Use of the oral antifungal medication fluconazole during pregnancy may increase the risk of spontaneous abortion, according to a new study published in JAMA.

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An oral antifungal sometimes prescribed in pregnancy may be linked to spontaneous abortion.

Pregnant women have a higher risk of developing the yeast infection vaginal candidiasis due to an increased secretion of sex hormones; in the US, around 10% of pregnant women develop the condition.

Although intravaginal formulations of topical azole antifungals are the first-line treatment for pregnant women, oral fluconazole is often used.

However, there is a lack of safety information for the drug; in addition, previous studies have suggested evidence of a distinct pattern of craniofacial and skeletal birth defects in babies born to women treated long term with high-dose fluconazole during pregnancy.

Ditte Mølgaard-Nielsen, of the Statens Serum Institut in Copenhagen, Denmark, and colleagues evaluated the association between oral fluconazole exposure during pregnancy and the risk of spontaneous abortion and stillbirth.

In a nationwide cohort study, the team studied 1,405,663 pregnancies from 1997-2013 in Denmark.

Each oral fluconazole-exposed pregnancy was compared with up to four unexposed pregnancies, matched on maternal age, calendar year and gestational age. Filled prescriptions for oral fluconazole were obtained from the National Prescription Register.

Results showed a significantly increased risk of spontaneous abortion associated with fluconazole exposure. Among 3,315 women exposed to oral fluconazole from 7-22 weeks’ gestation, 147 experienced a spontaneous abortion, compared with 563 among 13,246 women who were not exposed to antifungals.

The association between fluconazole exposure and stillbirth was not significant: of 5,382 women exposed to fluconazole from gestational week 7 to birth, 21 experienced a stillbirth, compared with 77 among 21,506 unexposed matched women. However, the researchers note that since the number of stillbirths overall was low, more information is needed to draw definitive conclusions about the risk.

Compared with topical azole exposure, 130 of 2,823 women exposed to fluconazole had a spontaneous abortion, compared with 118 of 2,823 exposed to topical azoles; 20 of 4,301 women exposed to fluconazole had a stillbirth, compared with 22 of 4,301 who were exposed to topical azoles.

A possible confounding factor could be that in more severe cases of vaginal candidiasis, the candida can ascend from the vagina to cause intrauterine candidiasis, potentially leading to prematurity and fetal loss.

Nevertheless, the authors comment:

Oral fluconazole use in pregnancy was associated with a significantly increased risk of spontaneous abortion. Until more data on the association are available, cautious prescribing of fluconazole in pregnancy may be advisable. Although the risk of stillbirth was not significantly increased, this outcome should be investigated further.”

Medical News Today previously reported that some antifungal drugs can pose a risk of skin cancer in lung transplant patients.