John Carey, MD - 2024 Fetal Care Center Navigating Perinatal Care for Trisomy 13 & 18

Um, all right, so last but certainly not least, we're going to conclude our speaker series today with Doctor John Carey. Doctor Carey is an emeritus professor and formerly vice chair of academic affairs in the Department of Pediatrics at the University of Utah School of Medicine. Throughout his career, Doctor Carey has been interested in the cause of human birth defects and the care of children with these conditions. After his undergraduate years in medical school, he trained in pediatrics and genetics and dysmorphology at the University. University of California, San Francisco. He joined the faculty at the University of Utah Health in 1979 and became chief of the division of Medical Genetics in 1985. He has authored over 400 papers, chapters, and editorials focusing primarily on the etiology, description, and delineation of birth defects and associated syndromes. He co-authored the widely used textbook for medical students, Medical Genetics by Jordi, Carey and Bamshad, now in its 6th edition. And is the co-editor of the book Cassidy and Allison's Management of Genetic Syndromes, now in its 4th edition. Doctor Carey serves as a medical advisor and founding professional for the Support Organization for Trisomy 18-13 and related disorders, also known as SOFT, and the medical and ethical aspects of the care of persons with chromosomal syndromes is currently his major academic interest. So thank you so much for being with us, Doctor Carrie. I'm looking forward um to your view to the future. Well, thank you. Everyone hear me OK? This has been a fabulous conference, I have to say, for someone who has been struggling, pondering, celebrating these issues for more than 40 years, uh, it is heartwarming to see so many presentations all pulled together at one time. So it is an honor and a privilege for me to be here today. I want to present what I would view as one person's view. I'd also like to add that the pictures I'm gonna show of a lot of persons with trisomy 18 and 13, I have parents enthusiastic permission to show. So my purpose is to identify the important themes in the care and management of children which rise to 13 and 18, already well reiterated today, and to provide a concise and focused summary of recent advances in care and research. So I included a number of slides in the beginning of my presentation where those data or those issues have already been discussed brilliantly. So I'm gonna skip through some of those because I wasn't sure how much of them would be covered, and we'll see how it goes. So I do have a unique lens, as Leandra already mentioned, I am the chair of the medical advisory board of SOF. But I assume the care of this 2 year old, which was from 18, Carey, you can see on the left and in the middle. And uh her mother, Chris, on the right, who founded Soft, and I helped them with that founding in 1979 and 198,980, and I've been involved very closely with the organization since then, and I've been to all of their annual conferences since the first one in 1987 in Salt Lake City. Thus, I've had this rather uh skill, this privilege, if you will, this honor of seeing the families and how they valued and celebrated their children who would have what we would call, you know, profound disabilities and now life-limiting conditions. Picture down on the far right, there are the 1st 5 kids at the first meeting in Salt Lake City in 1980. So here's the poster that Soft usually shows at various meetings, including genetics meetings. A lot of the individuals up on the, the far left. Megan is now in her early 40s. She lives in Oklahoma. Stacy on the far right is the daughter of the former president of Soft. She passed away a few years ago of some medical complications and other children in the gallery. I just wanted to bring your attention to a book that Soft has just published. I had the chance to help write some of it for expectant parents. So for all the fetal care centers, this book is available online and also available uh to be downloaded or to purchase by printed copy. You can see the website underneath. You don't have to write it down though. It is available on Soft's website, Trisomy.org, uh, and you can see it on one of the first dropdowns. The Trisomy 13 book is now being prepared, and ideally will be completed and published by March. Another picture of the number of children I know who I both cared for in Salt Lake City, Utah, as well as know from soft meetings and other encounters. The girl on our right, on the bottom part of the picture is now in her early 20s and was the first child who had open heart surgery at Primary Children's Hospital, um, since the time I had moved there in 1979. Little guy with that fancy tie on the bottom left is from Uruguay. He has trisomy 13, and he came to Primary Children's and our Shriners for care over the years, um, and sadly passed away a few years ago of a significant pneumonia. So here's my outline. I'm gonna go through the 1st 12 or so slides fairly quickly. It's really gonna, it's really going to like summarize what has already been stated. I have a slide on the American Association of Thoracic Surgeons, like we've already heard from 3 other speakers so far today. Um, so, I'm gonna go through those quickly, try to get down to my last