Oral Antifungal Use During Pregnancy Might Increase Some Birth Defects

By Will Boggs MD

December 17, 2019

NEW YORK (Reuters Health) - The use of oral fluconazole or itraconazole during pregnancy might increase the risk of certain birth defects, according to a systematic review and meta-analysis.

Topical azoles (clotrimazole, miconazole, and others) are typically recommended for treating vulvovaginal candidiasis during pregnancy, and the safety of oral antifungal agents during pregnancy remains controversial.

Dr. Lingli Zhang and colleagues from Sichuan University and West China Second University Hospital, in Chengdu, China, assessed the fetal safety of oral antifungal agents based on nine observational studies that enrolled more than 14,000 pregnant women who used fluconazole and 1,311 pregnant women who used itraconazole.

Overall, there was no significant difference in the risk of birth defects between pregnant women exposed to fluconazole or itraconazole and unexposed women, the researchers report in the International Journal of Gynecology and Obstetrics.

With fluconazole exposure, there was a significantly increased frequency of congenital heart defects (1.52% vs. 0.77% in the general population) and limb defects (0.62% vs. 0.56%). Itraconazole exposure was associated with a significantly increased frequency of eye defects (0.56% vs. 0.04% in the general population).

Neither oral antifungal was significantly associated with other birth defects, spontaneous abortion, or stillbirth.

"The current evidence suggests that the administration of oral antifungal agents in early pregnancy may not be associated with an increased risk of birth defects, spontaneous abortion, or stillbirth," the researchers conclude. "Nonetheless, the risk of congenital heart defects and limb defects in the fluconazole-exposed population and eye defects in the itraconazole-exposed population should be cautiously investigated."

Julianna Briglio, a nurse practitioner in the Obstetrics and Gynecology Department at the Group Health Centre, in Sault Ste. Marie, Canada, who was not involved in the study, previously reported that oral fluconazole is often used during pregnancy despite safety concerns.

She told Reuters Health by email, "Oral fluconazole is not prescribed in our office for our pregnant population. The tried and trusted clotrimazole is the first line and continues to be the safest option. Yeast (infection) is a common complaint of pregnancy, and I typically do not treat asymptomatic presentations, due to the high recurrence after treatment."

Dr. Ditte Molgaard-Nielsen of Statens Serum Institute, in Copenhagen, has reported in separate studies that oral fluconazole did not increase the risk of 14 of 15 birth defects (the exception being tetralogy of Fallot), but did increase the risk of spontaneous abortion.

She told Reuters Health by email that the new meta-analysis did not include two studies (including hers) that showed a significantly increased risk of spontaneous abortion with fluconazole exposure during pregnancy.

"Considering the current evidence reporting a small increased risk of some specific birth defects and spontaneous abortion and the fact that that topical azoles are both available and recommended as first-line treatment during pregnancy," she said, "cautious prescribing of fluconazole in pregnancy may be advisable."

The authors report no conflicts of interest.

Dr. Zhang did not respond to a request for comments.

SOURCE: https://bit.ly/2Kw4Lzx, International Journal of Gynecology and Obstetrics, online November 5, 2019.