{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T17:26:57Z","timestamp":1785691617429,"version":"3.56.0"},"reference-count":34,"publisher":"American Medical Association (AMA)","issue":"7","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Netw Open"],"abstract":"Importance<\/jats:title>Neurocutaneous syndromes are associated with cancer predisposition and sometimes associated with perinatal factors. A better understanding of the association between neurocutaneous syndromes, perinatal factors, and childhood cancer is key for earlier cancer detection.<\/jats:p><\/jats:sec>Objective<\/jats:title>To evaluate the association of neurocutaneous syndromes and perinatal factors with childhood cancer risk in a cohort of Swedish children.<\/jats:p><\/jats:sec>Design, Setting, and Participants<\/jats:title>In this nationwide cohort study, all children and adolescents up to age 20 years, from 1973 to 2015, were identified through the Swedish National Medical Birth Register (MBR), provided they had information on both biological parents. Analyses were conducted from April 2021 through May 2023.<\/jats:p><\/jats:sec>Exposures<\/jats:title>Diagnoses of neurocutaneous syndromes were obtained from the MBR, National Patient Register, and Cause of Death register. Perinatal factors (birth weight, gestational age, birth weight by gestational age, 5-minute Apgar score, and head circumference) were obtained from the MBR.<\/jats:p><\/jats:sec>Main Outcomes and Measures<\/jats:title>Childhood cancer risk (&amp;lt;20 years at diagnosis; identified from the National Cancer Register), including leukemia, lymphoma, and central nervous system (CNS) tumors.<\/jats:p><\/jats:sec>Results<\/jats:title>Among 4\u202f173\u202f108 included children (2\u202f143\u202f133 [51.4%] male, median [IQR] follow-up 20 [9.7-20] years), 1783 had neurofibromatosis type 1 (NF1), 444 tuberous sclerosis, 63 von Hippel-Lindau disease, and 39 ataxia-telangiectasia. An increased cancer risk was observed among children with any neurocutaneous syndrome (HR, 34.9; 95% CI, 30.8-39.6) and was particularly pronounced for CNS tumors (HR, 111.7; 95% CI, 96.8-128.8), except among children with ataxia-telangiectasia, where the increased risk was associated with lymphomas (HR, 233.1; 95% CI, 75.0-724.1). Leukemia risk was increased only among children with NF1 (HR, 4.1; 95% CI, 1.7-9.8). Several perinatal factors, including high birth weight, being born large for gestational age, preterm birth, low 5-minute Apgar score, and large head circumference had lesser associations with childhood cancer. Adjusting for neurocutaneous syndromes did not affect these associations.<\/jats:p><\/jats:sec>Conclusions and Relevance<\/jats:title>In this nationwide cohort study, neurocutaneous syndromes were associated with an increased risk of childhood cancer, especially CNS tumors. Several perinatal factors had lesser associations with childhood cancer, independently of the presence of neurocutaneous syndromes. Other biological mechanisms likely underlie the association between perinatal factors and childhood cancer.<\/jats:p><\/jats:sec>","DOI":"10.1001\/jamanetworkopen.2023.25482","type":"journal-article","created":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T15:43:57Z","timestamp":1690299837000},"page":"e2325482","source":"Crossref","is-referenced-by-count":7,"title":["Neurocutaneous Syndromes, Perinatal Factors, and the Risk of Childhood Cancer in Sweden"],"prefix":"10.1001","volume":"6","author":[{"given":"Christina-Evmorfia","family":"Kampitsi","sequence":"first","affiliation":[{"name":"Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ann","family":"Nordgren","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"},{"name":"Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Mogensen","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emeli","family":"Pont\u00e9n","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Feychting","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giorgio","family":"Tettamanti","sequence":"additional","affiliation":[{"name":"Unit of Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"10","published-online":{"date-parts":[[2023,7,25]]},"reference":[{"issue":"1, Child Neurology","key":"zoi230739r1","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1212\/CON.0000000000000562","volume":"24","author":"Rosser","year":"2018","journal-title":"Continuum (Minneap Minn)"},{"issue":"3","key":"zoi230739r2","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1038\/jid.2014.465","article-title":"Incidence and mortality of neurofibromatosis: a total population study in