title: Time- and Region-Specific Season of Birth Effects in Multiple Sclerosis in the United Kingdom.
abstract: OBJECTIVE
  The reports of seasonal variation in the births of people who later develop multiple sclerosis (MS) have been challenged and attributed to the background pattern in the general population, resulting in a false association.
  
  
  OBJECTIVE
  To study the seasonality of MS births after adjusting for temporal and regional confounding factors.
  
  
  METHODS
  A study was conducted using case-control data from 8 MS-specialized centers from the United Kingdom, MS cases from a population-based study in the Lothian and Border regions of Scotland, and death records from the UK Registrar General. Participants included 21 138 patients with MS and control data from the UK Office of National Statistics and the UK government office regions. The seasonality of MS births was evaluated using the Walter and Elwood test, after adjusting for temporal and regional variations in the live births of the UK population. The study was conducted from January 16, 2014, to September 2, 2015.
  
  
  METHODS
  Diagnosis of multiple sclerosis.
  
  
  RESULTS
  Analysis of the general population indicated that seasonal differences are present across time and region in the United Kingdom, with both factors contributing to the monthly distribution of live births. We were able to demonstrate that, when adjusting for the temporal and regional variations in the live births of the UK population, there was a significant season of birth effect in patients with MS, with an increased risk of disease in the peak month (April) compared with the trough month (November) (odds ratio, 1.24; 95% CI, 1.10-1.41) and 15.68% fewer people who developed MS being born in November (observed to expected birth ratio, 0.840; 95% CI, 0.76-0.92).
  
  
  CONCLUSIONS
  Season of birth is a risk factor for MS in the United Kingdom and cannot be attributed to the background pattern in the general population. The reasons for the variations in birth rates in the general population are unclear, but not taking them into consideration could lead to false-positive associations.
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Pedro María
authors.initials: PM
authors.lastname: Rodríguez Cruz
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Lucy
authors.initials: L
authors.lastname: Matthews
authors.affiliation: The Townsville Hospital, Queensland, Australia.
authors.forename: Mike
authors.initials: M
authors.lastname: Boggild
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Ana
authors.initials: A
authors.lastname: Cavey
authors.affiliation: University of Nottingham, Nottingham, England.
authors.forename: Cris S
authors.initials: CS
authors.lastname: Constantinescu
authors.affiliation: University of Nottingham, Nottingham, England.
authors.forename: Nikos
authors.initials: N
authors.lastname: Evangelou
authors.affiliation: Barts and The London School of Medicine and Dentistry, London, England.
authors.forename: Gavin
authors.initials: G
authors.lastname: Giovannoni
authors.affiliation: South Eastern Health and Social Care Trust, Belfast, Northern Ireland.
authors.forename: Orla
authors.initials: O
authors.lastname: Gray
authors.affiliation: Belfast Trust, Belfast, Northern Ireland.
authors.forename: Stanley
authors.initials: S
authors.lastname: Hawkins
authors.affiliation: Imperial College London, London, England.
authors.forename: Richard
authors.initials: R
authors.lastname: Nicholas
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Maylin
authors.initials: M
authors.lastname: Oppenheimer
authors.affiliation: Cardiff University, Cardiff, Wales.
authors.forename: Neil
authors.initials: N
authors.lastname: Robertson
authors.affiliation: University of St Andrews, St Andrews, Scotland.
authors.forename: John
authors.initials: J
authors.lastname: Zajicek
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Peter M
authors.initials: PM
authors.lastname: Rothwell
authors.affiliation: Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, England.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Palace
mesh_terms: D018672:Community Health Planning; D004777:Environment; D005260:Female; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000453:epidemiology*; D012307:Risk Factors; D012621:Seasons; D018709:Statistics, Nonparametric; D006113:United Kingdom / Q000453:epidemiology