Evaluating Oxidative stress marker F2a-Isoprostanes relations to early life adversity and as a predictor of neurodevelopment in infants and toddlers

Background: Experiencing early life adversity (ELA) and chronic stress activation early in childhood increases the risk for altered developmental trajectories that lead to lifelong impacts on physical and mental health. This results in a toxic stress response,the dysregulation of neuroendocrine, immune and metabolic functions that causes allostatic load and a higher risk for poor health. A major challenge in current pediatric screening practices for identifying toxic stress is the typically use of parent retrospective or child prospective Adverse Childhood Experience (ACEs) questionnaires, which are no better than chance in predicting poor health outcomes. We have proposed that the adaptative processes to ELA converge on mitochondrial function and is measurable in several ways, including the gold standard marker of oxidative stress, F2a Isoprostanes (F2aIsoPs). The aim of this study was to evaluate the relation between F2a-IsoPs measures and child neurodevelopment and how those relations change over critical developmental periods. Methods: In our ongoing Family First longitudinal study, F2aIsoPs were measured from child urine samples collected at 6,12, and 24 months. Maternal adversity was assessed using the ACES questionnaire at 6 and 12months. The Bayley 4 was administered to assess neurodevelopment at all study time points. Results: Maternal ACEs scores were significantly correlated to higher F2aIsoPs levels at 12 months. Elevated infant F2aIsoPs at 6 months were correlated significantly with lower language and motor scores Bayley scores. Assessment of the relation between maternal ACEs on changes in F2aIsoPs levels over the first year of life demonstrated there were significantly different F2aIsoPs trajectories for infants whose mothers endorsed 0, 1 to 2, or 3 or more ACEs. Conclusions: The data indicate that there are specific physiologic contributions of mitochondrial generated oxidative stress to a toxic stress response in young children. A broader approach to pediatric screening for toxic stress predictability may be the incorporation of F2aIsoPs measures in the first two years postnatal.