Fluconazole during pregnancy: risk of spontaneous abortion

Abstract

Treatment with oral fluconazole during pregnancy appears to increase the risk of spontaneous abortion, and high-dose exposure appears to increase the risk of cardiac septal closure anomalies, according to findings of a Canadian study published in the CMAJ.1 Three nested case-controls studies of data from the Quebec Pregnancy Cohort (1998–2015) evaluated the effects of low-dose fluconazole (≤150mg) and high-dose fluconazole (>150mg) during pregnancy on the risks of spontaneous abortion, stillbirth, and major congenital malformations. For each case of spontaneous abortion or stillbirth, up to five matched pregnant controls were selected. All liveborn neonates served as controls for cases of major congenital malformation. Prescription data were obtained from the Quebec Prescription Drug Insurance database. The total cohort included 441 949 pregnancies, of which 320 868 were included in the study on spontaneous abortions, 226 599 were included in the study on major congenital malformations, and 7832 were included in the study on stillbirths. Overall, 69.5% of women received a single low dose of fluconazole and 30.5% received a high dose. The risk of spontaneous abortion was significantly increased by exposure to low-dose fluconazole (adjusted odds ratio [aOR] 2.23; 95% CI 1.96, 2.54) and high-dose fluconazole (aOR 3.20; 95% CI 2.73, 3.75) during early pregnancy, compared with no exposure. Although exposure to fluconazole during the first trimester did not significantly increase the overall risk of major congenital malformations compared with no exposure, high-dose fluconazole during the first trimester significantly increased risk of cardiac septal closure anomalies (aOR 1.81; 95% CI 1.04, 3.14). There was no association between exposure to fluconazole and the risk of stillbirth. Any maternal exposure to fluconazole during pregnancy may increase risk of spontaneous abortion and doses higher than 150 mg during the first trimester may increase risk of cardiac septal closure anomalies, concluded the authors. Topical azoles, rather than low-dose fluconazole, should be first-line treatment for vulvovaginal candidiasis in early pregnancy, commented Vanessa Paquette and Chelsea Elwood from the British Columbia Women’s Hospital and Health Centre, Vancouver, Canada, in an accompanying editorial published in the CMAJ.2 For women with disseminated fungal disease, all treatment risks should be considered in the context of the health of the mother. If treatment is indicated, a risk–benefit discussion should take place, but appropriate treatment should not be deferred if indicated, they said.