#079 - [NeoHeart Special] - Dr. Christopher Smyser MD - Optimizing Neurodevelopmental Outcomes in Neonates with CHD

Christopher Smyser, M.D., M.S.C.I., is the director of the Neonatal Neurology Clinical Program and head of the Pediatric Neurocritical Care Section in the Division of Pediatric and Developmental Neurology at Washington University/St. Louis Children’s Hospital, where he is a Professor of Neurology, Pediatrics and Radiology. He also co-directs the Baker Family Fellowship in Neonatal Neurology and Cardiac Neurodevelopmental Follow-Up Program. He is a pediatric neurologist with additional training in neonatal neurology. With a background in biomedical engineering, Dr. Smyser’s research focuses on the use of advanced neuroimaging techniques to provide greater understanding of early brain development and the pathway to neurodevelopmental disabilities. He is co-director of the Washington University Neonatal Developmental Research (WUNDER) Laboratory. Dr. Smyser’s recent research efforts have centered upon the use of resting state-functional connectivity MRI and diffusion MRI to investigate functional and structural brain development in high-risk pediatric populations from infancy through adolescence. He is currently the principal investigator for multiple NIH-funded longitudinal studies focused upon defining the deleterious effects of prematurity, brain injury and environmental exposures on neurodevelopmental and psychiatric outcomes through development and application of state-of-the-art neuroimaging approaches.

Find out more about Chris and this episode at: www.the-incubator.org
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Transcript

Ben  0:54  
Welcome Hello, everybody. Welcome back to the continued coverage of new heights. 2022. We are getting close to right we're getting close to the end of our coverage. And it's been really phenomenal and yeah, we're very we're very happy that we got to speak to all these great people and I think they are individuals that we may not have encountered otherwise so great job for the conference say

Daphna  1:25  
I thought this was going to help with my with my FOMO but I still have BOMA in person at the conference.

Ben  1:37  
Yeah, it's it's hard. It's hard but hopefully 2023 years, the year of the conferences for the incubator. So hopefully we'll be in person at a lot of conferences, and we will all let you know. So the actually the guest that we have on right now is Dr. Christopher's miser and he is a neurologist and, and it's kind of cool to talk to him about neurodevelopmental impairment. He's he has a whole session on how to optimize northern mental outcomes for neonates with CHD. And so, if you do not know who Chris is, he's the director of the neonatal neurology clinical program and the head of the pediatric neurocritical care section in the Division of pediatric endometrial neurology at Washington University St. Louis Children's Hospital, where he is a professor of neurology, pediatrics and radiology. He is also the co director of the Baker Family fellowship in neonatal neurology and cardiac neuro metal Follow Up program. He is a pediatric neurologist with additional training in neonatal neurology. He has a background in biomedical engineering. His research focuses on the use of advanced neural imaging techniques to provide greater understanding of early brain development and the pathway to neurodevelopmental disabilities. He is the co director of the Wonder Lab, which we'll talk about during the interview. And his recent research efforts have centered on upon the use of resting state functional connectivity, MRI and diffusion MRI to investigate functional and structural brain development in high risk pediatric population from infancy through adolescence. He is the principal investigator of multiple NIH funded grants and yeah, so he's an amazing amazing clinician recently as

Daphna  3:21  
an expert in the in the in this topic of interest rate

Ben  3:25  
reading these BIOS have given me my my dose of humility. So please join us in welcoming to the show Dr. Chris miser.

Dr. Chris miser, thank you so much for being on the podcast with us today.

Unknown Speaker  3:47  
Thanks for having me. Happy to be here.

Ben  3:49  
So you're presenting at Neo heart on Thursday, and the title of your talk is understanding and applying neuroplasticity, and more specifically, how we can optimize neurodevelopmental outcome in outcomes in neonates with congenital heart disease. And that's something that we're Daphna and I are both very interested in. So we've been looking forward to chatting with you. I guess. The first question I wanted to ask you is some of the data that you're presenting in your initial slides are quite interesting. And you're mentioning that 90% of infants with CHD are expected to survive, and of those 50% can be, unfortunately, seem to have some form of neurodevelopmental impairment. I wanted to ask you in terms of the evidence that is currently available, what does it say about the mechanisms that are underlying this impressive Association?

