Purpose: Vulvovaginal candidiasis is highly prevalent among pregnant women, and its treatment is crucial. However, there is a lack of evidence regarding the risks on fetal outcomes associated with the use of antifungal medications during the first trimester of pregnancy in Japan. This study examined the association between topical antifungal use during the first trimester of pregnancy and the risk of major congenital malformations (MCMs) in infants using a Japanese database.
Methods: We conducted a cohort study using a pregnancy cohort nested in the JMDC Claims Database from Japan. This dataset included 12 472 women who gave birth between 2010 and 2019 and were diagnosed with vulvovaginal candidiasis. Among the antifungal medications frequently dispensed or prescribed during the first trimester of pregnancy in this cohort, miconazole, oxiconazole, and isoconazole were assessed for the risk of MCMs, using clotrimazole, an antifungal medication with established safety during pregnancy, as a reference.
Results: Among 12 472 women, the overall prevalence of MCMs was 5.8% (n = 249) in women exposed to topical antifungals, while unexposed were 6.2% (n = 508). Using propensity score overlap weight (wOR), no increased risk of MCMs in infants was observed in pregnancies exposed to oxiconazole, isoconazole, and miconazole compared to clotrimazole (overlap weighted odds ratio [95% confidence interval]: 0.875 [0.599-1.277], 1.001 [0.611-1.640], and 0.887 [0.497-1.581], respectively).
Conclusion: There was no significant association between topical antifungal use during the first trimester of pregnancy and the risk of MCMs in infants in Japan.
Keywords: antifungal medications; database; malformation; pregnancy.
Vulvovaginal candidiasis is common during pregnancy, and antifungal medications are frequently used to treat it. However, concerns have been raised about whether using these medications in early pregnancy could increase the risk of major congenital malformations in infants. This study investigated the safety of commonly used topical antifungal medications during early pregnancy using a large claims database in Japan. We compared pregnant women who were exposed to oxiconazole, isoconazole, and miconazole in early pregnancy with those who were exposed to clotrimazole in early pregnancy, and examined the risks of major congenital malformations in infants. We found no significant association between exposure to topical antifungal medications in early pregnancy and increased risk of major congenital malformations in infants.
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