Hello friends 👋
In this engaging episode of The Incubator podcast, Dr. Terrie Inder, a pioneer in neonatal neurology, shares her journey and insights into newborn brain development. Dr. Inder discusses the complexities of neonatal brain injury, emphasizing that it's not just about visible hemorrhages, but also about the brain's overall maturation process. She highlights the importance of understanding "brain dysmanturation" and how the NICU environment significantly impacts neurodevelopment.
Dr. Inder challenges the neonatal community to rethink their approach to brain care, advocating for more family involvement, enriched environments, and tailored interventions for babies with brain injuries. She stresses the need for better hemodynamic management and a sociocultural shift in NICU care delivery.
The conversation also touches on the controversial topic of routine MRI scans, with Dr. Inder arguing for their value in risk profiling and guiding care. She encourages neonatologists to embrace learning about brain imaging and improve their communication skills with families.
Throughout the episode, Dr. Inder's passion for improving outcomes for NICU babies shines through, offering listeners valuable insights and a call to action for enhancing neonatal brain care.
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Short Bio: Dr. Terrie Inder is a dual board-certified neonatologist who provides comprehensive care for critically ill premature and full-term infants and a child neurologist at CHOC in Orange County, California. Dr. Inder’s research focus is on the newborn brain. She also undertakes clinical service within the neonatal intensive care unit. As all her research activities are clinical investigations, the research studies and clinical care of high-risk infants are tightly integrated. Dr. Inder’s primary research is targeted at understanding the timing, mechanisms and impact of cerebral injury and altered cerebral development in infants at high risk for adverse neurodevelopmental outcome, including the prematurely born infant, the sick term-born infant and the infant with congenital heart disease. Her aim in her investigations is to investigate means of accurate, early diagnosis of brain injury as well as developing treatments and preventive strategies to reduce subsequent disabilities. This research work has utilized technologies including near infrared spectroscopy, electroencephalography and magnetic resonance imaging. Dr. Inder is the director of the new Center for Neonatal Research at CHOC, and she has held previous leadership positions in neonatal medicine as director of the Intellectual and Developmental Disabilities Research Center at Washington University in St Louis and the chair and Mary Ellen Avery Professor of the Department of Pediatric Newborn Medicine at the Brigham and Women’s Hospital in Boston. Her mission has been to develop programs that integrate discovery and innovation alongside translation into clinical excellence while mentoring the next generation of academic clinicians.
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The articles covered on today’s episode of the podcast can be found here 👇
Inder TE, Volpe JJ, Anderson PJ.N Engl J Med. 2023 Aug 3;389(5):441-453. doi: 10.1056/NEJMra2303347.PMID: 37530825 Review. No abstract available.
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The transcript of today's episode can be found below 👇
Daphna Barbeau (00:00.142)
We're recording, but we'll cut this part out. I know you're always working on a number of things simultaneously, but if there's something you want to make sure we get to that you have going on that's new and exciting that we should be looking forward to, if there's something like that you'd like us to get to at the end and ask a question about, you can let us know.
Terrie Inder (00:03.184)
I know.
Terrie Inder (00:23.184)
Yeah, no, I think you'll probably hit on it. Most of our work at the moment is on modifying the environment one way or another. Some of it's trying to move in a more sophisticated way and others is really at the most fundamental bit.
Ben Courchia MD (00:35.592)
That's great. Okay then. So then we'll begin then. Hello everybody. Welcome back to the Incubator podcast. We are back this Sunday with a special interview. We have the pleasure of having on today Dr. Terry Inder. Daphna, first of all, how are you?
Daphna Barbeau (00:35.822)
Perfect.
Daphna Barbeau (00:51.502)
I'm doing well, you know, we've been really looking forward to this. This is a special interview for me because I have, Dr. Indra's work is part of the reason I chose my professional interests. So this is a special interview for me. We're really excited to have you on.
Terrie Inder (00:51.664)
I'm.
Ben Courchia MD (01:10.12)
Dr. Inder, thank you so much for making the time to be on with us this morning.
Terrie Inder (01:14.224)
Thank you so much, both Ben and Daphne, for your invitation and for your attention to that difficult area, but important area of the newborn brain.
Ben Courchia MD (01:26.504)
That's right. For people who are not familiar and shame on them if they are not familiar with who you are. You trained in New Zealand. You did your medical school in the University of I hope I'm pronouncing this correctly, the Otago School of Medicine. And you did thank you. And you did your residency in New Zealand as well. And you then moved to the US to do your fellowship in neonatology at Boston Children's Hospital.
Terrie Inder (01:40.016)
That's correct. Yes. Good job.
Ben Courchia MD (01:52.424)
And you are a pioneer in neonatal neurology. You are currently the director of the new Center for Neonatal Research at CHOC, the Children's Hospital of California. And I guess our first question for you today is what prompted your initial interest in neonatology and then this sub specialization into neonatal neurology and learning more about the newborn brain?
Terrie Inder (02:19.984)
Yeah, thanks, Ben. So just a little fill in the gaps there. You know, my parents hadn't got to college. My father is very intelligent, but was sort of had a number of other jobs. And I was inspired by my family doctor to go into medicine, which we do from high school in New Zealand. So we go in and I'd been accelerated through the school system. So I was very young and I went in because I was going to be a family doctor just like him.
