Dr Bob Underwood (Host): Welcome to Pedscast, a podcast brought to you by Children's of Alabama. I'm your host, Dr. Bob Underwood. Today, we're exploring a critical topic in neonatology, outcomes in babies with neonatal encephalopathy. And with us is the Assistant Professor from the Division of Neonatology at Children's of Alabama and Director of the Neuro-NICU, Dr. Vivek Shukla. Dr. Shukla will help us understand the intricacies of this condition that poses a unique challenge in neonatal care. Let's dive into this topic with Dr. Shukla as our guide. Dr. Shukla, welcome to the podcast.

Dr Vivek Shukla: Thank you, Dr. Underwood, for having me.

Host: Absolutely. So, can you provide us a brief overview of what neonatal encephalopathy is and the significance it has in neonatology?

Dr Vivek Shukla: Neonatal encephalopathy is an umbrella term, which comprises of several different diseases. It is a condition where the baby or the neonate is having depressed mental or the neurological exam. And there are several causes to it. It could be several different infections. There could be diseases with genetics, metabolic disorders. There could be neurological events like stroke that might have happened before, or it could also be due to the perinatal period in which while the baby was getting delivered had a lack of oxygen or decreased oxygen. Or it could even mean like there was a period before the delivery that this lack of oxygen or decreased oxygen happened before. So, all these things combined will lead to a picture where the baby is having depressed neurological exam at birth, and that is defined as neonatal encephalopathy, the condition.

Host: So, is diagnosing this really complex? You said it's mostly based off of exams. So, what are some of the challenges or advancements in diagnosing neonatal encephalopathy in neonates?

Dr Vivek Shukla: Some of the history and physical exams would point towards a cause. And there are a few times that the cause might not be apparent until later. And we would have to do special tests to better diagnose. The majority of neonatal encephalopathies are due to perinatal hypoxic ischemic events. And by perinatal, I mean when the baby is getting delivered or before when the baby is getting delivered. And we have a specific criteria to kind of diagnose that, which includes a neurological exam, events, the fetal heart rate before the delivery happened, and several other criteria to kind of help us decide whether this is perinatal hypoxic ischemic event or are there any other things that might be contributing. And depending on baby to baby, we would then further investigate what the cause is.

Host: So, it goes based off of the fetal strip monitoring, the exam. What about any imaging? Is that part of the diagnostic criteria too?

Dr Vivek Shukla: Yeah. So, I was just elaborating on the initial presentation, but we also have imaging modalities like MRI with different newer techniques to understand what exactly is happening in the brain, like MR spectroscopy. And then, there are diffusion-weighted imaging sequence and newer imaging sequence that help us identify exactly what is the problem. And then, we have EEG, which gives us an idea of how the underlying brain activity is. So, those other things. And depending on the etiology, there might be further genetic metabolic tests that we do and try to help identify what is the cause in a given baby.

Host: What are some current treatment strategies for neonatal encephalopathy? I mean, how have these evolved over the years?

Dr Vivek Shukla: Let's talk about the perinatal hypoxic ischemic encephalopathy. If that's the cause, then, initially, we didn't have too many good options. And then, in about early 2000s, we started doing clinical trials on therapeutic hypothermia, which is a cooling therapy where the baby is cooled to 33 to 34 degrees centigrade, and it's for 72 hours. And the whole intention there is to try to reduce the metabolic demand. And it also helps in reducing the ongoing injury that might happen after the initial insult. So, that is a big intervention that we have for babies with perinatal hypoxic ischemic event. And these babies are also at high risk for seizures. So, we are very diligent in terms of monitoring for seizures, doing EEG identification of seizures, and seizures can itself lead to worse outcomes. So, we are on top of controlling seizures if they are present and monitoring the babies closely. So, these things in combination, along with several subspecialties that are involved in taking care of such babies. So, a multidisciplinary team approach with that, we manage all the babies. There are several ongoing studies and proposed studies that might give us further insights on how to better help these babies and there might be some interventions coming up in the future as well.