dozen or so slides on research and care methods. But hopefully, that, as I said, will summarize some of our previous talks as we end today. So, as has been stated, the basic premises, which I called conventional or traditional, uh, in the, in the paper that Dan cited from 2012, uh, non-intervention of currently comfort care done, we know nowadays in a compassionate way by our pediatric palliative care teams, or varying degrees of intervention that Dan outlined so well in the Journal of Pediatrics paper. Starting around 2006 with a paper published by Tomiki Kosho from Nagano Children's, which I'll show you in a moment, there's really been an emerging dialogue, and I think that the paradigm has really shifted, and today's talks really underscore that in a way I couldn't have envisioned 10 years ago. There are some landmark papers in this history. I'm gonna just point to them here, so you know about them. I'm gonna recommend reading all of them, and then I'll go through some of the other ones as well. The paper by Duff and Campbell really first brought up the idea that maybe it was ethically appropriate not to intervene or treat in children with trisomy 13 and 18, Pediatrics, 1973. The paper by Bozael in Lancet Group from Holland, actually really laid the case out that trisomy 18, in this particular case, was a condition with a hopeless outcome, and they made a fairly firm recommendation for non-intervention. So, three milestone papers leading up to the reasoning that might be that we could call the previous paradigm, what's existed until recent years, was as I mentioned, the paper by Duffin Campbell in Pediatrics, the Bowes paper, and thirdly, the paper by Emilton from the UK in 1996 where The paper sort of came out like, these kids all have central apnea, that's gonna take their lives. There's no reason to consider cardiac surgery. I obviously oversimplified it, but that pretty much was where that led to, and I think led to the platform in the 80s and 90s and so on. There's Tomihiko showdown on the far right, neonatologist and geneticist like Dan Swar. Um, and he published his paper, American Journal of Medical Genetics 2006, where he offered 24 families with in Japan, full intervention, although they could only tie off the ductus, they could do no other cardiac surgery. And all 24 families chose full intervention, and as you can see, 22 or 24 versus 12 out of 24 survived the first week, and uh 6 out of 24 survived the first year. I think that really was the initial paper that addressed the question, does intervention. Increase or improve survival in trisomy 18. And of course, a lot of it would apply to trisomy 13. In pediatrics in 2008, McGraw and Perlman, two neonatologists, polled New York neonatologists with a case where, where over half of them indicated they would not resuscitate the baby with trisomy 18 in the delivery room, who also had VSD. But more importantly, read the discussion, because McGraw and Perlman bring out in the discussion, this idea that the best interest standard should be our organizing principle, yet the pendulum was swinging more toward parent autonomy in a way what might be the best interest of the child. Again, read the paper, see the tone. I think that was a biopsy of where we were in the, in, in the late 2000s. I'm gonna skip this slide. Another neonatology survey by Jacobs Eal uh showed the opinions of neonatologistists published in the American Journal of Medical Genetics that didn't, 00, it did show up here, sorry, in um 2016, and they pulled them on certain views, and as you can see from the views, um, 60% said active treatment of a fetus and newborn is futile. 45% said trisomation is incompatible with life this 2016. And uh over 50% said an infant should not be resuscitated. So, again, kind of give us a feeling of the views, but it's somewhat of a contrast with that, in a study that I'm gonna tell you about that we're still looking for funding for called the TR study, I'll tell you about it, one of the last slides. We polled the neonatologists that represented over 40 NICUs in the country about some of their views. And almost 70% felt that the conditions were compatible with life and providing interventions prolonged survival. But about a third felt that children could not live a meaningful life. And also they had concerns that parents really couldn't understand what the health challenges were, just to kind of give you a sense of where those views were. Dan cited my paper in his first presentation, 2012 invited Paper in Kins of Pediatrics, where again, we've heard the word balance nicely depicted in the, the, the Zen stones that were stacked, uh, striving for balance. And I, I think uh I'm gonna read my sort of summary key point, and I think I would still stand by this summary now 12 years later. The counseling process should include presentation of accurate survival figures, avoidance of language that assumes outcome, communicational developmental outcome that does not predispose perception of quality of life, and respect for family's choice, as it was stated in our last speaker, or whether it's comfort care or intervention. So various key papers, Doctor Jean Pierre's paper in pediatrics that polled social networks for views of families, over 400 families. Parents recognized the challenges, saw the joy, and felt there was a good quality