And it wasn't until I was in my sixth or seventh year, I realized that, no, I actually wasn't meant to do that. And I suppose that's the message that to me, life is kind of a serendipitous adventure park and that these rides come along that, you know, if it feels right, hop on it and try it. And so I trained then in pediatrics, was fortunate to get through the exam and found somewhat sort of excitingly that I was pregnant.
and wanted to work part -time, which you couldn't do clinically. And that was when I got offered the opportunity to work part -time in research. I wasn't a researcher. I didn't know research was. In fact, I was just like reluctant would be a great way of describing it. So I went in because I wanted to work part -time and I worked part -time for a couple of years doing research in actually free radical mediated injury to the newborn lung. And
started my neonatal fellowship, finished a PhD, and then went on and finished neonatology in New Zealand, actually, before I had a friend's brother who had a child with very severe cystic PVL. And I wanted to understand why that happened to him. So I found this textbook written by this guy that I decided I would read so I could understand what this was all about.
Daphna Barbeau (04:10.798)
Hmm? Hmm?
Terrie Inder (04:15.44)
And I became fascinated with the brain. And then I wanted to go and train with the guy who wrote the book. And so I found, I rang him up and took me a while to find him because it said it was in St. Louis, but he was in Boston. And so I rang up and said, I really want to come and train with you. And he goes, yeah, we have this thing called residency here and you'd have to do another one. So I was fully a pediatrician, neonatologist. I'd finished research.
Daphna Barbeau (04:16.878)
Mm -hmm.
Daphna Barbeau (04:36.142)
Heh.
Terrie Inder (04:42.768)
And I came and did another three years in child neurology residency. So I think my family thought I was never going to stop training at that point. And I wasn't sure I was either because I loved learning. But I came to Boston and did that. And then after that, returned to New Zealand as a child neurologist and an neonatologist, really trying to understand what was happening and believing that if we could just prevent brain injury, all these babies would be fine.
Ben Courchia MD (05:11.4)
Hmm.
Terrie Inder (05:12.464)
You know, the journey has not allowed me to do that, but the journey has allowed me to understand and shed light on a lot more than just brain injury alone as being an important mediator. So, yeah, I think that, you know, the reality is I often speak that, you know, if you can find your purpose in life and live that purpose, then life has an extraordinary...
Ben Courchia MD (05:24.2)
The journey hasn't allowed you to do that yet.
Daphna Barbeau (05:26.606)
Hmm.
Terrie Inder (05:41.872)
sense of meaning. And so for me, I was very fortunate to be able to, you know, follow the serendipitous adventure path to find this purpose. And then along the way, it's really been the people. And I think for all of us, we're often inspired by people. And so if you can find the people who allow you to continue to live your purpose, you're in a very fortunate place in life.
Ben Courchia MD (06:07.816)
That's great.
Daphna Barbeau (06:08.201)
I love that. I mean, I have chills hearing your story. Truthfully, I think it's easy to say you took the serendipitous route, but I think there's actually a lot of courage in being able to accept change and make change not knowing exactly what that outcome might look like. And I feel like a lot of people are stuck along their career. They're not totally happy, but they are happy enough. So they feel like, well,
I don't want to risk the unknown. And hopefully you can speak a little bit about how you kind of, you know, convince yourself to take that. So many big steps, so many big steps that have obviously been very fruitful for you.
Terrie Inder (06:50.672)
Yeah, sometimes my kids now who are between 25 and 32, you know, they look at me and they're like, we remember standing in Melbourne Airport with 10 suitcases on our way to America, literally. And they were between six and 13. And they're like, and you just kept moving forward, you know, and they're like, you knew no one.
Daphna Barbeau (07:00.686)
And they were how old at the time?
Daphna Barbeau (07:10.062)
Yeah.
Daphna Barbeau (07:16.43)
Mm.
Terrie Inder (07:19.344)
You were going to a place which was so different, but you just knew this was the right step for us. And as a family, it has worked out really well. But yeah, I think that life hasn't always been easy. I've made mistakes and I've learned more from those mistakes than I have from the successes. And I think what I've learned a lot
Daphna Barbeau (07:37.582)
Mm -hmm.
Ben Courchia MD (07:45.608)
Hmm.
Terrie Inder (07:48.624)
is the open heartedness to take it all and to try and grow from it. And so, you know, I suppose I have courage to believe that I'm meant to be in a certain place. I do have a belief that I'm not in charge, actually, that I'm kind of pointed in the right direction. And then if I don't fulfill that direction, there's always this little voice inside me saying, are you doing the right thing?
Ben Courchia MD (07:52.808)
Mm -hmm.
Terrie Inder (08:19.248)
So sometimes, you know, this most recent move took about two years to ferment, I'll say. And there was a lot of considerations that went into where and why, including being able to be close to my eldest daughter and now my granddaughter. And so, you know, balancing these things hasn't been something I've always done well. But I think that, yeah, I think as women and
Ben Courchia MD (08:35.912)
Hmm.
Terrie Inder (08:48.688)
I don't mean to exclude you from this, Ben, because I know this self -doubt occurs in men too. But even as I think as high performing physicians, we're built with a very high level of criticism internally. And we tend to sit there and self -doubt all the time. And it doesn't matter if everything has gone right, like the exam that we sat, we'll focus on the one question we got wrong. And we do this in life.
ourselves all the time. And I think if we can focus on the fact that life is always going to be a little bit of a compromise and if this feels like it's the right pathway, we have to quieten, I call them the mean girls in my head, we have to quieten the mean girls and go sit with the cheerleaders and try and move forward. And that does mean, risk means the opportunity for a mistake.
Daphna Barbeau (09:33.134)
Mm -hmm.
Ben Courchia MD (09:37.832)
Mm -hmm.
Daphna Barbeau (09:38.062)
That's right.
Terrie Inder (09:47.824)
But to me, if I'm not living in a place where I'm taking some risk, it doesn't quite feel right.
Daphna Barbeau (09:55.022)
Yeah. I mean, I love that. It totally resonates with me. I'm sure it resonates with a lot of our listeners. And, you know, I wonder, we usually get to this at the end of the interview, but since you brought it up, you know, I wonder like what has worked for you in the past to like quiet that, you know, the downtrodden inner voice, the mean girl, inner voice, you know, what has worked for you to push past that sometimes.
