Anita Moon-Grady, MD, FAAP, FACC, discusses congenital heart disease (CHD), the most common cause of infant death due to birth defect in the United States, and the advantages of prenatal diagnosis of CHD in regard to survival rates, length of hospital stays, improved surgical outcomes and costs.
Refer to Fetal Treatment Center I'm really happy to be here as part of this kind of conference where we talk about cardiovascular care through the continuum instead of just focusing on, you know, fetal diagnosis of congenital heart disease, being an obstetrics problem or pediatric diagnosis of heart disease being a pediatric problem. This is really um, as we've gotten better and better at neonatal cardiac surgery, we're seeing um uh more of our patients survive and their surviving into adulthood and they have jobs and they have health insurance of their own. And uh and so I think this is a great idea. So I'm going to talk about the prenatal side and what exactly that entails and where we're going um with that. Um, and I'd like to think of my job as being rewarding because um, I can make a difference. I'm a I'm a doctor, I went into this for for that reason. And so the question some people ask sometimes as well, what difference does it make? Can you make a difference with prenatal diagnosis? Are we able to affect survival, short term morbidity? What about the long term And then, um from the other perspective of the health care system, are we able to make a difference in terms of cost for the care of that child or for this group of patients collectively? Uh are we able to maybe impact overall disease prevalence? Uh and what other aspects may we be able to make a difference in not just for the individual family, but but overall To put this in perspective, congenital heart disease needing intervention by one year of life is approximately three per 1000 live births which if you think about it is so much more than almost any other disease that we deal with. And certainly it's the most common birth defect that causes infant death in the United States. Um and several years ago now. So this number is only hire the C. D. C. Was estimating health care costs for treatment of these conditions to be over. Uh almost $2 billion per year. So a huge amount of money huge problem. And uh so I think that it's very important. It's also important no matter who you are across uh country's socioeconomic status. This is not a third world problem, is not a first world problem. The incidence of congenital heart disease. This is a paper by Julian Hoffman who's an emeritus professor here um and is really considered the paper on the subject. I found that there's no evidence for significant differences in incidence of congenital heart disease in different countries. Um And trying to detect it in my own experience is also something that that is across countries what they do with the information may be different. Um But countries in Thailand are promoting efforts to increase prenatal diagnosis. This paper is from Nigeria where they piloted a program and uh and found benefits too uh to prenatal diagnosis of congenital heart disease and screening for it and then here in North America. Uh We also have studied this uh prenatal diagnosis. Not the only the impact, but also the uptake and the costs uh in quite a bit of detail. So this is a worldwide problem affects everyone no matter what race color, educational status. Um, they are and what is it that we're trying to do with prenatal diagnosis. It's not just information to know something earlier. There are several what I think of the categories of congenital heart disease that really stand to benefit. Uh the family knowing ahead of time, those are the ones that are severe what we call ductal dependent at birth. They need to have medications started at birth to keep certain fetal connections open so that the that the baby can be stable enough to make it to surgery. So these are hypoplastic left heart syndrome, pulmonary atresia, some some names and and codes you may have have have heard of interrupted aortic arch. So there's a list of these and these are fairly common. Then there are also uh, fetal heart lesions that really no matter what they can do at a nursery, what the patient really needs is to be in the close proximity of a surgeon or a cardiologist. They need something either balloon dilated open or they may need urgent surgery and they just can't be stabilized with other medical measures or medications. And so those patients are real emergency need definitely need to be delivered at a tertiary center. Whereas the previous ones, songs we know about the diagnosis, they can initiate their care elsewhere. And then there are of course the babies who don't ever make it to being delivered uh because they are at risk of dying in utero from their congenital heart disease. So these three broad categories um I think really highlight what it is that we can do. We also of course detect small holes and minor valve abnormalities and things that uh that worry the parents but would have been fine if they had just been discovered post natally. But going into it, we can't know whether it's going to be serious or not until we actually look. So it seems like a good idea, right? Initiate a