E-cigarette aerosol-induced neurotoxicity during early brain development: mechanisms and outcomes

Electronic cigarettes (e-cigs) use has risen among youth, and sustained use during reproductive years increases the likelihood of consumption during gestation, bringing concerns as to neurodevelopmental consequences. Although often perceived as safer than combustible cigarettes, mounting evidence confirms neurotoxic effects of nicotine in e-cig aerosols, and indicates that components other than nicotine can be detrimental to the developing brain. This state-of-the-art review summarizes evidence that e-cig aerosol exposure interferes with several physiological processes during early stages of brain development. In animal models, negative effects include blood-brain-barrier disruption, neuroinflammation and oxidative stress disbalance, altered epigenetic processes, and deregulated gene expression. Those have been associated with cognitive deficits and behavioral alterations that model neuropsychiatric disorders later in live. Cohort studies have linked prenatal e-cig exposure to a higher likelihood of preterm birth. However, results concerning small-for-gestational-age and low birth weight remain inconsistent. Recent data point to neonate nicotine withdrawal and poor motor maturity. Future expansion of cohorts to include school-aged children and adolescents will enable the investigation of behavioral, cognitive, and mood outcomes. In conclusion, while additional research is needed to fully estimate effects of e-cigs, data strongly suggest that exposure poses a potential hazard to the developing brain. IMPACT: Summarizes current translational preclinical and clinical evidence on the potential risks of maternal e-cigs use for offspring brain development. Confirms the detrimental impact of nicotine and demonstrates that non-nicotine components of e-cig aerosols contribute to adverse effects of e-cigs aerosols in the offspring brain function and behavior. Highlights the need for comprehensive, multifaceted studies that account for the complexities of e-cig aerosols exposure during sensitive periods of brain development to fully understand e-cigs risks and better protect future generations.