The window to assess newborns for hypoxic ischemic encephalopathy (HIE) is short. Neonatal teams must act within the first few hours of life to plan appropriate intervention.
Currently, a neurological exam is the only tool for assessing the encephalopathy clinical severity of babies following a perinatal ischemic insult – but these exams are not definitive in newborns and capture only a snapshot of their often-fluctuating condition.
Recent research shows that continuous electroencephalogram (EEG) monitoring can help neonatal teams assess newborns more objectively and effectively. Both background EEG and brain network activity aid grading of HIE severity and even predict future outcomes.
Lina Chalak, M.D., Division Chief of Neonatology at Children’s Medical Center Dallas, part of Children's HealthSM, and Professor at UT Southwestern, led much of this research in her lab and sees it as the beginning of a new era of neurocritical care.
“The knowledge we’re building today will enable timely, individualized care for infants based on how their brain is actually functioning, not just how they look from the outside,” she says.
Testing a user-friendly EEG platform
Today, continuous EEG monitoring at bedside requires a trained neurologist to interpret the data which might not be available at all hospitals. But “user-friendly” EEG is on the horizon.
In one recent study, Dr. Chalak’s team used a prototype platform in collaboration with scientists in Helsinki that summarizes background EEG in a simple score that any team member can understand at a glance. The platform uses advanced technology to analyze the EEG data, and prior research showed the platform identifies features 92% as accurately as human experts. The output score ranges from 0 to 100, and the platform’s developers call this measurement ‘brain state of newborn’ (BSN).
“Our new study proved BSN can reliably identify newborns across the HIE spectrum (no insult, mild, moderate and severe) and within the short timeframe required to start interventions says,” Dr. Chalak.
The team also compared BSN scores recorded at birth to developmental abnormalities the children exhibited at age 2. They found that babies with scores higher than 85 are less likely to develop abnormalities, while those with lower scores are more likely.
“With BSN we can break down multiple barriers – bringing EEG to the bedside, assessing severity with objective data and predicting outcomes,” Dr. Chalak says.
Going beyond background EEG
BSN uses background EEG, which provides a general sense of brain function – but doesn’t measure the wealth of network activity occurring across the brain.
Another study in Dr. Chalak’s lab delved into network activity and found that, like BSN, it also fluctuates according to HIE severity. The study focused on EEG amplitudes and correlations across specific cortical areas scientifically known as phase amplitude coupling or PAC – may be most useful in practice. Change in amplitude is easy to see and doesn’t require a calculation at bedside. Correlations are valuable because they indicate how information from the neuronal firings is being decoded to internal regions of the brain.
“The nature of those correlations may also suggest future problems with memory and cognition – enabling us to plan targeted therapy for a bright future,” Dr. Chalak says.
In addition, brain network activity confirms that HIE severity exists on a continuum rather than in hard-edged categories.
“In other words, a ‘mild’ case of HIE (although not studied in the past trials) isn’t free from danger. The brain can be struggling in ways we don’t see, and the status can easily worsen,” says Dr. Chalak.
Combining EEG with neurological exams
In the future, Dr. Chalak expects objective measures like EEG will accompany the neurological exam, not replace it. In fact, she recently completed a study that shows assessing newborns with a combination of an exam and EEG is the best way to predict long-term outcomes.
The team found that combining EEG data with exam findings predicted death or disability by age 2 more accurately than using any of these methods alone or in pairs.
This study also underlined how mild HIE often proves to be not so mild.
“We found that neurodevelopmental outcomes at age 2 are not significantly different for mild, moderate and severe HIE. A child can be born ‘mild’ and have severe disability later in life,” Dr. Chalak says.
More evidence to come
In addition to the studies above highlighting the mechanisms of injury and classification of HIE, validation in large trials is needed. A full accounting of these methods for enhancing HIE care will be utilized in the ongoing COOL PRIME trial currently recruiting over 300 newborns with mild HIE across 18 institutions that will reveal the two years of outcomes in 2028. That trial will guide whether monitoring, and/or interventions with therapeutic hypothermia can lead to improved outcomes in this previously unstudied population. At the same time, COOL PRIME will also track EEG and MRI biomarkers mentioned above and further test their utility in grading severity and predicting outcomes.
“We’ve learned so much in recent years, and we have much yet to learn and try,” says Dr. Chalak. “Children with HIE irrespective of labels as mild, moderate or severe, deserve all the innovation we can muster.”
Learn more about breakthroughs in neonatal care and research at Children’s health.
