{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:50:20Z","timestamp":1785487820383,"version":"3.56.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T00:00:00Z","timestamp":1605225600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Hospital-acquired venous thromboembolism (HA-VTE) in children comprises multiple risk factors that should not be evaluated separately due to collinearity and multiple cause and effect relationships. This is one of the first case-control study of pediatric HA-VTE risk factors using a Directed Acyclic Graph (DAG) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Material and methods<\/jats:title>\n                    <jats:p>Retrospective, case-control study with 22 cases of objectively confirmed HA-VTE and 76 controls matched by age, sex, unit of admission, and period of hospitalization. Descriptive statistics were used to define distributions of continuous variables, frequencies, and proportions of categorical variables, comparing cases and controls. Due to many potential risk factors of HA-VTE, a directed acyclic graph (DAG) model was created to identify confounding, reduce bias, and increase precision on the analysis. The final model consisted of a DAG-informed conditional logistic regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In the initial conventional univariable model, the following variables were selected as potential risk factors for HA-VTE: length of stay (LOS, days), immobility, ICU admission in the last 30 days, LOS in ICU, infection, central venous catheter (CVC), number of CVCs placed, L-asparaginase, heart failure, liver failure, and nephrotic syndrome. The final model using the set of variables selected by DAG analysis revealed LOS (OR = 1.106, 95%CI = 1.021\u20131.198, p = 0.013), L-asparaginase (OR = 26.463, 95%CI = 1.609\u2013435.342, p = 0.022), and nephrotic syndrome (OR = 29.127, 95%CI = 1.044\u2013812.508, p = 0.004) as independent risk factors for HA-VTE.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The DAG-based approach was useful to clarify the influence of confounders and multiple causalities of HA-VTE. Interestingly, CVC placement\u2014a known thrombotic risk factor highlighted in several studies\u2014was considered a confounder, while LOS, L-asparaginase use and nephrotic syndrome were confirmed as risk factors to HA-VTE. Large confidence intervals are related to the sample size; however, the results were significant.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0242311","type":"journal-article","created":{"date-parts":[[2020,11,13]],"date-time":"2020-11-13T13:24:45Z","timestamp":1605273885000},"page":"e0242311","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":9,"title":["Risk factors for the development of hospital-acquired pediatric venous thromboembolism\u2014Dealing with potentially causal and confounding risk factors using a directed acyclic graph (DAG) analysis"],"prefix":"10.1371","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1569-7360","authenticated-orcid":true,"given":"Leonardo Rodrigues","family":"Campos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maur\u00edcio","family":"Petroli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavio Roberto","family":"Sztajnbok","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elaine Sobral","family":"da Costa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7711-4530","authenticated-orcid":true,"given":"Leonardo Rodrigues","family":"Brand\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo Gerardin Poirot","family":"Land","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2020,11,13]]},"reference":[{"issue":"4","key":"pone.0242311.ref001","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1542\/peds.2009-0768","article-title":"Dramatic increase in venous thromboembolism in children\u2019s hospitals in the United States from 2001 to 2007","volume":"124","author":"L Raffini","year":"2009","journal-title":"Pediatrics"},{"issue":"2","key":"pone.0242311.ref002","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1002\/pbc.23388","article-title":"Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases","volume":"59","author":"BA Setty","year":"2012","journal-title":"Pediatr Blood Cancer"},{"issue":"Suppl 1","key":"pone.0242311.ref003","doi-asserted-by":"crossref","first-page":"S68","DOI":"10.1002\/ajh.23131","article-title":"Current and future management of pediatric venous thromboembolism","volume":"87","author":"BA Kerlin","year":"2012","journal-title":"Am J Hematol"},{"issue":"11","key":"pone.0242311.ref004","doi-asserted-by":"crossref","first-page":"1952","DOI":"10.3324\/haematol.2010.026989","article-title":"Post-thrombotic syndrome in children: a systematic review of frequency of occurrence, validity of outcome measures, and prognostic factors","volume":"95","author":"NA Goldenberg","year":"2010","journal-title":"Haematologica"},{"issue":"3","key":"pone.0242311.ref005","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1017\/S1047951112001126","article-title":"Cardiac findings and long-term thromboembolic outcomes following pulmonary embolism in children: a combined retrospective-prospective inception cohort study","volume":"23","author":"HS Hancock","year":"2013","journal-title":"Cardiol Young"},{"issue":"5","key":"pone.0242311.ref006","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1111\/j.1365-2141.2008.07243.x","article-title":"Clinical features and outcome of pulmonary embolism in children","volume":"142","author":"TT Biss","year":"2008","journal-title":"Br J Haematol"},{"issue":"8","key":"pone.0242311.ref007","first-page":"1045","article-title":"Hospital-associated venous thromboembolism in pediatrics: a systematic review and meta-analysis of risk factors and risk-assessment models","volume":"100","author":"A Mahajerin","year":"2015","journal-title":"Haematologica"},{"key":"pone.0242311.ref008","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1186\/1471-2288-8-70","article-title":"Reducing bias through directed acyclic graphs","volume":"8","author":"I. Shrier","year":"2008","journal-title":"BMC Med Res Methodol"},{"issue":"11","key":"pone.0242311.ref009","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1111\/jth.13848","article-title":"Recommendations for standardized risk factor definitions in pediatric hospital-acquired venous thromboembolism to inform future prevention trials: communication from the SSC of the ISTH","volume":"15","author":"BR Branchford","year":"2017","journal-title":"J Thromb Haemost"},{"key":"pone.0242311.ref010","unstructured":"Defining Childhood Obesity | Overweight & Obesity | CDC. 2018 Jul 3 [cited 27 June 2019]. In: CDC website [Internet]. https:\/\/www.cdc.gov\/obesity\/childhood\/defining.html"},{"key":"pone.0242311.ref011","unstructured":"CDC. Premature Birth. 2019 Oct 17 [cited 27 June 2019]. In: CDC website [Internet]. https:\/\/www.cdc.gov\/reproductivehealth\/features\/premature-birth\/index.html"},{"issue":"11","key":"pone.0242311.ref012","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1111\/jth.13140","article-title":"Definition of Clinically Relevant Non-Major Bleeding in Studies of Anticoagulants in Atrial Fibrillation and Venous Thromboembolic Disease in Non-Surgical Patients: Communication From the SSC of the ISTH","volume":"13","author":"Subcommittee on Control of Anticoagulation","year":"2015","journal-title":"J Thromb Haemost"},{"issue":"1","key":"pone.0242311.ref013","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1097\/00001648-199901000-00008","article-title":"Causal diagrams for epidemiologic research","volume":"10","author":"S Greenland","year":"1999","journal-title":"Epidemiol Camb Mass"},{"issue":"3","key":"pone.0242311.ref014","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1093\/ije\/dyt083","article-title":"Matched designs 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