Jian-Rong He1,2,3, Jane E Hirst1,3, Gabriella Tikellis4, Gary S Phillips5, Rema Ramakrishnan1,3,6, Ora Paltiel7, Anne-Louise Ponsonby4, Mark Klebanoff8, Jørn Olsen9, Michael F G Murphy1, Siri E Håberg10, Stanley Lemeshow11, Sjurdur F Olsen12, Xiu Qiu2, Per Magnus10, Jean Golding13, Mary H Ward14, Joseph L Wiemels15, Kazem Rahimi1,3, Martha S Linet16, Terence Dwyer1,3. 1. Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK. 2. Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China. 3. George Institute for Global Health, University of Oxford, Oxford, UK. 4. Murdoch Children's Research Institute, Royal Children's Hospital, University of Melbourne, Melbourne, VIC, Australia. 5. Retired from Center for Biostatistics, Department of Biomedical Informatics, Ohio State University, Columbus, OH, USA. 6. University of New South Wales, Faculty of Medicine, Sydney, NSW, Australia. 7. Braun School of Public Health, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. 8. Center for Perinatal Research, Abigail Wexner Research Institute at Nationwide Children's Hospital, Columbus, OH, USA. 9. Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark. 10. Centre for Fertility and Health, Norwegian Institute of Public Health, Oslo, Norway. 11. Division of Biostatistics, College of Public Health, Ohio State University, Columbus, OH, USA. 12. Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark. 13. Centre for Academic Child Health, Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. 14. Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA. 15. Department of Preventative Medicine, University of Southern California, Los Angeles, CA, USA and. 16. Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: Among 312 879 children with a median follow-up of 13.6 years, 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 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; 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. CONCLUSIONS: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: Among 312 879 children with a median follow-up of 13.6 years, 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 (1.10-2.58)] and subtypes ALL [1.49 (0.87-2.56)] and AML [2.70 ([0.93-7.86)], but not with any cancer [1.13 (0.85-1.51)]. Respiratory tract infection was associated with increased risk of any leukaemia [1.57 (1.06-2.34)], ALL [1.43 (0.94-2.19)], AML [2.37 (1.10-5.12)] and any cancer [1.33 (1.09-1.63)]; 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. CONCLUSIONS: 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.
Authors: Gabriella Tikellis; Terence Dwyer; Ora Paltiel; Gary S Phillips; Stanley Lemeshow; Jean Golding; Kate Northstone; Andy Boyd; Sjurdur Olsen; Akram Ghantous; Zdenko Herceg; Mary H Ward; Siri E Håberg; Per Magnus; Jørn Olsen; Marin Ström; Somdat Mahabir; Rena R Jones; Anne-Louise Ponsonby; Jacqueline Clavel; Marie Aline Charles; Edwin Trevathan; Zhengmin Min Qian; Milena M Maule; Xiu Qiu; Yun-Chul Hong; Silvia Brandalise; Eve Roman; Melissa Wake; Jian-Rong He; Martha S Linet Journal: Paediatr Perinat Epidemiol Date: 2018-11-22 Impact factor: 3.980
Authors: Jeffrey S Chang; Mi Zhou; Patricia A Buffler; Anand P Chokkalingam; Catherine Metayer; Joseph L Wiemels Journal: Cancer Epidemiol Biomarkers Prev Date: 2011-06-08 Impact factor: 4.254
Authors: Ludmil B Alexandrov; Serena Nik-Zainal; David C Wedge; Peter J Campbell; Michael R Stratton Journal: Cell Rep Date: 2013-01-10 Impact factor: 9.423