of life. You already saw the slide on the right down there, that was a balance from what we had in textbooks, two of other Doctor Jean Viere's papers. I'm gonna skip this slide since I'll mention in a moment. And Dan also mentioned the paper by Marty McCaffrey, where he kind of made a parallel between where we are now, and this, this was 2016, and trisomy 18, similar to where we were in the 1970s when I was a pediatric resident, um, in the care of Down syndrome, where it was common to not offer surgery when a child with Down syndrome had duodenal attrition. It, we've already heard shared decision-making at least twice today, and I'll close my last slide with just mentioning it as the model, um, but as you know, somewhat easier said than done. But how in her paper and her colleagues in JAMA Pediatrics in 2017 really outlines, this was a review article, really outlines scripts and ways to approach this and the ingredients of shared decision making. Again, I recommend this paper. And then, Brascoe and Chris Fritner from CHP had a very elucidative accompanying editorial. Again, key papers to read when you're thinking about this, so. I'm really gonna run through the yellowed part here, the highlighted part, because this was really covered by all of the talks today. I was gonna talk if it hadn't been covered so brilliantly. Survival outcomes and evolving data. But we've already heard about the high frequency of congenital malformations, especially the heart. We know about increased neonatal infant mortality from the population studies, and we've heard about and know about the developmental outcomes. I won't reiterate it here. I think one of the points to emerge, and it's been brought up today when we talk about life-limiting. Uh, sort of, we go through this list, sort of the common functional issues and challenges in both trisomy 13 and 18, that we're talking about a condition of medical complexity. And I think that our complex and comprehensive care colleagues are developing and have, have come up with ways to approach ongoing care, which are beyond just checklists of tumor screening, your early intervention referral, and so on. I think we're gonna see more on that from those colleagues. But here, I'm gonna go through quickly, we've already heard this, Dan already mentioned. The key population studies, these were population studies over time. Best ways, I think, looking at survival as opposed to hospital-based studies. But basically, bottom line, you know, as of 2014, about 50% or higher of children died in the first week of life, and one-year survival ranged from 0 to 2, averaged about 5%. 1 in 20 surviving the first year, median usually in single digits. But we started to see papers that you've already heard about on increased surgeries and hospitalizations um in the latter first part of the last decade, and the papers by, you've already heard this too, by Meyer, the multi-state study, large numbers of kids, 1-year survival, 13 and 11% for 18 and 13, respectively. Uh, we, we've already heard somewhat about those, but they were a marked contrast to the population studies of before, and we've discussed Nelson's study, um, at least 2 other times. But importantly, Nelson's study, as did Meyer's multi-state study, raised the question, does intervention increase or improve survival, which, which the study, Journal of Pediatrics, Doctor Cortezo, Uh, Leandra and Dan Swar, brilliant paper, population retrospective cohort. Dan went through the data. I won't report it, but it demonstrated, based on numbers we would all say are small, that intervention does increase survival. So just as a place or slide here, 33 patients of mine I've known for a number of years, uh, all showing that there are other ways to get around and ambulate, uh, other than error. Two legs. So, let, let me talk more now in our remaining moments, um, about some key issues that lay the groundwork for future research. Someone I would call sort of like a compilation of themes around bioethics, which I alluded to in the McGraw Perlman paper. They brought up issues that are brought up in a lot of other papers, um, who makes a decision, allocation of resource always comes up. Well, quality of life has to go to the decision, the pain and suffering that the families and the child may experience, but again, that this notion of the best interest of the child. And the papers by Lorenzo and Hardart and also Pyle and Mark Mercurio, uh, in recent years, also bring out these issues. Again, I recommend them strongly, if you wanna like make the list and think about it, work, work the, the discourse one way or the other, um, and again, bring out the importance of the internet that we're talking about. People know, uh, there are older kids when they come to the fetal care centers and so on. But I found this paper by Ben Wilfon, pictured on the right. I'm gonna mention in a few more slides, pulmonologist and bioethicist, um, colleague from Seattle Children's, and he took this work. He's a senior author on this paper. They've published this and other reports, but this is in the Hastings in 2019, and this idea when we talk about the best interest or other standards, they brought out this really intriguing notion. Of a standard based on the moral value of the caring relationship of the parent, and I would say, and the child, but also