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孕期常见母体感染与儿童期白血病:来自六个国际出生队列的研究结果。

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

机构信息

Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, UK.

Division of Birth Cohort Study, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.

出版信息

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


DOI:10.1093/ije/dyab199
PMID:34519790
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9425514/
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.

摘要

背景:先前的流行病学研究发现,母体感染与儿童白血病之间存在正相关关系;然而,来自前瞻性队列研究的证据却很少。我们旨在使用大规模的前瞻性数据来检验这些关联。

方法:本研究的数据来自澳大利亚、丹麦、以色列、挪威、英国和美国的六个基于人群的出生队列(招募时间为 20 世纪 50 年代至 2000 年代)。主要结局是任何儿童白血病和急性淋巴细胞白血病(ALL);次要结局是急性髓细胞白血病(AML)和任何儿童癌症。暴露因素包括母亲自我报告的感染(流感样疾病、普通感冒、任何呼吸道感染、阴道假丝酵母菌病、阴道感染和尿路感染(包括膀胱炎))和感染相关症状(发热和腹泻)。使用多层次 Cox 模型估计调整协变量后的危险比(HR)和 95%置信区间(CI)。

结果:在 312879 名儿童中,中位随访时间为 13.6 年,发现 167 例白血病,包括 129 例 ALL 和 33 例 AML。母体尿路感染与任何白血病(HR[95%CI]1.68[1.10-2.58])和亚型 ALL[1.49[0.87-2.56])和 AML[2.70[0.93-7.86])风险增加相关,但与任何癌症(1.13[0.85-1.51])无关。呼吸道感染与任何白血病(1.57[1.06-2.34])、ALL[1.43[0.94-2.19])、AML[2.37[1.10-5.12])和任何癌症(1.33[1.09-1.63])风险增加相关;流感样疾病也表现出类似的模式,但估计值不太精确。没有证据表明其他感染与任何结果之间存在关联。

结论:妊娠期间的尿路感染和呼吸道感染可能与儿童白血病有关,但考虑到该结果罕见,绝对风险较小。

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本文引用的文献

[1]
Maternal Infection in Pregnancy and Childhood Leukemia: A Systematic Review and Meta-analysis.

J Pediatr. 2019-12-4

[2]
Maternal urinary tract infection during pregnancy and long-term infectious morbidity of the offspring.

Early Hum Dev. 2019-7-15

[3]
Association Between Birth Defects and Cancer Risk Among Children and Adolescents in a Population-Based Assessment of 10 Million Live Births.

JAMA Oncol. 2019-8-1

[4]
Long-term Risk of Neuropsychiatric Disease After Exposure to Infection In Utero.

JAMA Psychiatry. 2019-6-1

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Childhood cancer burden: a review of global estimates.

Lancet Oncol. 2019-1

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Paediatr Perinat Epidemiol. 2018-11

[7]
Neonatal Inflammatory Markers Are Associated with Childhood B-cell Precursor Acute Lymphoblastic Leukemia.

Cancer Res. 2018-9-15

[8]
Maternal infection during pregnancy and type 1 diabetes mellitus in offspring: a systematic review and meta-analysis.

Epidemiol Infect. 2018-8-28

[9]
Multiple imputation of missing data in nested case-control and case-cohort studies.

Biometrics. 2018-12

[10]
A causal mechanism for childhood acute lymphoblastic leukaemia.

Nat Rev Cancer. 2018-8

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