Oral Fluconazole in First Trimester Tied to Musculoskeletal Malformations in Babies

By Lisa Rapaport

June 10, 2020

(Reuters Health) -- Oral fluconazole use during the first trimester of pregnancy is associated with an increased risk of musculoskeletal malformations in offspring but not with conotruncal malformations or oral clefts, a new study suggests.

The population based cohort study examined data on 1.97 million pregnancies, including 37,650 pregnancies (1.9%) when women used oral fluconazole and 82,090 (4.2%) when women used topical azoles during the first trimester.

Doses of oral fluconazole above 450 mg were associated with a roughly doubled risk of musculoskeletal malformations (adjusted relative risk 1.98), while the risk of these malformations was less pronounced at doses from 150 mg to 450 mg and at doses below 150 mg (aRR 1.24 and 1.29, respectively).

"For patients with uncomplicated vulvovaginal candidiasis, topical azoles are available as effective and safe alternatives to oral fluconazole," said lead study author Yanmin Zhu, a postdoctoral research fellow at Brigham and Women's Hospital and Harvard Medical School in Boston.

"Therefore, the patients and clinicians should weigh the risks and benefits of oral fluconazole accordingly to make the clinical decision," Zhu said by email.

When women have complicated cases of vulvovaginal candidiasis, they may still require oral fluconazole at higher doses or for a longer duration, Zhu said.

Overall, the risk of musculoskeletal malformations associated with oral fluconazole was 52.1 cases per 10,000 pregnancies, compared with 37.3 per 10,000 with topical azoles.

For conotruncal malformations, the risk was 9.6 versus 8.3 per 10,000 pregnancies for oral fluconazlone and topical azoles, respectively.

And for oral clefts, the risk was 9.3 versus 10.6 per 10,000 pregnancies for oral fluconazole and topical azoles, respectively.

One limitation of the analysis is that researchers were unable to determine whether women took any prescribed medication as directed, the study team notes in The BMJ.

Another limitation is that the study was limited to live births, and it's possible that some cases of severe birth defects resulted in miscarriage or stillbirth, the researchers point out.

In addition, researchers lacked data on why women were prescribed the medications, such as what type of fungal infection they had, said Dr. Sascha Dublin, a senior scientific investigator at Kaiser Permanente Washington Health Research Institute in Seattle who wasn't involved in the study. Only about 20% of the women in the study had a code for a vaginal yeast infection, making it possible that women taking higher doses had other, more serious infections.

Even so, the results matter because fluconazole is widely prescribed and because many pregnancies are unplanned, potentially leading to unintended first trimester exposure to this medication, Dr. Dublin said by email.

"Right now, the recommendation is for pregnant women to use topical azoles as the first line treatment for vaginal yeast infections, instead of oral fluconazole, because it's thought the topical treatments are safer," Dr. Dublin said.

SOURCE: https://bit.ly/3f6TTov The BMJ, online May 20, 2020.

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