BACKGROUND AND PURPOSE:

• Vaginal candidiasis is common in pregnancy (10%; 2-10 higher than general population)
• High-dose fluconazole has been associated with significant birth defects
• Bérard et al. (CMAJ, 2019) assessed the impact of fluconazole exposure during pregnancy on the occurrence of spontaneous abortions, major congenital malformations and stillbirths

METHODS:

• Nested case-control studies
  • Secondary analysis of Quebec Pregnancy cohort
• Women had been exposed to
  • Low (≤ 150 mg) fluconazole
  • High-dose (> 150 mg) fluconazole
  • No fluconazole exposure
• For each case of spontaneous abortion or stillbirth, up to 5 controls were randomly selected and matched for
  • Spontaneous abortion: Gestational age at diagnosis
  • Stillbirth (index date): Year of the last menstrual period
• All liveborn births acted as controls for cases of major congenital malformation

RESULTS:

• Overall cohort of 441,949 pregnancies
  • For analysis of spontaneous abortions: 320,868 pregnancies included
  • Major congenital anomalies: 226,599 pregnancies included
  • Stillbirths: 7,832 pregnancies were included
• Exposure
  • Low dose: 69.5% of women
  • High dose: 30.5% of women
• Spontaneous abortion
  • Oral fluconazole exposure was associated with an increased risk of spontaneous abortion compared with no exposure
  • Low dose (n=345 exposed): Adjusted odds ratio (OR) 2.23 (95% CI, 1.96–2.54)
  • High dose (n-249 exposed) adjusted OR: OR 3.20 (95% CI, 2.73–3.75)
• Major Malformations (overall)
  • No associated risk with first trimester exposure
• Cardiac septal closure anomalies
  • Increaed risk with high dose exposure during the first trimester
  • Adjusted OR 1.81 (95% CI, 1.04–3.14)
• Stillbirth: No associated risk

CONCLUSION:

• Fluconazole exposure in pregnancy may increase risk of spontaneous abortion
• Dose > 150 mg in first trimester may increase risk of cardiac septal closure anomalies
• Professional bodies urge caution in prescribing fluconazole in pregnancy advise that other alternative antifungal agents be used to treat candidiasis in pregnancy (see ‘Learn More’ and ‘Related ObG Topics’ below)

Learn More – Primary Sources: 

Associations between low- and high-dose oral fluconazole and pregnancy outcomes: 3 nested case–control studies 

SOGC Statement on the Use of Fluconazole during Pregnancy 

Related ObG Topics:

FDA Reviews Fluconazole in Pregnancy

Is Oral Fluconazole Use in Pregnancy Linked to Stillbirths?

Desquamative Vaginitis—How to Recognize and Treat It