The antibiotic trimethoprim acts as a folate antagonist. Since trophoblasts are very sensitive to drugs that interfere with the folic acid cycle and thereby inhibit DNA synthesis, use of trimethoprim during the first trimester could be associated with miscarriage. A nationwide cohort study including all women in Denmark with a registered pregnancy between 1997 and 2005 was conducted. We used nationwide registers to identify all women giving birth, having a record of miscarriage or induced abortion. Data on exposure to trimethoprim were obtained from the National Prescription Register. Cox proportional hazard regression analysis with exposure to trimethoprim as a time-dependent variable was used to estimate the risk of miscarriage. The adjusted hazard ratio of having a miscarriage after exposure to trimethoprim in the first trimester compared to non-exposure was 2∙04 (95% confidence interval 1∙43-2∙91). Our results indicate that trimethoprim exposure in the first trimester is associated with a doubling of the hazard of miscarriage.

译文

抗生素甲氧苄啶起叶酸拮抗剂的作用。由于滋养细胞对干扰叶酸循环从而抑制DNA合成的药物非常敏感,因此在孕早期使用甲氧苄啶可能与流产有关。进行了一项全国性的队列研究,包括丹麦所有有注册怀孕1997年和2005的妇女。我们使用全国范围的登记册来识别所有有流产或人工流产记录的分娩妇女。甲氧苄啶暴露的数据来自国家处方登记册。使用暴露于甲氧苄啶作为时间相关变量的Cox比例风险回归分析来估计流产的风险。与未接触相比,在孕早期暴露于甲氧苄啶后流产的调整的风险比为2*04 (95% 置信区间1*43-2*91)。我们的结果表明,孕早期甲氧苄氨嘧啶暴露与流产危险加倍有关。

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