The safety of oral fluconazole during the first trimester of pregnancy: a systematic review and meta-analysis

BJOG. 2019 Dec;126(13):1546-1552. doi: 10.1111/1471-0528.15913. Epub 2019 Sep 18.

Abstract

Background: Oral fluconazole is used to treat vulvovaginal candidiasis during pregnancy. However, there are concerns regarding the pregnancy outcomes following exposure to fluconazole.

Objectives: To evaluate the pregnancy outcomes associated with exposure to oral fluconazole during the first trimester of pregnancy.

Search strategy: A systematic literature search was conducted to identify relevant studies published from inception until April 2019.

Selection criteria: Relevant English-language citations using the terms oral fluconazole and pregnancy in humans.

Data collection: Two reviewers independently abstracted data and assessed study quality.

Main results: Oral fluconazole use during the first trimester of pregnancy was marginally associated with an increased risk of congenital malformations (odds ratio [OR] 1.09, 95% CI 0.99-1.2, P = 0.088; n = 6 studies), whereas in the subgroup analysis, this association existed only for high-dose users (>150 mg) (OR 1. 19, 95% CI 1.01-1.4, P = 0.039; n = 2). Exposure to fluconazole also increased the risk of heart malformations (OR 1.31, 95% CI 1.09-1.57, P = 0.003; n = 4), cardiac septal defects (OR 1.3, 95% CI 1.1-1.67, P = 0.047; n = 3), and tetralogy of Fallot (OR 3.39 95% CI 1.71-6.74, P < 0.001; n = 2) in the offspring. In addition, exposure to fluconazole was significantly associated with an increased risk of spontaneous abortion (OR 1.99, 95% CI 1.38-2.88, P < 0.001; n = 3).

Conclusions: Oral fluconazole use during the first trimester of pregnancy appears to be associated with heart malformations and spontaneous abortion, but a causal link cannot be proven.

Tweetable abstract: Oral fluconazole during the first trimester of pregnancy may be associated with unfavourable pregnancy outcomes.

Keywords: Antifungal; maternal; neonatal; prenatal.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Abnormalities, Drug-Induced
  • Administration, Oral
  • Antifungal Agents / administration & dosage*
  • Antifungal Agents / adverse effects
  • Candidiasis, Vulvovaginal / drug therapy*
  • Craniofacial Abnormalities / chemically induced*
  • Female
  • Fluconazole / administration & dosage*
  • Fluconazole / adverse effects
  • Humans
  • Patient Safety
  • Pregnancy
  • Pregnancy Trimester, First

Substances

  • Antifungal Agents
  • Fluconazole