Background Studies have suggested increased risks of childhood leukaemia after prenatal exposure to antibiotics, particularly nitrofurantoin. However, these findings may be related to the underlying maternal infection. This multinational study aimed to investigate the association between prenatal nitrofurantoin exposure and childhood leukaemia while accounting for maternal infection. Methods In a population-based cohort study of children born in Denmark, Finland, Norway or Sweden from 1997 to 2013, prenatal exposure to nitrofurantoin or pivmecillinam (active comparator) was ascertained from national Prescription Registries. Childhood leukaemia was identified by linkage to national Cancer Registries. Poisson regression was used to estimate incidence rate ratios (IRRs) and incidence rate differences (IRDs) with inverse probability of treatment weights applied to account for confounding. Results We included 44 091 children prenatally exposed to nitrofurantoin and 247 306 children prenatally exposed to pivmecillinam. The children were followed for 9.3 years on average (standard deviation 4.1). There were 161 cases of childhood leukaemia. The weighted IRR for prenatal nitrofurantoin exposure when compared with pivmecillinam was 1.34 (95% confidence interval 0.88, 2.06), corresponding to an IRD of 15 per million person-years. Higher point estimates were seen for first- and third-trimester exposure. There was no evidence of a dose–response relationship. Conclusions Prenatal exposure to nitrofurantoin was not substantially associated with childhood leukaemia, although a slightly elevated IRR with confidence intervals including the null was observed, corresponding to a small absolute risk. The lack of a dose–response relationship and a clear biological mechanism to explain the findings suggests against a causal association.

中文翻译：

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产前暴露于呋喃妥因和儿童白血病风险：在四个北欧国家进行的基于登记的队列研究

背景研究表明，产前接触抗生素，特别是呋喃妥因后，儿童白血病的风险增加。然而，这些发现可能与潜在的母体感染有关。这项多国研究旨在调查产前呋喃妥因暴露与儿童白血病之间的关联，同时考虑母体感染。方法 在一项针对 1997 年至 2013 年在丹麦、芬兰、挪威或瑞典出生的儿童的基于人群的队列研究中，从国家处方登记处确定了产前暴露于呋喃妥因或 pivmecillinam（活性比较剂）的情况。通过与国家癌症登记处的联系确定了儿童白血病。泊松回归用于估计发病率比 (IRR) 和发病率差异 (IRD)，并应用治疗权重的逆概率来解释混杂因素。结果 我们纳入了 44 091 名产前暴露于呋喃妥因的儿童和 247 306 名产前暴露于吡美西林的儿童。这些儿童平均随访 9.3 年（标准差 4.1）。有 161 例儿童白血病。与 pivmecillinam 相比，产前呋喃妥因暴露的加权 IRR 为 1.34（95% 置信区间 0.88, 2.06），对应于每百万人年 15 的 IRD。孕早期和孕晚期暴露的估计值更高。没有证据表明存在剂量反应关系。结论 产前暴露于呋喃妥因与儿童白血病没有显着相关性，尽管观察到 IRR 略有升高，置信区间包括空值，对应于较小的绝对风险。缺乏剂量反应关系和解释这些发现的明确生物学机制表明存在因果关系。