Abstract

The aim of this narrative review was to summarize the current evidence on the safety of systemic antifungal agents during pregnancy and to provide a state-of-the-art overview of their rational use in this setting. A comprehensive literature search was conducted to identify articles published between January 1, 2016, and December 31, 2025, including newly approved agents. We concluded that most available data focus on first trimester exposure, whereas evidence for second- and third-trimester use remains limited. Amphotericin B remains the first-line agent for many invasive fungal infections during pregnancy, owing to decades of clinical experience and the absence of consistent evidence of teratogenicity. In contrast, systemic azoles, particularly fluconazole at higher doses and during early pregnancy, have been associated with increased risks of miscarriage and congenital anomalies. Echinocandins and newer antifungal agents, including oteseconazole, ibrexafungerp, and rezafungin, are not recommended during pregnancy because of limited human data and evidence of teratogenicity from animal studies. Overall, the use of systemic antifungal therapy during pregnancy requires an individualized, risk–benefit approach, with careful consideration of gestational age, infection severity, and available safety data. Ongoing post-marketing surveillance and prospective studies are needed to better guide evidence-based management of fungal infections in pregnant patients.

Key words: Antifungal Safety; Fetal outcomes; Pregnancy; Systemic fungal infections; Teratogenicity