prenatal diagnosis program. You can you can cut down on transport costs, you can prepare the family. Uh so if we just do the ultrasound and look at the heart, we will we will see these. Right? Uh this is the 21st century. Uh So how are we doing? Well, the answer is not too well. These are two companion papers uh from they were published in 2000 and nine. The data was from 2000 and 4 to 2000 and five. And I participated in the northern California paper uh and some colleagues of mine in the southern California paper, where they asked these are all of the major surgery, surgical centers in either northern or southern California. And they asked the parents a simple question when their baby was admitted for heart surgery or for urgent intervention. Did you know about this before the baby was born? And the answer was, in northern California, only 28% of the time was the answer? Yes. So were these people not getting prenatal care? No, 99 plus percent of these women had an ultrasound in the middle of their pregnancy to tell the sex of the baby or if it had its fingers and toes or with their brain there and they just missed the heart disease. So what happened? Was it too difficult to tell? Was it too early? Was that 2005? Was that just California? The answer, of course, is no. Um this is a paper that came out very recently, 2015. Looking at the Society of Thoracic Surgeons database, at patients infants who were operated on in different regions of the country. And whether or not they were prenatally diagnosed. And again, now, this is what did I show you before? 30% for 2004. This is 2015. We have not gotten any better in California. So something needs to change and we should be able to change this. If we look at just a beating four chamber of the, of the fetal heart, you probably have seen this if you've had an ultrasound or you're Uh your daughter's daughter in laws or friends partners have had ultrasounds. You can see the heart beating and it has four chambers, or it looks like this tiny little picture up here. If we add looking specifically at the arteries that exit the heart, we should be able to detect an additional 40%. So the four chamber view should be able to detect 60%. And adding outflow tract views should allow us to identify almost 97% of congenital heart disease in the second trimester of pregnancy. It's already there. This is a birth defect that formed when the fetus formed back in the before the mom even knew she was pregnant. Um So we should be able to do better. And I have been part of a lot of efforts to try to improve this, make people understand what it is that they're looking at to recognize the difference between normal and abnormal and to do a complete exam. That includes both the four chamber view and the outflow tracts on every pregnant woman. Um Is there evidence that this does make a difference? I think I've I've already sort of made a pretty good case for that, but um but I do like to be evidence not anecdote based. Uh this was the first paper that really uh convincingly showed that there was a difference in survival if a baby with hypoplastic left heart syndrome was born uh with a prenatal diagnosis in a controlled setting in a tertiary care center versus was born outside the tertiary center and waited until they presented with either a murmur or shock or something else and had to be transported in. So prenatal diagnosis versus postnatal diagnosis, they showed a significant uh increase in survival in the patients who were prenatally diagnosed. This was here out of UCSF, one of my colleagues, Wayne Gretzky, who's in boston now, Uh and these patients went up until 1999. As you can see, I have circled this paper has been cited multiple times and this is the one that we usually site when we say prenatal diagnosis does make a difference in survival. Um And it leads people like me to stand up here and say prenatal diagnosis allows coordinated delivery of infants in an appropriate specialized setting. I think I even have that on our website. It sounds so good. The problem is, the problem is it's actually may or may not be true. Um There are conflicting studies about congenital heart disease in general that needs neonatal intervention and specifically about transposition and hypoplastic left heart syndrome. So, just to show you a little bit of what the what I'm talking about and what the problem is. Um as far as mortality in congenital heart disease overall. Um Josh Koppel from Yale showed way back in the 1990s that there was no difference in survival uh in their cohort on the east coast. This was followed up in the same setting by a junior attending named Levi. Um But the same new york area In 2010 again, if they looked at all comers of Children who had heart surgery before, they were a year old prenatal diagnosis versus post natally diagnosed didn't actually affect their survival. And uh a disturbing paper from 2014 the prenatal diagnosis patients, which is the graph, the dotted line that's on the bottom are the prenatally diagnosed patients. So they actually did worse. However, the speculation from this type of data is that there were probably there's probably more severe disease in the prenatal diagnosis group because the paper wasn't adjusted. So they treated