Research Unit of Clinical Epidemiology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
Center for Clinical Epidemiology, Odense University Hospital, Odense, Denmark.
Pediatr Blood Cancer. 2015 Jul;62(7):1155-61. doi: 10.1002/pbc.25477. Epub 2015 Mar 19.
The role of infection in the aetiology of childhood leukaemia is unknown. We used prescriptions of antibiotics from Danish pharmacies as a proxy measure for the occurrence of infections.
We investigated the association between exposure to antibiotics, from conception to leukaemia diagnosis, and the risk of leukaemia. Incident cases of leukaemia among children in Denmark, 1995-2008, with mothers having their earliest conception date in 1995, were individually matched to population controls by age, sex and municipality. Conditional logistic regression analyses assessed antibiotic redemptions in different time periods from conception up to 6 months before the diagnoses of all leukaemia types, acute lymphoblastic leukaemia [ALL] and ALL in 2- to 5-year-old children, adjusting for several potential confounders.
A total of 120/360 (33.3%) leukaemia mothers and 1,081/3,509 (30.8%) control mothers redeemed antibiotics during pregnancy (P = 0.32). For children, the equivalent numbers were 276 (76.7%) and 2,665 (75.9%) (P = 0.76). Histograms of antibiotic redemptions showed no temporal differences between leukaemia mothers/children and controls, which was confirmed in adjusted regression analyses (OR [95% CI]: 1.02 [0.75-1.38]). Only antibiotics redeemed during the first year after birth differed from this (OR [95% CI] for ALL diagnosed in 2- to 5-year-old children: 0.46 [0.31-0.66]).
In this hypothesis generating study, the similar amount and pattern of antibiotic redemptions in children with and without leukaemia indicate that infections play a minor role in the aetiology of childhood leukaemia. However, less antibiotic redemptions during the first year of life conform to Greaves' 'delayed infection hypothesis'.
感染在儿童白血病病因学中的作用尚不清楚。我们使用丹麦药店的抗生素处方作为感染发生的替代指标。
我们研究了从受孕到白血病诊断期间接触抗生素与白血病风险之间的关联。1995 年至 2008 年丹麦儿童白血病的发病病例,其母亲最早受孕日期为 1995 年,按年龄、性别和市与人群对照进行个体匹配。条件逻辑回归分析评估了所有白血病类型、2 至 5 岁儿童急性淋巴细胞白血病(ALL)和 ALL 诊断前 6 个月内不同时间段内的抗生素处方情况,同时调整了几个潜在的混杂因素。
共有 120/360(33.3%)白血病母亲和 1081/3509(30.8%)对照母亲在怀孕期间使用了抗生素(P=0.32)。对于儿童,相应的数字分别为 276(76.7%)和 2665(75.9%)(P=0.76)。抗生素处方的直方图显示白血病母亲/儿童和对照组之间没有时间差异,这在调整后的回归分析中得到了证实(OR[95%CI]:1.02[0.75-1.38])。只有出生后第一年使用的抗生素有所不同(2 至 5 岁儿童 ALL 诊断的 OR[95%CI]:0.46[0.31-0.66])。
在这项假设生成研究中,患有和不患有白血病的儿童抗生素使用量和模式相似,表明感染在儿童白血病的病因学中作用较小。然而,生命第一年抗生素使用量较少符合 Greaves 的“延迟感染假说”。