Ben Courchia MD (10:05.448)
That's great.
Ben Courchia MD (10:14.696)
the meat girls.
Terrie Inder (10:17.2)
Yeah.
Daphna Barbeau (10:24.366)
she's really mean so right
Terrie Inder (10:26.56)
yeah, we all have them and she's never going away. She still lives here all the time. She's never going away. It doesn't matter whether I put something on in the mirror and I'm looking at it and I'm like, really? Like, I thought it would look like this and it really doesn't. You know, I think there's, and I don't know whether it's some of the more challenging things that I faced that made me a lot more humble about who I am and what I am.
Daphna Barbeau (10:35.694)
Mmm.
Mmm.
Terrie Inder (10:55.728)
that there's at some point there comes an acceptance that you are who you are and can you love yourself just the way you are even though you're imperfect right as Brené Brown or others would say you're perfectly imperfect you're flawed you've got these things that are actually somewhat hard for others sometimes to live with and I think when you learn that and you learn that
that really a lot of things that happen in life really are not to be taken personally. They're really not about you. They just happen. And just don't take it personally. Don't blow it up. And try not to judge. You know, you don't, you know, we make assumptions about what other people are doing or mean or say, or whether it's why our grant got turned down or why the paper got turned down or why somebody
Daphna Barbeau (11:30.862)
Hmm.
Ben Courchia MD (11:33.224)
Mm -hmm.
Terrie Inder (11:55.568)
made that decision on the floor when you're like, really? Or why somebody's in a really, really bad space and not being as kind as they should be. You don't know what's happening inside that person at the moment. And most of the time, if you can buffer it with kindness, you'll find that there's a whole different existence that you can look. And so I think learning that the men girls are always going to be there.
Daphna Barbeau (11:58.638)
Hehehehe
Ben Courchia MD (11:59.176)
you
Daphna Barbeau (12:17.198)
Hmm.
Terrie Inder (12:24.752)
the perspective setting of where you are in life, what you're really here to do each day. And a lot of that has been a help for me by I actually really enjoy walking with the dog at night and just letting the day go and letting the day go and being able to perspective set on where you're at. And when you can perspective set that, yeah, that may not have gone well.
Ben Courchia MD (12:38.152)
That's great.
Daphna Barbeau (12:38.99)
She knows you're talking about her.
Terrie Inder (12:53.296)
but look at all these other things in life, then there's a different level of peace and acceptance that comes of this is just the way it's meant to be. I might not understand it, but I don't have to spend energy in negative space dealing with that when I can put my energy into something that could be more positive.
Daphna Barbeau (13:04.238)
Yeah.
Daphna Barbeau (13:13.966)
I love that. That's such great advice for neonatology, but for life. Absolutely. And I mean, go ahead.
Terrie Inder (13:19.12)
Well, I think these, yeah, those are the things we're not taught, right? We're taught how to run a ventilator. We're taught how to, you know, do fluids. We're taught how to, we're not always taught how to live well. And, you know, when we live well, we can take care of others around us well, including the patients we serve.
Daphna Barbeau (13:24.366)
Right. That's right.
Daphna Barbeau (13:32.366)
Mm.
Daphna Barbeau (13:40.75)
I love that. And I do think for us to keep doing the work in the, in the NICU, it just takes this level of being able to put some of that aside and, and just, and go for some of the things that you think are important. I think that's actually a perfect segue. You didn't disclose, but the, the, the, the authors, the book, the author of the book you were talking about was Dr. Volpe. And so you just went and you did a cold call and you ended up.
Terrie Inder (14:07.536)
Thank you.
Daphna Barbeau (14:07.95)
training together. So it just shows how being able to take risks and it can get you some amazing places. So tell us a little bit about that experience.
Terrie Inder (14:15.92)
Yeah, and we just finished the seventh edition, so it's really like a full circle now because now I get the privilege or not, the responsibility to help navigate the book, which is an honor I could never have even imagined would.
Daphna Barbeau (14:21.934)
That's right.
Terrie Inder (14:40.24)
But yes, mentorship and Dr. Volpe has been and continues to be a huge influence in my life. His inspiration and his dedication to intellectual endeavors in terms of always pushing forward. Let me get him a treat and see if that'll work.
Like put them down for one minute.
Ben Courchia MD (15:10.984)
No problem.
Terrie Inder (15:25.712)
He's chasing a fly. Talk about intellectual endeavors. Now, hopefully he'll see this tree and be just as excited by the tree. Anyway, Dr. Volpe's mentorship and, you know, his dedication to high quality intellectual endeavor is truly what inspired me and
Daphna Barbeau (15:28.014)
That's awesome. That's right.
Daphna Barbeau (15:38.382)
the treat.
Terrie Inder (15:54.384)
As time has gone by, you know, he has come to know the person as well as the quality of my science. And there's no one I pick up the phone as often to about something I'm thinking about in terms of, you know, a concept or a decision that I'm making about myself. My youngest daughter calls
calls him and Sarah, his wife, her godparents, because they literally are like that for our family. So that's the true, incredibly, encompassment of a mentor relationship. And I've had many, many mentors in the field. Donna Ferreiro, Linda DeVries, many women mentors, Petra Hoopi.
They have all inspired me in ways that are both professional and personal in the way they carry themselves as leaders.
Ben Courchia MD (17:00.232)
Mm -hmm.
