Foetal exposure to anaesthesia during pregnancy: anaesthesia-induced neurotoxicity, surgery & anaesthesia conduct

Indications for exposure of pregnant women to anaesthesia include (emergent) maternal non-obstetric surgery (e.g., laparoscopic appendectomy), maternal obstetric surgery (e.g., cervical cerclage) and foetal surgery (e.g., prenatal surgery on the foetus to repair spina bifida). Maternal non-obstetric surgery is the most frequent indication with an incidence of 0.4-1% of pregnant women. In all these cases, the anaesthetic drugs administered to the mother easily cross the placenta and reach the foetus. Foetal brain development is a complex and delicate process which may be disturbed by anaesthetic drugs (referred to as anaesthesia-induced neurotoxicity), but also by maternal surgery and the conduct of anaesthesia (aiming to maintain physiologic maternal homeostasis during anaesthesia). Therefore, the effects of these three factors on foetal brain development were further investigated in this thesis. Anaesthetic drugs and surgery Before starting the preclinical and clinical studies of this thesis, we performed a systematic review and meta-analysis of all studies investigating the effects of general anaesthesia during pregnancy on the neurocognitive development of the foetus. This meta-analysis concluded that anaesthesia-induced neurotoxicity during pregnancy was a consistent finding in preclinical studies, but translation of these results to the clinical situation was limited by several factors. Only one clinical study has been published after completion of this meta-analysis, but this study has several important limitations. The sensitivity analysis of our meta-analysis suggested that neurodevelopmental effects were much smaller in models mimicking typical clinical situations (e.g., realistic durations of exposure to anaesthesia) and applying clinically routine monitoring standards. Therefore, we investigated in the sheep model the neurodevelopmental effects of cumulative durations of prenatal anaesthesia exposure corresponding to approximately 5 and 10 hours in humans and compared this with unexposed sheep. Clinical routine monitoring standards were performed during this anaesthesia for a maternal laparotomy. This study could not find evidence for either neuronal injury or neurobehavioural impairments of the lambs after a cumulative duration of prenatal anaesthesia exposure corresponding to even 10 hours in humans. Luckily, exposure of pregnant women to more than 10 hours of general anaesthesia is required in only 0.5% of pregnant women requiring non-obstetr