a baby with hypoplastic left heart syndrome, the same as a baby with just a small ventricular septal defect. They both need surgery in the newborn period. Well, the baby with hypoplastic left heart syndrome was more likely to die anyway from the surgery, we don't have perfect survival. So, and hypoplastic left heart syndrome is a little bit more obviously abnormal on a four chamber screen, more likely to get picked up. So, so there was no adjustment there and that I think is the problem with looking at this kind of data to say, prenatal diagnosis doesn't improve your survival. What about for specific heart lesions then comparing like with like this is for transposition of the great arteries, this is usually a single heart surgery done in the newborn period. And these individuals often don't need another surgery for their entire life. They are normal, they can exercise. They they are expected. Now, we don't know because we're doing the surgery since uh for too long just since the eighties, but we are expecting that they're going to have uh normal lifespan 70 80 90 years. So this is a great one to study. Um and in uh 1999 excuse me, in France Bonnie at all did show that there was a reduction in both pre operative mortality and operative mortality if the patients were prenatally diagnosed. However, in a different setting. Um, this was not found to be true. And as a as a matter of fact, the prenatal diagnosis patients were hospitalized longer. Um again, comparing the positive. Yes, it affects mortality with the United States in a slightly different era. No reduction. But as you see, I've I've listed the things that actually were different. So that starts to come out that well, they're not dying. But we're so good at this surgery now that none of the Children should actually die, even if they're very, very sick when they present. And that's what the, what the difference was, was in um in pre operative mortality and acidosis and ventilator days initially was not different. But as we've gotten better, this has become different. Um these prenatal diagnosis patients actually might have been in worse shape. They were delivered earlier and I'll come back to that. So, um and then this goes on since I was a little late. I'm gonna skip all of the data because I think I've made the point that it's not as cut and dried as we like to think it is. And as the websites say, um there is only this one contemporary paper that uh looked at transposition and total anomalous pulmonary venous return, which both of these need urgent intervention. So it's good if they don't have a huge transport ahead of them. Um And the in this paper, thank goodness. Uh we're back to showing that prenatal detection is at least associated with a shorter hospitals day and uh lower pre operative in a trough scores or in other words, better condition. Uh the baby's in better shape going into the surgery. Um This has also been true uh with prenatal diagnosis of hypoplastic left heart syndrome, that there's conflicting information that Turetzky article that I showed you at first. And then a contemporary article that that contradicted it. And uh the Children's Hospital of philadelphia, same thing, no reduction in pre op mortality and hypoplastic left heart syndrome. But starting to see improvements in uh in uh in the condition of the patients. And then uh what I really wanted to show is is this comparison to just to this group because this is the turetsky paper that was UCSF up until 1999 we asked them for uh just where the date cut off was for that and went back into our database 10 years later and looked at the next uh 10 years worth of patients to see if it was still true. Since so many papers had been refuting this turetsky article. We said, well, let's look at at our um environment again. So, same surgeons, same icu different authors um in this uh this current era paper and we looked at 81 patients. We saw more preoperative intubation and longer ventilation for the missed patients. For the post natal diagnosis patients, they were more acid attic, they had more multi organ failure. They had like a spit valve regurgitation, ventricular dysfunction. Yes, there was no survival difference between pre and post natal diagnosis. So we're agreeing with everybody else. It's not about surviving anymore, but but the babies were more stable if they were prenatally diagnosed, which should translate into better candidates for surgery. However, caveat, they were also i a tre genetically born earlier. They were lower birth weight. And uh and this is a huge problem because 38 weeks versus 39 weeks actually makes a big difference in terms of your neuro development and your survival and your overall complications. So, the prenatal diagnosis patients were having this diatribe genic early delivery because we knew that they had this and we wanted them to be born here. So we didn't wait for the moms to go into labor. Um So, so this was something that really opened my eyes and I've been sort of on this bandwagon about it ever since other contemporary data uh is starting to agree with us. This is uh from Jason where they had no difference in survival between prenatal and postnatal diagnosis. But the post natal diagnosis patients were intubated more