, Naestved Hospital, Naestved, Denmark.
authors.forename: Tine Marie
authors.initials: TM
authors.lastname: Pedersen
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark2Department of Pediatrics, Naestved Hospital, Naestved, Denmark.
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Vinding
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sunna
authors.initials: S
authors.lastname: Thorsteinsdóttir
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Lambang
authors.initials: L
authors.lastname: Arianto
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henrik W
authors.initials: HW
authors.lastname: Hallas
authors.affiliation: Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Lene
authors.initials: L
authors.lastname: Heickendorff
authors.affiliation: Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark.
authors.forename: Susanne
authors.initials: S
authors.lastname: Brix
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark5Department of Food Science, Faculty of Science, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Morten A
authors.initials: MA
authors.lastname: Rasmussen
authors.affiliation: Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
mesh_terms: D000328:Adult; D001249:Asthma / Q000175:diagnosis / Q000517:prevention & control; D002675:Child, Preschool; D002762:Cholecalciferol / Q000008:administration & dosage*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012135:Respiratory Sounds; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014815:Vitamins / Q000008:administration & dosage*
chemical_list: D014815:Vitamins; D014807:Vitamin D; D002762:Cholecalciferol; C104450:25-hydroxyvitamin D