Sexual Dimorphisms in Neurodevelopment May Affect TBI Recovery in Pediatric Patients

Traumatic brain injury (TBI) is a leading cause of death and disability, with broad heterogeneity in recovery outcomes particularly noted in pediatric patients. Children post-TBI are vulnerable to aberrant neurodevelopment, specifically in structural and functional neural networks as they correlate with cognitive, behavioral, and motor function outcomes. Consideration for sex as a biological variable which innately influences neuroanatomy, neurodevelopment, and functional organization may elucidate risk factors for negative outcomes in pediatric TBI. For example, TBI damage in sexually dimorphic neural structures and networks may explain deficits in social cognition, working memory, as well as internalizing and externalizing behaviors, which differentially impact the quality of life in male versus female TBI patients. However, characterization of sex in conjunction with developmental patterns in normal and injured pediatric populations is limited due to small sample sizes, the low representation of females, a lack of longitudinal data, and the utilization of analyses that are not sensitive enough to detect subtle differences in TBI pathologies and recovery between the sexes. This review aims to analyze and synthesize the existing evidence regarding the influence of sex on the developmental trajectories of neuroanatomical structures, white and gray matter compartments, and the network disruptions that align with sex-specific functional recovery outcomes following pediatric TBI. The delineation of these sex influences will facilitate better precision-based medicine approaches to improve patient outcomes.