and in the subgroup of patients with hypoplastic left heart syndrome, there actually were more deaths in the post natal group, although it didn't reach statistical significance. Um there's been enough information now to give us the ability to do a meta analysis. That overall is a sort of favoring prenatal diagnosis as really. Um probably making a difference for planned neonatal cardiac surgery. They have better ph lower lactate, fewer aina tropes and better ventricular function and are better candidates for surgery. So, we're trying to drop the mortality as an endpoint for this. Our goal is actually to have every baby who has heart surgery survived the surgery, but we want them to survive it and to do well. What about the cost um cost related to uh increases in hospitalization, increased costs due to transport and intubation and lifetime costs related to neurologic sequelae are all potential targets. Um The California, the northern California paper that I showed you at the beginning to took a second look at those patients. Um the 30% 28% who were prenatally diagnosed versus the ones who are post natally diagnosed and compared pre operative costs. So it's it's hard to control with that small of a number of patients carter control for all of the potential costs beginning with the operation. But we're assuming that all the patients had the same operation and have the same post op care. We just looked at the pre operative costs including transport PG. E. Intubation um length of stay length to to get them stabilized. And as you might expect, we showed a significant difference in healthcare system costs associated with the missed diagnosis group of patients. So we can uh affect the costs related to the immediate term as far as the lifetime costs of taking care of that patient. There has not been really uh really any good data. The California experience was mirrored in this paper from, I can't remember this one is from I think this is from Australia but it's just sort of what you would expect. But people actually scientifically showing that uh A small increase in prenatal diagnosis. This is from uh let's see a detection rate of 30%. If you move that detection rate to 50%, you get that huge reduction in cost. So improving the prenatal diagnosis also will save the health care system. Um uh money. So where are we in 2018 2019. Now we know that prenatal diagnosis decreases the need for transport intubation PG results in a better candidate for surgery. They're less Asiatic, have less cardiac dysfunction. Which probably will lead to better neuro development in the long run it may result in improved mortality for select congenital heart disease but that's no longer the goal? Um What about The mother? I've spent all this time talking about the baby, but what about the mother? Prenatal diagnosis and maternal stress is something that that is also very, I think, interesting to our group because as you can imagine, you're 20 weeks pregnant, you go in to find out if your baby is a boy or a girl and they tell you that the baby has a serious, life threatening heart condition, that's going to require neonatal surgery. You have, you can't have your home delivery or your delivery, you know, close to your house that you always dreamed of. Uh and your baby is going to be in the hospital for a month after birth is going to have two more surgeries by the time they go to kindergarten and oh, by the way, there's only a seven out of 10 chance that they're even gonna survive to age five. That would be quite a bit of stress. Now, we're telling them the same thing after baby's born. If there's no prenatal diagnosis, we're telling them the same thing. So are the ones with prenatal diagnosis better able to handle the stress? Do they have more time to process the answer is probably um, it's probably not. They score the same, this is prenatal versus postnatal and black versus white, but you don't need to know which is which to see that they're all the same. Um, optimism state anxiety, trade anxiety. Um and other events were all studied in the immediate term after the baby was born and the women with prenatal diagnosis didn't score better. Um And actually as a matter of fact, if you go out six months, the women with a prenatal diagnosis were still stressed way more than the women without. So we could do better with this. Uh Not only because it's the right thing to do, but there have also been some animal studies and uh even some human studies showing that stress effects on the fetus and no neurologic development in the fetus are affected by maternal stress and maternal cortisol levels. So we probably need to do better at managing the stress that these families take on when they are prenatally diagnosed. But it's an intervention that we can do and it does need to be more more studied. Prenatal diagnosis also gives us the opportunity to um to mitigate short term morbidity is for these patients. Um because we can risk stratify within and between diagnostic groups to develop a tailored management plan and individualized estimation of risk. So we can get really detailed prenatally before the kid ever has to get sick about what they're gonna need. Maybe this one can deliver up in humboldt probably not, but maybe they can