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

JR He, Jane E Hirst, G Tikellis, GS Phillips, Rema Ramakrishnan, O Paltiel, AL Ponsonby, M Klebanoff, Jørn Olsen, Michael F G Murphy, SE Haberg, S Lemeshow, Sjúrður Fróði Olsen, X Qiu, P Magnus, J Golding, MH Ward, Joseph L Wiemels, Kazem Rahimi, MS LinetT Dwyer

Research output: Contribution to journalArticlepeer-review

Abstract

BackgroundPrevious 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.MethodsData 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.ResultsAmong 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.ConclusionsUrinary 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.
Original languageEnglish
Pages (from-to)769-777
Number of pages9
JournalInternational Journal of Epidemiology
Volume51
Issue number3
DOIs
Publication statusPublished - 14 Sep 2021

Keywords

  • maternal infection
  • childhood leukaemia
  • cohort study
  • prenatal
  • childhood leukemia

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