{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T08:55:53Z","timestamp":1762073753501,"version":"build-2065373602"},"reference-count":40,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Portuguese national funds","award":["UIDB\/00317\/2020"],"award-info":[{"award-number":["UIDB\/00317\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Healthcare"],"abstract":"<jats:p>Autism spectrum disorder (ASD) is the most common neurodevelopmental disorder with a huge prevalence increasing every year (1\/44 children). Still diagnosed as a mental disorder, the last 10 years of research found possible causes, risks, genetics, environmental triggers, epigenetics, metabolic, immunological, and neurophysiological unbalances as relevant aetiology. Umbrella methodology is the highest level of scientific evidence, designed to support clinical and political decisions. A literature search for autism aetiology, pathophysiology, or causes, conducted in the last 10 years, at PubMed, Embase, Cochrane, Scopus, and the Web of Science, resulted in six umbrella reviews. Nevertheless, only one quantitative analysis reported risk factors and biomarkers but excluded genetics, experiments on animal models, and post-mortem studies. We grouped ASD\u2019s multi-factorial causes and risks into five etiological categories: genetic, epigenetic, organic, psychogenic, and environmental. Findings suggest that autism might be evaluated as a systemic disorder instead of only through the lens of mental and behavioural. The overview implications of included studies will be qualitatively analysed under ROBIS and GRADE tools. This umbrella review can provide a rational basis for a new urgent health policy to develop better and adequate integrated care services for ASD. The methodological protocol has the register CRD42022348586 at PROSPERO.<\/jats:p>","DOI":"10.3390\/healthcare10112200","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T03:11:21Z","timestamp":1667445081000},"page":"2200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Autism Spectrum as an Etiologic Systemic Disorder: A Protocol for an Umbrella Review"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6071-0715","authenticated-orcid":false,"given":"Lara Teixeira","family":"Lopes","sequence":"first","affiliation":[{"name":"Institute of Biomedical Sciences, University of Porto, 4099-030 Porto, Portugal"},{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5892-1855","authenticated-orcid":false,"given":"Jorge Magalh\u00e3es","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]},{"given":"Celeste","family":"Baccarin","sequence":"additional","affiliation":[{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9532-0773","authenticated-orcid":false,"given":"Kevin","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-5442-6723","authenticated-orcid":false,"given":"Manuela","family":"Abreu","sequence":"additional","affiliation":[{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]},{"given":"Victor","family":"Ribeiro","sequence":"additional","affiliation":[{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3786-6559","authenticated-orcid":false,"given":"Z\u00e9lia Ca\u00e7ador","family":"Anast\u00e1cio","sequence":"additional","affiliation":[{"name":"Research Center on Child Studies, Institute of Education, University of Minho, 4804-533 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4570-5445","authenticated-orcid":false,"given":"Jorge Pereira","family":"Machado","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences, University of Porto, 4099-030 Porto, Portugal"},{"name":"Center of BioSciences in Integrative Health, 4200-355 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"ref_1","first-page":"1","article-title":"Estimated Prevalence of Autism and Other Developmental Disabilities Following Questionnaire Changes in the 2014 National Health Interview Survey","volume":"87","author":"Zablotsky","year":"2015","journal-title":"Natl. 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