Speaker 3  4:44  
Yeah, so you touch on the highlights that are most important, from my view, in the sense that, you know, optimizing outcomes is what we're all keenly focused on right and the different ways that we can modify variables beginning in the fetal period extending through the ICU course and then and into the outpatient setting as well, as we're all keenly interested in in terms of what we can modify what we can gain in terms of additional data or understanding to really allow us to try and optimize outcomes. But it's a complicated problem, as we all know, and one that's very multifactorial, for lack of a better term for it. And there's a number of different factors, genetic, environmental, clinical, management based monitoring based, all of which contribute to this increased risk for neurodevelopmental impairment. And frankly, it's likely not one factor or even a small subset of factors that likely are most important in terms of determining risk. And for there still, we know there's a great deal of heterogeneity in this population, where no two kiddos are the general sense exactly the same. No two families are exactly the same. And there's a confluence or interjection of a lot of different variables at play here. So, you know, we know broad categories of important variables, we know ones that we can modify, we know ones that we frankly cannot like genetics, we just need to think through how to maximally click data that allows us to make informed management decisions beginning before a child is born, and then extending all the way through childhood adolescence, and now we're learning into adulthood. So that's a long and not very specific answer, because it's one for which there's probably not a very specific or granular answer that I can give you. You know, the only other thing I'll add is that we're learning a lot. And we're learning a lot in a relatively short period of time, regarding pretty much all of those different broad categories that I just rattled off. So the genetics underlying congenital heart disease and neurodevelopmental risk are one in which the field is very rapidly evolving. There's accumulating evidence on different ways we can modify the ICU environment, the home environment supports we can provide for parents. All of these are relatively nascent in the context of the literature in this space, but ones that we think are cumulatively very important, and Further still, many of them are demonstrating more and more ways in which we can thoughtfully improve or optimize the care that we provide. So it's a nonspecific answer at this point, one that will hopefully gain some specificity and one in which we will increasingly recognize the opportunities available to us in terms of improving outcomes for these kiddos.

Daphna  7:15  
What I loved about your presentation is, obviously there are some things that we can't like you said the non kind of modifiable things which we're working on with our improvements in care, you know, timing of surgery last time on bypass, certain things that we are doing, clinically for, for these babies. But I love how you talked a lot about some of these modifiable factors that we can do while they're in the ICU. And obviously, this is a growing interest in NICUs. But we are lagging behind what's happening in pediatric ICUs and cardiac ICU. So it seems like the CDI C's have really embraced this feeling that like our environment in the ICU matters to these babies, and we should do something about it. And can you speak a little bit about what you think are kind of the low hanging fruit in the environment,

Speaker 3  8:09  
for sure. And you raised an important point in terms of the kind of mutual information that's available across ICUs, where we provide care in the hospital. So there's definitely lessons learned that we can take bidirectionally from other ICUs into the cardiac ICU and then from the cardiac ICU elsewhere in the hospital. So again, I think the more we can kind of pool expertise and data and thought processes in this space, the more powerful or interventions have the possibility of being in the in the longer term. But in terms of some of the ICU specific modifications that we can make, and and those that we are increasingly applying in our ICU at St. Louis Children's Hospital. So, you know, ICUs are noisy, they're chaotic, they have a lot of sound, a lot of light, a lot of activity. So the more we can mitigate or minimize those types of negative or deleterious exposures, the better. We think things are in terms of the environment that we can provide. So sound abatement, different types of reassuring or positive sounds like voice or music therapy, different types of environmental modifications, light cycled lighting, positioning, the types of bedding that we put the infants in, all of these things are variables that we can directly control and do so consistently and readily in terms of the actual environment itself. And then to piggyback on it further the type of care that we provide, what we kind of lump more generally under developmental care or targeted care in that space. So I mean, Family Centered rounding opportunities involving the therapy services, our colleagues and collaborators in that space, physical occupational speech therapy early and often allowing them to help co manage the care that we provide things like kangaroo care, skin to skin massage, again, there's cumulating evidence demonstrating the benefits in this space. And then we can think through breastfeeding and nutrition more generally, which is a In an interrelated concept here, that is something that we can think about in terms of the environment or the care that we provide. And really just following the behavioral cues of the infants that we're taking care of helping them drive this process, which is something we're increasingly tuned into is one I think, can be increasingly important as well.

