{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T02:05:30Z","timestamp":1789005930228,"version":"build-2803163510"},"reference-count":32,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T00:00:00Z","timestamp":1645747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002794","name":"cancerfonden","doi-asserted-by":"publisher","award":["2015\/724"],"award-info":[{"award-number":["2015\/724"]}],"id":[{"id":"10.13039\/501100002794","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004359","name":"vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2017-02913"],"award-info":[{"award-number":["2017-02913"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Birth defects have been consistently associated with elevated childhood cancer risks; however, the relationship between congenital heart disease (CHD) and childhood cancer remains conflicting. Considering the increasing patient population with CHD after improvements in their life expectancies, insights into this relationship are particularly compelling. Thus, we aimed to determine the relationship between CHD and cancer in Swedish children.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods and findings<\/jats:title>\n<jats:p>All individuals registered in the Swedish Medical Birth Register (MBR) between 1973 and 2014 were included in this population\u2013based cohort study (<jats:italic>n =<\/jats:italic> 4,178,722). Individuals with CHD (<jats:italic>n =<\/jats:italic> 66,892) were identified from the MBR and National Patient Register, whereas cancer diagnoses were retrieved from the Swedish Cancer Register. The relationship between CHD and childhood cancer (&lt;20 years at diagnosis) was evaluated using Cox proportional hazards regression models. We observed increased risks of cancer overall, leukemia, lymphoma, and hepatoblastoma in children with CHD, but after adjustment for Down syndrome, only the increased lymphoma (hazard ratio (HR) = 1.64, 95% confidence interval (CI) 1.11 to 2.44) and hepatoblastoma (HR = 3.94, 95% CI 1.83 to 8.47) risk remained. However, when restricting to CHD diagnoses from the MBR only, i.e., those diagnosed around birth, the risk for childhood cancer overall (HR = 1.45, 95% CI 1.23 to 1.71) and leukemia (HR = 1.41, 95% CI 1.08 to 1.84) was more pronounced, even after controlling for Down syndrome. Finally, a substantially elevated lymphoma risk (HR = 8.13, 95% CI 4.06 to 16.30) was observed in children with complex CHD. Limitations of the study include the National Patient Register not being nationwide until 1987, in addition to the rareness of the conditions under study providing limited power for analyses on the rarer cancer subtypes.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We found associations between CHD and childhood lymphomas and hepatoblastomas not explained by a diagnosis of Down syndrome. Stronger associations were observed in complex CHD.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pmed.1003903","type":"journal-article","created":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T18:30:42Z","timestamp":1645813842000},"page":"e1003903","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["The relationship between congenital heart disease and cancer in Swedish children: A population-based cohort study"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3907-4360","authenticated-orcid":true,"given":"Christina-Evmorfia","family":"Kampitsi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5195-8065","authenticated-orcid":true,"given":"Hanna","family":"Mogensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-0060","authenticated-orcid":true,"given":"Maria","family":"Feychting","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5210-7219","authenticated-orcid":true,"given":"Giorgio","family":"Tettamanti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,2,25]]},"reference":[{"key":"pmed.1003903.ref001","first-page":"421","author":"LE Rosenberg","year":"2012","edition":"1"},{"key":"pmed.1003903.ref002","author":"T. Tulchinsky","year":"2017","edition":"1"},{"issue":"4","key":"pmed.1003903.ref003","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1002\/bdra.23364","article-title":"Risk of cancer among children with birth defects: a novel approach","volume":"103","author":"S Dawson","year":"2015","journal-title":"Birth Defects Res A Clin Mol Teratol"},{"issue":"17","key":"pmed.1003903.ref004","doi-asserted-by":"crossref","first-page":"1314","DOI":"10.1002\/bdr2.1390","article-title":"Congenital heart disease complexity and childhood cancer risk","volume":"110","author":"RT