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丹麦基于人群的队列研究中母亲使用膀胱炎药物与儿童癫痫的关系。

Maternal use of cystitis medication and childhood epilepsy in a danish population-based cohort.

机构信息

Department of Epidemiology, School of Public Health, University of California, Los Angeles, CA 90095-1772, USA.

出版信息

Paediatr Perinat Epidemiol. 2012 Nov;26(6):589-95. doi: 10.1111/j.1365-3016.2012.01317.x. Epub 2012 Aug 29.

DOI:10.1111/j.1365-3016.2012.01317.x
PMID:23061695
Abstract

BACKGROUND

Maternal infections during pregnancy have been associated with an increased risk for neurological outcomes in the child, including epilepsy. We examined cystitis antibiotics commonly used during pregnancy, as a marker of cystitis, and the risk of childhood epilepsy in a population-based cohort in Denmark.

METHODS

We examined all liveborn singletons born in Denmark between January 1996 and September 2004, identified from the Danish National Birth Registry. Epilepsy diagnoses were obtained from the Danish National Hospital Register and maternal antibiotic use from the National Register of Medicinal Product Statistics. Cystitis antibiotics consisted of pivmecillinam, sulphamethizole and nitrofurantoin. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazard regression models.

RESULTS

The study followed 447629 singletons for up to 9.9 years and identified 2848 children diagnosed with epilepsy. We found slightly increased risks of epilepsy in children whose mothers had redeemed prescriptions during pregnancy for pivmecillinam HR=1.2 [95% CI 1.0, 1.4], sulphamethizole HR=1.2 [95% CI 1.1, 1.4] or nitrofurantoin HR=1.1 [95% CI 0.8, 1.5], compared with those unexposed. Among mothers with multiple redeemed prescriptions during pregnancy, adjusted HR were for pivmecillinam HR=1.3 [95% CI 1.1, 1.5], sulphamethizole HR=1.3 [95% CI 1.1, 1.5] and nitrofurantoin HR=1.3 [95% CI 1.0, 1.8].

CONCLUSIONS

Similar magnitudes of associations between chemically different drugs, used almost exclusively to treat cystitis, may suggest an impact of maternal infection on the fetal brain. However, direct drug effects or confounding factors are also possible explanations.

摘要

背景

母体妊娠期间的感染与儿童神经发育结果(包括癫痫)的风险增加有关。我们在丹麦的一个基于人群的队列中,以妊娠期间常用的膀胱炎抗生素(一种膀胱炎标志物)为指标,研究了其与儿童癫痫发病风险的关系。

方法

我们从丹麦国家出生登记处获得了 1996 年 1 月至 2004 年 9 月期间所有在丹麦出生的活产单胎,通过丹麦国家医院登记处获得癫痫诊断,通过国家药品统计登记处获得母亲抗生素使用情况。膀胱炎抗生素包括匹美西林、磺胺甲恶唑和呋喃妥因。使用 Cox 比例风险回归模型估计风险比(HR)和 95%置信区间(CI)。

结果

本研究对 447629 名单胎儿童进行了长达 9.9 年的随访,共发现 2848 名患有癫痫的儿童。我们发现,母亲在妊娠期间使用匹美西林[HR=1.2(95%CI 1.0,1.4)]、磺胺甲恶唑[HR=1.2(95%CI 1.1,1.4)]或呋喃妥因[HR=1.1(95%CI 0.8,1.5)]的儿童,癫痫发病风险略有增加,与未暴露者相比。对于妊娠期间多次使用抗生素的母亲,匹美西林[HR=1.3(95%CI 1.1,1.5)]、磺胺甲恶唑[HR=1.3(95%CI 1.1,1.5)]和呋喃妥因[HR=1.3(95%CI 1.0,1.8)]的调整 HR 相似。

结论

不同化学结构的药物(几乎专门用于治疗膀胱炎)之间关联的幅度相似,这可能提示母体感染对胎儿大脑的影响。但是,也有可能是直接的药物作用或混杂因素所致。

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