By Nicole R. Bush and Kirstin Aschbacher, JAMA Pediatrics, November 4, 2019
Evidence of an association between early-life adversity and heightened risk of chronic disease in adulthood has been found, but the optimal biomarkers for identifying vulnerable or resilient individuals remain unclear. Global trends, including widening socioeconomic disparities, the refugee crises, and climate change, increasingly sculpt trauma exposure and call for scalable early-risk identification and treatment strategies. Pediatricians often serve on the frontline of early identification and treatment of at-risk children, intervening during crucial windows of opportunity to prevent longer-term bioembedding that confers risk of disease across the life course. However, problems of scale need solutions that scale, which is one reason why the discoveries by Rasmussen et al, reported in this issue, represent a promising step forward. Using high-quality assessments of multidomain, multireporter adversity exposure, these investigators present prospective, longitudinal evidence from a large, socioeconomically diverse sample that soluble urokinase plasminogen activator receptor (suPAR) may be a useful immune biomarker of early-life adversity, having a stronger and more exposure-specific association than current clinical markers, such as C-reactive protein. This type of rigorous epidemiologic “big data” work, complemented with “deep data,” will accelerate biomarker discovery for clinical diagnosis and treatment of early risk and resilience profiles and provide the foundation for precision medicine strategies in pediatrics.
Large data sets, including this study of suPAR and beyond, will be crucial to the identification of novel markers with broad population relevance. As the intersection of omics with artificial intelligence increasingly enables biomarker discovery and strong predictive algorithms, we have a previously unforeseen opportunity to transform the treatment of trauma and its adverse effects. This data-driven trend is already increasingly affecting various domains of medicine, including advancing diagnoses in pediatrics.
Nonetheless, to progress from markers to biologically informed treatments, we must go deeper, elucidating for whom, under what circumstances, and by what mechanisms trauma promotes inflammation. Through thoughtful study design, the data in the study by Rasmussen et al show how not all stress exposures are equally associated with physiologic markers. Rather, from the perspective of the immune cell, trauma’s potency is modulated by the timing, severity, and frequency of the trauma. Specifically, suPAR levels were significantly higher among individuals who experienced early-life exposure to stress and violence or long-term exposure during early childhood and adolescence, particularly for domestic violence and multiple violent events. That childhood events (before 12 years of age) more so than events that occur during adolescence were associated with inflammatory markers at 18 years of age provides support for sensitive periods for biological embedding of trauma, which likely occurs, in part, through epigenetic changes.
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