Ben Courchia MD (17:07.784)
Yeah. And Donna Ferreiro, I think was on the podcast with our colleagues from at the bench with Misty Good and Elizabeth Crouch and David McCauley to talk about research and so on. So that was, that was a great episode as well. I want to go back to this concept of making mistakes and learning from them, but I'd be remiss if we didn't talk about the successes because you are such an accomplished physician and neonatologist. And, and I've always appreciated your approach to neonatal brain injury because
I think that from the periphery, if we talk about neonatal brain injury, many people who are not experts in the field might say, yes, the IVH, right? Intraventricular hemorrhage, that's what the preemies get, right? That's what you learn in med school. But over time, we've learned from your work and other people's work that it's much more complex than that and that all areas of the brain could be affected by prematurity.
whether it is indeed IVH, whether it is white matter injury or cerebellar injury, I think all these things are potential complications that we don't always think about, especially at the bedside because they have long -term ramifications. Can you tell us a little bit, what is the proper framework to think about brain injury? Because I think that's so important for us to understand so that we can give proper counseling to families.
Terrie Inder (18:25.296)
Yes, those are great questions Ben and I think we have one we've not always done a great service to the newborn brain because we don't spend a lot of time learning about the newborn brain and it seems I mean most of us were scared of neuroscience when we did it we just wanted to get it done and get out of there. So I try to explain the brain and I do this to families like a big computer system right we've got
hard drives, there's the cortical gray matter, you've got all the cables that are the white matter, but in that mature brain, they're all uninsulated naked wires. And then you've got the system administrator, you know, the deep gray who sits in the middle and organizes all of the signaling going across the brain, of which about 20 % goes out of the brain down the spinal cord. And, you know, there's modifiers with the cerebellum as well. But as you rightly say, the whole system.
is actually affected by preterm birth because the system is undergoing massive development. It's a warehouse that's under construction in a big way. And so IVH is important. IVH is like a building crew. The Germinal Matrix was like a building crew that had things, work still to be done. And when you eliminate it,
there are loss of progenitor cells and hormone effects that may not have major cerebral palsy or major impact, but they still have impact. And then of course, when it becomes more significant and causes blood in the ventricles and the complications of either a parenchymal stroke with a high grade parenchymal bleed or hydrocephalus, these are really associated with potentially devastating developmental impact. So we want to...
Ben Courchia MD (20:00.328)
Mm.
Terrie Inder (20:19.888)
We want to eliminate IDH. It's the tip of the iceberg because we can see blood on ultrasound, right? That's what you can see. So that's what you learn to care about because that's all you can see. And the rest of the warehouse, you've got no inspectors to be able to look around. So you don't even know what's going wrong out there. You just know if there's a big spillage in the middle of the warehouse that you can see where the tar is everywhere and it's going to cause problems.
Ben Courchia MD (20:29.8)
That's right.
Terrie Inder (20:49.264)
When we get to IVH alone, I've tried to turn a lot more attention to teaching on this in recent years just because it's pretty sad when you look at our rates of IVH across the country. We haven't gone down, we've actually gone up more recently. We're stuck at around 25 to 30 % of all of our very low birth weight babies. And particularly as we resuscitate smaller and smaller babies where the rates are higher and higher.
And we have not made any improvement despite antenatal steroids going up, despite late -call clamping, despite, you know, maybe in the sort of 28, 29 week as we're starting to see a little downtrend. So what are we doing wrong? What is it that we should be actually paying attention to? And there's only two studies that really give us clues on this. One is a nursing study out of the UK that shows that if we just
for 72 hours do keep that head midline and prevent all these big fluxes with legs up, heads up, throwing them around the bed, which none of us do. But the more important thing is drawing back on the lines. And so I pride myself actually on the golden hour time and getting my lines in fast, getting my labs off, flushing those lines, having the lines in great position and then walking away all within that golden hour time.
I'm not sure that that's been helpful for us because when you take two and a half cc's of blood off a 750 gram baby, you're taking essentially 4 % of their blood volume off them. Woosh. That would be for you and I about 200 cc's. Woosh. Straight off us. Most of us would feel a little lightheaded. If we had a person who came and put a needle in our arm and drew off 200 cc's,
Most of us would not be happy that that was occurring. And we've got auto regulation and other wonderful protective mechanisms in our brains. Our babies don't. And so the biggest difference this intervention did was they had a stopwatch and they timed that it had to be at least half a minute and ideally a minute that they drew back every blood test off the line and they flushed the line that slowly.
Terrie Inder (23:12.56)
We just don't do that. I flush my lines, bang. And I don't realize how much that little volume is inside that very small circulation. And I'm sure we're causing a lot of cerebral perfusion changes. The other thing, of course, is we see blood pressure drop at around 12 hours. What do we do? We put up what Patrick McNamara says we never should, dopamine. What do we do with dopamine? We vasoconstrict everything.
Ben Courchia MD (23:20.136)
Mm -hmm.
Terrie Inder (23:40.4)
We actually don't help the brain at all, but we cause wonderful systolic fluxes. I can tell you, because I've got the data. The systolic go, we only look at the maps because our maps come up, we go off to bed, we feel happy, we're fine, the nurse is happy. But we're doing all sorts of harm by these things. And then finally, I think Patrick has shown as well with his targeted echo that if you have a targeted echo at 12 hours,
Daphna Barbeau (23:45.102)
for you.
Daphna Barbeau (23:52.846)
Mm -hmm.
Daphna Barbeau (23:56.846)
Hmm.
Terrie Inder (24:07.408)
and really inform your hemodynamic decision making. Should I be using dobutamine? Should I be using Tylenol? Should I be using fluids? Should I be using blood? What should I be doing? And I do believe that should be informed by neuro -infrared spectroscopy. Unfortunately, the trial didn't support that, but the trial also didn't tell us who was looking at the monitor and what they were doing with the data. So monitoring is useless unless you have information that you use.
Ben Courchia MD (24:10.92)
Mm -hmm.
