阴道抗真菌药物与自然流产风险。

Department of Public Health, Beer-Sheva, Israel; Faculty of Health Sciences, Beer-Sheva, Israel; Clalit Health Services (Southern District), Beer-Sheva, Israel.

Department of Public Health, Beer-Sheva, Israel; Faculty of Health Sciences, Beer-Sheva, Israel.

Am J Obstet Gynecol. 2018 Jun;218(6):601.e1-601.e7. doi: 10.1016/j.ajog.2018.02.013. Epub 2018 Mar 3.

BACKGROUND

Spontaneous abortions are the most common complication of pregnancy. Clotrimazole and miconazole are widely used vaginal-antimycotic agents used for the treatment of vulvovaginal candidiasis. A previous study has suggested an increased risk of miscarriage associated with these azoles, which may lead health professionals to refrain from their use even if clinically indicated.

OBJECTIVE

The aim of the current study was to assess the risk for spontaneous abortions following first trimester exposure to vaginal antimycotics.

STUDY DESIGN

A historical cohort study was conducted including all clinically apparent pregnancies that began from January 2003 through December 2009 and admitted for birth or spontaneous abortion at Soroka Medical Center, Clalit Health Services, Beer-Sheva, Israel. A computerized database of medication dispensation was linked with 2 computerized databases containing information on births and spontaneous abortions. Time-varying Cox regression models were constructed adjusting for mother's age, diabetes mellitus, hypothyroidism, obesity, hypercoagulable or inflammatory conditions, recurrent miscarriages, intrauterine contraceptive device, ethnicity, tobacco use, and the year of admission.

RESULTS

A total of 65,457 pregnancies were included in the study: 58,949 (90.1%) ended with birth and 6508 (9.9%) with a spontaneous abortion. Overall, 3246 (5%) pregnancies were exposed to vaginal antimycotic medications until the 20th gestational week: 2712 (4.2%) were exposed to clotrimazole and 633 (1%) to miconazole. Exposure to vaginal antimycotics was not associated with spontaneous abortions as a group (crude hazard ratio, 1.11; 95% confidence interval, 0.96-1.29; adjusted hazard ratio, 1.11; 95% confidence interval, 0.96-1.29) and specifically for clotrimazole (adjusted hazard ratio, 1.05; 95% confidence interval, 0.89-1.25) and miconazole (adjusted hazard ratio, 1.34; 95% confidence interval, 0.99-1.80). Furthermore, no association was found between categories of dosage of vaginal antimycotics and spontaneous abortions.

CONCLUSION

Exposure to vaginal antimycotics was not associated with spontaneous abortions.

背景

自然流产是妊娠最常见的并发症。克霉唑和咪康唑是广泛用于治疗外阴阴道假丝酵母菌病的阴道抗真菌药物。先前的研究表明，这些唑类药物与流产风险增加有关，这可能导致即使临床需要，卫生保健专业人员也避免使用它们。

目的

本研究旨在评估初次妊娠三个月内接触阴道抗真菌药物与自然流产的风险。

研究设计

这是一项历史队列研究，纳入了 2003 年 1 月至 2009 年 12 月期间在以色列贝尔谢巴的克拉利特卫生服务索罗卡医疗中心分娩或自然流产的所有临床可见妊娠。一个药物配给的计算机数据库与包含分娩和自然流产信息的两个计算机数据库相关联。构建了时变 Cox 回归模型，以调整母亲的年龄、糖尿病、甲状腺功能减退、肥胖、高凝或炎症状态、复发性流产、宫内节育器、种族、吸烟和入院年份。

结果

共有 65457 例妊娠纳入研究：58949 例（90.1%）分娩，6508 例（9.9%）自然流产。总体而言，3246 例（5%）妊娠在妊娠 20 周前接触阴道抗真菌药物：2712 例（4.2%）接触克霉唑，633 例（1%）接触咪康唑。作为一个整体，接触阴道抗真菌药物与自然流产无关（粗危害比 1.11；95%置信区间 0.96-1.29；调整危害比 1.11；95%置信区间 0.96-1.29），特别是克霉唑（调整危害比 1.05；95%置信区间 0.89-1.25）和咪康唑（调整危害比 1.34；95%置信区间 0.99-1.80）。此外，阴道抗真菌药物剂量类别与自然流产之间也未发现关联。