Fetal outcomes after maternal exposure to oral antifungal agents during pregnancy: A systematic review and meta-analysis

Int J Gynaecol Obstet. 2020 Jan;148(1):6-13. doi: 10.1002/ijgo.12993. Epub 2019 Nov 5.


Objective: To assess the risk of adverse fetal outcomes after exposure to oral antifungal agents during pregnancy.

Search strategy: PubMed, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched up to October 2018.

Selection criteria: Cohort studies and case-control studies investigating fetal outcomes following maternal exposure to oral antifungal agents.

Data collection and analysis: Two reviewers independently assessed studies for inclusion, assessed risk of bias, and extracted data. Pooled estimates were calculated for the frequency of adverse fetal outcomes.

Main results: Overall, eight cohort studies and one case-control study were included. The oral antifungal agents used during pregnancy were fluconazole and itraconazole. The data indicated that oral fluconazole exposure during pregnancy might slightly increase the risk of congenital heart defects and limb defects relative to the general population; oral itraconazole during pregnancy might increase the risk of eye defects. No difference was found between oral fluconazole/itraconazole exposure and non-exposure in the risk of other birth defects, spontaneous abortion, or stillbirth.

Conclusion: Oral fluconazole or itraconazole may not increase the risk of birth defects. Nonetheless, the risk of congenital heart defects and limb defects after fluconazole exposure and eye defects after itraconazole exposure should be cautiously investigated.

Keywords: Abortion; Birth defects; Fluconazole; Itraconazole; Meta-analysis; Stillbirth.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Abortion, Spontaneous / epidemiology
  • Abortion, Spontaneous / etiology
  • Antifungal Agents / adverse effects*
  • Case-Control Studies
  • Cohort Studies
  • Congenital Abnormalities / epidemiology
  • Congenital Abnormalities / etiology
  • Female
  • Fluconazole / adverse effects*
  • Humans
  • Itraconazole / adverse effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / epidemiology
  • Stillbirth / epidemiology


  • Antifungal Agents
  • Itraconazole
  • Fluconazole