Pregnancy: Birth Defects Risks with Oral Fluconazole Interview with:
Ms. Mølgaard-Nielsen

Statens Serum Institut
Artillerivej 5, 2300
Copenhagen S, Denmark What are the main findings of the study?

Answer: Use of oral fluconazole during early pregnancy did not increase the risk of birth defects overall in common therapeutic doses. We also looked at 15 individual birth defects of previous concern and oral fluconazole was not associated with an increased risk for 14 of these birth defects.  However, we did see an increase in the risk of tetralogy of Fallot, an uncommon congenital heart defect, but the number of exposed cases was few. Were any of the findings unexpected?

Answer: In 2011, the U.S. Food and Drug Administration, FDA, issued a warning on the teratogenic risk associated with fluconazole based on birth defects seen in 5 infants whose mothers had been treated with high- and long-term doses during pregnancy due to severe fungal infections. Similar defects had been observed in animal studies. With the use of the unique Danish national registries, we identified all pregnant women in Denmark in the period 1996-2011 and conducted the largest study ever examining the association between fluconazole in common therapeutic doses and birth defects. Our findings were not unexpected, but still, a large comprehensive study was necessary to address any concerns that the teratogenic effects seen for high- and long term fluconazole doses translated into similar effects for common therapeutic use. What should clinicians and patients take away from your report?

Answer: Many pregnant women suffer from vaginal candidiasis, which is the most common clinical indication for use of oral fluconazole. First-line treatment for vaginal candidiasis during pregnancy is vaginal preparations of topical azole antifungal drugs because of their minimal systemic absorption. However, in cases when topical treatment is ineffective this study provides comprehensive safety information and may help inform clinical decisions when treatment with oral fluconazole is considered in pregnancy. Furthermore, pregnant women can be reassured since this study does not support a teratogenic effect of fluconazole used in common therapeutic doses during pregnancy. What recommendations do you have for future research as a result of this study?

Answer: In our study, the increased risk of tetralogy of Fallot is based on only 7 cases born of mothers using fluconazole, and we therefore suggest that this association needs to be confirmed in another and preferably larger study before anything certain can be concluded.


Use of Oral Fluconazole during Pregnancy and the Risk of Birth Defects

Ditte Mølgaard-Nielsen, M.Sc., Björn Pasternak, M.D., Ph.D., and Anders Hviid, Dr.Med.Sci.

N Engl J Med 2013; 369:830-839August 29, 2013DOI: 10.1056/NEJMoa1301066