Blood Biomarkers for Evaluation of Perinatal Encephalopathy

Abstract

Recent research in identification of brain injury after trauma shows many possible blood biomarkers that may help identify the fetus and neonate with encephalopathy. Traumatic brain injury shares many common features with perinatal hypoxic-ischemic encephalopathy. Trauma has a hypoxic component, and one of the 1st physiologic consequences of moderate-severe traumatic brain injury is apnea. Trauma and hypoxia-ischemia initiate an excitotoxic cascade and free radical injury followed by the inflammatory cascade, producing injury in neurons, glial cells and white matter. Increased excitatory amino acids, lipid peroxidation products, and alteration in microRNAs and inflammatory markers are common to both traumatic brain injury and perinatal encephalopathy. The blood-brain barrier is disrupted in both leading to egress of substances normally only found in the central nervous system. Brain exosomes may represent ideal biomarker containers, as RNA and protein transported within the vesicles are protected from enzymatic degradation. Evaluation of fetal or neonatal brain derived exosomes that cross the blood-brain barrier and circulate peripherally has been referred to as the “liquid brain biopsy.” A multiplex of serum biomarkers could improve upon the current imprecise methods of identifying fetal and neonatal brain injury such as fetal heart rate abnormalities, meconium, cord gases at delivery, and Apgar scores. Quantitative biomarker measurements of perinatal brain injury and recovery could lead to operative delivery only in the presence of significant fetal risk, triage to appropriate therapy after birth and measure the effectiveness of treatment.

Exposure to intrauterine inflammation alters metabolomic profiles in the amniotic fluid, fetal and neonatal brain in the mouse

“…In the current study, we sought to identify metabolites that may provide insight regarding the mechanisms underlying the pathogenesis of fetal brain injury and/or lead to biomarker discovery. Over the past few decades there has been great interest in discovering novel biomarkers of various perinatal neurological injuries [ 25 , 26 ]. Currently, reliable biomarkers that can accurately predict inflammation-induced fetal brain injury do not exist.…”

A review of the clinical utility of serum S100B protein levels in the assessment of traumatic brain injury

“…Thus, S100B may represent a similar surrogate marker of injury for outcome prediction and monitoring to detect secondary injuries as in the adult population. Other areas where S100B might provide important information about cerebral injuries are in the assessment of preterm newborns [163] and following hypoxic-ischemic injuries [53], recently reviewed respectively.…”

A Controversial Medicolegal Issue: Timing the Onset of Perinatal Hypoxic-Ischemic Brain Injury

“…Besides mere recognition of abnormal patterns and support to definite diagnosis, in fact, clinicians show interest in neuroimaging as it can lead to an earlier assessment of disease and even prognosis [ 89 , 90 ]. Dealing with the first issue in someone's opinion, the hypoxic injury pattern on MRI is not diagnostic for 7–14 days [ 91 ], as perinatal brain lesions are at their most visually obvious state between 1 and 2 weeks from delivery [ 92 ]. This fact could be an important limitation in those cases characterized by a shorter survival interval [ 93 ].…”