title: Stressful life-events in childhood and risk of multiple sclerosis: a Danish nationwide cohort study.
abstract: BACKGROUND
  Current knowledge concerning the association between exposure to stressful life-events (SFLEs) in childhood and later risk of multiple sclerosis (MS) is sparse.
  
  
  OBJECTIVE
  We studied the associations between SFLEs in childhood and subsequent risk of MS in a nationwide cohort of 2.9 million Danes born from 1968 to 2011.
  
  
  METHODS
  A SFLE in childhood was defined as exposure before age 18 years to parental divorce, parental death, or death of a sibling, using information from the Danish Civil Registration System. MS cases in the cohort were identified in the Danish Multiple Sclerosis Registry. Associations of SFLE with MS risk were evaluated by incidence rate ratios (RR) of MS obtained in log-linear Poisson regression models.
  
  
  RESULTS
  Persons exposed to any SFLE in childhood were at 11% elevated risk of MS (RR = 1.11; 95% confidence interval: 1.03-1.20), compared to non-exposed persons. Stratification by subtype of SFLE showed that parental death and death of a sibling were not associated with MS risk. However, persons exposed to parental divorce were at 13% increased risk of developing MS compared to non-exposed (RR = 1.13; 1.04-1.23).
  
  
  CONCLUSIONS
  Associations of SFLEs in childhood with risk of MS are weak. However, parental divorce is somehow associated with modestly increased risk of MS.
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Artillerivej 5, 2300 Copenhagen S, Denmark NMN@ssi.dk.
authors.forename: Nete Munk
authors.initials: NM
authors.lastname: Nielsen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Denmark.
authors.forename: Bo V
authors.initials: BV
authors.lastname: Pedersen
authors.affiliation: The Danish MS Registry, the Danish MS Research Center, Rigshospitalet, Copenhagen/Institute of Regional Health Research/Multiple Sclerosis Clinic of Southern Jutland (Sønderborg, Vejle, Esbjerg), Department of Neurology, Sønderborg, Denmark and National Institute of Public Health, University of Southern Denmark, Denmark.
authors.forename: Egon
authors.initials: E
authors.lastname: Stenager
authors.affiliation: The Danish MS Registry, the Danish MS Research Center, Rigshospitalet, Copenhagen, Denmark/Clinical Institute, Department of Clinical Epidemiology, Aarhus University, Denmark.
authors.forename: Nils
authors.initials: N
authors.lastname: Koch-Henriksen
authors.affiliation: Department of Epidemiology Research, Statens Serum Institut, Denmark.
authors.forename: Morten
authors.initials: M
authors.lastname: Frisch
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D004243:Divorce; D005260:Female; D006801:Humans; D007223:Infant; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000453:epidemiology*; D012042:Registries; D012307:Risk Factors; D035781:Siblings; D055815:Young Adult
keywords: Multiple sclerosis; childhood; epidemiology; stressful life-events