Risk of congenital malformations and miscarriages following maternal use of oral fluconazole during the first trimester of pregnancy: a systematic review and meta-analysis

IF 7.7 1区医学 Q1 PUBLIC, ENVIRONMENTAL & OCCUPATIONAL HEALTH

European Journal of Epidemiology Pub Date : 2024-12-11 DOI:10.1007/s10654-024-01177-7

Mathilde Latour, Catherine Vauzelle, Elisabeth Elefant, Florence Tubach, Stephanie Padberg, Brigitte Martin, Kristen Joseph-Delaffon, Agnès Dechartres, Benoit Marin

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引用次数: 0

Abstract

The risks related to fluconazole use during the first trimester of pregnancy (T1) remain controversial. The aims of this systematic review and meta-analysis were to assess the association between oral fluconazole during T1 and major congenital malformations (MCM) overall and by subtype, minor malformations and miscarriages.

We searched MEDLINE, EMBASE, Cochrane, ICTRP and ClinicalTrials.gov from inception to 02/12/24. Randomized controlled trials and observational studies were included. ROBINS-I was used for risk of bias assessment. Both fixed- and random-effects models meta-analyses were performed. GRADE was used to assess the certainty of the evidence.

Among 1403 references, nine observational studies were included (3,764,897 pregnancies, including 116,425 exposed to fluconazole). The association between any fluconazole use during T1 and overall MCM was significant when combining crude estimates (ORc 1.18, 95%CI (1.08–1.29), I² 23%, seven studies), but not when combining adjusted estimates (ORa 1.02, 95%CI (0.98–1.07), I² 0%, six studies). Results were consistent for cumulative dose of fluconazole. In sensitivity analyses considering only studies with a valid definition of MCM, the association between fluconazole > 150 mg and overall MCM remained significant when combining adjusted estimates. For the subtypes of MCM (cardiac, genito-urinary, musculoskeletal) we found no significant association. A significant association was found between fluconazole use and miscarriages (ORa 1.60, 95% CI (1.06–2.42).

Fluconazole use during T1 does not significantly increase the risk of MCM overall or by subtype when considering adjusted estimates. However, potential risks, particularly at cumulative doses greater than 150 mg which show a potential association with MCM, deserve much attention.

PROSPERO Registration The protocol was registered on the 23rd September 2021 (registration number: CRD42021274003).

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来源期刊

European Journal of Epidemiology 医学-公共卫生、环境卫生与职业卫生

CiteScore

21.40

自引率

1.50%

发文量

109

审稿时长

6-12 weeks

期刊介绍： The European Journal of Epidemiology, established in 1985, is a peer-reviewed publication that provides a platform for discussions on epidemiology in its broadest sense. It covers various aspects of epidemiologic research and statistical methods. The journal facilitates communication between researchers, educators, and practitioners in epidemiology, including those in clinical and community medicine. Contributions from diverse fields such as public health, preventive medicine, clinical medicine, health economics, and computational biology and data science, in relation to health and disease, are encouraged. While accepting submissions from all over the world, the journal particularly emphasizes European topics relevant to epidemiology. The published articles consist of empirical research findings, developments in methodology, and opinion pieces.