Collins","year":"2018","journal-title":"Birth Defects Res"},{"issue":"2","key":"pmed.1003903.ref005","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1001\/jamainternmed.2016.7765","article-title":"Survivorship in Children and Young Adults With Congenital Heart Disease in Sweden.","volume":"177","author":"Z Mandalenakis","year":"2017","journal-title":"JAMA Intern Med"},{"issue":"1","key":"pmed.1003903.ref006","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.pcl.2014.09.013","article-title":"Genetic and nongenetic risk factors for childhood cancer","volume":"62","author":"LG Spector","year":"2015","journal-title":"Pediatr Clin North Am"},{"key":"pmed.1003903.ref007","article-title":"Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population\u2013Based Assessment of 10 Million Live Births.","author":"PJ Lupo","year":"2019","journal-title":"JAMA Oncol"},{"issue":"7","key":"pmed.1003903.ref008","doi-asserted-by":"crossref","first-page":"e0181246","DOI":"10.1371\/journal.pone.0181246","article-title":"Pediatric cancer risk in association with birth defects: A systematic review","volume":"12","author":"KJ Johnson","year":"2017","journal-title":"PLoS ONE"},{"issue":"11","key":"pmed.1003903.ref009","doi-asserted-by":"crossref","first-page":"1742","DOI":"10.1016\/j.amjcard.2016.08.057","article-title":"Prevalence of Cancer in Adults With Congenital Heart Disease Compared With the General Population.","volume":"118","author":"M Gurvitz","year":"2016","journal-title":"Am J Cardiol"},{"issue":"2","key":"pmed.1003903.ref010","doi-asserted-by":"crossref","first-page":"e0116844","DOI":"10.1371\/journal.pone.0116844","article-title":"The risk of cancer in patients with congenital heart disease: a nationwide population\u2013based cohort study in Taiwan.","volume":"10","author":"YS Lee","year":"2015","journal-title":"PLoS ONE"},{"issue":"3","key":"pmed.1003903.ref011","first-page":"474","article-title":"Congenital anomalies and childhood cancer in Great Britain","volume":"60","author":"SA Narod","year":"1997","journal-title":"Am J Hum Genet"},{"issue":"1","key":"pmed.1003903.ref012","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1017\/S1047951112002144","article-title":"Cancer risk among patients with congenital heart defects: a nationwide follow\u2013up study","volume":"24","author":"M Olsen","year":"2014","journal-title":"Cardiol Young"},{"issue":"9199","key":"pmed.1003903.ref013","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0140-6736(99)05264-2","article-title":"Risks of leukaemia and solid tumours in individuals with Down\u2019s syndrome","volume":"355","author":"H Hasle","year":"2000","journal-title":"Lancet"},{"key":"pmed.1003903.ref014","article-title":"The Swedish Medical Birth Register\u2013a summary of content and quality.","author":"B K\u00e4ll\u00e9n","year":"2003","journal-title":"Soc Forces"},{"issue":"11","key":"pmed.1003903.ref015","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1007\/s10654-009-9350-y","article-title":"The Swedish personal identity number: possibilities and pitfalls in healthcare and medical research","volume":"24","author":"JF Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol"},{"key":"pmed.1003903.ref016","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1186\/1471-2458-11-450","article-title":"External review and validation of the Swedish national inpatient register.","volume":"11","author":"JF Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"issue":"5","key":"pmed.1003903.ref017","doi-asserted-by":"crossref","first-page":"1170","DOI":"10.1016\/S0735-1097(01)01272-4","article-title":"Task force 1: the changing profile of congenital heart disease in adult life","volume":"37","author":"CA Warnes","year":"2001","journal-title":"J Am Coll Cardiol"},{"issue":"1","key":"pmed.1003903.ref018","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1080\/02841860802247664","article-title":"The completeness of the Swedish Cancer Register: a sample survey for year 1998.","volume":"48","author":"L Barlow","year":"2009","journal-title":"Acta Oncol"},{"issue":"7","key":"pmed.1003903.ref019","first-page":"1457","article-title":"International classification of childhood cancer, third edition.","volume":"103","author":"E Steliarova\u2013Foucher","year":"2005","journal-title":"Cancer\u2013Am Cancer Soc"},{"issue":"2","key":"pmed.1003903.ref020","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s10654-016-0117-y","article-title":"Registers of the Swedish total population and their use in medical research","volume":"31","author":"JF