Terrie Inder (24:33.072)
So for brain hemorrhage, IDH, and I believe white matter injury and cerebellar hemorrhage are all occurring in the same three to five day bad early period. Once you're out of that window, it's all about brain maturation. And we can talk a lot about that, but that first window is all about hemodynamic cerebrovascular stability, ventilatory cardiovascular management. And we're just not doing it well at the moment and we need help.
Daphna Barbeau (24:46.414)
Mm -hmm.
Ben Courchia MD (25:01.352)
And can you talk a little bit about this? Because I think, as you mentioned, that blood in the ventricles is the tip of the iceberg, as you mentioned earlier. And you're right. I think we have no idea what we don't know. In this recent paper that you co -authored with Dr. Volpe in the New England, you mentioned the rates of cerebellar hemorrhage and how most of the literature would agree that it's about like 3%. But if you actually ultrasound through the mastoid funnel, you would get 9%. But if you get MRI, it's more like 20%, which
irrespective of what the numbers are, it just shows we don't even know what we're looking at. Is that the same for IVH? Because as you discussed, we think we understand IVH, but the classification has been put in question. And then we then wonder, well, is there truly impact of these lower grade IVH? Some people say yes. Some people say no. We agree that maybe high grades are quite bad. But it always goes back to, do we really understand this as well as we think we are?
Terrie Inder (25:58.352)
So to me, what IVH lower grade, particularly a grade one is, it's a marker that that brain took an ischemic injury. So you should immediately know that brain did not feel well for a period of time because it ruptured its blood vessels and it's lost those precursor cells, which were destined to be interneurons, which were going to help with neuronal transmission and may well have not had their true role revealed until you're
you know, in fifth grade trying to do more complex math. But regardless, we'd rather avoid that. But to me, the more important thing is this is now a marker that this brain took an ischemic insult. And so you're already dealing with a brain that's vulnerable, that's taken an injury. And now that brain needs to be cared for as a brain that took an ischemic injury. And how can we better support that brain? And to me, that would include, of course, being able to better define
how that brain looks at the time you're going to go home from the hospital. But in addition, during the time you're in the hospital, can we be making sure you're getting the rehabilitation, the therapy services, the optimal nutrition, and of course the environmental enrichment by everything being optimal for brain care for that recovery of that brain that took an injury. So to me,
You know, grade one IVH is a marker, and that means I should pay more attention to this brain. If I don't see any grade one or any IVH, do I think that brain is healthy? No. I'm sorry. You know, the reality is you're right. The number of times I look at ultrasounds, even when I got here before we started really banging the door, you know, the mastoid views aren't always done, right?
How many times is the cerebellum not even looked at? You definitely won't see cerebellum hemorrhage if you never look. You know, that's for sure. If you look, you'll see the larger ones. And certainly people sometimes argue, well, do the smaller ones matter? Everything matters. You know, your brain did not want to have blood in those areas and it is a marker for injury. So you're right, it's the tip of the iceberg. But I do like to distinguish
Daphna Barbeau (28:09.998)
Mm -hmm.
Terrie Inder (28:22.736)
brain injury and the main forms of brain injury, that being IVH, white matter injury, which of course is also associated with infection, inflammation in the neck, and cerebellar hemorrhage from brain dysmaturation. There's a big overlap. If you have injury, you're more at risk for dysmaturation of your brain. But even without injury that's visible at all, you can still unfortunately be vulnerable to
of your brain during your neonatal intensive care unit course. I'll finally just say that although the very, very immature babies are very vulnerable to IDH, they're a little bit less vulnerable to white matter entry for some reason. And so because the oligodendroglial cell, that little sheathing thing is very vulnerable between 26 and 28 weeks, I think we're starting to forget about the 27, 28 week is.
Daphna Barbeau (29:07.31)
Mm -hmm.
Daphna Barbeau (29:19.79)
Mm -hmm.
Terrie Inder (29:20.304)
are actually pretty vulnerable species themselves because we're putting all our energy into these 22, 23 weekers and we're forgetting about this other group that are particularly vulnerable to injury as well, but a different type of injury that's often not visible on ultrasound.
Daphna Barbeau (29:37.486)
I think this is just such an incredible concept and I hope people rewind and listen to what you just said because I feel very much in our neonatal community, we get a lab test, we get the imaging test and we say, the brain's normal and this baby's good from a developmental perspective and that's...
just certainly not the case. Certainly our professionals in early intervention and early childhood and our pediatrician friends in general practice can tell us that that's just not the case. And so I wonder without having the quote unquote concrete data that neonatologists seem to require, how can we kind of change the narrative in the community? So exactly like you said, it's this
this brain under construction the entire time they're in the NICU that should be not outside of the womb at this time. And we're doing all these things to it. So I just feel like the total narrative about our culture in the NICU around the brain and development needs to change. So how do we do that?
Terrie Inder (30:52.368)
Yeah, you're so right to think that exactly what you've just said was the provoking point for writing that New England Journal article actually was just that how do I, how do I wake them up? Like everybody is like, there's no hemorrhage, everything's great, you know, and when you look at our outcomes and I show these slides often first up and in any talk and I do it to remind myself of why I'm here. And that is that when you look at our
Daphna Barbeau (31:00.494)
Mm -hmm.
Daphna Barbeau (31:05.678)
Mm -hmm.
Terrie Inder (31:20.624)
neurodevelopmental disability rates for the last two decades across any study that's been done, that's been repeated, which like Australia's done cohort after cohort after cohort, or you look at the United States for the two cohorts in the NRN or Europe, we've made no improvement. Now we've made a little tiny improvement in CP because we've reduced cystic PDL and the reasons for doing that are not entirely clear, but
probably do relate to antenatal steroids, but we're not 100 % sure. But without a doubt, our rates of neurodevelopmental disability for our kids less than 30 weeks sit stuck at 40 to 50%, irrespective of controlling for how many more little babies we have and everything. We have not moved the needle at all. And these are kids with neurodevelopmental disabilities identified at two that are not minor. They're going to have significance.
