{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T21:12:29Z","timestamp":1784581949263,"version":"3.55.0"},"reference-count":36,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2021,9,14]],"date-time":"2021-09-14T00:00:00Z","timestamp":1631577600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"China Scholarship Council-University of Oxford Joint Scholarship"},{"name":"Research Council of Norway through its Centres of Excellence funding scheme","award":["262700"],"award-info":[{"award-number":["262700"]}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,6,13]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Previous epidemiological studies have found positive associations between maternal infections and childhood leukaemia; however, evidence from prospective cohort studies is scarce. We aimed to examine the associations using large-scale prospective data.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were pooled from six population-based birth cohorts in Australia, Denmark, Israel, Norway, the UK and the USA (recruitment 1950s-2000s). Primary outcomes were any childhood leukaemia and acute lymphoblastic leukaemia (ALL); secondary outcomes were acute myeloid leukaemia (AML) and any childhood cancer. Exposures included maternal self-reported infections [influenza-like illness, common cold, any respiratory tract infection, vaginal thrush, vaginal infections and urinary tract infection (including cystitis)] and infection-associated symptoms (fever and diarrhoea) during pregnancy. Covariate-adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using multilevel Cox models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 312\u200a879 children with a median follow-up of 13.6\u2009years, 167 leukaemias, including 129 ALL and 33 AML, were identified. Maternal urinary tract infection was associated with increased risk of any leukaemia [HR (95% CI) 1.68 (1.10\u20132.58)] and subtypes ALL [1.49 (0.87\u20132.56)] and AML [2.70 ([0.93\u20137.86)], but not with any cancer [1.13 (0.85\u20131.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06\u20132.34)], ALL [1.43 (0.94\u20132.19)], AML [2.37 (1.10\u20135.12)] and any cancer [1.33 (1.09\u20131.63)]; influenza-like illness showed a similar pattern but with less precise estimates. There was no evidence of a link between other infections and any outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Urinary tract and respiratory tract infections during pregnancy may be associated with childhood leukaemia, but the absolute risk is small given the rarity of the outcome.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ije\/dyab199","type":"journal-article","created":{"date-parts":[[2021,9,8]],"date-time":"2021-09-08T11:26:03Z","timestamp":1631100363000},"page":"769-777","source":"Crossref","is-referenced-by-count":27,"title":["Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts"],"prefix":"10.1093","volume":"51","author":[{"given":"Jian-Rong","family":"He","sequence":"first","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford, UK"},{"name":"Division of Birth Cohort Study, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University , Guangzhou, China"},{"name":"George Institute for Global Health, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane E","family":"Hirst","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford, UK"},{"name":"George Institute for Global Health, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Tikellis","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital, University of Melbourne , Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary S","family":"Phillips","sequence":"additional","affiliation":[{"name":"Retired from Center for Biostatistics, Department of Biomedical Informatics, Ohio State University , Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6784-8319","authenticated-orcid":false,"given":"Rema","family":"Ramakrishnan","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford, UK"},{"name":"George Institute for Global Health, University of Oxford , Oxford, UK"},{"name":"University of New South Wales , Faculty of Medicine, Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8324-3873","authenticated-orcid":false,"given":"Ora","family":"Paltiel","sequence":"additional","affiliation":[{"name":"Braun School of Public Health, Hadassah-Hebrew University Medical Center , Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6581-3657","authenticated-orcid":false,"given":"Anne-Louise","family":"Ponsonby","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital, University of Melbourne , Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Klebanoff","sequence":"additional","affiliation":[{"name":"Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital , Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00f8rn","family":"Olsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Epidemiology, Aarhus University , Aarhus, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael F G","family":"Murphy","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siri E","family":"H\u00e5berg","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stanley","family":"Lemeshow","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, College of Public Health, Ohio State University , Columbus, OH, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sjurdur","family":"F Olsen","sequence":"additional","affiliation":[{"name":"Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut , Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1248-229X","authenticated-orcid":false,"given":"Xiu","family":"Qiu","sequence":"additional","affiliation":[{"name":"Division of Birth Cohort Study, Guangzhou Women and Children\u2019s Medical Center, Guangzhou Medical University , Guangzhou, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Magnus","sequence":"additional","affiliation":[{"name":"Centre for Fertility and Health, Norwegian Institute of Public Health , Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"Golding","sequence":"additional","affiliation":[{"name":"Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol , Bristol, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary H","family":"Ward","sequence":"additional","affiliation":[{"name":"Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute , Rockville, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph L","family":"Wiemels","sequence":"additional","affiliation":[{"name":"Department of Preventative Medicine, University of Southern California , Los Angeles, CA, USA and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4807-4610","authenticated-orcid":false,"given":"Kazem","family":"Rahimi","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford, UK"},{"name":"George Institute for Global Health, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martha S","family":"Linet","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute , Bethesda, MD, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2091-7663","authenticated-orcid":false,"given":"Terence","family":"Dwyer","sequence":"additional","affiliation":[{"name":"Nuffield Department of Women\u2019s and Reproductive Health, University of Oxford , Oxford, UK"},{"name":"George Institute for Global Health, University of Oxford , Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the International Childhood Cancer Cohort Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,9,14]]},"reference":[{"key":"2022083010174971300_dyab199-B1","doi-asserted-by":"crossref","first-page":"e42","DOI":"10.1016\/S1470-2045(18)30761-7","article-title":"Childhood cancer burden: a review of global estimates","volume":"20","author":"Bhakta","year":"2019","journal-title":"Lancet Oncol"},{"key":"2022083010174971300_dyab199-B2","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrc1164","article-title":"Origins of chromosome translocations in childhood leukaemia","volume":"3","author":"Greaves","year":"2003","journal-title":"Nat Rev Cancer"},{"key":"2022083010174971300_dyab199-B3","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41568-018-0015-6","article-title":"A causal mechanism for childhood acute lymphoblastic leukaemia","volume":"18","author":"Greaves","year":"2018","journal-title":"Nat Rev Cancer"},{"key":"2022083010174971300_dyab199-B4","doi-asserted-by":"crossref","first-page":"5458","DOI":"10.1158\/0008-5472.CAN-18-0831","article-title":"Neonatal inflammatory markers are associated with childhood B-cell precursor acute lymphoblastic leukemia","volume":"78","author":"Soegaard","year":"2018","journal-title":"Cancer Res"},{"key":"2022083010174971300_dyab199-B5","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1158\/1055-9965.EPI-11-0162","article-title":"Profound deficit of IL10 at birth in children who develop childhood acute lymphoblastic leukemia","volume":"20","author":"Chang","year":"2011","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2022083010174971300_dyab199-B6","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1097\/00002371-199703000-00001","article-title":"Considerations on a possible viral etiology for B-precursor acute lymphoblastic leukemia of childhood","volume":"20","author":"Smith","year":"1997","journal-title":"J Immunother"},{"key":"2022083010174971300_dyab199-B7","volume-title":"Prenatal Infections with Subsequent Immune Tolerance Could Explain the Epidemiology of Common Childhood Cancers","author":"Zur