Safety of Prenatal Anti‐Infective Use and Offspring Outcomes: A Panoramic Assessment by Indication, Drug Class, and Exposure Characteristics

ABSTRACT

Ensuring safe and effective anti‐infective use during pregnancy is a global priority, yet evidence remains fragmented across heterogeneous clinical contexts and study designs. We thus comprehensively assessed the safety of prenatal anti‐infective exposure and strengthen the evidence base for safer medication. Six databases were searched to include meta‐analyses evaluating prenatal exposure to anti‐infective agents in humans and reporting neonatal outcomes or long‐term offspring outcomes. Overlapping primary studies were quantified using citation matrices, prioritizing the most recent and comprehensive analyses. A total of 138 evidence syntheses comprising 1298 non‐overlapping meta‐analyses were included, covering 127 drug exposures and 109 offspring outcomes. Harmful associations were identified in 160 meta‐analyses, including 51 classified as increased risk and 109 as suspected increased risk. Increased risks supported by at least low‐certainty evidence were identified for several commonly used agents, including macrolides, metronidazole, tetracyclines, sulfonamides, fluconazole, protease inhibitor‐based and zidovudine‐containing antiretroviral regimens, quinine, and chloroquine. Notably, 43% of implicated exposures involved FDA pregnancy category B agent. This panoramic assessment clarifies where existing evidence is relatively robust versus uncertain and identifies drug classes warranting heightened scrutiny. Future research should prioritize indication‐specific, rigorously controlled studies to better disentangle medication‐related risks from those associated with underlying maternal infections.