Finland.","volume":"135","author":"Uusitalo","year":"2015","journal-title":"J Invest Dermatol"},{"issue":"1","key":"zoi230739r3","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.pcl.2014.09.013","article-title":"Genetic and nongenetic risk factors for childhood cancer.","volume":"62","author":"Spector","year":"2015","journal-title":"Pediatr Clin North Am"},{"issue":"12","key":"zoi230739r4","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1007\/s10654-015-0063-0","article-title":"Perinatal risk factors for acute myeloid leukemia.","volume":"30","author":"Crump","year":"2015","journal-title":"Eur J Epidemiol"},{"issue":"12","key":"zoi230739r5","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1093\/aje\/kws212","article-title":"Perinatal and family risk factors for Hodgkin lymphoma in childhood through young adulthood.","volume":"176","author":"Crump","year":"2012","journal-title":"Am J Epidemiol"},{"issue":"12","key":"zoi230739r6","doi-asserted-by":"publisher","first-page":"923","DOI":"10.1093\/jnci\/djs225","article-title":"Perinatal and family risk factors for non-Hodgkin lymphoma in early life: a Swedish national cohort study.","volume":"104","author":"Crump","year":"2012","journal-title":"J Natl Cancer Inst"},{"issue":"3","key":"zoi230739r7","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1111\/bjh.13146","article-title":"A retrospective observational study of leucoreductive strategies to manage patients with acute myeloid leukaemia presenting with hyperleucocytosis.","volume":"168","author":"Kuo","year":"2015","journal-title":"Br J Haematol"},{"issue":"7","key":"zoi230739r8","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1002\/cncr.v121.7","article-title":"Perinatal and familial risk factors for acute lymphoblastic leukemia in a Swedish national cohort.","volume":"121","author":"Crump","year":"2015","journal-title":"Cancer"},{"issue":"4","key":"zoi230739r9","doi-asserted-by":"publisher","first-page":"1042","DOI":"10.1158\/1055-9965.EPI-09-1273","article-title":"Fetal growth, preterm birth, neonatal stress and risk for CNS tumors in children: a Nordic population- and register-based case-control study.","volume":"19","author":"Schmidt","year":"2010","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"zoi230739r10","doi-asserted-by":"publisher","first-page":"729","DOI":"10.2147\/CLEP","article-title":"Parental age and risk of genetic syndromes predisposing to nervous system tumors: nested case-control study.","volume":"10","author":"Adel Fahmideh","year":"2018","journal-title":"Clin Epidemiol"},{"issue":"7","key":"zoi230739r11","doi-asserted-by":"publisher","first-page":"1173","DOI":"10.1002\/ajmg.a.v179.7","article-title":"Neurofibromatosis type 1 of the child increases birth weight.","volume":"179","author":"Lepp\u00e4virta","year":"2019","journal-title":"Am J Med Genet A"},{"issue":"10","key":"zoi230739r12","doi-asserted-by":"publisher","first-page":"2641","DOI":"10.1002\/ajmg.a.v173.10","article-title":"The pregnancy in neurofibromatosis 1: a retrospective register-based total population study.","volume":"173","author":"Lepp\u00e4virta","year":"2017","journal-title":"Am J Med Genet A"},{"key":"zoi230739r13","doi-asserted-by":"publisher","first-page":"200","DOI":"10.1016\/j.jpeds.2021.08.009","article-title":"Birth characteristics among children diagnosed with neurofibromatosis type 1 and tuberous sclerosis.","volume":"239","author":"Tettamanti","year":"2021","journal-title":"J Pediatr"},{"issue":"11","key":"zoi230739r15","doi-asserted-by":"publisher","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":"Ludvigsson","year":"2009","journal-title":"Eur J Epidemiol"},{"issue":"1","key":"zoi230739r16","doi-asserted-by":"publisher","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":"Barlow","year":"2009","journal-title":"Acta Oncol"},{"issue":"2","key":"zoi230739r17","doi-asserted-by":"publisher","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":"Ludvigsson","year":"2016","journal-title":"Eur J Epidemiol"},{"issue":"9","key":"zoi230739r18","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1007\/s10654-017-0316-1","article-title":"The Swedish cause of death register.","volume":"32","author":"Brooke","year":"2017","journal-title":"Eur J Epidemiol"},{"key":"zoi230739r19","doi-asserted-by":"publisher","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":"Ludvigsson","year":"2011","journal-title":"BMC Public Health"},{"issue":"7","key":"zoi230739r20","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.1002\/cncr.20910","article-title":"International Classification of Childhood Cancer, third