Ludvigsson","year":"2016","journal-title":"Eur J Epidemiol"},{"issue":"9","key":"pmed.1003903.ref021","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s10654-017-0316-1","article-title":"The Swedish cause of death register","volume":"32","author":"HL Brooke","year":"2017","journal-title":"Eur J Epidemiol"},{"issue":"3","key":"pmed.1003903.ref022","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1097\/00125817-200205000-00002","article-title":"Cardiovascular disease in neurofibromatosis 1: report of the NF1 Cardiovascular Task Force","volume":"4","author":"JM Friedman","year":"2002","journal-title":"Genet Med"},{"issue":"4","key":"pmed.1003903.ref023","doi-asserted-by":"crossref","first-page":"e810","DOI":"10.1542\/peds.2007-1519","article-title":"Maternal smoking and congenital heart defects","volume":"121","author":"S Malik","year":"2008","journal-title":"Pediatrics"},{"issue":"11","key":"pmed.1003903.ref024","doi-asserted-by":"crossref","first-page":"e0165040","DOI":"10.1371\/journal.pone.0165040","article-title":"Maternal Smoking and the Risk of Cancer in Early Life\u2013A Meta\u2013Analysis.","volume":"11","author":"IK Rumrich","year":"2016","journal-title":"PLoS ONE"},{"issue":"4","key":"pmed.1003903.ref025","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s10654-019-00511-8","article-title":"The longitudinal integrated database for health insurance and labour market studies (LISA) and its use in medical research.","volume":"34","author":"JF Ludvigsson","year":"2019","journal-title":"Eur J Epidemiol"},{"issue":"7","key":"pmed.1003903.ref026","doi-asserted-by":"crossref","first-page":"e196762","DOI":"10.1001\/jamanetworkopen.2019.6762","article-title":"Risk of Cancer Among Children and Young Adults With Congenital Heart Disease Compared With Healthy Controls.","volume":"2","author":"Z Mandalenakis","year":"2019","journal-title":"JAMA Netw Open"},{"issue":"3","key":"pmed.1003903.ref027","doi-asserted-by":"crossref","first-page":"e59098","DOI":"10.1371\/journal.pone.0059098","article-title":"Use of primary care during the year before childhood cancer diagnosis: a nationwide population\u2013based matched comparative study","volume":"8","author":"JM Ahrensberg","year":"2013","journal-title":"PLoS ONE"},{"issue":"5","key":"pmed.1003903.ref028","doi-asserted-by":"crossref","first-page":"371","DOI":"10.2353\/jmoldx.2009.080132","article-title":"Down syndrome and malignancies: a unique clinical relationship: a paper from the 2008 william beaumont hospital symposium on molecular pathology","volume":"11","author":"AC Xavier","year":"2009","journal-title":"J Mol Diagn"},{"issue":"3","key":"pmed.1003903.ref029","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1158\/1055-9965.EPI-07-2630","article-title":"Cancer risk in children with birth defects and in their families: a population based cohort study of 5.2 million children from Norway and Sweden","volume":"17","author":"T Bjorge","year":"2008","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"20","key":"pmed.1003903.ref030","first-page":"e348","article-title":"Diagnosis and Management of Noncardiac Complications in Adults With Congenital Heart Disease: A Scientific Statement From the American Heart Association","volume":"136","author":"GK Lui","year":"2017","journal-title":"Circulation"},{"issue":"13","key":"pmed.1003903.ref031","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1161\/CIRCULATIONAHA.117.029138","article-title":"Exposure to Low\u2013Dose Ionizing Radiation From Cardiac Procedures and Malignancy Risk in Adults With Congenital Heart Disease","volume":"137","author":"S Cohen","year":"2018","journal-title":"Circulation"},{"issue":"2","key":"pmed.1003903.ref032","doi-asserted-by":"crossref","first-page":"541","DOI":"10.21037\/qims.2020.01.05","article-title":"Assessing a recent South Korean cohort study of cancer risk following diagnostic radiation exposure at younger ages","volume":"10","author":"J McBain\u2013Miller","year":"2020","journal-title":"Quant Imaging Med Surg"}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003903","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,25]],"date-time":"2022-02-25T18:31:13Z","timestamp":1645813873000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1003903"}},"subtitle":[],"editor":[{"given":"Wei","family":"Zheng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,25]]},"references-count":32,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2022,2,25]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1003903","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,25]]}}}