Case reports suggest that long-term, high-dose Fluconazole ( Diflucan ) treatment for severe fungal infections during pregnancy causes a pattern of birth defects. It is unclear whether commonly used lower doses increase the risk of specific birth defects.
In a registry-based cohort of liveborn infants in Denmark, researchers have evaluated first-trimester oral Fluconazole exposure and the risk of birth defects overall and of birth defects previously linked to azole antifungal agents.
The majority of Fluconazole-exposed pregnancies were in women who received common therapeutic doses of 150 mg ( 56% of pregnancies ) or 300 mg ( 31% ). Oral fluconazole exposure was not associated with an increased risk of birth defects overall ( 210 birth defects among 7352 Fluconazole-exposed pregnancies [ prevalence, 2.86% ] and 25,159 birth defects among 968,236 unexposed pregnancies [ prevalence, 2.60% ]; adjusted prevalence odds ratio, OR=1.06 ).
In addition, oral Fluconazole exposure was not associated with a significantly increased risk of 14 of 15 types of birth defects previously linked to azole antifungal agents: craniosynostosis, other craniofacial defects, middle-ear defects, cleft palate, cleft lip, limb defects, limb-reduction defects, polydactyly, syndactyly, diaphragmatic hernia, heart defects overall, pulmonary-artery hypoplasia, ventricular septal defects, and hypoplastic left heart.
A significantly increased risk of tetralogy of Fallot was observed ( 7 cases in Fluconazole-exposed pregnancies [ prevalence, 0.10% ] as compared with 287 cases in unexposed pregnancies [ prevalence, 0.03% ]; adjusted prevalence OR=3.16 ).
In conclusion, oral Fluconazole was not associated with a significantly increased risk of birth defects overall or of 14 of the 15 specific birth defects of previous concern. Fluconazole exposure may confer an increased risk of tetralogy of Fallot. ( Xagena )
Mølgaard-Nielsen D et al, N Engl J Med 2013; 369:830-839