Sex differences in neurodevelopmental abnormalities caused by early-life anaesthesia exposure: a narrative review

Exposure to anaesthetic drugs during the fetal or neonatal period induces widespread neuronal apoptosis in the brains of rodents and non-human primates. Hundreds of published preclinical studies and nearly 20 clinical studies have documented cognitive and behavioural deficits many months or years later, raising the spectre that early life anaesthesia exposure is a long-term, perhaps permanent, insult that might affect the quality of life of millions of humans. Although the phenomenon of anaesthesia-induced developmental neurotoxicity is well characterised, there are important and lingering questions pertaining to sex differences and neurodevelopmental sequelae that might occur differentially in females and males. We review the relevant literature on sex differences in the field of anaesthesia-induced developmental neurotoxicity, and present an emerging pattern of potential sex-dependent neurodevelopmental abnormalities in rodent models of human infant anaesthesia exposure.