Daphna Barbeau (32:17.006)
Right.
Terrie Inder (32:17.296)
on the rest of their lives. And so to me, unless you can ring that gong and everybody wakes up and says, oops, that's great. We're doing so well with improving survival, but oops, we've got a real problem here. If half of our kids are leaving the unit with neurodevelopmental disability, that's not something we should be accepting and how can we fight to fix it? And the way to fight to fix it is to say,
you know, at least half of those brains have got no visible hemorrhage. So there's something else going on. And how can I be starting to pay attention to that and understand it? And unless neonatologists are prepared to lead, what I actually believe is going to be really difficult for us, which is focus on this hemodynamic area and then focus on a big sociocultural change in the way we deliver care.
Unless we lead this with our nursing partners, it's not going to happen.
Daphna Barbeau (33:21.262)
Yeah.
Ben Courchia MD (33:21.52)
And so I want to get to that specifically because you make such profound points throughout your work. But I want to backtrack a little bit because you use that term that you've brought up before the concept of brain dysmaturation, which I think is fascinating. The ability. I mean, you'll tell us a little bit. How do we measure this? How does this manifest itself, whether it is on imaging or otherwise, but just this ability of the brain to do brain things and just make connections and develop? I think that's
exceptional and I've before learning and reading your work, I'd never really thought about it in those terms. So I'm wondering if for the audience who are not familiar with that term, you could expand a little bit on what is brain dysmaturation in the context of a preterm baby.
Terrie Inder (34:06.864)
Yeah, thanks, Ben. So, you know, as you have rightly said, the brain is undergoing this rapid construction process with enormous numbers of connections and building. And this is dependent upon a number of inputs. And some of those inputs, you know, we are still not knowledgeable yet about in terms of the growth factors that the placenta may have provided that obviously we can't at the moment replace. But
there are other things that drive this process. Obviously, if you don't feed the construction workers, then the construction workers can't do their job. So nutrition is actually very important as I believe a permissive element for this. It's not, some elements may be directly feeding it, but we've studied things like DHA and others and nothing's been a big gong there, but it's permissive. So if you don't feed the workers, they can't do their job. But more importantly,
the workers are going to pay attention where things are happening and they're going to respond to alarm bells, literally, and they're going to ignore any area where there's no action. So if there's nothing happening over here, they're not going to spend time over there, they're going to spend all their time where the alarms are going off. And that is what we have found with the newborn brain in that I think the most stunning
study that we have done even still to date, because it was completely against the hypothesis we led, was that we found that disturbances, particularly in a vulnerable region of the human brain, the temporal lobe, were driven by stressful experiences that the babies were having. And that we could measure this by a nursing developed partnered scale.
Daphna Barbeau (35:49.518)
Mm -hmm.
Terrie Inder (35:56.784)
and we could quantify it and we could show, independent of how small, how sick, how long you're on the ventilator, everything, the amount of painful and stressful procedures and experiences. This could even be an eye exam. You know, you were undergoing related directly to disturbances and development in the temporal lobe. And so we said, great, we're going to put them in the Hilton, right? We're going to put them in a quiet, beautiful room. You know, we're not quite going to do massage therapy, but they could just...
they were going to feel so much better than being in our train station of an open bay. And I was sure it was going to fix the temporal lobe and it was going to make everybody perform better at two years. And of course I was wrong. You know, their room environment adversely affected their language development by eight IQ points and that's persisted. And it disturbed the way the hemisphere developed.
Ben Courchia MD (36:29.192)
Yeah.
Daphna Barbeau (36:45.87)
That's right.
Daphna Barbeau (36:53.742)
Mm -hmm.
Terrie Inder (36:54.256)
We lost hemispheric asymmetry between the left and the right hemisphere in the private room because it was too quiet. They lost human language. And I was just, I mean, even David Van Essen, who's like a hardcore big, you know, cortical folding neuroscientist, he was like, I have never seen environment alter structural human brain development that has functional consequences, right?
Daphna Barbeau (37:12.686)
Mm -hmm.
Terrie Inder (37:20.656)
So we saw the loss of the asymmetry in language and we saw the detriment in language performance two years after discharge. So what happens with us now, I am fundamentally driven to try and impact in the neonatal intensive care unit because everything we're doing after that, we are playing catch up on, trying to correct what was done wrong in the environment.
Daphna Barbeau (37:42.894)
That's right.
Terrie Inder (37:49.296)
And I don't have all the answers about what the perfect environment looks like, but I can tell you that I truly believe it's way off where we are now. And that one of the biggest elements that's missing is enrichment and nurturing. And when you look at, and I just presented even in Iowa, where of course they're very good at caring for very, very tiny babies, the Swedish data about how quickly skin to skin.
Daphna Barbeau (37:58.51)
Nothing.
Terrie Inder (38:17.04)
and how long skin to skin can be done for quickly, i.e. within three to four days in their 22 to 23 weekers and up to six hours a day. And the reason they published it was they didn't think it was good enough. They wanted more. So we have so far to go to get our families. And one of the saddest moments for me in visiting any neonatal intensive care unit is when I walk around and I see how few families are.
Daphna Barbeau (38:30.734)
-huh.
Ben Courchia MD (38:32.456)
Mm -hmm.
Ben Courchia MD (38:46.024)
Mm -hmm.
Terrie Inder (38:46.864)
in single rooms with their babies and their babies are in a plastic box in the room all on their own in an isolation suite.
Ben Courchia MD (38:55.016)
You have given, you've given fuel for Daphne to speak for the next two hours, by the way, just so you know.