Hausen","year":"2014"},{"key":"2022083010174971300_dyab199-B8","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1128\/CMR.00023-08","article-title":"Neuropathogenesis of congenital cytomegalovirus infection: disease mechanisms and prospects for intervention","volume":"22","author":"Cheeran","year":"2009","journal-title":"Clin Microbiol Rev"},{"key":"2022083010174971300_dyab199-B9","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/bdra.23588","article-title":"Parvovirus B19 infection during pregnancy and risks to the fetus","volume":"109","author":"Ornoy","year":"2017","journal-title":"Birth Defects Res"},{"key":"2022083010174971300_dyab199-B10","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1001\/jamaoncol.2019.1215","article-title":"Association between birth defects and cancer risk among children and adolescents in a population-based assessment of 10 million live births","volume":"5","author":"Lupo","year":"2019","journal-title":"JAMA Oncol"},{"key":"2022083010174971300_dyab199-B11","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/S1473-3099(11)70341-3","article-title":"Uninfected but not unaffected: chronic maternal infections during pregnancy, fetal immunity, and susceptibility to postnatal infections","volume":"12","author":"Dauby","year":"2012","journal-title":"Lancet Infect Dis"},{"key":"2022083010174971300_dyab199-B12","doi-asserted-by":"crossref","first-page":"3422","DOI":"10.1016\/S0264-410X(03)00343-8","article-title":"The impact of maternal infection or immunization on early-onset autoimmune diabetes","volume":"21","author":"Goldman","year":"2003","journal-title":"Vaccine"},{"key":"2022083010174971300_dyab199-B13","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/S2213-2600(14)70152-3","article-title":"Maternal propensity for infections and risk of childhood asthma: a registry-based cohort study","volume":"2","author":"Stokholm","year":"2014","journal-title":"Lancet Respir Med"},{"key":"2022083010174971300_dyab199-B14","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1017\/S0950268818002455","article-title":"Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis","volume":"146","author":"Yue","year":"2018","journal-title":"Epidemiol Infect"},{"key":"2022083010174971300_dyab199-B15","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.earlhumdev.2019.07.002","article-title":"Maternal urinary tract infection during pregnancy and long-term infectious morbidity of the offspring","volume":"136","author":"Cohen","year":"2019","journal-title":"Early Hum Dev"},{"key":"2022083010174971300_dyab199-B16","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1016\/j.jpeds.2019.10.046","article-title":"Maternal infection in pregnancy and childhood leukemia: a systematic review and meta-analysis","volume":"217","author":"He","year":"2020","journal-title":"J Pediatr"},{"key":"2022083010174971300_dyab199-B17","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1136\/bmj.290.6467.509","article-title":"Long term effects of exposure to viral infections in utero","volume":"290","author":"Fine","year":"1985","journal-title":"Br Med J (Clin Res Ed)"},{"key":"2022083010174971300_dyab199-B18","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1136\/bmj.2.5812.485","article-title":"Reported influenza in pregnancy and subsequent cancer in the child","volume":"2","author":"Fedrick","year":"1972","journal-title":"Br Med J"},{"key":"2022083010174971300_dyab199-B19","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S1470-2045(17)30186-9","article-title":"International incidence of childhood cancer, 2001-10: a population-based registry study","volume":"18","author":"Steliarova-Foucher","year":"2017","journal-title":"Lancet Oncol"},{"key":"2022083010174971300_dyab199-B20","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/ppe.12519","article-title":"The International Childhood Cancer Cohort Consortium (I4C): a research platform of prospective cohorts for studying the aetiology of childhood cancers","volume":"32","author":"Tikellis","year":"2018","journal-title":"Paediatr Perinat Epidemiol"},{"key":"2022083010174971300_dyab199-B21","author":"Therneau","year":"2015"},{"key":"2022083010174971300_dyab199-B22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1007\/s10654-014-9974-4","article-title":"A new comparison of nested case-control and case-cohort designs and methods","volume":"30","author":"Kim","year":"2015","journal-title":"Eur J Epidemiol"},{"key":"2022083010174971300_dyab199-B23","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/s10549-015-3369-4","article-title":"Family history and risk of pregnancy-associated breast cancer (PABC)","volume":"151","author":"Johansson","year":"2015","journal-title":"Breast Cancer Res