and maybe they can just come down later or maybe we need to get an entire O. R. Ready so that the baby can go immediately to the O. R. So we can we can risk stratify patients within their general diagnostic category to to decide exactly how much uh time and effort. And do we need to spend as a health care system and exactly what does the do the parents have to give up or do? Uh in order to uh to encourage the best possible outcome? So we call this perinatal management planning and tailored counseling. Um Alice I think told you a bit about that we have our whole fetal treatment center is set up to do exactly this type of thing, provide a correct diagnosis and multidisciplinary team to come up with the best plan for that baby and to to present the options to the family. We also do medical perinatal management. So we're not just giving people information. We're actually using science to uh help decide what we're gonna do with that information. How are we going to manage that pregnancy now that we know that the baby has heart disease where when how C. Section or vaginal delivery what would be our triggers? Why would we deliver? And how does that stand to affect outcomes as far as morbidity, mortality and neurodevelopmental and functional status. Um The options um are the sort of the, yeah the the options for where to deliver the baby um have been pretty well worked out in these risk stratification schemes mary d'onofrio from Washington D. C. Has really spearheaded this this particular paper is uh is from stanford. Uh But she's written about this as well where you can sort of look at the at the overall heart disease and other things that are wrong with the fetus and decide are they going to go for comfort care? That's one level. Or that can they level one deliver at a local hospital? That might just be a small VSD. Or do they need to deliver level three tertiary nicu level four level five. So uh so people are starting to use these types of levels. This was in the american heart association statement that we wrote a few years ago on management of fetal heart disease. Um There are lots of papers showing the reasons why you might want to deliver at a tertiary center um and uh sort of broken up by by physiology that we can easily see with fetal echo. Um So that's the where it depends on what the heart diseases. How about when? Well for this we have a little bit less data. There's data from from normal newborns showing that late preterm and early term birth in non anomalous infants is associated with increased respiratory problems. Nicu admissions, hypoglycemia, sepsis and death. Early term meaning 38 weeks. Um 38 to 39 weeks infants born at 39 to 40 weeks have higher I. Q scores higher academic achievements. And Jeff generally do better than their 37 to 38 week counterparts. So we used to think 37 weeks was term. Let's get them out. We do not think that that is good enough anymore. Certainly for normal newborns. What about for those with congenital heart disease? Is it the same or do they get some benefit of being born early from their congenital heart disease? The answer from the again from the society of thoracic surgeons database Is no. That u shaped relationship that crosses the line right here between 39 and 40 weeks Is also true for congenital heart disease patients, they have fewer problems and better survival if they're born when they're supposed to be born at 38 to 40 weeks Um complications as well. Come down. Uh if you deliver at 40 weeks. Our general guideline based on these, on this data is that Neo Nate's who undergo cardiac surgery should be delivered at 39-40 weeks. And that in the absence of fetal or maternal indications for an earlier delivery. The potential logistical advantages of scheduling the elective delivery of fetuses because mom lives too far away or she lives over a bridge or it's not convenient for her. This should be carefully considered and discouraged. Um These socially social reasons for delivering earlier. So we did where we did when what about how the majority of fetal cardiac lesions can be managed expectantly, they can be induced. There's new data showing that induction of labor at term is just as safe as waiting for natural onset of labor and C Section should only be reserved for specific cases that really require a lot of coordination for the most part. Um There's no improvement in app gars uh ph at birth, neonatal distress uh in C. Section versus vaginal delivery. The group at chop have also looked at hypoplastic left heart syndrome in particular and shown that the C. Section babies versus the vaginal delivery babies, they do the same. They're fine to deliver vaginally. So knowing all of that information, how are we doing here in California? This is a consortium that has been going for several years now. The five UCS that do prenatal diagnosis, the five UC. Campuses. So that's all of the U. C. Campuses and are associated uh sort of demographic that we treat. We looked at prenatally diagnosed congenital heart disease patients and how often they were having a C. Section shown in this graph, The blue is the sea sections 50%. So we were not practicing what we're preaching here in California. Um As a matter of fact the c. section rates at the general population in California at the time was only 33%. So and here at UCSF our general C. Section rate was only 15%. 