Are Vaginal Antimycotics Associated with an Increased Risk for Miscarriage?

BACKGROUND AND PURPOSE:

  • Vulvovaginal candidiasis (VVC) may occur in more than 20% of pregnant women
  • A previous study suggested an increased risk of miscarriage after the use of vaginal-antimycotic agents for vulvovaginal candidiasis
  • Daniel et al. (AJOG, 2018) examined whether risk for spontaneous abortions is increased following first-trimester exposure to vaginal antimycotics

METHODS:

  • Population-based retrospective cohort study
  • Participants: All clinically apparent pregnancies admitted for birth or spontaneous abortion
  • A computerized database of medication dispensation was linked with computerized databases containing information on births and spontaneous abortion
  • Time-varying Cox regression models, adjusted for confounding variables such as mother’s age, hypothyroidism, diabetes mellitus, hypercoagulable or inflammatory conditions, recurrent miscarriage, IUD, ethnicity, tobacco use and the year of admission were used to assess the association

RESULTS:

  • 65,457 pregnancies were included in the study
    • 58,949 (90.1%) ended with birth
    • 6,508 (9.9%) ended with spontaneous abortion
  • Overall, 5% of pregnancies were exposed to vaginal antimycotic medications until the 20th gestational week
    • 4.2% were exposed to clotrimazol
    • 1% were exposed to miconazole
  • Exposure to vaginal antimycotics was not associated with spontaneous abortions as a group
    • Crude hazard ratio (HR) 1.11; 95% CI, 0.96–1.29
    • adjusted HR 1.11; 95% CI, 0.96–1.29
  • Clotrimazole was not associated with increased risk
    • adjusted HR 1.05; 95% CI, 0.89–1.25
  • Miconazole was also not associated with increased risk
    • adjusted HR 1.34; 95% CI, 0.99–1.80
  • Dosage did not impact the findings

CONCLUSION:

  • This study found no evidence that taking antimycotics (clotrimazole and miconazole) during the first trimester is associated with increased risk for miscarriage

Learn More – Primary Sources:

Vaginal antimycotics and the risk for spontaneous abortions

FDA Reviews Fluconazole in Pregnancy

SUMMARY:

Following a Danish study in 2016 by Nielsen et al. (JAMA, 2016), which concluded that fluconazole was associated with miscarriage, the FDA undertook a review to determine the safety of fluconazole in pregnancy. The FDA concluded (October 2019) that 

Based on our reviews of several studies, FDA has determined that the available data do not provide conclusive evidence of an increased risk of miscarriage or stillbirth with a single 150 mg dose of oral fluconazole (Diflucan)

We reviewed the 2016 study cited in this DSC and four additional epidemiological studies

We approved updated prescribing information in 2018 to include all available information on the use of fluconazole in women who are pregnant or breastfeeding

It adequately addresses the potential risk of harm to unborn babies

  •  

CDC 2015 Sexually Transmitted Diseases Treatment Guidelines: Vulvovaginal Candidiasis

Vulvovaginal candidiasis occurs frequently during pregnancy. Only topical azole therapies, applied for 7 days, are recommended for use among pregnant women

  • Imidazoles inhibit the enzyme that converts lanosterol to ergosterol, disrupting the structure and function of the fungal membrane
  • Azole options can be found below in the ObG Related Entry ‘Diagnosis and Treatment of Vulvovaginal Candidiasis’ 

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Learn More – Primary Sources:

Fluconazole (Diflucan): Drug Safety Communication – FDA Evaluating Study Examining Use of Oral Fluconazole (Diflucan) in Pregnancy

ACOG Practice Bulletin 215: Vaginitis in Nonpregnant Patients 

CDC 2015 Sexually Transmitted Diseases Treatment Guidelines: Vulvovaginal Candidiasis

Association Between Use of Oral Fluconazole During Pregnancy and Risk of Spontaneous Abortion and Stillbirth

Use of oral fluconazole during pregnancy and the risk of birth defects

Exposure to fluconazole and risk of congenital malformations in the offspring: A systematic review and meta-analysis 

Fluconazole use and birth defects in the National Birth Defects Prevention Study

SOGC Statement on the Use of Fluconazole during Pregnancy