Maternal exposure to even a single dose of oral fluconazole during pregnancy may increase the risk of spontaneous abortion, according to new Canadian research. Moreover, doses higher than 150mg during the first trimester may increase the risk of cardiac septal closure anomalies.

The authors identified women exposed to low- (150mg or less) and high-dose (more than 150mg) oral fluconazole and matched each case of spontaneous abortion or stillbirth with up to five controls.

The researchers analysed 320,868 spontaneous abortions, 226,599 major congenital malformations and 7,832 stillbirths. About two-thirds (69.5 per cent) of women exposed to fluconazole in pregnancy received a single dose of 150mg.

Using oral fluconazole during early pregnancy was associated with a two- to three-fold increase in the risk of spontaneous abortion compared with no exposure (adjusted odds ratios 2.23 for low dose, 3.20 for high dose).

Taking fluconazole during the first trimester did not increase the risk of major congenital malformations but exposure to high-dose fluconazole during the first trimester was associated with an 81 per cent increase in the risk of cardiac septal closure anomalies. No association emerged between fluconazole and stillbirth.

The study has limitations, such as a lack of information on possible confounders including smoking, use of OTC folic acid and alcohol intake, leading the authors to comment that the “findings are consistent with other studies in the literature, but require replication”.