Trajectory Analysis of Serum Biomarker Concentrations Facilitates Outcome Prediction after Pediatric Traumatic and Hypoxemic Brain Injury

Abstract

Traumatic brain injury (TBI) and hypoxic ischemic encephalopathy (HIE) are leading causes of morbidity and mortality in children. Several studies over the past several years have evaluated the use of serum biomarkers to predict outcome after pediatric brain injury. These studies have all used simple point estimates such as initial and peak biomarker concentrations to predict outcome. However, this approach does not recognize patterns of change over time. Trajectory analysis is a type of analysis which can capture variance in biomarker concentrations over time and has been used with success in the social sciences. We used trajectory analysis to evaluate the ability of the serum concentrations of 3 brain-specific biomarkers – S100B, neuron-specific enolase (NSE) and myelin basic protein (MBP) – to predict poor outcome (Glasgow Outcome Scale scores 3–5) after pediatric TBI and HIE. Clinical and biomarker data from 100 children with TBI or HIE were evaluated. For each biomarker, we validated 2-, 3- and 4-group models for outcome prediction, using sensitivity and specificity. For S100B, the 3-group model predicted poor outcome with a sensitivity of 59% and specificity of 100%. For NSE, the 3-group model predicted poor outcome with a sensitivity of 48% and specificity of 98%. For MBP, the 3-group model predicted poor outcome with a sensitivity of 73% and specificity of 61%. Thus, when the models predicted a poor outcome, there was a very high probability of a poor outcome. In contrast, 17% of subjects with a poor outcome were predicted to have a good outcome by all 3 biomarker trajectories. These data suggest that trajectory analysis of biomarker data may provide a useful approach for predicting outcome after pediatric brain injury.

P3‐193: Serum Neurofilament Light Protein Predicts Clinical Outcome in Traumatic Brain Injury

“…S100B showed similar dynamics as in previous studies with the highest concentrations within 48 hours of admittance to the NICU 25 . Previous studies of S100B in the context of sTBI, have also observed a secondary peak, where the secondary peaks were correlated to secondary injury, however, in the current study, we did not observe any obvious secondary peaks [26][27][28] . It is worth mentioning that the delta value for the secondary peak observed in the previous studies was very small compared with the S100B levels found at day 1.…”

Relation between prognosis and changes of MBP and S100B in premature infants with periventricular leukomalacia

“…S100B cannot penetrate the blood-brain barrier in the normal condition; however, when neuroglial cells undergo necrosis, S100B is leaked and penetrates across the injured blood-brain barrier, increasing its level in serum (Chen et al, 2008). The serum S100B level reflects the degree of damage, and is useful in the evaluation of the therapeutic efficiency of drugs and of the prognosis of the central nervous system (Fishler et al, 1965;Egberts et al, 2008;Murabayashi et al, 2008;Berger et al, 2010;Gyorgy et al, 2011). In this study, the results showed that the S100B level of preterm infants with cerebral white damage 1 day after birth had no significant difference with that of normal preterm infants, and that S100B concentration increased on the 3rd day and peaked on the 7th day; however, with the improvement of body condition, there was an obvious decrease on the 14th day.…”

“…Therefore, serum MBP could reflect brain injury severity, therapeutic efficiency, and prognosis (Egberts et al, 2008;Murabayashi et al, 2008;Gyorgy et al, 2011;Zhou et al, 2013). Berger et al (2010) reported that the detection of S100B and MBP serum concentrations is important for predicting prognosis, and that MBP had an accuracy of 73% and specificity of 61%, and S100B had a sensitivity of 59% and specificity of 100%. Gyorgy et al (2011) also demonstrated that higher S100B and MBP serum levels indicated poorer prognosis.…”

Predicting outcome after childhood brain injury: Figure 1:

“…80 Although associations between increased levels of biomarkers and poorer outcomes may be statistically significant, the specificity and sensitivity of isolated measurements are low. More sophisticated analyses of temporal profiles of biomarkers, 81 multiple profiles of biomarkers 82 and biomarker profiles in combination with clinical data 83 have been proposed. Neurophysiological biomarkers of brain function soon after injury that predict outcome have also been developed, although most of them are research tools and are not in widespread clinical use.…”