Prenatal Exposure to Anxiolytics: A Critical Review on Brain Development and Neurobehavioral Manifestations in...

Anxiety disorders are among the most common mental health conditions affecting women of reproductive age, and a significant proportion of pregnant women experience clinically relevant anxiety symptoms. In some cases, pharmacological treatment may be required to manage severe or persistent symptoms; however, concerns remain regarding the potential impact of prenatal exposure to anxiolytic medications on fetal brain development. The developing nervous system undergoes critical processes during gestation, including neuronal proliferation, migration, and synaptic formation, which may be sensitive to pharmacological influences. This review examines available clinical and preclinical evidence regarding the neurodevelopmental consequences of prenatal exposure to commonly used anxiolytic medications, especially benzodiazepines (BZDs) and azapirones (AZPs). Evidence from observational human studies has shown associations between prenatal exposure to BZDs and certain neonatal and neurodevelopmental outcomes. However, results remain inconsistent and may be influenced by confounding factors, including maternal psychiatric conditions, co-medication use, and environmental variables. In contrast, data on prenatal exposure to AZPs, especially buspirone, are relatively limited, with most of the available evidence coming from small cohorts and preclinical models. Experimental studies provide mechanistic insights suggesting that early-life exposure to anxiolytic agents may influence neurotransmitter systems, neuronal morphology, and behavioral development in offspring. However, translating findings from animal models to the human clinical context remains challenging. Overall, the current literature highlights substantial knowledge gaps regarding dose-dependent effects, critical developmental windows, and long-term neurobehavioral outcomes. Further well-controlled longitudinal and translational studies are needed to clarify the potential implications of prenatal exposure and to support evidence-based clinical decision-making during pregnancy.