15% is the international target for C. Section rates. So 50% was a glaring problem for us. Uh And so we've developed some care pathways of the five U. C. Campuses uh prior to the birth plan being uh set with the mother. Uh the clinicians enter data into a red cap database. What decision they're making when they're going to deliver, how they're going to deliver and there are general guidelines for what they should be choosing and then they have to enter in the database why they chose something else. So just by studying this we saw the preliminary data at R. U. C. Meeting last week. Just by studying it, we've gotten the C. Section rate down below 40% Closer I think to 33%. So um we didn't really tell people what to do. We just put the data out there and said if you're going to see section this woman tell us why. And I think it's it's been a good intervention and imagine cutting down that many C. Sections in the state of California. How much money that's saving. There's an operation, there's a three or four day hospitals day and there are women who have complications from their C. Section that the vaginal delivery patients are not going to have. So um So I think we're headed the right direction. Still a long way to go um As far as this perinatal management, the how the when the why we're trying to to now emphasize maternal fetal health for better long term outcomes um allowing the delivery and a specialized center might be beneficial for certain lesions. Uh We should still avoid eye, a transgenic late term and early. Term delivery. No C section unless there's a maternal indication. And in doing all of these things, we think that we can continue to push the needle to have better long term developmental um uh outcomes. Um So what about what about the longer term I um I think this is the real this is the brass ring. The cardiac surgeons and cardiac I. C. U. S. Are very good at getting these Children to to survive. But we don't want to have survival at the expense of long term disabilities. And uh most of these babies are probably born with reasonably normal uh neurologic status and we want to keep it that way. So what about this longer term uh morbidity? Where is it coming from? We do know that that Children who have repaired congenital heart disease have higher uh scores at school age for attention difficulties for uh for both gross motor and fine motor early in life delays. Um We used to just blame the surgeons for this, right? I'm a cardiologist. Easy to blame the surgeon. You know, I gave you a perfect baby and you gave me this kid. Um But unfortunately we can't do that anymore. It looks like their brains, even though they look normal on cT scan or MRI it looks like the brains are actually less mature than they should be. And we don't know why yet. We're actively studying this here at UCSF. My colleague Champagne Bondi is uh is leading the prenatal effort and Patrick McQuillan post natally looking at brain development in the setting of a fetus and then an infant with congenital heart disease. This data is similar to what we've seen but but is actually from uh from Kathy lymberopoulos group, Audrey du Plessy that our Children's national um looking at just one measure brain development and s Attila sparked to Colin ratio. Don't worry about that. But gestational age, this is a feta fetuses that are growing, The red is normal And the blue is congenital heart disease. The dark blue is hypoplastic left heart syndrome. So what we get from this graph is that the term baby with congenital heart disease is born with a brain maturity. That's at least 4-6 weeks lagging. And if we look at primi babies versus term babies, we know that preemies are at increased risk for brain injury and for things like cerebral palsy and developmental delay later in life. And so is this the same kind of phenomenon that it's just brain immaturity. And if we could somehow protect against injury or at least mitigate that brain injury by diagnosing them in a surgery center. Doing better brain protection at the time of surgery, smarter things. Uh maybe we could improve overall outcomes for for these patients. Um as I said neurologic morbidity um is prominent in our population but it is decreased in the presence of prenatal diagnosis. Um Brain injury on M. R. I. Was higher in this paper. Was higher in patients who had a post natal diagnosis of congenital heart disease than those with prenatal diagnosis. So not only are the are all of the babies having less mature brains, but the post natal diagnosis patients actually have more superimposed injury on that immaturity. And so more evidence that prenatal diagnosis is probably a good thing. Uh This is that same paper. I'll skip that. So do we maybe have the opportunity to change the prenatal natural history for some of these patients? I get asked this all the time. Okay, you've diagnosed my baby with uh with this disease and you're the fetal treatment center. Can't you just fix it now? Why do we have to wait until the baby's born? And the answer to that is sometimes we can, most of the time we can't. Um But there are certain diseases that are amenable to fetal