to the child. That, that was an organizing principle that would lead us in terms of how we might be guided about decisions that we, we'd call bioethics. Of other, other sort of bodies of work that's emerged in the last 5 years have been the qualitative studies on parent narratives. Again, Doctor Koshu, I showed you early, early on how a paper in the American Journal of Medical Genetics, and his appendix has more than 50 paragraphs or sentences about parents and their perspectives. I'm not gonna read the one there. I'll refer you again to the paper. Uh, that really reflected parents' voices along with Doctor Javier's work, I think, for the first time. But there are 5 other papers in the last 10 years. This is a body of work that I'm saying we should be plunging into more, and Doctor Henner really gave us a good sense of that in her talk. Uh, I, Doctor Beer, one of my colleagues at the University of Utah, we actually polled 46 families of trisomy 18 at a SOF conference about their story and published that recently in the American Journal of Medical Genetics. And one of the quotes that Ryan had was, her daughter was born alive. Again, the expectation issue. This was such an accomplishment after all the negative possibilities we have faced during her pregnancy. See how we're doing here, OK. I'm really, I'm not gonna discuss the cardiac surgery part. Um, there was even two recent papers on cardiac surgery. I will show you them in a second. Here, of course, again, is the AATS study, which I'm glad to hear that we're so much there today. That's a younger picture of Doctor Saint Louis there down on the left. Um, but, here's a summary statement that I think reflects the change of where we are compared to, let's see, where we are at McGraw and Perlman in 2008. Based on our analysis of recent data, we recommend that decisions should not be based solely on the presence of trisomy, but instead should be made on a case by case basis, considering both the severity of the baby's heart disease as well as the presence of other anomalies. These recommendations are for a framework to assist parents and clinicians in surgical decision-making. For children who have trisomy 13 or 18 with congenital heart defects. I, I will say that I do regret as a co-author, and we did discuss this, that we did not get a lot of parent input in this process that we had to come up with these recommendations, but we're hoping that we'll get a lot of perspective after. So again, some recent studies of note that this by my colleague, Doctor Kosa, actually, this paper submitted to JAMA Pediatrics, but it was uh, this actually took fetal care centers and cardiologists' perspective in their particular subgroup in the fetal care centers, and how they viewed discussing cardiac surgery uh in the fetal care center. That's Doctor Kosov there on the left. And while this paper, of course, is going to be under review, uh, it, it did show that there was a difference. And there were, in a previous study, only about a third of cardiologists discussed this prenatally. Well, now, over 60% did. Well, it was almost 100% they discussed cardiac surgery uh in trisomy 21 Down syndrome. Also in the way of, of future, I was so intrigued by the surgery presentations today because I, I don't think it's well known, but Soft actually has a surgery registry with hundreds of children recorded who've had various surgeries, and I keep wanting to pull it together. Today's talk motivated me again with some of my junior colleagues to work on that, but we did put together, sort of, we have 201 families who have had Cardiac surgery with trisomy 18, and now almost 40 with trisomy 13. And I, I've, our, our goal of our surgery, which I'm working with Doctor Kosev and others, uh, is to actually pull these families now, um, and to see where the children are now. Most of these surgeries were performed in the last 12 years. Uh, you saw this picture again, in the last study, but, uh, Doctor Lebanov, one of my, uh, former colleagues, uh, polled some families with trisomy 13 and living with trisomy 13. Uh, database, their, their Facebook, and we reported adult issues in trisomy 13. This is really to say there's so much more work to be done on adolescents and adults with these syndrome. The only thing we know comes from being at support group meetings, soft and other ones, cause there's so little reported. Most of the case reports are in individuals who are 10 years or less. I noticed 3 of the individuals, including the girl in the pinkish red shirt, did walk unassisted, usually after the age of 6. So here's some other key papers sort of bringing up issues of present research, but of stimulating future research. So, this nurse midwifery group had a recent paper on family-centered antenatal care with life-limiting fetal conditions, a developmental theory guided approach. I just found to be a really novel way to look at qualitative research. This, by the way, was in trisomy 18 and 13. And Doctor Baird's group at Boston Children's also has a recent paper. Doctor Green, the first author of the operative uh Outcomes that we heard about from, from Children's Cincinnati today. Uh, another paper of that, there's, uh, 5 other ones in recent years. And then there's work on tracheoesophageal fistula and trisomy trisomy 18 and 13, primarily trisomy 18. Most of it's come from