title: Neonatal vitamin D status and risk of multiple sclerosis: A population-based case-control study.
abstract: OBJECTIVE
  As previous research has suggested that exposure to vitamin D insufficiency in utero may have relevance for the risk of multiple sclerosis (MS), we aimed to examine the direct association between level of neonatal vitamin D and risk of MS.
  
  
  METHODS
  We carried out a matched case-control study. Dried blood spots samples (DBSS) belonging to 521 patients with MS were identified in the Danish Newborn Screening Biobank. For every patient with MS, 1-2 controls with the same sex and birth date were retrieved from the Biobank (n = 972). Level of 25-hydroxyvitamin D (25[OH]D) in the DBSS was measured using liquid chromatography tandem mass spectroscopy. The association between different levels of 25(OH)D and risk of MS was evaluated by odds ratios (OR) calculated in conditional logistic regression models.
  
  
  RESULTS
  We observed that lower levels of 25(OH)D in neonates were associated with an increased risk of MS. In the analysis by quintiles, MS risk was highest among individuals in the bottom quintile (<20.7 nmol/L) and lowest among those in the top quintile of 25(OH)D (≥48.9 nmol/L), with an OR for top vs bottom of 0.53 (95% confidence interval [CI] 0.36-0.78). In the analysis treating 25(OH)D as a continuous variable, a 25 nmol/L increase in neonatal 25(OH)D resulted in a 30% reduced risk of MS (OR 0.70, 95% CI 0.57-0.84).
  
  
  CONCLUSIONS
  Low concentrations of neonatal vitamin D are associated with an increased risk of MS. In light of the high prevalence of vitamin D insufficiency among pregnant women, our observation may have importance for public health.
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. NMN@ssi.dk.
authors.forename: Nete Munk
authors.initials: NM
authors.lastname: Nielsen
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Kassandra L
authors.initials: KL
authors.lastname: Munger
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: David M
authors.initials: DM
authors.lastname: Hougaard
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Melinda
authors.initials: M
authors.lastname: Magyari
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Kristian T
authors.initials: KT
authors.lastname: Jørgensen
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Marika
authors.initials: M
authors.lastname: Lundqvist
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Simonsen
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Tine
authors.initials: T
authors.lastname: Jess
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Arieh
authors.initials: A
authors.lastname: Cohen
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Egon
authors.initials: E
authors.lastname: Stenager
authors.affiliation: From the Department of Epidemiology Research (N.M.N., K.T.J., J.S., T.J.) and the Danish Centre for Neonatal Screening, Department for Congenital Disorders (D.M.H., M.L., A.C.), Statens Serum Institut, Copenhagen, Denmark; Departments of Nutrition (K.L.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; The Danish Multiple Sclerosis Registry (N.K.-H., M.M., E.S.), Danish Multiple Sclerosis Centre, Department of Neurology, University of Copenhagen (M.M.), and Danish Multiple Sclerosis Research Centre, Department of Neurology, Neuroscience Centre (M.M.), Rigshospitalet, Copenhagen, Denmark; Institute of Regional Health Research (E.S.), University of Southern Denmark, Odense, Denmark, and National Institute of Public Health (E.S.), University of Southern Denmark, Copenhagen; Department of Neurology (E.S.), Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Sønderborg, Denmark; Department of Clinical Epidemiology, Clinical Institute (N.K.-H.), University of Aarhus, Aarhus, Denmark; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA.
authors.forename: Alberto
authors.initials: A
authors.lastname: Ascherio
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D018672:Community Health Planning; D003718:Denmark / Q000453:epidemiology; D005260:Female; D006801:Humans; D007231:Infant, Newborn / Q000097:blood*; D008297:Male; D009103:Multiple Sclerosis / Q000097:blood / Q000453:epidemiology*; D015999:Multivariate Analysis; D016017:Odds Ratio; D010290:Parents; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000453:epidemiology
chemical_list: D014807:Vitamin D; C104450:25-hydroxyvitamin D