Daphna Barbeau (38:59.918)
I won't get on my soapbox because you're the world expert. So, I mean, this is, this totally fuels, Ben's right, fuels me for what I believe we've missed as an opportunity for a number of things. The first is which is, like you said, we're playing catch up if we miss this golden period in the NICU while the brain is developing. The second, which I'll get to is that
Mm -hmm.
Daphna Barbeau (39:28.462)
once we have brain injury, a lot of neonatologists throw their hands up and they say, well, it's the brain is injured. What are we going to do? And I think there's still plenty for us to do in terms of rehabilitation, right? That's right.
Terrie Inder (39:39.024)
It's under construction. It just gets rebuilt. You know, I rebuilt some of my kids who've got hardcore big MCA strokes. You wouldn't even know because I work with them right from, and the nurses will tell you the crib has turned a certain way, the enrichments from a certain, I mean, we do this with neuroscience and every other area. Why don't the babies get the same chance?
Daphna Barbeau (39:46.734)
Yeah.
Daphna Barbeau (39:52.142)
-huh.
Daphna Barbeau (40:00.654)
Yeah, and I think, I like to think that neurodevelopment is absolutely intertwined with like our infant bonding. And you've mentioned this a little bit with our focus on kangaroo care. And obviously we're trying to change the culture about family centered care, family integrated care. But I'm hoping you can speak a little bit to viewing ourselves as healthcare professionals interacting with infants.
as modifiers in this brain maturation while they're here in the NICU, where sometimes we can't, the parents can't get there for so many reasons, right? So many of our societal challenges of getting parents to NICU, or we still have a culture problem in our unit where the parents are not the primary caregivers of the NICU, we're working on that, but we know that healthcare providers are going to interact with that baby at least every three hours.
So what should we do on a moment to moment basis to act as a modifier?
Terrie Inder (40:59.728)
Yeah. So not to lose the first two points you just said, though, before I get to your third, we can do more. We are not using our voices to advocate for families to be with their babies. And many countries, Canada, the UK, Australia, and New Zealand, all have paid parental leave for babies in the NACU. We could be advocating at a state level for our parents to have extended
Daphna Barbeau (41:08.526)
Hmm.
Daphna Barbeau (41:20.814)
Mm -hmm.
Terrie Inder (41:27.12)
disability leave with their babies so that we could remove that financial barrier. The second is when you talk to parents about why they're not in the NICU, it's nothing to do with transport and the siblings and everything else. We make that up because what we present are other sociological, I really believe it's a sociological experiment now, sociological barriers in the way that our unit values this. And if I could have a...
Daphna Barbeau (41:37.038)
Hmm.
Terrie Inder (41:54.672)
a drug as powerful as the parent presence for every baby, I would be paying a lot of money for it. But thirdly, if we can't, for some reason, get around these barriers today, what can we be doing today? And what you can be doing today is evaluating and valuing it. When you do rounds, yes, do respiratory cardiovascular fluids.
Daphna Barbeau (42:00.398)
Mm -hmm.
Ben Courchia MD (42:01.352)
Mm -hmm.
Terrie Inder (42:18.48)
And then, you know, don't just ask, has anybody talked to the parents or where are they or what's this baby's life been like today? But really do that. Like, don't leave it as kind of a tag on that you never get to. Really think about what is this baby experiencing today and are there non -pharmacological ways that I can make this baby's life better? So if I was living in this bed today, how could I have a better life?
Ben Courchia MD (42:41.704)
huh.
Terrie Inder (42:46.928)
And it might be that it's, I love music therapy, right? It might be music. It might be who's reading to this baby. The number of times I'm like, okay, who's reading to the baby today? You know, the parents, have they got the books? We have free books downstairs. You know, can we pick up some books for the parents? Can they get some books? I want 30 minutes of reading today, twice a day for this baby. What about, you know, me, you know, when I examine this baby, am I talking to my baby? Am I actually asking them how they're feeling? Am I...
really engaging in a gentle way that I examine the baby where I'm paying attention and teaching everybody around me what I'm seeing and what I'm interacting with another human. If I go up to another human and I touch them and they jump, then I'm feeling pretty bad about myself, right? That I like, you know, yeah, like just calmly sort of give them a little bit of support and speak a little more gently.
Daphna Barbeau (43:36.302)
Yeah, you slow down. You take a minute. Yeah.
Terrie Inder (43:44.976)
and engage with them. It's a human being that you have got a relationship with, that you are taking care of. And how can you model treating them like that? And then what other ways, I mean, you know, even for our sick babies, I love mops, you know, babies smell and taste mother's milk. You know, what other types of things could you be doing in the environment? What is the way this baby is supported in terms of their bedding? What other ways can we be making their lives better?
And so really thinking about that, if it's a baby with brain injury, we go into a rehabilitation mode. You know, how can we be providing the type of enrichment, knowing the regional neuroanatomy of where this baby's deficits are likely to be to help this baby recover? Think of granny and her stroke, or think of you're not going to be sitting there for two years watching and saying, we'll just wait and see on follow up. And then finally, I would say we can advocate for therapists.
Daphna Barbeau (44:35.79)
That's right.
That's right.
Daphna Barbeau (44:43.246)
Mm -hmm.
Terrie Inder (44:43.408)
in our unit and we can not only advocate for them, we can work with them. So how many times do we actually talk to our therapists about what they see and what their plan is for the baby, whether it's developmental or whether it's rehab. And then finally, we can do a lot more to advocate for rehab. And I don't like the word early intervention because I think that that's done us a big disservice, but we can do a lot to advocate in our states for
more services for the babies who need it. And we can use neuroimaging to risk profile. So we're not just saying everybody needs the same thing, but that we can risk profile what these babies really need, whether it's more around helping their brains recover. Hopefully we're going to one day get to the level we prevent the disturbances in brain development. But if we don't, how can we help support the families and the babies during that transition period and that critical first hundred days after they are?
