Understanding how anaesthetic management during elective C-section influences methylation in these genes could reveal important insights into the epigenetic origins of neonatal and later-life health outcomes.

Currently, there is limited data on the relationship between anaesthesia exposure during C-section and neonatal epigenetic modifications.

The intrauterine environment plays a crucial role in shaping the long-term health and development of the offspring. Epigenetic modifications, especially DNA methylation, are fundamental mechanisms by which environmental exposures during the perinatal period can influence gene expression without altering the DNA sequence itself. These epigenetic changes are dynamic and sensitive during critical developmental windows especially childbirth. Anaesthesia, administered during caesarean section (C-section), exposes the foetus to various pharmacological agents and physiological changes. Both general and spinal anaesthesia may alter foetal oxygenation, stress hormone levels and immune responses, potentially influencing epigenetic programming. Although spinal anaesthesia is widely preferred due to its safety profile, factors such as local anaesthetic dose, maternal hemodynamic fluctuations with use of vasopressors/vasodilators and adjunct medications could have possible effects on the foetus. Similarly, general anaesthesia involves multiple agents that may impact foetal neurodevelopment and immune function. Emerging evidence suggests that neonatal DNA methylation patterns in genes related to stress response (e.g., NR3C1), neurodevelopment (e.g., BDNF), social bonding (e.g., OXTR), inflammation (e.g., IL6), and epigenetic regulation (e.g., DNMT3A) can be altered by perinatal exposures. Understanding how anaesthetic management during elective C-section influences methylation in these genes could reveal important insights into the epigenetic origins of neonatal and later-life health outcomes.

We plan to conduct this observational study aims to fill this gap by investigating associations between clinical anaesthesia parameters and site-specific DNA methylation in key neonatal genes, thus providing groundwork for future translational research in perinatal anaesthesia epigenetics.