Researchers move forward with biomarker test to uncover babies' brain injury
April 18, 2017 12:00 AM
By Jill Daly / Pittsburgh Post-Gazette
Emergency rooms see many babies, for many reasons. There’s a fever, a seizure, an accident, vomiting and diarrhea. There could be fussiness, lethargy or problems with feeding.
Many infants are easily treated and sent home, but doctors say some of these same little patients may show up next time with a brain injury caused by abuse — one that leads to permanent disability or death.
Sorting out which babies have hidden brain trauma from abuse isn’t easy, if they seem relatively well when brought into the hospital with any in a list of common symptoms.
At Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine, researchers have created a blood test to detect bleeding in the brain that may have resulted from abusive head trauma — sometimes called shaken baby syndrome. They published an explanation of how the test was developed in last week’s JAMA Pediatrics journal.
“This is for those instances where they look well,” said lead author Rachel Berger, chief of the Child Advocacy Center at Children’s. A physician who also holds a master’s in public health, Dr. Berger said good pediatric emergency room doctors generally use their clinical judgment to detect 70 percent of the cases of acute intracranial hemorrhage. Imaging with ionizing radiation then can confirm the condition.
But because radiation isn’t good for babies’ brains, the decision to scan isn’t taken lightly.
“This gives about 90 percent sensitivity with a blood test,” Dr. Berger said. It comes with both false negative and false positive results but lowers the number of babies who are sent on to have a CT scan to make a definitive diagnosis, she said. She pointed out that the test itself doesn’t diagnose abuse: A doctor must find out the cause of the bleeding.
To develop the formula — called the Biomarkers for Infant Brain Injury Score — researchers used blood serum from 99 babies 30 days to 364 days old, which had been stored in a databank at the Safar Center for Resuscitation Research at Pitt.
Then the study used the tool on blood samples from 599 babies in that age group brought in by a parent or caregiver to one of three hospitals with concerning symptoms. They had no fever, no history of trauma and looked well — scoring high on a scale that describes how alert and functioning the infant seems to be. However, they did have at least one symptom from the following: vomiting without diarrhea, alarming events (such as extensive coughing or gagging, turning blue, periods of no breathing), soft tissue swelling of the scalp, bruising and other symptoms such as lethargy, fussiness or poor feeding.
The three-biomarker panel, used with a sample of hemoglobin in the test, is the result of years of research following the 2001 discovery that biomarkers can be used to detect blood in the brain, Dr. Berger said. Much of the research, based on children with severe injury, was done at the Safar Center, she added. The automated testing system was developed by Axela, a Canadian molecular diagnostics company.
“Most babies who are vomiting have a bug,” Dr. Berger said. However, between 2 and 4 percent of those babies have bleeding in their brain.
“Because they have acute blood in their head, they get really fussy. You don’t want to miss that small percent who have blood in their brain.”
The test takes about 45 minutes, she said, and uses less than a drop of blood.
“It’s a new test where there’s no test,” she said. “The current standard test is clinical judgment.” She said many steps still have to be taken to get BIBIS into clinical practice.
“It’s a long way before it’s used in the ER setting,” she said.
“If you talk to pediatric ER doctors, they’ll tell you missing child abuse is one of the things they fear in their career,” she said, because it could happen to the infant again and end in death.
Finding a test for bleeding in infants’ brains is important, said Jennifer Preiss, internist and pediatrician with Allegheny Health Network, who is not involved in the research.
“It’s pretty important in terms of outcomes, being able to sort out who will [get worse] and require intervention and who can be treated less intensively. Also, when can they be discharged from a general ward, if everything looks good.”
A tool that would define and score the possibility of bleeding in the brain would be important in the emergency room, Dr. Preiss said.
It could determine which child would need to go to the intensive care unit, she said.
If bleeding is not addressed, Dr. Preiss said, “They can go on to have extreme swelling and brain damage in the long term.” She said if it’s not taken care of immediately it can cause stroke-like problems, such as weakness on one side or vision loss on one side. Neurosurgery might be needed.
“It’s a fascinating study,” she said, “but it’s very important for emergency room physicians,” to decide what to do with babies who appear well but may have hidden dangerous bleeding.
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