Biomarkers, Genetics, and Epigenetic Studies to Explore the Neurocognitive Effects of Anesthesia in Children

Exposure to commonly used anesthetic agents causes widespread neuronal degeneration in the developing mammalian brain and has been shown to impair neurodevelopment in a variety of newborn vertebrate animal species. Although retrospective studies have suggested an association between anesthesia exposure in childhood and subsequent neurodevelopmental abnormalities, a causal relationship in humans has yet to be demonstrated. Unfortunately, translation of findings from bench to bedside is limited by several factors and histologic assessment in healthy children following exposure to anesthesia is not possible. Therefore, to prove that anesthesia-induced neurotoxicity occurs in humans, alternative approaches are necessary. Here we present the summary of a focus group discussion regarding the utility of biomarkers in translational studies of anesthetic neurotoxicity as part of The 2016 Pediatric Anesthesia NeuroDevelopmental Assessment (PANDA) Symposium at Columbia University Medical Center. The experts agreed that defining intermediate phenotypes using advanced neuroimaging as a biomarker is a highly feasible and reasonable modality to provide new insights into the deleterious effects of anesthetic exposure in the developing human brain and could illuminate a viable investigative path forward. Ultimately, well-defined intermediate phenotypes may allow us to fully understand the neurodevelopmental impact of anesthesia-induced neurotoxicity and permit us to develop the safest and most effective anesthetic strategies for the infants and children we care for.