Treat"},{"key":"2022083010174971300_dyab199-B24","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1080\/01621459.1993.10594284","article-title":"Approximate inference in generalized linear mixed models","volume":"88","author":"Breslow","year":"1993","journal-title":"J Am Stat Assoc"},{"key":"2022083010174971300_dyab199-B25","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1111\/j.0006-341X.2000.01016.x","article-title":"Estimation of multivariate frailty models using penalized partial likelihood","volume":"56","author":"Ripatti","year":"2000","journal-title":"Biometrics"},{"key":"2022083010174971300_dyab199-B26","doi-asserted-by":"crossref","DOI":"10.1002\/9780470316696","volume-title":"Multiple Imputation for Survey Nonresponse","author":"Rubin","year":"1987"},{"key":"2022083010174971300_dyab199-B27","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1002\/sim.7141","article-title":"Meta-analysis using individual participant data: one-stage and two-stage approaches, and why they may differ","volume":"36","author":"Burke","year":"2017","journal-title":"Stat Med"},{"key":"2022083010174971300_dyab199-B28","doi-asserted-by":"crossref","first-page":"59","DOI":"10.7453\/gahmj.2013.061","article-title":"Urinary tract infection as a preventable cause of pregnancy complications: opportunities, challenges, and a global call to action","volume":"2","author":"Gilbert","year":"2013","journal-title":"Glob Adv Health Med"},{"key":"2022083010174971300_dyab199-B29","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/01443615.2017.1370579","article-title":"Urinary tract infection during pregnancy: current concepts on a common multifaceted problem","volume":"38","author":"Kalinderi","year":"2018","journal-title":"J Obstet Gynaecol"},{"key":"2022083010174971300_dyab199-B30","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1001\/jamapsychiatry.2019.0029","article-title":"Long-term risk of neuropsychiatric disease after exposure to infection in utero","volume":"76","author":"Al-Haddad","year":"2019","journal-title":"JAMA Psychiatry"},{"key":"2022083010174971300_dyab199-B31","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1038\/sj.bjc.6690609","article-title":"Pre- and perinatal risk factors for childhood leukaemia and other malignancies: a Scottish case control study","volume":"80","author":"McKinney","year":"1999","journal-title":"Br J Cancer"},{"key":"2022083010174971300_dyab199-B32","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1016\/j.celrep.2012.12.008","article-title":"Deciphering signatures of mutational processes operative in human cancer","volume":"3","author":"Alexandrov","year":"2013","journal-title":"Cell Rep"},{"key":"2022083010174971300_dyab199-B33","doi-asserted-by":"crossref","first-page":"12688","DOI":"10.1021\/acs.chemrev.6b00296","article-title":"Functions and malfunctions of mammalian DNA-cytosine deaminases","volume":"116","author":"Siriwardena","year":"2016","journal-title":"Chem Rev"},{"key":"2022083010174971300_dyab199-B34","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1002\/pds.3806","article-title":"Exposure to systemic antibacterial medications during pregnancy and risk of childhood cancer","volume":"24","author":"Momen","year":"2015","journal-title":"Pharmacoepidemiol Drug Saf"},{"key":"2022083010174971300_dyab199-B35","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.1111\/biom.12910","article-title":"Multiple imputation of missing data in nested case-control and case-cohort studies","volume":"74","author":"Keogh","year":"2018","journal-title":"Biometrics"},{"key":"2022083010174971300_dyab199-B36","doi-asserted-by":"crossref","first-page":"4021","DOI":"10.1002\/sim.5818","article-title":"Using full-cohort data in nested case-control and case-cohort studies by multiple imputation","volume":"32","author":"Keogh","year":"2013","journal-title":"Stat Med"}],"container-title":["International Journal of Epidemiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ije\/article-pdf\/51\/3\/769\/45617520\/dyab199.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ije\/article-pdf\/51\/3\/769\/45617520\/dyab199.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,9,8]],"date-time":"2024-09-08T01:05:42Z","timestamp":1725757542000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ije\/article\/51\/3\/769\/6370078"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,14]]},"references-count":36,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2021,9,14]]},"published-print":{"date-parts":[[2022,6,13]]}},"URL":"https:\/\/doi.org\/10.1093\/ije\/dyab199","relation":{},"ISSN":["0300-5771","1464-3685"],"issn-type":[{"value":"0300-5771","type":"print"},{"value":"1464-3685","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,6,1]]},"published":{"date-parts":[[2021,9,14]]}}}