Daphna Barbeau (45:38.994)
I'm going to go ahead and close the video.
Terrie Inder (45:43.12)
out of the unit. So that was a lot, but...
Daphna Barbeau (45:44.974)
No, if I could have said anything, that's how I would have said it. So I especially like your point about this term, quote unquote, early intervention. But I think what we're learning from the data is that it's too late, right? So we have to be doing the early intervention while we have them in the NICU. I know we're running short on time. So you did mention imaging. And so I wanted to ask you a kind of a controversial question.
How do you think the like the choosing wisely publication, you know, recommending against routine discharge MRIs has impacted our anticipatory guidance? And in light of that publication, who should we absolutely get additional imaging on?
Terrie Inder (46:34.896)
So, you know, I don't, you know, I respect the group that wrote Choosing Wisely. You know, it's very unfortunate, even when you read the short paragraphs that they say it's the best predictor of outcome. But of course, you know, a test does not influence outcome. And so they said, you can't have it because the test doesn't determine the outcome. Well, no test determines outcome. If I do a CBC and C anemia, the test didn't determine the outcome. It's what I do with the test, right?
Daphna Barbeau (46:53.838)
Mm -hmm.
Daphna Barbeau (47:00.974)
That's right.
Terrie Inder (47:04.4)
And so, and I understand for most neonatologists, it probably rolled out too fast and it was too scary for them. But, you know, if you don't look, you won't ever know. And you will never get your radiologist comfortable with reading and you will never feel like you can understand how to use this information to risk profile these babies. But if you had to at the moment, start doing that, you know, the kids who have any IVH at all would be a great population of
preterms to image because you will see the rest of their disturbance. Any baby with BPD that you really want to be able to delineate what kind of risk profile they're in. And we've got more and more data now coming out about the BPD brain. Kids who have actually I think the kids that are often ignored are kids with complex surgical conditions who've spent a lot of time in our units too that may have been a little early. But for the preterm, I would definitely say anybody who's got any other marker that you're concerned about.
And don't forget the kids with neck or postnatal infections, because sometimes once they get better, no one thinks. It's like the PPHN baby who had HIE, everybody just focused on the oxygenation and forgot the kid was encephalopathic and could benefit from saving their brain, which at the end of the day matters more to the parents, unfortunately, than being able to breathe. So, you know, I think we need to re -embrace getting familiar with MRI.
I love teaching the neonatologists how to read MRI. It's not hard. It's just that it's scary because there's so many different pictures up there. So the more people can start to get over their fear and understand what's driving their fear, like if it's just like, I don't know what to say to the parents and I'd rather not have that conversation. I don't think that's okay because I think what you need to do is learn some things about what we know and what we don't know.
Daphna Barbeau (48:49.134)
Hmm?
Ben Courchia MD (48:51.528)
Mm -hmm.
Terrie Inder (48:59.344)
and how knowledge is power, and that's been shown people compared discharge ultrasound to discharge MR, that the parents had lower anxiety with an MRI than they did with an ultrasound. And that you have then set that baby up for life with that knowledge.
Daphna Barbeau (49:06.83)
Hmm.
Ben Courchia MD (49:14.632)
I just would like to wrap up with one last question. We're so thankful for your time. As you mentioned in the beginning, the being comfortable with making mistakes. I think we're all very afraid of the newborn brain because it is such a high stakes organ for our patients. How do we embrace making mistakes on the path to knowledge?
Terrie Inder (49:36.88)
Yeah, I think we have to understand that we don't get everything right all the time and we have to be okay with that. And I think we have to learn. One of the things I think we find scariest about the MRI and talking with parents is that we're not necessarily trained well in communication. And I think if we can also embrace the opportunity to say, you know what?
I don't necessarily feel really good about how I communicate these kinds of things with families. I'd like to go and learn a bit more about that and not be afraid to embrace that opportunity to know, to learn more about the brain and then to, or for the larger units, I think dedicate one person who's going to really learn a lot about this area who becomes your go -to person.
Ben Courchia MD (50:33.096)
Mm -hmm.
Terrie Inder (50:33.68)
and then that go -to person can help you know how to speak to the family. But I think it's a double skill. I think being able to understand the brain and embrace the fact that we have more to learn. But that should encourage us to want to look, to learn.
Ben Courchia MD (50:52.744)
And Terry, and thank you so much for making the time for people who have enjoyed this conversation. It's my pleasure to say that you'll be with us at the Delphi conference this September. So if you are listening to this episode and you'd like to meet Terry Ender and listen to her talk and engage with her, then definitely come join us in September. It was phenomenal. We could have spoken to you for another two hours. I have taken speak on behalf of Daphna on this. This was phenomenal.
Terrie Inder (51:13.904)
I'm going to go back.
Well, I look forward to coming back in the future and maybe it'll be the redesign of the incubator or the redesign of the culture or the redesign of music therapy for our babies.
Daphna Barbeau (51:17.518)
Absolutely.
Ben Courchia MD (51:24.536)
I want to share something. I listened to one of your talks one day. You presented on innovation, I think. It had a huge impact on my career. And you opened up with a slide from the Wall Street Journal that had this very bizarre incubator. And it's still etched in my mind. Just a good view. This has really been something that I've taken with me. So I thank you for that. And again, thank you for your time today.
Daphna Barbeau (51:28.75)
Mm -hmm.
Daphna Barbeau (51:37.678)
Yeah.
Terrie Inder (51:38.896)
I'm sorry.
Terrie Inder (51:47.92)
Thank you both for everything you do for our field. You are innovators and leaders and we are all the better for your presence and your purpose. Thank you.
Daphna Barbeau (51:56.462)
very kind.
Ben Courchia MD (51:56.744)
Thank you.