Fundamentals of fetal toxicity relevant to sevoflurane exposures during pregnancy.

Over the last three decades, advances in medical and surgical techniques have proven life saving and life-improving for young children. Consequently, early and repeated exposure to general anesthetics in childhood has increased. However, accumulating evidence suggests that general anesthetics may be neurotoxic in children. Of particular concern is the neurotoxicity fetuses may suffer from maternal exposure to sevoflurane during surgeries and fetal intervention procedures performed during the second trimester, as this can cause neurodevelopmental impairment in offspring. In this review we demonstrate that the pathology associated with fetal toxicity resulting from exposure to sevoflurane during pregnancy involves oxidative stress, neuroinflammation, neuroapoptosis, and alteration of synaptic properties. The mechanisms remain to be elucidated, but may include increased tau protein phosphorylation and abnormal methylation. These findings highlight the need for a global and comprehensive understanding of the potential neurotoxicity of anesthetic exposure in fetuses and its long-term effects.