Daphna  10:18  
You speak in my language. It's my favorite thing to talk about. And I love how much emphasis you've placed on what we do for parents. I think that, like you said, there's this growing body of literature that what happens to our parents in the ICU also impacts development. And I was especially impressed by your toolkit, quote, unquote, for supporting parents and how really comprehensive it is, because it's some of the things you mentioned, like, you know, asking their opinion on rounds. But it seems like it's so much more than that, for us to really support them in the right way,

Speaker 3  11:01  
for sure. And you know, the numbers are the data when you look at parental wellbeing. And this is one of those concepts that transcends ICUs. And, you know, again, is something we see across all the critical care settings in the hospital, but the rates of parental, you know, socio emotional symptoms, or psycho pathology is strikingly high. So, you know, some different symptoms or categories, that parents report are as high as 75, or 80%. You know, 25 to 50%, will have some form of depressive or anxiety, lytic symptoms, you know, there's different types of psychological distress with rates that are very high. So the first thing is, we need to be asking about it, we need to be thinking about it, we need to be supporting our parents. And the reason that we think that is so important is because that starts to affect parent child interactions and the supports and care that they're able to contribute to at the bedside in the ICU. And so that process begins with, you know, asking, it continues with supporting the parents, that's something that transcends to one of the common messages here, not just that ICU window of time, but one that extends into the outpatient setting as well. It's providing support for parents in a whole host of different ways from the care that we provide to their children, in terms of consolidating it and making it multidisciplinary and well rounded, performing psychosocial assessments, care coordination with kind of a combined medical home sort of model, which is important for any multidisciplinary care plan. And then, you know, thinking through the different types of support networks and education that we can provide to parents, and in some instances, financial supports as well. So I'm trying to bundle all this together, you know, we've coined the phrase toolkit that you raised earlier. But it's really just meant to highlight the fact that any of these variables in isolation are important, but cumulatively, they can make a huge difference. And we don't think that that's, you know, something that we need to earn, excuse me, it is something that we think we need to continue to pay additional attention to as we move forward.

Ben  13:09  
In your presentation, you you have some discussion about brain imaging, and and you highlight pretty well how we have so many tools to do imaging, fetal MRI, head ultrasound, MRI, CAT scan. And And yet, despite having all these tools, our outcomes are still I mean, it's not. It's a bit bleak in terms of the long term outcomes of these babies with congenital heart disease. And I am wondering if you are thinking about how we utilize brain imaging tools to identify potential babies at higher risk of neurodevelopmental impairment? Or how can we modify the way we use brain imaging to improve long term outcomes for babies with CHD?

