Serum Panel Identifies Infants With Acute Intracranial Hemorrhage
By Will Boggs MD
NEW YORK (Reuters Health) – A panel of three serum biomarkers accurately identifies infants with acute intracranial hemorrhage after abusive head trauma.
“When we started this research, one of our concerns was that there would not be significant differences in the serum biomarkers between well-appearing infants who had symptoms, such as vomiting, which were the result of brain injury, and infants with the same symptoms, which were the result of a common virus or another etiology which is far more common,” Dr. Rachel Pardes Berger from University of Pittsburgh School of Medicine in Pennsylvania told Reuters Health by email. “Our data demonstrate that the serum biomarker patterns are different when the cause of the symptoms is an acute intracranial hemorrhage.”
Nonspecific symptoms, inaccurate histories from caretakers, and often-normal physical exams contribute to the frequent missed diagnosis of abusive head trauma. Several individual biomarkers have been studied as potential screening tools for acute intracranial hemorrhage in infants at risk of missed abusive head trauma.
Dr. Berger and colleagues used a retrospective cohort of 99 patients followed by a prospective cohort of 599 patients to derive and validate their Biomarkers of Infant Brain Injury Score (BIBIS).
They measured multiple biomarkers simultaneously and rapidly using 2 mcL of serum on the fully automated Ziplex system.
A model containing serum hemoglobin plus three serum biomarkers – matrix metallopeptidase-9 (MMP-9), vascular cellular adhesion molecule-1 (VCAM-1), and neuron-specific enolase (NSE) – provided the greatest predictive value for acute intracranial hemorrhage, with a sensitivity of 95.8% and specificity of 54.9% at a cutoff of 0.182 in the derivation cohort.
In the validation cohort, the BIBIS formula yielded 89.34% sensitivity, 48.0% specificity, 21.3% positive predictive value, and 95.6% negative predictive value for acute intracranial hemorrhage, according to the April 10th JAMA Pediatrics online report.
The model was unable to identify abnormalities other than acute intracranial hemorrhage, including atraumatic abnormalities, chronic intracranial hemorrhage, and isolated skull fracture.
“If a physician suspects abusive head trauma, there really isn’t a role for BIBIS,” Dr. Berger said. “BIBIS is meant to be a ‘point to the brain’ test, in the same way that an AST and ALT are ‘point to the liver’ tests. So when a physician is concerned about the possibility of brain injury as the cause of an infant’s symptoms, then BIBIS can help.”
“If BIBIS is positive, it suggests that neuroimaging (e.g., head CT) would be helpful,” she said. “If that CT were to show an acute hemorrhage, then the possibility of abusive head trauma needs to be strongly considered and additional testing, such as a skeletal survey and dilated eye examination, is needed.”
“With the exception of hemoglobin, the components of BIBIS are not yet available clinically,” Dr. Berger said, “but in the meantime, physicians could consider using PIBIS (The Pittsburgh Infant Brain Injury Score).”
She added, “Abusive head trauma is the leading cause of death from traumatic brain injury in infants and the leading cause of death from physical abuse in the U.S. Despite multiple efforts at education of physicians about early identification of abusive head trauma in its mild form, clinical judgment has been consistently about 70% sensitive over at least the last 15 years (so about 30% of cases are missed using clinical judgment alone).”
“Multiple efforts at primary prevention have also not been successful,” she explained. “BIBIS and PIBIS offer objective clinical tools which have the potential to improve early diagnosis of abusive head trauma which is critical for decreasing morbidity and mortality.”
“Future studies will focus on combining BIBIS with the Pittsburgh Infant Brain Injury Score (PIBIS) to determine whether a combined score is more accurate than either score alone,” the researchers note. “Future research must also focus on bringing brain biomarker measurement from the bench to the bedside as it relates to commercialization of the Ziplex device.”
“Finally,” they write, “while our focus is development of an accurate screening tool, for BIBIS to be successful in clinical practice, physicians will need to know when to use it. Developing and evaluating strategies to help physicians do this is an important future step.”
JAMA Pediatr 2017.
Reuters Health Information © 2017
Cite this article: Serum Panel Identifies Infants With Acute Intracranial Hemorrhage – Medscape – Apr 11, 2017.