title: Month of birth and risk of multiple sclerosis: confounding and adjustments.
abstract: A month of birth effect on multiple sclerosis (MS) risk has been reported from different countries. Recent critics have suggested that this finding is caused by confounding and that adequately adjusting for year and place of birth would markedly reduce this effect. All inhabitants in Norway are registered in the Norwegian Population Registry (Statistics Norway), making this an ideal area for performing adjusted analyses. Using the entire Norwegian population born between 1930 and 1979 (n = 2,899,260), we calculated the excess between observed and expected number of births for each month for 6649 Norwegian MS patients, 5711 mothers, 5247 fathers, and 8956 unaffected siblings. The analyses were adjusted for year of birth and place of birth according to the 19 counties in Norway. An unadjusted analysis revealed 13% fewer MS births than expected in February (P = 0.0015; Bonferroni corrected P = 0.018), 10% more in April (P = 0.0083; Bonferroni corrected P = 0.0996) and 15% more in December (P = 0.00058; Bonferroni corrected P = 0.007). Adjustments for both year and place of birth significantly altered our results for February and December, but even after these adjustments there were still 10% more MS births than expected in April (P = 0.00796; Bonferroni corrected P = 0.096). MS patients had a higher incidence of April births than their siblings (Fisher-exact test; P = 0.011), mothers (Fisher-exact test; P = 0.004), and fathers (Fisher-exact test; P = 0.011) without MS. Adjustments for confounding significantly affected our results. However, even after adjustments, there appears to be a persistent higher than expected frequency of April births in the MS population.
authors.affiliation: The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital Bergen, Norway ; Kristian Gerhard Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen Bergen, Norway.
authors.forename: Oivind
authors.initials: O
authors.lastname: Torkildsen
authors.affiliation: The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital Bergen, Norway ; Kristian Gerhard Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen Bergen, Norway.
authors.forename: Jan
authors.initials: J
authors.lastname: Aarseth
authors.affiliation: Department of Neurology, Nordland Hospital Bodø, Norway.
authors.forename: Espen
authors.initials: E
authors.lastname: Benjaminsen
authors.affiliation: Department of Neurology, Oslo University Hospital, Ullevål Oslo, Norway.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Celius
authors.affiliation: Department of Neurology, Akershus University Hospital Lørenskog, Norway ; Institute of Clinical Medicine, University of Oslo Oslo, Norway.
authors.forename: Trygve
authors.initials: T
authors.lastname: Holmøy
authors.affiliation: Department of Neurology, Institute of Clinical Medicine, University of Tromsø Tromsø, Norway ; Department of Neurology, University Hospital of North Norway Tromsø, Norway.
authors.forename: Margitta T
authors.initials: MT
authors.lastname: Kampman
authors.affiliation: Institute of Clinical Medicine, University of Oslo Oslo, Norway ; Department of Neurology, Innlandet Hospital Trust Lillehammer, Norway.
authors.forename: Kristin
authors.initials: K
authors.lastname: Løken-Amsrud
authors.affiliation: Department of Neurology, Molde Hospital Molde, Norway.
authors.forename: Rune
authors.initials: R
authors.lastname: Midgard
authors.affiliation: The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital Bergen, Norway ; Kristian Gerhard Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen Bergen, Norway.
authors.forename: Kjell-Morten
authors.initials: KM
authors.lastname: Myhr
authors.affiliation: Department of Public Health and Primary Health Care, University of Bergen Bergen, Norway.
authors.forename: Trond
authors.initials: T
authors.lastname: Riise
authors.affiliation: The Norwegian Multiple Sclerosis Competence Centre, Department of Neurology, Haukeland University Hospital Bergen, Norway ; Kristian Gerhard Jebsen Centre for MS-Research, Department of Clinical Medicine, University of Bergen Bergen, Norway.
authors.forename: Nina
authors.initials: N
authors.lastname: Grytten