title: Associations of maternal and fetal 25-hydroxyvitamin D levels with childhood lung function and asthma: the Generation R Study.
abstract: BACKGROUND
  Exposure to low levels of vitamin D in fetal life might be a risk factor for childhood asthma.
  
  
  OBJECTIVE
  We examined whether 25-hydroxyvitamin D levels in mid-gestation and at birth were associated with higher airway resistance and inflammation, and increased risks of wheezing and asthma in school-age children.
  
  
  METHODS
  We performed a population-based prospective cohort study among 3130 mothers and their children. Maternal blood samples in mid-gestation and umbilical cord blood samples at birth were used to determine 25-hydroxyvitamin D levels. At age of 6, airway resistance (Rint) was measured by interrupter technique and airway inflammation by fractional exhaled nitric oxide (FENO) using NIOX chemiluminescence analyser. Wheezing and asthma were prospectively assessed by annual questionnaires until age 6.
  
  
  RESULTS
  Maternal levels of 25-hydroxyvitamin D in mid-gestation were not associated with Rint, FeNO, wheezing patterns, or asthma. Children in the lowest tertile of 25-hydroxyvitamin D levels at birth had a higher Rint (Z-score (95% confidence interval [95% CI]): -0.42 (-0.84, -0.01), P-value for trend< 0.05), compared to those in the highest tertile group. The effect estimate attenuated when child's current 25-hydroxyvitamin D level was taken into account [Z-score (95% CI): -0.55 (-1.08, 0.01)].
  
  
  CONCLUSIONS
  Low levels of 25-hydroxyvitamin D at birth were associated with a higher airway resistance in childhood. Additional adjustment for child's current 25-hydroxyvitamin D level reduced the effect size of the association. Further studies are needed to replicate these findings and to examine mechanisms underlying the observed association and the long-term consequences.
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Division of Respiratory Medicine, Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Institute of Epidemiology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia.
authors.forename: T
authors.initials: T
authors.lastname: Gazibara
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Division of Respiratory Medicine, Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: H T
authors.initials: HT
authors.lastname: den Dekker
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: J C
authors.initials: JC
authors.lastname: de Jongste
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Qld, Australia.|Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Brisbane, Qld, Australia.
authors.forename: J J
authors.initials: JJ
authors.lastname: McGrath
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Qld, Australia.|Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Brisbane, Qld, Australia.
authors.forename: D W
authors.initials: DW
authors.lastname: Eyles
authors.affiliation: Queensland Brain Institute, The University of Queensland, Brisbane, Qld, Australia.|Queensland Centre for Mental Health Research, Park Centre for Mental Health, Wacol, Brisbane, Qld, Australia.
authors.forename: T H
authors.initials: TH
authors.lastname: Burne
authors.affiliation: Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: I K
authors.initials: IK
authors.lastname: Reiss
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: O H
authors.initials: OH
authors.lastname: Franco
authors.affiliation: Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Child and Adolescent Psychiatry/Psychology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Psychiatry, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: The Generation R Study Group, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: V W V
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Division of Respiratory Medicine, Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.|Division of Neonatology, Department of Pediatrics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Duijts
mesh_terms: D000328:Adult; D001249:Asthma / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D002853:Chromatography, Liquid; D015331:Cohort Studies; D005260:Female; D005333:Fetus; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009035:Mothers; D011446:Prospective Studies; D012129:Respiratory Function Tests; D053719:Tandem Mass Spectrometry; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-hydroxyvitamin D; Rint; asthma; birth; child; fractional exhaled nitric oxide; pregnancy