The safety of oral fluconazole during the first trimester of pregnancy: a systematic review and meta‐analysis. (18th September 2019)

• Record Type: Journal Article
• Authors: Zhang, Z; Zhang, X; Zhou, Y‐y; Jiang, C‐m; Jiang, H‐y
• Is Part Of: BJOG. Volume 126:Number 13(2019)
• Page Start: 1546
• Page End: 1552
• Publication Date: 2019-09-18
• Subjects: Antifungal -- maternal -- neonatal -- prenatal; Obstetrics -- Periodicals; Gynecology -- Periodicals; 618
• DOI: 10.1111/1471-0528.15913
• Languages: English
• ISSNs: 1470-0328

Abstract

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