cardiac intervention. This was a movie that doesn't actually play, but it doesn't matter. It shows us intervening in utero with a needle to inflate a balloon across the aortic valve in a fetus, a 26 week fetus who had a valve blockage and that was causing the left side of their heart to no longer grow properly. We relieve the blockage in the valve and the heart starts to grow again and that baby is not born with hypoplastic left heart syndrome. It doesn't work in very many patients. And we have an active clinical trial here at UCSF looking and following the patients out to see if we actually are achieving what we want to do with this balloon procedure. But it has shown some promise worldwide that sometimes sometimes if we identify congenital heart disease early enough we may be actually able to fix it in utero um fetal arrhythmias are definitely treatable in utero. And the only way to know about them is to diagnose them. Uh So we can give mom's therapy uh if we don't there's a 50% perinatal mortality with fetal super ventricular tachycardia with maternal trans placental therapy. We can get that mortality down less than 10%. So this has been a huge boon for for fetal medicine and fetal cardiology as the ability to use these oral or I. V. Pharmacologic medications, things like the Jackson soda lol fleck. And I'd um magnesium possibly lidocaine for ventricular tachycardia. So we have this toolkit now um and we have shown good response to so it'll all primary treatment with soda lol here in san Francisco in europe. They go to primary treatment with fleck and I but they've also showed uh great survival for that. And so so occasionally yes the prenatal diagnosis does allow us to change the natural history of disease um uh before birth. Um does it alter disease prevalence. I mentioned this early on. This is a real touchy subject obviously because the way that we would be altering the number of babies born with these diseases is since we don't know how to prevent them. Embry a logically would be termination of pregnancy prior to the to the birth. And so you can look and find different disease prevalence now in different countries for a long time France. Had a very low birth rate for hypoplastic left heart syndrome. Why? Because they had high prenatal diagnosis rates and high termination rates. Um so a touchy subject to study. Um but the data are out there. It definitely depends on the overall environment and whether termination of pregnancy is considered an option in your healthcare environment. More data. This is my last slide just to get people thinking, what about other aspects of prenatal diagnosis. Um as we are getting better and better transducer technology and more knowledge. We're starting to look earlier and earlier. I can now offer routine Uh fetal heart assessment between 12 and 14 weeks of pregnancy. So if the obe has already identified something might be wrong, We can see the patient and get them their answer as the heart normal or not as early as 14 weeks, we always have them come back. Um but what this is allowing us to do is is watching, we're pushing to almost the point where the heart is still developing and it's giving us some insight into developmental processes. We see a lot Of things now at 12 or 14 weeks that we've never seen because they don't make it to birth, but it's helping us to to come up with more ideas of, you know, what is normal development and what is abnormal development and to generate more hypotheses about heart development. Um And also, if we are looking early enough does start to allow for potential prenatal therapies like stem cell and immune tolerance. If you think of baby's gonna need a heart transplant, you know about it in utero, you can already start working on that baby's immune system. It's being done for other diseases to try to induce tolerance and decreased the incidents of rejection. So more patients are transplant candidates. So that's sort of the science fiction pie in the sky. But all the other stuff that I told you really is here, The biggest problem that we're having is in educating the frontline providers to get the patients here once the patient comes to me, the chance that I'm gonna miss their major heart disease is vanishingly small. But if they're out in the communities thinking they have a low risk pregnancy, they have less than 50 50 chance of having their doctor actually recognize that there's something wrong with their baby. And if the doctor or Sinatra furs or nurse practitioners, midwives don't recognize that there's something wrong with the heart and send them to me, There's nothing I can do. Um So finally, what is the impact Can we make a difference. Well, yes, we can provide the family with informed choices, prepare them if they choose to continue the pregnancy, prepare the healthcare team, uh, and appropriately, so that so that we're only spending a lot of money when it's necessary and potentially reduce costs of transport, et cetera. We can improve perinatal outcome for critical neonatal heart disease and for cardiovascular pathologies associated with compromise before birth. We're gaining more insights with the potential to intervene in utero and uh, potential to alter the spectrum of severe heart disease at birth.