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Reference lists of eligible studies were also screened.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Eligibility criteria for selecting studies<\/jats:title>\n                    <jats:p>Human studies assessing health outcomes after aluminium adjuvanted vaccination, including randomised controlled trials, cohort studies, case series, and ecological studies. Investigational vaccines, case reports, and review articles were excluded.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Data extraction and synthesis<\/jats:title>\n                    <jats:p>Two reviewers screened studies (with AI assistance for the 2023-25 update), extracted data, and assessed risk of bias (using RoB 2.0, ROBINS-I, or an adapted tool for case series). Certainty of evidence was rated using GRADE (Grading of Recommendations Assessment, Development, and Evaluation).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The review included 59 studies (37 case series, 11 randomised controlled trials, nine cohort studies, two ecological studies). High quality evidence from randomised controlled trials and large cohorts consistently showed no association between aluminium adjuvanted vaccines and serious or long term health outcomes, such as asthma, autism spectrum disorders, or other chronic conditions. Studies on macrophagic myofasciitis were generally small and methodologically limited, and did not provide credible evidence of a causal association (very low certainty). Localised persistent nodules or granulomas were observed infrequently after diphtheria-tetanus-pertussis vaccines, consistent with delayed type hypersensitivity (&lt;1%, self-limited; moderate to low certainty). For common adverse events (eg, headache, myalgia), high certainty randomised controlled trials found no consistent increase in risk with aluminium adjuvanted formulations. When differences were observed, they were small and predominantly mild to moderate in severity. Evidence was dominated by methodologically limited studies, with most case series and ecological studies at serious or critical risk of bias. Conclusions are primarily supported by higher quality randomised controlled trials and cohort evidence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Current evidence does not support causal associations between aluminium adjuvanted vaccines and serious or long term health outcomes. The most consistently documented reactions were persistent nodules or granulomas that are uncommon, local, and self-limited hypersensitivity reactions. These findings are broadly consistent with post-licensure surveillance findings. The predominance of methodologically limited studies for some outcomes highlights the need for higher quality research.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>PROSPERO CRD42023462831.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmj-2025-088921","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:10:57Z","timestamp":1778112657000},"page":"e088921","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Aluminium adjuvants in vaccines and potential health effects: systematic review"],"prefix":"10.1136","volume":"393","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8738-0055","authenticated-orcid":false,"given":"Pamela","family":"Doyon-Plourde","sequence":"first","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Chong","sequence":"additional","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elissa M","family":"Abrams","sequence":"additional","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"},{"name":"Section of Allergy and Clinical Immunology, Department of Pediatrics, University of Manitoba, Winnipeg, MB, Canada"},{"name":"Division of Allergy and Immunology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Pless","sequence":"additional","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelsey","family":"Young","sequence":"additional","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Tunis","sequence":"additional","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5261-3333","authenticated-orcid":false,"given":"Joseline","family":"Zafack","sequence":"additional","affiliation":[{"name":"Centre for Immunization Surveillance and Programs, Public Health Agency of Canada, Ottawa, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,6]]},"reference":[{"key":"2026050621001141000_393.may06_7.e088921.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00166-4"},{"key":"2026050621001141000_393.may06_7.e088921.2","doi-asserted-by":"publisher","DOI":"10.1016\/S0264-410X(02)00169-X"},{"key":"2026050621001141000_393.may06_7.e088921.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.vaccine.2018.08.036"},{"key":"2026050621001141000_393.may06_7.e088921.4","doi-asserted-by":"publisher","DOI":"10.1007\/s40264-015-0350-4"},{"key":"2026050621001141000_393.may06_7.e088921.5","first-page":"337","article-title":"Macrophagic myofasciitis and aluminum-containing vaccines","volume":"74","year":"1999","journal-title":"Wkly Epidemiol Rec"},{"key":"2026050621001141000_393.may06_7.e088921.6","first-page":"281","article-title":"June 2012","volume":"87","year":"2012","journal-title":"Wkly Epidemiol Rec"},{"key":"2026050621001141000_393.may06_7.e088921.7","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(04)00927-2"},{"key":"2026050621001141000_393.may06_7.e088921.8","doi-asserted-by":"publisher","DOI":"10.3109\/10408444.2013.835784"},{"key":"2026050621001141000_393.may06_7.e088921.9","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2025-074874"},{"key":"2026050621001141000_393.may06_7.e088921.10","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2021-058795"},{"key":"2026050621001141000_393.may06_7.e088921.11","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71"},{"key":"2026050621001141000_393.may06_7.e088921.12","unstructured":"Adverse events potentially associated with aluminum adjuvants included in vaccines: a systematic review. 2024. 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