Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts

Jian-Rong He; Jane E Hirst; Gabriella Tikellis; Gary S Phillips; Rema Ramakrishnan; Ora Paltiel; Anne-Louise Ponsonby; Mark Klebanoff; Jørn Olsen; Michael F G Murphy; Siri E Håberg; Stanley Lemeshow; Sjurdur F Olsen; Xiu Qiu; Per Magnus; Jean Golding; Mary H Ward; Joseph L Wiemels; Kazem Rahimi; Martha S Linet; Terence Dwyer; International Childhood Cancer Cohort Consortium

doi:10.1093/ije/dyab199

Common maternal infections during pregnancy and childhood leukaemia in the offspring: findings from six international birth cohorts

Int J Epidemiol. 2022 Jun 13;51(3):769-777. doi: 10.1093/ije/dyab199.

Authors

Jian-Rong He^{1

2

3}, Jane E Hirst^{1

3}, Gabriella Tikellis⁴, Gary S Phillips⁵, Rema Ramakrishnan^{1

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 Rahimi^{1

3}, Martha S Linet¹⁶, Terence Dwyer^{1

3}; International Childhood Cancer Cohort Consortium

Affiliations

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.

Keywords: Maternal infection; childhood leukaemia; cohort study; prenatal.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acute Disease
Birth Cohort
Child
Female
Humans
Influenza, Human* / complications
Influenza, Human* / epidemiology
Leukemia, Myeloid, Acute* / complications
Leukemia, Myeloid, Acute* / epidemiology
Precursor Cell Lymphoblastic Leukemia-Lymphoma*
Pregnancy
Prospective Studies
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding