{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,9]],"date-time":"2026-06-09T14:18:48Z","timestamp":1781014728818,"version":"3.54.1"},"reference-count":33,"publisher":"American Academy of Pediatrics (AAP)","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,2,1]]},"abstract":"<jats:p>BACKGROUND. Ischemic stroke is a known complication of varicella disease. Although there have been case reports of ischemic stroke after varicella vaccination, the existence and magnitude of any vaccine-associated risk has not been determined.<\/jats:p>\n               <jats:p>OBJECTIVE. The purpose of this work was to determine whether varicella vaccination is associated with an increased risk of ischemic stroke and encephalitis in children within 12 months after vaccination.<\/jats:p>\n               <jats:p>PATIENTS AND METHODS. We conducted a retrospective cohort study based on computerized data from children 11 months through 17 years old enrolled for \u226512 months in the Vaccine Safety DataLink from 1991 through 2004. International Classification of Disease codes identified cases of ischemic stroke (433\u2013436, 437.1, 437.4, 437.6, 437.8\u2013437.9) and encephalitis (052.0, 323.5, 323.8\u20139). Cox regression was used to model the risk in the 12 months after vaccination relative to all other person-time. Covariates included calendar time, gender, and stroke risk factors (eg, sickle cell disease).<\/jats:p>\n               <jats:p>RESULTS. Varicella vaccine was administered to 35.3% of the 3.2 million children in the cohort. There were 203 new inpatient ischemic stroke diagnoses, including 8 that occurred within 12 months after vaccination; there was no temporal clustering. The adjusted stroke hazard ratio was not elevated during any of the time periods in the 12 months after vaccination. Stroke was strongly associated with known risk factors such as sickle cell disease and cardiac disease. None of the 243 encephalitis cases occurred during the first 30 days after vaccination, and there was no association between encephalitis and varicella vaccination at any time in the 12 months after vaccination.<\/jats:p>\n               <jats:p>CONCLUSION. Our retrospective cohort study of &amp;gt;3 million children found no association between varicella vaccine and ischemic stroke.<\/jats:p>","DOI":"10.1542\/peds.2008-2384","type":"journal-article","created":{"date-parts":[[2009,1,26]],"date-time":"2009-01-26T12:23:44Z","timestamp":1232972624000},"page":"e228-e234","source":"Crossref","is-referenced-by-count":41,"title":["Varicella Vaccination and Ischemic Stroke in Children: Is There an Association?"],"prefix":"10.1542","volume":"123","author":[{"given":"James G.","family":"Donahue","sequence":"first","affiliation":[{"name":"Marshfield Clinic Research Foundation, Marshfield, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burney A.","family":"Kieke","sequence":"additional","affiliation":[{"name":"Marshfield Clinic Research Foundation, Marshfield, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. Katherine","family":"Yih","sequence":"additional","affiliation":[{"name":"Department of Ambulatory Care and Prevention, Harvard Medical School and Harvard Pilgrim Health Care, Boston, Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas R.","family":"Berger","sequence":"additional","affiliation":[{"name":"Marshfield Clinic Research Foundation, Marshfield, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy S.","family":"McCauley","sequence":"additional","affiliation":[{"name":"Marshfield Clinic Research Foundation, Marshfield, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Baggs","sequence":"additional","affiliation":[{"name":"Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth M.","family":"Zangwill","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roger","family":"Baxter","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Vaccine Study Center, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen M.","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason M.","family":"Glanz","sequence":"additional","affiliation":[{"name":"Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Hambidge","sequence":"additional","affiliation":[{"name":"Institute for Health Research, Kaiser Permanente Colorado, Denver, Colorado"},{"name":"Denver Health Community Health Services, Denver, Colorado"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola P.","family":"Klein","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Vaccine Study Center, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin M.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Vaccine Study Center, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Michael","family":"Marcy","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Southern California, Pasadena, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allison L.","family":"Naleway","sequence":"additional","affiliation":[{"name":"Center for Health Research, Kaiser Permanente Northwest, Portland, Oregon"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Nordin","sequence":"additional","affiliation":[{"name":"HealthPartners Research Foundation, Minneapolis, Minnesota"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Ray","sequence":"additional","affiliation":[{"name":"Kaiser Permanente Vaccine Study Center, Oakland, California"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward A.","family":"Belongia","sequence":"additional","affiliation":[{"name":"Marshfield Clinic Research Foundation, Marshfield, Wisconsin"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Vaccine Safety DataLink Team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"417","published-online":{"date-parts":[[2009,2,1]]},"reference":[{"key":"2021120822570216600_R1","doi-asserted-by":"crossref","unstructured":"Earley CJ, Kittner SJ, Feeser BR, et al. Stroke in children and sickle-cell disease: Baltimore-Washington Cooperative Young Stroke Study. Neurology.\u20081998;51(1):169\u2013176","DOI":"10.1212\/WNL.51.1.169"},{"key":"2021120822570216600_R2","doi-asserted-by":"crossref","unstructured":"Giroud M, Lemesle M, Gouyon JB, Nivelon JL, Milan C, Dumas R. Cerebrovascular disease in children under 16 years of age in the city of Dijon, France: a study of incidence and clinical features from 1985 to 1993. J Clin Epidemiol.\u20081995;48(11):1343\u20131348","DOI":"10.1016\/0895-4356(95)00039-9"},{"key":"2021120822570216600_R3","doi-asserted-by":"crossref","unstructured":"Lynch JK, Hirtz DG, deVeber G, Nelson KB. Report of the National Institute of Neurological Disorders and Stroke workshop on perinatal and childhood stroke. Pediatrics.\u20082002;109(1):116\u2013123","DOI":"10.1542\/peds.109.1.116"},{"key":"2021120822570216600_R4","doi-asserted-by":"crossref","unstructured":"Fullerton HJ, Wu YW, Zhao S, Johnston SC. 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Pediatr Infect Dis.\u20081984;3(6):505\u2013509","DOI":"10.1097\/00006454-198411000-00004"},{"key":"2021120822570216600_R15","doi-asserted-by":"crossref","unstructured":"Chaves SS, Haber P, Walton K, et al. Safety of varicella vaccine after licensure in the United States: experience from reports to the Vaccine Adverse Event Reporting System, 1995\u20132005. J Infect Dis.\u20082008;197(suppl 2):S170\u2013S177","DOI":"10.1086\/522161"},{"key":"2021120822570216600_R16","doi-asserted-by":"crossref","unstructured":"DeStefano F. The Vaccine Safety DataLink project. Pharmacoepidemiol Drug Saf.\u20082001;10(5):403\u2013406","DOI":"10.1002\/pds.613"},{"key":"2021120822570216600_R17","doi-asserted-by":"crossref","unstructured":"Therneau TM, Grambsch PM. Modeling Survival Data: Extending the Cox Model. New York, NY: Springer; 2000","DOI":"10.1007\/978-1-4757-3294-8"},{"key":"2021120822570216600_R18","doi-asserted-by":"crossref","unstructured":"Moriuchi H, Rodriguez W. 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