title: Vitamin D over the first decade and susceptibility to childhood allergy and asthma.
abstract: Vitamin D (25(OH)D) deficiency has been implicated as a possible risk factor for asthma development, but studies at selected time points measuring 25(OH)D levels during childhood have yielded conflicting findings. Prospective studies tracking 25(OH)D levels during the initiation phase of asthma in early childhood have not been reported.
  
  
  
  We sought to elucidate relationships between 25(OH)D levels from birth to age 10 years and susceptibility to allergic sensitization, respiratory tract infections, and asthma.
  
  
  
  Asthma-, allergy-, and respiratory tract infection-associated phenotypes (including pathogen identification) were characterized in a high-risk birth cohort. Plasma 25(OH)D concentrations were quantified at birth and at clinical follow-ups at the ages of 0.5, 1, 2, 3, 4, 5, and 10 years, and relationships with clinical outcomes were examined.
  
  
  
  Cross-sectional analyses demonstrated inverse associations between 25(OH)D concentrations and the risk for concurrent sensitization at age 0.5, 2, and 3 years, and mixed-effects regression demonstrated inverse longitudinal associations of 25(OH)D levels with both sensitization and eczema. Multivariate regression modeling suggested that the number of 25(OH)D-deficient follow-ups was positively associated with risk for asthma/wheeze, eczema, and sensitization at 10 years; adjustment for sensitization (particularly by 2 years) in the asthma/wheeze models reduced 25(OH)D associations with these latter outcomes. 25(OH)D levels were also inversely associated with early nasopharyngeal colonization with Streptococcus species and age of first febrile lower respiratory illness, both of which are known asthma risk factors.
  
  
  
  25(OH)D deficiency in early childhood is associated with increased risk for persistent asthma, potentially through modulating susceptibility to early allergic sensitization, upper respiratory tract colonization with bacterial pathogens, or both. These relationships are only evident if 25(OH)D status is monitored prospectively and longitudinally.
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Elysia M
authors.initials: EM
authors.lastname: Hollams
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Melbourne, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia; School of BioSciences, University of Melbourne, Melbourne, Australia.
authors.forename: Shu Mei
authors.initials: SM
authors.lastname: Teo
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Merci
authors.initials: M
authors.lastname: Kusel
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Holt
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Melbourne, Australia; Department of Biochemistry and Molecular Biology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne, Australia.
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.affiliation: Centre for Systems Genomics, University of Melbourne, Melbourne, Australia; School of BioSciences, University of Melbourne, Melbourne, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Inouye
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Nicholas H
authors.initials: NH
authors.lastname: De Klerk
authors.affiliation: School of Public Health, Curtin University, Perth, Australia.
authors.forename: Guicheng
authors.initials: G
authors.lastname: Zhang
authors.affiliation: University of Queensland, Brisbane, Australia.
authors.forename: Peter D
authors.initials: PD
authors.lastname: Sly
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia.
authors.forename: Prue H
authors.initials: PH
authors.lastname: Hart
authors.affiliation: Telethon Kids Institute, University of Western Australia, Perth, Australia; University of Queensland, Brisbane, Australia. Electronic address: Patrick.Holt@telethonkids.org.au.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Holt
mesh_terms: D001249:Asthma / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007114:Immunization; D007073:Immunoglobulin E / Q000097:blood; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011446:Prospective Studies; D012306:Risk; D014807:Vitamin D / Q000097:blood*
chemical_list: D014807:Vitamin D; D007073:Immunoglobulin E
keywords: Streptococcus; Vitamin D; allergy; asthma; childhood; longitudinal birth cohort; microbiome; respiratory infections