Speaker 3  13:52  
Yeah, so like, with everything, I'm repeating the message, there's a lot to learn, there's a lot we have learned, and there's still a long ways to go in this space. So, you know, there are a number of neuro imaging tools available to us, you're speaking to the neurologist heart here in terms of, you know, the different types of neuroimaging and neuro monitoring that we can perform. You know, in a big picture sense, I think we need to use neuro imaging in a very complementary fashion, meaning that we have different modalities that should be used for different purposes. So head ultrasound, obviously at the bedside for screening, looking for things like intraventricular hemorrhage and doing serial monitoring, once we know imagenes. There are some injuries there that can be done at the bedside and done so successfully. But there are other types of data that we want to think about in terms of incorporating into our evaluation and care management plan. So MRI is obviously the big additional modality that provides us with the best set of pictures that we can can garner in terms of looking at not just brain injury, but also brain development. So things like growth and folding that we know are important markers of what's to come. There are there ongoing investigations here and l software that are trying to leverage more advanced neuroimaging techniques as well that I think, are a bit or maybe even more than a bit off of being incorporated into standard clinical practice at this point, things like diffusion cryptography or functional connectivity, there might be a space for that. But we're still understanding how to best acquire, interpret, analyze those data in this context, what we've cumulatively learned is that there are strong links between injury or abnormalities on neuro imaging and impaired outcomes. But like everything, there's no singular finding or set of findings that we think are far and away of greatest importance in terms of stratifying. That risk, there are patterns that have clearly been identified. So if you have injury to the posterior limb of the internal capsule, or click on an MRI, you are at high risk for having motor outcomes. And that's something that's pretty clearly established when in terms of thinking, more broad scale in terms of these kiddos in the many different domains that they can have impairments in, there's no very specific combination of factors that we've identified, the so very long winded way, perhaps of saying, we've got a long way to go in terms of understanding how to best interpret and apply these imaging modalities. But at this point, there's a lot of very valuable information from my view as a neurologist who spends a lot of time in the cardiac ICU in terms of identifying infants at risk stratifying, risk counseling and educated families, and making sure that we think through things in a very informed big picture sense.

Ben  16:31  
And that's an optimistic approach. I still hear the optimism in that answer. But I want to then continue on this on this trajectory, because we've always been interested as physicians to try to get some signal from the brain, right? I mean, and as an analyst, you probably appreciate that, in your in your talk, you mentioned other forms of brain monitoring, like EEG and near infrared spectroscopy. And in the case of EEG, it's always a bit frustrating, because it helps you diagnose seizures. But obviously, if you reach the point where you already have seizure, it's already pretty, pretty bad. And the outcomes are quite worse. And so in this context, how is nears then the next best thing? And what kind of data do you see it providing in helping you on your quest to minimize neurotic mental impairment and these babies?

Speaker 3  17:20  
So I think all these tools need to be used in a complementary fashion so that it encompasses the neuroimaging as well. So you're imaging, EEG and the nears from a neuro monitoring perspective. So I think amongst the three modalities that I just rattled off there, nears is obviously more nascent in terms of its kind of more standardized use. neuroimaging has been around in a few different contexts or forms for an extended window. EEG is something that we have increasingly utilized across the ICU settings. But nears is the next tool that we need to really thoughtfully incorporate into our respective toolkits in terms of understanding the impact in real time, so to speak, with respect to our management decisions and optimizing the oxygenation or other measures that we can extract from that. And we know that thinking about this dimensionally, is important. So things like the, you know, variability within a specific temporal window, the kind of maximal values within specific settings, pre Peri, and post operative. So those are all data that we can take in really leverage or use in combination with other modalities to try. And again, I keep coming back to the set of terms, stratify risk, and optimize outcomes. We have now, just to piggyback on that point, really, very mathematically, or technically sophisticated ways in which we can analyze these data not just within one modality or across modalities. So you know, taking everything that we get from a vital sign, years EEG, data perspective, and really looking across modalities in a way to configure these risk profiles for these kiddos. So we are still, at least, from my view, figuring out how to best use nears as a tool, I definitely think it provides valuable data, I definitely think the real time element is appealing to me as a neurologist in terms of understanding the implications of my decisions. I love the fact that you can take it into the bar with you and then have data pre Peri and post operatively. That is appealing as well. So I think we just need to figure out where the best windows in populations are to use it. And, you know, again, kind of zooming out a level for the talk. My goal is really to make sure that we're introducing these concepts thinking through how to maximally implement them, making sure sites are cognizant of the evolving or emerging data that highlights the importance of these modalities in terms of their use. And as a neurologist, as we've referenced a few times now, I love the data. I love the opportunity to think through the brain and be proactive and diligent in terms of monitoring. And these are important elements of that more holistic sort of care approach.

