Vaginal antimycotics and the risk for spontaneous abortions

Published:March 03, 2018DOI:


      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.


      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.


      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.


      Exposure to vaginal antimycotics was not associated with spontaneous abortions.

      Key words

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        American Journal of Obstetrics & GynecologyVol. 219Issue 6
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          We thank Drs Xu and Du for their comment on our study. An adverse effect of a drug may develop in 2 ways: the first is a remote or a cumulative effect, in which an adverse phenomenon occurs relatively far from the exposure; the second is an acute effect, in which the adverse phenomenon occurs in the days after the exposure.
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      • Vaginal antifungal during pregnancy and risk of spontaneous abortions
        American Journal of Obstetrics & GynecologyVol. 219Issue 6
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          We read with interest the article “Vaginal antimycotics and the risk for spontaneous abortions” by Daniel et al.1 The researchers used the medical center–based cohort of 65,457 pregnancies and compared those that were exposed to vaginal antifungal medications with up to 20 unexposed pregnancies. They found an insignificantly increased risk of spontaneous abortion associated with antimycotics exposure (crude hazard ratio, 1.11; 95% confidence interval, 0.96–1.29). Daniel et al concluded that “No increased risk for spontaneous abortions was detected following exposure to vaginal anti-mycotic drugs and the study reinforces the safety of use of these drugs (vaginal antimycotics) during the first trimester of pregnancy.” This is in accordance with the currently recommended advice that intravaginal formulations of topical azole antifungals are the first-line treatment for pregnant women.
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