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Pediatr."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> This study aimed to identify potential risk factors for severe hand-foot-mouth disease (HFMD).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> The PubMed, Embase, the Cochrane Library, Sinomed, WanFang, CNKI, and VIP databases were searched (up to August 2021).<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Twenty-nine studies (9,241 and 927,355 patients with severe HFMD and controls, respectively; all from China) were included. EV71 was associated with higher odds of severe HFMD compared with other agents (OR = 4.44, 95%CI: 3.12\u20136.33, <jats:italic>p<\/jats:italic> &amp;lt; 0.001). Being home-raised (OR = 1.99, 95%CI: 1.59\u20132.50, <jats:italic>p<\/jats:italic> &amp;lt; 0.001), higher number of children in the family (OR = 2.09, 95%CI: 1.93\u20132.27, <jats:italic>p<\/jats:italic> &amp;lt; 0.001), poor hand hygiene (OR = 2.74, 95%CI: 1.78\u20134.23, <jats:italic>p<\/jats:italic> &amp;lt; 0.001), and no breastfeeding (OR = 2.01, 95%CI: 1.45\u20132.79, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) were risk factors for severe HFMD. First consulting to a district-level or above hospital (OR = 0.34, 95%CI: 0.25\u20130.45, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) and diagnosis of HFMD at baseline (OR = 0.17, 95%CI: 0.13\u20130.24, <jats:italic>p<\/jats:italic> &amp;lt; 0.001) were protective factors against severe HFMD. Fever, long fever duration, vomiting, lethargy, leukocytosis, tic, and convulsions were each associated with severe HFMD (all <jats:italic>p<\/jats:italic> &amp;lt; 0.05), while rash was not.<\/jats:p><jats:p><jats:bold>Conclusions:<\/jats:bold> EV71, lifestyle habits, frequent hospital visits, and symptoms are risk factors for severe HFMD in children in China, while early diagnosis and admission to higher-level hospitals are protective factors.<\/jats:p>","DOI":"10.3389\/fped.2021.716039","type":"journal-article","created":{"date-parts":[[2021,11,10]],"date-time":"2021-11-10T10:42:53Z","timestamp":1636540973000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Risk Factors for Severe Hand-Foot-Mouth Disease in China: A Systematic Review and Meta-Analysis"],"prefix":"10.3389","volume":"9","author":[{"given":"Peiqing","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuge","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danping","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sida","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dandan","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,10]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"165","DOI":"10.4103\/0378-6323.107631","article-title":"Hand, foot, and mouth disease: current scenario and Indian perspective","volume":"79","author":"Sarma","year":"2013","journal-title":"Indian J Dermatol Venereol Leprol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1007\/s00430-016-0465-y","article-title":"Hand, foot and mouth disease (HFMD): emerging epidemiology and the need for a vaccine strategy","volume":"205","author":"Aswathyraj","year":"2016","journal-title":"Med Microbiol Immunol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"537","DOI":"10.3949\/ccjm.81a.13132","article-title":"Hand, foot, and mouth disease: identifying and managing an acute viral syndrome","volume":"81","author":"Repass","year":"2014","journal-title":"Cleve Clin J Med"},{"key":"B4","unstructured":"GenevaWorld Health OrganizationA Guide to Clinical Management and Public Health Response for Hand, Foot and Mouth Disease (HFMD)2018"},{"key":"B5","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1080\/23744235.2018.1493217","article-title":"Epidemiological and aetiological characteristics of hand, foot and mouth disease cases 2011\u20132017 in Yixing, China","volume":"50","author":"Xiao","year":"2018","journal-title":"Infect Dis (Lond)."},{"key":"B6","doi-asserted-by":"publisher","first-page":"270","DOI":"10.3390\/ijerph15020270","article-title":"Epidemiological characteristics and spatial-temporal distribution of hand, foot, and mouth disease in Chongqing, China, 2009-2016","volume":"15","author":"Qi","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"B7","doi-asserted-by":"publisher","first-page":"678","DOI":"10.1086\/314032","article-title":"Deaths of children during an outbreak of hand, foot, and mouth disease in Sarawak, Malaysia: clinical and pathological characteristics of the disease. 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