Daphna  20:00  
one of your slides, I think, really is a good reminder that the time that, you know, children babies spend with us is so short compared to what their full development is right across a lifespan. And, you know, so what role do we have as intensivist? In highlighting some of you know, what is our role really in the anticipatory guidance and highlighting for families? What are the top things they can do to improve outcomes in in their, in their children once they leave our units?

Speaker 3  20:37  
Yeah, so, you know, people have heard me talk with families, you know, always heard me say, it seems very simple, but the things you can control make the biggest difference, right? So home environment, the types of exposures experiences, we provide nutrition, which is something that we all have an opportunity to try to legislate maintenance of relationships with therapists throughout the window of time that extends from the ICU to the outpatient setting. These are the things that have been around in many instances for the longest, and they are the ones that we have the most data to suggest make the greatest impact in terms of outcomes. So, you know, again, simple things being simple controlling what you can control it, these are the types of conversations that having them early and often with families is important, you know, interrelated with that, though, is acknowledging across to the ICU conversations that we don't have a crystal ball here, right, as a neurologist, as any sort of provider in this space, we would love the ability to very concretely or specifically, say this is exactly what's going to come for your child as you're having a conversation with a parent, but just being open and as transparent as possible with what we know and what we don't know. And highlighting, again, that these are the clinical variables that we can control, which is a message that kind of keep coming back to that can make the biggest outcome. And I think the intensivists are, oftentimes the individuals that families have most consistent relationships with during that very hyper acute or acute period. And having everybody coordinated in terms of communication. And starting that messaging as early as possible, at the appropriate time is hugely valuable, from my viewpoint as somebody who spends a lot of time in the outpatient setting as well. So those coordinated and collaborative conversations, and hearing them from trusted voices, like the intensivist, very early on, really holds a lot of weight in terms of the family and their approach to many of these variables as they move from the inpatient to the outpatient setting. And our specialty assumes in an increasing role.

Ben  22:43  
You're talking about the multidisciplinary approach, which is I guess, leading me to my last question, and I think as a neurologist, you're the best person to answer this question. How early should we bring on this multidisciplinary team to care for these babies? I feel like sometimes we say, oh, you know, no, the baby is moving, moving all extremities. So don't need for a neurologist. And that's a, that's a huge mistake. But but then the Yoopers, do you perceive that the team should be accompanying these patients and the ICU team from the beginning? Or is there a critical time by which, in your case, at least neurology has to be brought in to make sure that they're coordinating with the rest of the team?

Speaker 3  23:23  
Well, my biases will be very apparent in my answer here. But I, as the neurologist would love to be involved as early as possible. And I'll, you know, be a little more specific as I talk through our practices here at St. Louis Children's Hospital. So we oftentimes will even meet families in the Fetal Care Center if there's specific questions about imaging and or neurodevelopmental outcomes. So that's obviously as proximal as we can get here in terms of interfacing with families, but our team, very consistently, particularly for those babies with the high risk cardiac lesions are consulted essentially, as soon as possible after delivery. My preference is to have an opportunity to meet a child in a family. Before any sort of surgery or very again, I use the term hyper acute or acute setting when a baby is very sick and might be under the effects of sedation or even paralytic medications. And I don't have an ability to get an exam at that point in time. You know, we like to be involved very collaboratively with our intensive care partners in terms of decision making about neuro imaging and neuro monitoring. And we obviously avail our opinions or expertise in that space as well. And then, you know, the goal of meeting the families in the hospital is not just focused on that acute period but transcends into the outpatient, multidisciplinary, cardiac neurodevelopmental care clinic that we have. And so I like nothing more than to meet families while they're in the hospital but then have the opportunity to follow those kiddos into the outpatient setting. And, you know, the context of that provides that care we provide in the ICUs is hugely important from my view, and having an opportunity to see a family, not just email or call them because a child is very sick or has an abnormal MRI scan or something that's sparked in acute concern, but also have that ability to work from that hyper acute window of time to where we're talking about walking and talking normal, typical developmental milestones are talking about challenges that a child is facing and having that important longitudinal relationship in the context that it provides to those conversations. So my again, my biased answer is as early and as often as possible. And we're fortunate to have that opportunity at our hospital. And I think that's been hugely valuable as we standardize that as part of routine clinical practice.

