The HEAL Study looking at therapeutic hypothermia (cooling) and a medication called erythropoietin is one of the most recent, and most significant, clinical trials in the context of HIE research over the last decade. The results were technically “negative” – meaning erythropoietin didn’t show a clinical benefit – but the data collection and size of the cohort, 500 families strong across multiple centers, has led to many additional opportunities to increase knowledge and understanding of neonatal HIE.
The science can sometimes be overwhelming and complex to understand, so we hope this helps families gain a better understanding of these new “secondary analyses” that are being published from the data. This is another testimony of the importance of participating in clinical trials and research, as we can only move forward the state of HIE with family participation.
So, what have we learned recently? Dr. Yvonne Wu, one of the principal investigators of the HEAL Study recently shared the published secondary analyses so we can share them with you!
In addition to the research shared below, several posters with additional secondary analyses will be shared at the upcoming Pediatric Academic Society meeting, with our own Betsy Pilon as a collaborator, representing the patient-family perspective in this work. We will add on to this blog when those graphics are available!
First, what’s a biomarker?
A biomarker refers to a measurable substance or characteristic in the body that can indicate a normal or abnormal biological process, a condition, or a response to treatment. Biomarkers can be found in various bodily fluids like blood, urine, or tissue samples, or they can be measured through imaging techniques like MRI scans.
In medical research and clinical practice, biomarkers play a vital role in diagnosing diseases, monitoring disease progression, predicting outcomes, and assessing the effectiveness of treatments. They can also help in identifying individuals at risk of developing certain conditions, allowing for early intervention and personalized healthcare approaches.
What they wanted to know: In the HEAL study, researchers wanted to see if a plasma inflammatory mediator biomarker could better predict neurodevelopmental outcomes compared to clinical information gathered at follow up appointments alone.
What they found: 180 babies out of the 500 enrolled had enough information and data collected to analyze. Of those analyzed, they found six meaningful biomarkers that improved estimations of death or neurodevelopmental impairments at age 2 compared to just a clinical exam alone.
What this means: This could give families more information about predicted outcomes for their babies, allowing for more accurate counseling from physicians.
MRI is routinely used in assessing the full clinical picture of a baby born with HIE. For a long time, MRI was thought to have immense predictive value of outcomes and HIE families often talk about MRI Day and the difficult prognosis conversations that come with understanding MRI results of their baby’s brain.
What they wanted to know: How well neonatal neuroimaging matches up with neurodevelopmental outcomes in babies with HIE to see if it’s a helpful piece of the complete picture when communicating about predicted outcome.
What they found: Severe MRIs were more accurate in predicting outcome, but in the absence of severe injury, brain MRI/MRS does not accurately predict the degree of neurodevelopmental impact.
What this means: This actually matches up to what we have seen shared in our community of over 10,000 families, worldwide. MRI is not great at giving an accurate prognosis. It’s a piece of the puzzle of a child’s HIE, but it’s definitely not the whole puzzle.
We know it’s important to get a baby into therapeutic hypothermia before six hours old, but there is still much that is unknown to the potential of cooling quicker and if that shows improved outcomes.
What they wanted to know: Is time to reaching target temperature with therapeutic hypothermia associated with death or disability at age 2 with HIE?
What they found: Time to reaching targeted temperature isn’t independently associated with the risk of death or disability at age 2 years old.
What this means: Physicians can more accurately answer questions families may have about timing with cooling and the potential impact to outcomes.
Many families are told about their child’s SARNAT exam, an evaluation scale used to measure the degree of encephalopathy at birth. The communication to families varies greatly in the use and context of this exam, and some families may never hear the details of what stage their baby was given at birth. Many times this is because the clinical significance can change as a baby goes through cooling and in their recovery after birth.
What they wanted to know: Researchers wanted to know if comparing the SARNAT scale at birth and after rewarming were associated with outcome. In particular, do these two time points and the potential change between the two give a better prediction of outcomes?
What they found: The trajectory of outcome was “strongly associated” to the SARNAT exam changes between timepoints.
What this means: The SARNAT exam used in this context more widely as a tool could decrease variability in its use, standardize and improve communication with families.
HIE is under the umbrella of Neonatal Encephalopathy — the most common cause of NE, but there are others including genetic, metabolic, and congenital brain malformation causes. Genetic testing is becoming more prevalent with Neonatal Encephalopathy, both in the ability to identify babies who truly do not have HIE and families can be directed to appropriate support, and in understanding the influence genetics may have in neonatal HIE causation.
What they wanted to know: How many babies in the HEAL study had genetic or preexisting brain anomalies/congenital issues, since genetic testing has not previously been so widely and accurately available.
What they found: 5% of the cohort of 500 babies had either a genetic or brain anomaly. The babies with these findings had worse neurodevelopmental outcomes than infants with HIE alone.
What this means: Etiology, or cause, is important not only for clinicians and researchers, but for families to understand for not only their own knowledge about their child’s medical information, but for family planning, recurrence probability, appropriate community support and potentially targeted genetic therapeutic interventions that are or may become available.
What questions do you want answered in research with HIE?
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