木瓜直播

Oral fluconazole in pregnancy was linked to increased risk for congenital bone and muscle abnormalities in a population-based cohort study.

Mothers who took low-dose fluconazole -- an antifungal agent used to treat vaginal yeast infections, among other things -- during the first trimester were 30% more likely to deliver infants with musculoskeletal malformations (relative risk 1.30, 95% CI 1.09-1.56), reported Yanmin Zhu, PhD, of the Brigham and Women's Hospital and Harvard School of Medicine in Boston, and colleagues.

Exposure to more than 450 mg of oral fluconazole, or around three doses, nearly doubled the risk of bone and muscle defects at birth, Zhu and colleagues reported in .

The group noted that the absolute risk for musculoskeletal malformations was small, and contrary to previous findings, they found no risk of heart defects or oral clefts associated with fluconazole use.

In an interview with 木瓜直播, Zhu said that this study is consistent with such findings.

Because vulvovaginal candidiasis is common among pregnant women, Zhu added that it is important to understand the risks of treatment options. Many women prefer the convenience of oral fluconazole, she said, but risks should be considered when weighing alternatives such as topical azoles, which are potentially safer.

Case reports have shown that a high dose of oral fluconazole may increase the risk of specific bone and muscle abnormalities, including thin ribs, femoral bowing, cleft palate, and craniofacial ossification, Zhu and colleagues wrote. Among controlled studies that have further investigated risk, results were inconsistent.

Fluconazole's acknowledges risks of fetal malformations with first-trimester exposure, primarily at doses of 400-800 mg/day. As well, it states, "[e]pidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials."

Study details

Zhu and colleagues used data from the nationwide Medicaid Analytic eXtract database for 2000 to 2014. They included pregnant women who were enrolled in Medicaid three months before their last menstrual period up to one month after delivery.

Pregnancies were excluded if they had chromosomal abnormalities, were exposed to another known teratogenic drug during the first trimester, had HIV diagnoses or other candidiasis infections, or received treatment for a fungal infection after the first trimester.

The participants in the oral fluconazole cohort were classified in three groups based on dosage: 150 mg, between 150 mg and 450 mg, and more than 450 mg.

Women receiving prescriptions for oral fluconazole were compared to two reference groups: those getting no first-trimester prescriptions for oral antifungal agents, and those prescribed topical azoles including butoconazole, clotrimazole, miconazole, terconazole, tioconazole, or nystatin.

Statistics included adjustments for maternal age, delivery year, race, multiple gestation, other drug use, visits to healthcare facilities, and maternal conditions such as hypertension, diabetes and obesity, among others.

Of nearly two million pregnancies in the analysis, 2% were exposed to oral fluconazole during the first trimester and 4% had topical treatment.

Two-thirds of pregnancies with oral fluconazole exposure involved a single 150-mg dose of oral fluconazole; most of the rest had cumulative doses between 150 mg and 450 mg.

The risk of bone and muscle malformations among babies exposed to oral fluconazole in the first trimester was 52.1 (95% CI 44.8-59.3) per 10,000 pregnancies, compared to a risk of 38 (95% CI 37.1-38.9) per 10,000 in those unexposed. Risk for pregnancies exposed to topical azoles was 37.3 (95% CI 33.1-41.4) per 10,000.

The risk of heart defects was 9.6 (95% CI 6.4-12.7) per 10,000 pregnancies with oral fluconazole, and 9.3 (95% CI 6.2-12.4) for oral clefts. Neither was significantly different from rates seen in the reference groups after adjustment for covariates.

Zhu and colleagues recognized that although this study had a large sample size, there were a small number of the least common malformations. The group was also unable to determine whether or not women consumed the dispensed prescriptions, and recognized that the Medicaid population was younger, racially diverse, and more likely to have disabilities, which could limit generalizability of results.

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