NEW YORK (360Dx) – Researchers at Children's Hospital of Pittsburgh of the University of Pittsburgh Medical Center, and the University of Pittsburgh School of Medicine have developed a blood-based test that has demonstrated 90 percent sensitivity in a study in identifying infants who have had bleeding in the brain resulting from abusive head trauma, more commonly called shaken baby syndrome.
In collaboration with Axela, the researchers came up with their test, described in a study published Monday in JAMA Pediatrics, leveraging three serum biomarkers —matrix metallopeptidase-9, neuron-specific enolase, and vascular cellular adhesion molecule-1. The test, they said, was able to detect acute intracranial hemorrhage due to abusive head trauma about 90 percent of the time compared to 70 percent with clinical judgement, and with a specificity of 48 percent.
In the study, the scientists said that while 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 US, diagnosing the condition has been challenging because caretakers may give inaccurate histories. Infants can also present with nonspecific symptoms, such as vomiting, and physical examinations can appear to be normal.
As a result, misdiagnosis is common and about 30 percent of abusive head trauma diagnoses are missed.
The researchers used binary logistic regression to develop a multivariable model incorporating the three biomarkers and hemoglobin. Multiplex biomarker measurements were done using Flow-Thru microarray technology on Axela's Ziplex system, a fully automated multiplex platform. The resulting model was then tested at the Children's Hospital of Pittsburgh UPMC; Primary Children's Hospital in Salt Lake City; and Lurie Children's Hospital in Chicago.
The multivariate model, called Biomarkers for Infant Brain Injury Score, was applied prospectively to 599 patients with a mean age of 4.7 months. The model, the researchers said, was not sensitive or specific for atraumatic brain abnormalities, isolated skull fractures, or chronic intracranial hemorrhage.
The test is not meant to replace the judgement of physicians in diagnosing shaken baby syndrome, said the paper's senior author Rachel Berger in a statement. "Rather, we believe that it can supplement clinical evaluation, and in cases where symptoms may be unclear, help physicians make a decision about whether an infant needs brain imaging."
Berger is also chief of the Child Advocacy Center at Children's Hospital and professor of pediatrics at the Pitt School of Medicine.
The researchers stressed that the test is not meant to diagnose shaken baby syndrome, and added that in developing their test, their goal was to create one with high sensitivity, rather than maximizing accuracy, "since missing a diagnosis has more serious consequences than performing brain imaging in babies without the condition."
As part of their future work, the team is developing and evaluating strategies to aid physicians in how to use the test.
Berger, the University of Pittsburgh, and Axela have filed a joint US patent on the technology.