Derivation and Validation of a Serum Biomarker Panel to Identify Infants With Acute Intracranial Hemorrhage

Abstract

IMPORTANCE Abusive head trauma is the leading cause of death from physical abuse. Missing the diagnosis of abusive head trauma, particularly in its mild form, is common and contributes to increased morbidity and mortality. Serum biomarkers may have potential as quantitative point-of-care screening tools to alert physicians to the possibility of intracranial hemorrhage. OBJECTIVE To identify and validate a set of biomarkers that could be the basis of a multivariable model to identify intracranial hemorrhage in well-appearing infants using the Ziplex System. DESIGN, SETTING, AND PARTICIPANTS Binary logistic regression was used to develop a multivariable model incorporating 3 serum biomarkers (matrix metallopeptidase-9, neuron-specific enolase, and vascular cellular adhesion molecule-1) and 1 clinical variable (total hemoglobin). The model was then prospectively validated. Multiplex biomarker measurements were performed using Flow-Thru microarray technology on the Ziplex System, which has potential as a point-of-care system. The model was tested at 3 pediatric emergency departments in level I pediatric trauma centers (Children'

24 vs. 72 hours of hypothermia for pediatric cardiac arrest: A pilot, randomized controlled trial

“…For example, a threshold of biomarker concentrations may prove useful in determining eligibility for neuroprotective therapy trials or to optimize the dose and/or duration of neuroprotective therapy being tested or provided clinically. Additionally, combining biomarkers with clinical or other variables in a validated panel could noticeably strengthen associations and thus confidence as a clinical tool 38,39 .…”

Abusive Head Trauma in Infants and Children

“…18,19 Additionally, early work using serum biomarkers to identify acute intracranial hemorrhage has shown promise in identifying infants with nonspecific clinical symptoms who warrant neuroimaging. 20 Although these diagnostic advancements show significant promise, their application to current-day pediatric practice is premature.…”

A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

“…Future studies will aim to determine if development affects the baseline or increase in mediators of blood brain barrier opening. Matrix metalloproteiniase-9 is a biomarker for intracranial hemorrhage, which is common in abusive head trauma ( Berger et al, 2017 ). Inherent age-dependent differences in the composition of the extracellular matrix, baseline abundance of enzymes that degrade it, or age-dependent upregulation of extracellular matrix enzymes after hemorrhage and seizure may be key to the extensive spreading of damage in “toddlers” but not in “infants”.…”

“…Patients with severe TBI often have seizures, but if it not known if seizures drive the tissue damage or if they are a symptom of the tissue damage. The efficacy of peripheral serum biomarkers of neuronal damage (neuron specific enolase) and hemorrhage (matrix metalloproteinases) to indicate hemispheric damage at 24 h post-injury is also being tested ( Berger et al, 2017 ; Costine et al, 2012 ; Price et al, 2018 ; Price et al, 2019 ).…”