edition.","volume":"103","author":"Steliarova-Foucher","year":"2005","journal-title":"Cancer"},{"issue":"4","key":"zoi230739r21","doi-asserted-by":"publisher","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":"Ludvigsson","year":"2019","journal-title":"Eur J Epidemiol"},{"issue":"2","key":"zoi230739r22","doi-asserted-by":"publisher","first-page":"40","DOI":"10.5306\/wjco.v14.i2.40","article-title":"Hereditary cancer syndromes.","volume":"14","author":"Imyanitov","year":"2023","journal-title":"World J Clin Oncol"},{"issue":"11","key":"zoi230739r23","doi-asserted-by":"publisher","first-page":"1014","DOI":"10.1136\/adc.2003.046219","article-title":"Cancers and immune related diseases associated with Down\u2019s syndrome: a record linkage study.","volume":"89","author":"Goldacre","year":"2004","journal-title":"Arch Dis Child"},{"issue":"4","key":"zoi230739r24","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1016\/j.det.2019.05.015","article-title":"Phakomatoses.","volume":"37","author":"Becker","year":"2019","journal-title":"Dermatol Clin"},{"issue":"12","key":"zoi230739r25","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1177\/0883073815604220","article-title":"Neurocutaneous syndromes and brain tumors.","volume":"31","author":"Ullrich","year":"2016","journal-title":"J Child Neurol"},{"issue":"4","key":"zoi230739r26","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1016\/j.ncl.2007.07.008","article-title":"Genetic causes of brain tumors: neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes.","volume":"25","author":"Farrell","year":"2007","journal-title":"Neurol Clin"},{"issue":"1","key":"zoi230739r27","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1186\/s13023-016-0543-7","article-title":"Ataxia telangiectasia: a review.","volume":"11","author":"Rothblum-Oviatt","year":"2016","journal-title":"Orphanet J Rare Dis"},{"issue":"17","key":"zoi230739r28","doi-asserted-by":"publisher","first-page":"1978","DOI":"10.1200\/JCO.2015.65.3576","article-title":"Distinctive cancer associations in patients with neurofibromatosis type 1.","volume":"34","author":"Uusitalo","year":"2016","journal-title":"J Clin Oncol"},{"issue":"2","key":"zoi230739r29","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1038\/sj.bjc.6603227","article-title":"A prospective study of neurofibromatosis type 1 cancer incidence in the UK.","volume":"95","author":"Walker","year":"2006","journal-title":"Br J Cancer"},{"issue":"11","key":"zoi230739r30","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1002\/ijc.v145.11","article-title":"Pediatric malignancies in neurofibromatosis type 1: a population-based cohort study.","volume":"145","author":"Peltonen","year":"2019","journal-title":"Int J Cancer"},{"issue":"4","key":"zoi230739r31","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2012-001095","article-title":"The 5-minute Apgar score as a predictor of childhood cancer: a population-based cohort study in five million children.","volume":"2","author":"Li","year":"2012","journal-title":"BMJ Open"},{"issue":"1","key":"zoi230739r32","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0210366","article-title":"Cancer risk in children and young adults born preterm: A systematic review and meta-analysis.","volume":"14","author":"Paquette","year":"2019","journal-title":"PLoS One"},{"issue":"1","key":"zoi230739r33","first-page":"40","article-title":"Neurofibromatosis in children: actually and perspectives.","volume":"9","author":"Sur","year":"2022","journal-title":"Children (Basel)"},{"key":"zoi230739r34","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","article-title":"Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations.","volume":"123","author":"Northrup","year":"2021","journal-title":"Pediatr Neurol"},{"key":"zoi230739r14","volume-title":"The Swedish Medical Birth Register\u2014a summary of content and quality","author":"K\u00e4ll\u00e9n","year":"2003"}],"container-title":["JAMA Network Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/articlepdf\/2807598\/kampitsi_2023_oi_230739_1689364233.74079.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,7,25]],"date-time":"2023-07-25T15:44:02Z","timestamp":1690299842000},"score":1,"resource":{"primary":{"URL":"https:\/\/jamanetwork.com\/journals\/jamanetworkopen\/fullarticle\/2807598"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,25]]},"references-count":34,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7,3]]}},"URL":"https:\/\/doi.org\/10.1001\/jamanetworkopen.2023.25482","relation":{},"ISSN":["2574-3805"],"issn-type":[{"value":"2574-3805","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,25]]}}}