Host: That's awesome. So, what can you tell us about outcomes right now based on the current therapeutics that are available for babies with neonatal encephalopathy?

Dr Vivek Shukla: So, it obviously depends on what the cause of neonatal encephalopathy is. In babies with perinatal hypoxic ischemic event, it's a condition with very high risk of adverse outcomes, long-term outcomes. So, we classify based on how the baby's exam is, whether it's mild, moderate, or severe encephalopathy.

Mild encephalopathy, we can expect with all the multidisciplinary approach that we have to have overall good outcomes. But in moderate and severe, they are at a much higher risk of adverse outcomes. And in the recent literature, about, I would say, two out of three babies would have an abnormal neurological exam. And about one of three babies would have death or severe disability, meaning moderate or severe disability at two years. These numbers are very high. And they were higher before the therapeutic hypothermia started. So, we are able to help these infants, but there is still a lot of opportunity to better serve or better help these infants. And that's why we have continuing research on what are the other options that we can give to these babies in terms of therapies and treatments to improve their overall outcomes.

Host: That's really, really important work. And it's exciting to know that there's more research that's ongoing. And even the concept of therapeutic hypothermia, I mean, we use that in adults, but I had not heard of it used in neonates. So, I think that that's really exciting, especially with the improvement of the outcomes that you're finding based on that.

Dr Vivek Shukla: Definitely. And as I said, there is lots of opportunity to further do more work and get better at this. We have obviously over the years achieved quite a bit of improvement, but there is a lot of work that needs to be done. This disease itself is a high risk condition for the baby to have disability or adverse outcomes. So, there is a lot of interest and a lot of foundational work that is happening, a lot of animal studies and a lot of human studies that have been proposed or are ongoing.

One of them is stem cells. there are several groups that are working on stem cell therapy for babies at high risk of adverse outcomes. There are newer approaches to medications that can be given and that have been proposed. Our group also is working on a few clinical trials, that in the coming years will help us understand how we can better serve these babies and even further improve the outcomes beyond therapeutic hypothermia.

Host: You made mention of multidisciplinary or interdisciplinary teams. How would that work and what's the importance of having that multidisciplinary team present?

Dr Vivek Shukla: This is one of the key components of our NICU care overall. And any baby who is at high risk of having adverse outcomes, we have multiple subspecialties who are involved. In particularly the neonatal encephalopathy babies, we have our neurology team involved. We have our occupational and physical therapy team involved for early identification of issues and doing interventions as necessary for the clinical exam that we find having concern with some areas or not. And then, optimizing all the therapies that are happening. And the family is a big part of this multidisciplinary approach because having a family, which is supportive and is engaged in all the activities, it benefits the baby the most I would say.

And continuity of care, having a dedicated team, which is following the baby and all the ongoing interventions and therapies and care. This does not stop off at an ICU discharge. It is an ongoing kind of approach or ongoing collaboration that happens as the baby grows, and until we have two-year or three-year understanding of how the baby is doing. So, it's a very intricate and involved multidisciplinary approach that we have.

Host: Anything you'd like to conclude with?

Dr Vivek Shukla: This is a fascinating and very important area of research that I'm very passionate about. We have a wonderful team with us here at Children's of Alabama and UAB. And we have excellent research and therapy support. So, we will do our best to hopefully further improve the outcomes in these babies. And I'm very proud of our team here and I feel very passionately, and our whole team feels very passionately about the subject.

Host: Dr. Shukla, thanks so much for joining us today. And thank you for shedding light on neonatal encephalopathy.

Dr Vivek Shukla: Thank you, Dr. Underwood, for this opportunity and I look forward to again meeting in the future and giving you more updates on what we have in the future. Thank you.

Host: For more information or to refer patients to Children's of Alabama, visit childrensal.org. That concludes this episode of Children's of Alabama Peds Cast. If you found this podcast helpful, please subscribe and review it and share this podcast on your social channels, and be sure to check out the entire Peds Cast library for other topics that might be of interest to you. Thanks for listening to this episode of Peds Cast. I'm your host, Dr. Bob Underwood.