State of the Science of Pediatric Traumatic Brain Injury: Biomarkers and Gene Association Studies

Abstract

Objectives Our objective is to review the most widely used biomarkers and gene studies reported in pediatric traumatic brain injury (TBI) literature, to describe their findings, and to discuss the discoveries and gaps that advance the understanding of brain injury and its associated outcomes. Ultimately, we aim to inform the science for future research priorities. Data sources We searched PubMed, MEDLINE, CINAHL, and the Cochrane Database of Systematic Reviews for published English language studies conducted in the last 10 years to identify reviews and completed studies of biomarkers and gene associations in pediatric TBI. Of the 131 biomarker articles, only 16 were specific to pediatric TBI patients, whereas of the gene association studies in children with TBI, only four were included in this review. Conclusion Biomarker and gene attributes are grossly understudied in pediatric TBI in comparison to adults. Although recent advances recognize the importance of biomarkers in the study of brain injury, the limited number of studies and genomic associations in the injured brain has shown the need for common data elements, larger sample sizes, heterogeneity, and common collection methods that allow for greater understanding of the injured pediatric brain. By building on to the consortium of interprofessional scientists, continued research priorities would lead to improved outcome prediction and treatment strategies for children who experience a TBI. Implications for nursing research Understanding recent advances in biomarker and genomic studies in pediatric TBI is important because these advances may guide future research, collaborations, and interventions. It is also important to ensure that nursing is a part of this evolving science to promote improved outcomes in children with TBIs.

Best Practices for Obtaining Genomic Consent in Pediatric Traumatic Brain Injury Research

“…The arduous process of enrollment in all TBI studies and particularly in pediatric TBI becomes especially problematic in the context of molecular genomic research. Without recruitment of a sufficient number of participants into sample repositories (biobanks), studies may lack sufficient power to detect statistically significant relationships between biological markers and clinical outcomes, delaying advances in precision health (Reuter-Rice, Eads, Boyce, & Bennett, 2015). Moreover, recruitment of large numbers of cases into biobanks promotes generalizability of findings to the clinical population of interest as well as fuels ongoing discovery by supporting secondary analysis and data sharing.…”

“…Biobanks are important because evidence suggests that some biomarkers may predict recovery or reflect pathological processes that could be targeted therapeutically (Au & Clark, 2017). Unfortunately, existing data is largely limited to adult studies and the state of the science lags behind for pediatric TBI (Reuter-Rice et al, 2015). Indeed, two recent literature reviews found pediatric-specific evidence was grossly underrepresented with biomarkers in pediatric TBI cases being examined in only 16 of 131 (Reuter-Rice et al, 2015) and 16 of 7,150 (Daoud et al, 2014) publications.…”

“…Unfortunately, existing data is largely limited to adult studies and the state of the science lags behind for pediatric TBI (Reuter-Rice et al, 2015). Indeed, two recent literature reviews found pediatric-specific evidence was grossly underrepresented with biomarkers in pediatric TBI cases being examined in only 16 of 131 (Reuter-Rice et al, 2015) and 16 of 7,150 (Daoud et al, 2014) publications. Both literature reviews searched multiple databases to identify studies of biomarkers and gene association in pediatric TBI.…”

“…The review conducted by Daoud et al (2014) did not limit the search to date of publication and excluded review articles. However, the review conducted by Reuter-Rice et al (2015) limited the scope to all papers (reviews and data-based) published in the last 10 years focusing on children aged 18 years or younger who were hospitalized. Due to these differences in search criteria, there was little overlap in the articles cited, with only six of the 16 papers included both reviews.…”

The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury

“…Although genetic studies in pediatric TBI are still in their infancy, there is evidence that genetic factors may exist, such as the potential role of the apolipoprotein E ( APOE ) gene in TBI outcome (Bennett, Reuter-Rice, & Laskowitz, 2016; Kurowski, Martin, & Wade, 2012; Reuter-Rice, Eads, Berndt, & Bennett, 2015). A more complete understanding of the relationship of CV to the mechanism by which APOE polymorphisms influence functional outcome in this setting may have therapeutic significance.…”