{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T20:13:55Z","timestamp":1780431235786,"version":"3.54.1"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2021,3,9]],"date-time":"2021-03-09T00:00:00Z","timestamp":1615248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100000269","name":"UK Economic and Social Research Council","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000269","name":"ESRC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000269","id-type":"DOI","asserted-by":"publisher"}]},{"name":"International Centre for Life Course Studies","award":["ES\/R008930\/1"],"award-info":[{"award-number":["ES\/R008930\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections such as the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20\u2009years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970 and 1994 were identified using the Swedish Total Population Register (n\u2009=\u20092\u200a422\u200a969). Multiple sclerosis diagnoses from age 20\u2009years and hospital-diagnosed infections before age 20\u2009years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11\u201319\u2009years) and earlier childhood (birth\u201310\u2009years) was estimated using Cox regression, with adjustment for sex, parental socio-economic position, and infection type. None of the infections by age 10\u2009years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21\u20131.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06\u20131.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11\u20133.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13\u20131.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30\u20131.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections.<\/jats:p>","DOI":"10.1093\/brain\/awab100","type":"journal-article","created":{"date-parts":[[2021,3,7]],"date-time":"2021-03-07T20:07:03Z","timestamp":1615147623000},"page":"2390-2400","source":"Crossref","is-referenced-by-count":22,"title":["Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis"],"prefix":"10.1093","volume":"144","author":[{"given":"Yin","family":"Xu","sequence":"first","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9811-908X","authenticated-orcid":false,"given":"Kelsi A","family":"Smith","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Hiyoshi","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, \u00d6rebro University, \u00d6rebro, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fredrik","family":"Piehl","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomas","family":"Olsson","sequence":"additional","affiliation":[{"name":"Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Clinical Epidemiology and Biostatistics, School of Medical Sciences, \u00d6rebro University, \u00d6rebro, Sweden"},{"name":"Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Epidemiology and Public Health, University College London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,9]]},"reference":[{"key":"2021090418513587400_awab100-B1","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1002\/ana.21117","article-title":"Environmental risk factors for multiple sclerosis. 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Part II: Noninfectious factors","volume":"61","author":"Ascherio","year":"2007","journal-title":"Ann Neurol"},{"key":"2021090418513587400_awab100-B3","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/S1474-4422(10)70094-6","article-title":"Multiple sclerosis: Risk factors, prodromes, and potential causal pathways","volume":"9","author":"Ramagopalan","year":"2010","journal-title":"Lancet Neurol"},{"key":"2021090418513587400_awab100-B4","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/nrneurol.2016.187","article-title":"Interactions between genetic, lifestyle and environmental risk factors for multiple sclerosis","volume":"13","author":"Olsson","year":"2017","journal-title":"Nat Rev Neurol"},{"key":"2021090418513587400_awab100-B5","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1002\/ana.20820","article-title":"Infectious mononucleosis and risk for multiple sclerosis: A 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