Japan, just on the hallmark of future research, just talking about the question of palliative approaches, non-intervention, and full repair in tracheoesophageal fistula. The one down on the bottom right is another neat qualitative study. So again, future thinking, future care models. We've actually heard about Doctor Megan Weaver's team approach at Children's, and I know that other people, I heard about Laurie today, um, Cincinnati, of course, our hospital primary Children's. I, I have the meeting after this of our monthly meeting of our team, uh, interdisciplinary care. So, I consider that in terms of care models, that's, of course, more than on the horizon and where we need to go. Of course, the goal in all this is what I call the ABC's. Accurate, balanced, and current information to allow parents to make their decision. So, um, let me, let me, I'm just about up my time here for the 25 minutes. So let me, uh, just mention two other, two other projects ongoing that will lead to research. It was alluded to earlier by our multi-center, multi-NICU study. We proposed NICHD but they changed the model. So we, we got scored but not funded. And it's a prospective longitudinal study investigating survival outcome. It tries to be 13 and 18, but importantly, to also obtain parent perspective, Doctor Jean Verre is one of our colleagues. We have a qualitative research team. We're actually applying to Pori now, if you're familiar with that database, and the study aims, uh, I won't go through them in the interest of time. Um, to, to look at, uh, in detail, in depth, at the NICU experience, and then the first year of life in babies who do survive, and then, Understand the impact of caring for an infant by qualitative modes, but also parent perspective by qualitative modes. So that, that's the goal. Another important project I want to mention, which will lead to current research, and all of you interested in Trisomy 13 and 18 research could now uh alert your ears. Um, so, Doctor Ben Wolfan is the director of vision of the Trisomy Collaborative. Some of you may be familiar with this particular undertaking. The vision and mission statements are there. There isn't a website yet, there will be one soon. But this particular project has its goal to lead to a funding resource for professionals and parents who are interested in gaining more information or developing models around education in trisomy 13 and 2018. So, follow the data. Summary Uh, you, you've heard that before. Follow the data, so. Summary, um 6 and now 19% based on the Cincinnati Children's Study. Children survived the first year. But we know that intensive intervention, including cardiac surgery, improves 1-year survival. Greater than 5-year survival is greater than 10% of, of those who are born. Children do progress in their milestones. Um, our, our goal is to give information as accurate, balanced, and current. Parents should be and are more often part of the decision-making process, and we'll put that under the umbrella of shared decision-making. So, I thank you for your attention. And uh I know we probably have to have some closing comments, and I turn it back to Leandra. Thank you so much for sharing that and for sharing kind of our vision for the future through the TRIE study and what we're hoping to accomplish there. Um, I'm not seeing any questions in the chat yet, but, um, Doctor Gilganser Hoffman, do you have any questions? Um, no. Thank you to everybody for joining us and listening to our experiences. Um, Doctor Currie, I was just curious, uh, what the various, uh, stakeholders or, uh, people have been in terms of supporting the study that you're trying to do. Is there a lot of enthusiasm enthusiasm behind it, or does it feel like you're kind of still walking uphill? Actually, there is a lot of enthusiasm. So when we went to the neonatal Research Network with the concept, first, as Leandra and Dan know, 2 years ago, uh, there were some comments, and we got some good feedback. So then we put in a better, our concept was just the beginning, and we put in a, a, a Project, which was actually approved by the steering committee, a little bit less than 2 years ago, but then NICHD changed the model. But because we weren't funded, there was enthusiasm to apply to the Patient Centered Outcomes Research Institute, which you probably know as Bakari. And in fact, all but 2 of the neonatal Research Network centers want to be a part of that study and have committed. So, we have, we have 20 centers, including some that are not part of the research network that have agreed to participate. And so, um, we, we're, we're seeing a lot of enthusiasm about continuing. The, the, this particular study has the benefit of larger numbers and also benefit of being prospective, so even the parent perspective is in real-time. That's what we've actually been. Be purporting. So, yes, we, we have actually seen enthusiasm from the neonatology community. If we do actually have all of those centers involved, the live births that would come from the NICUs involved would actually be 20% of all live borns with 13 and 18 in America. So it actually reflects, and that would be even ones who choose comfort care, or, you know, it would not only be those that are choosing intervention. Thank you for the question. And I, I loved your talk, by the way. Thank you.