Ben  25:45  
I had an inkling you were gonna say that, but I thought it needed to be stated on the show.

Unknown Speaker  25:49  
For sure, yeah.

Daphna  25:51  
Well, you know, we've talked on the show a few times about how this transition of care right at the discharge to the outpatient world, especially for us with with neonates, who they were born, they came to the hospital, now they're making this big leap. And I think we underestimate how valuable our sub specialists can be in in traversing kind of that bridge to the outpatient world and their new medical home. So thank you for your for your answer, which we agree with, obviously, the two of us. But my last question for you is, is so so what's on the horizon? What are the big things maybe that the Wonder lab I love that name your lab is working on, or gaps really in study of this population?

Speaker 3  26:41  
Well, our lab is very imaging centric or neural imaging focused and we're fortunate here at Washington University to have a lot of really smart people working in the neural imaging space. So, you know, we have colleagues or collaborators from the different ICU groups here from the neonatology, or newborn medicine group from neuroradiology, neurosurgery, all of whom are working in a big picture sense to try and take in leverage advanced neural imaging modalities, to provide us with a better understanding of the abnormalities in terms of brain development or brain injury and their longitudinal impact. Some of that work has encompassed fetal imaging as well, which is another horizon, that people are increasingly exploring in terms of role for neural imaging or fetal imaging and trying to understand how early aberrant brain development begins and or the longitudinal effects of imaging, excuse me of injury on on outcomes. So that's where our group has spent a lot of time is focused on using some of the imaging modalities I mentioned earlier, things like functional connectivity, or different types of microstructural, imaging of white and gray matter. And really looking at how those different modalities provide complementary information to what's available from routine clinical care, or clinical measures. And then further still, how we can use that to inform the effects of interventions or sorts of next steps from more improving outcomes perspective. So a lot of imaging, married with a lot of outcome measures. The other big space that I think is important, and that we, again, have referenced a few times is neurodevelopment is multidisciplinary and multilayered. So we spent a lot of time historically obviously focused on speech, motor language, but things like social emotional development. So anxiety, ADHD, autism symptoms, all of these sorts of deficits are, are more common in high risk populations, globally across pediatric medicine. But just thinking about how our understanding of that can be advanced as well, again, in the context of impaired neurodevelopment, or different clinical population. So that's where we're headed or have been spending some time and we'll continue to explore here, we will,

Ben  28:51  
we will link to your Twitter handle the WonderLab on Twitter, usually people who go for acronyms don't do such a good job, like definitely the WonderLab is awesome. It stands for Washington University, neonatal development research, and so that people can connect with you and, and continue to follow your work. You have a large team, and we're very much looking forward to the work that you guys are producing. So, Chris, thank you. Thank you so very much for making time to come on the show. And thank you for your presentation that in your heart and best of luck on your on your future work.

Speaker 3  29:26  
Perfect. Thanks so much for having me. I really appreciate it. Join the conversation. Great, great platform here for sure. Yeah,

Ben  29:32  
this was fun. Thank you. Thanks. Thank you for listening to the incubator podcast. If you'd like this episode, please leave us a review on Apple podcast or the Apple podcast website. You can find other episodes of the show on Apple podcast, Spotify, Google podcasts, or the podcast app of your choice. We would love to hear from you so feel free to send us questions, comments or suggestions to our email address NICU podcast@gmail.com. You can also message the show on Instagram or Twitter. are at NICU podcast, or through our website at WWW dot the dash incubator.org. This podcast is intended to be purely for entertainment and informational purposes and should not be construed as medical advice. If you have any medical concerns, please see your primary care professional. Thank you

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