Oral fluconazole use in pregnant women linked to musculoskeletal malformations in children

Women who used oral fluconazole — a common treatment for vulvovaginal candidiasis — during the first trimester of pregnancy were more likely to give birth to an infant with musculoskeletal malformations, but not oral clefts or conotruncal malformations, which were previously linked to the medication, according to a study published in BMJ.

“Oral fluconazole given in the first trimester of pregnancy has steadily increased over time, from 1.1% in 2000 to 2.6% in 2014 in the United States,” Yanmin Zhu, PhD, a postdoctoral research fellow in at the division of pharmacoepidemiology and pharmacoeconomics at Brigham and Women’s Hospital and Harvard Medical School, and colleagues wrote.

Previously, studies had shown that maternal oral fluconazole use in pregnancy was associated with a slight increase in risk for congenital heart defects in children.

Zhu and colleagues conducted a population-based cohort study of Medicaid beneficiaries using data from the Medicaid Analytic eXtract study from 2000 to 2014. Participants’ demographic information, diagnoses, inpatient and outpatient procedures, and dispensing records were assessed in the study.

 

Women who used oral fluconazole — a common treatment for vulvovaginal candidiasis — during the first trimester of pregnancy were more likely to give birth to an infant with musculoskeletal malformations, but not oral clefts or conotruncal malformations, which were previously linked to the medication, according to a study published in BMJ.

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Pregnant women aged 12 to 55 years who had been enrolled in Medicaid continuously for at least 3 months before their last menstrual period to at least 1 month after delivery were included in the analysis, along with liveborn infants who were enrolled from their birth to 3 or more months later.

Among 1,969,954 pregnancies included in the cohort, 37,650 (1.9%) had exposure to oral fluconazole and 82,090 (4.2%) pregnancies had exposures to topical azoles during the first trimester, according to the researchers.

Zhu and colleagues determined the risk for musculoskeletal malformations among infants was 52.1 per 10,000 pregnancies (95% CI, 44.8-59.3) in those exposed to fluconazole compared with 37.3 per 10,000 pregnancies (95% CI, 33.1-41.4) in those exposed topical azoles.

After adjusting for confounding variables, researchers found the relative risk of musculoskeletal malformations in pregnancies exposed to oral fluconazole compared with topical azoles was 1.30 (95% CI, 1.09-1.56), and the risk difference between them was 12.15 per 10,000 pregnancies (3.69-20.6).

Despite previous findings, researchers did not find an association between the use of oral fluconazole and oral clefts or conotruncal malformations.

When comparing the risk for musculoskeletal malformations with topical azoles vs. different doses of fluconazole, the adjusted relative risk was 1.29 (1.05-1.58) with 150 mg of fluconazole; 1.24 (0.93-1.66) for doses of more than 150 mg to 450 mg; and 1.98 (1.23-3.17) for doses more than 450 mg.

“Our study confirmed an increase in the risk of musculoskeletal malformations if fluconazole is used during the first trimester, and refuted large increased risks of conotruncal malformations, oral clefts, and other specific types of malformations,” Zhu and colleagues wrote.

They explained that during the first trimester, oral fluconazole, “especially prolonged treatment at higher than commonly used doses, should be prescribed with caution, and topical azoles should be considered as an alternative treatment.” – by Erin Michael

Disclosures: Zhu reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.