#456 - 📑 Journal Club - The Complete Episode from August 1st 2026

Which babies with critical congenital heart disease face the highest risk of brain injury, and does earlier surgery actually help? Why is infant CHD mortality climbing again after years of decline, and who's most affected? Can a mother's cardiovascular status in preeclampsia predict her newborn's circulatory transition? This week's Journal Club brings together five conversations on CHD, maternal-fetal physiology, and vaccine policy. Nim and Adrianne cover a meta-analysis on brain injury in critical CHD, a 25-year national mortality study, a pilot study on preeclampsia and neonatal cardiac output, and a look at RV diastolic function after CHD intervention. Ben and Eli close with Neo News on a controversial hepatitis B vaccine trial in Guinea-Bissau.

Transcript

Nim Goldshtrom (00:01.954)

All right, Adrian, how are you? Long time no seeing.

Adrianne Rahde Bischoff

Hi Nim. I'm good. I'm happy that it's spring when we're recording this. I don't know what time people are gonna listen, but I'm glad that spring, at least on the calendar, is finally here.

Nim Goldshtrom

I couldn't agree with you more. Snow is wonderful in waves. I think for you guys in Iowa it's much longer waves, but yeah, spring is a great time for us at least.

Adrianne Rahde Bischoff

Yeah. And it's a good time to catch up again and to get started on this year's series. I think we're gonna try to do something slightly different — we'll continue to do some cases, we'll continue to do journal club, and hopefully we'll even get some interviews in the next few episodes.

Nim Goldshtrom

Yeah, whole new world for our series, for our audience, to learn from not just us, but hopefully invited speakers and other experts on the topics of cardiovascular physiology, congenital heart disease, targeted echo. It should be a great year ahead for all of us. And so we have a nice smattering of both sides of the spectrum, right? A little bit of congenital heart disease and a little bit of targeted echo and echo evidence for the neonates today, which should be great.

Nim Goldshtrom (01:12.14)

So I'm going to kick things off with two topics to kind of start the new year off right, for whatever our audience gets to hear this on: congenital heart disease. We're gonna hear about the landscape of congenital heart disease and ischemic brain injury, and then the landscape of congenital heart disease trends globally — or actually in the United States specifically — over the last 25 years. And so to kick us off, let's start with this new, recent systematic review and meta-analysis, the title of which is "Prevalence of Ischemic Brain Injury in Neonates with Congenital Heart Disease: A Systematic Review and Meta-Analysis," published in Neurology just at the beginning of this year. First author is Dr. C. Kim, and last author is Dr. Thiviya Selvanathan. Apologies for the pronunciation. For those uninitiated to the topic, again, in critical congenital heart disease, especially in neonates, there is very high risk for neurological injury and later development of neurodevelopmental impairments.

A lot of prior work has reported widely variable rates for ischemic brain injury, limiting clinicians' ability to counsel families appropriately, design studies, and really gives us a not-great understanding of what the real burden is to this population. We'll talk in a little bit about the baseline physiology that exists for these kids, but the authors sought to determine the overall prevalence — looking at a wide variety of studies — of ischemic brain injury in neonates with CHD (congenital heart disease).

Identify potential risk factors and give us better evidence of how to counsel families, which I think is a great idea. So they performed a systematic review and meta-analysis. From several thousand potential studies, they were able to narrow it down to 31 eligible studies, most of which were cohort studies. Risk of bias was assessed using validated tools. They did pooled prevalence estimates using random-effects models, and meta-regression to explore associations with things like study year, age at surgery, and sex distribution, for example.

And ultimately, across the 31 studies, ranging all the way from the year 2000 to 2019 — so a nearly 20-year review of fairly recent data — their overall finding was that there was a pooled prevalence of any ischemic brain injury in the neonatal population of almost 70%, right? 68.5%, with low heterogeneity. So pretty good confluence of the grouped studies in that case. So almost three quarters of the population has some kind of ischemic brain injury.

Nim Goldshtrom (03:37.678)

In the neonatal period, in critical congenital heart disease — meaning they're going through surgery. So now let's break it down further. For pre-operative injury, the prevalence was about 35%. And here the heterogeneity starts to get more complicated, so not as clean a pooling of the data, but there's still no significant bias. For new post-operative injury, the prevalence increases up to 46.5%. And now when we look at the categories — the types of injury we have —

the highest-degree injury shown is white matter injury, the most common lesion, at almost 40%, but here there's a high degree of heterogeneity, which we'll talk about in a second. Followed by arterial ischemic stroke, which occurred in about 10 to 20% of patients. And lastly, hypoxic-ischemic injury, which is only about 3.5%, with a moderate amount of heterogeneity. Ultimately, they also found that age at surgery showed some association with white matter injury prevalence.

And while sex distribution was a little skewed for some prevalence of injury, this was all washed away basically when also controlling for CHD lesion type, which we'll explain a little in the discussion. So we have a study here focusing on ischemic brain injury, showing that it is extremely common, often clinically silent in our population. And lastly, out of all the methods evaluated by the study — which again I highly recommend the audience listen to — MRI (magnetic resonance imaging) still remains the most superior method, over ultrasound and definitely over CT (computed tomography), at detecting subtle lesions. With a high recommendation — not that this is what the study looked at — for considering other tools like EEG (electroencephalogram) to look for non-structural but functional parameters in our population, which we know CHD can have a significant amount of clinical or subclinical seizures as well. So I think this is wildly interesting to see how vast

and how prevalent this is in our population. And yet we don't have the answer to the question that this evidence is begging: so you have an injury, but does that mean your child is going to have a problem? Adrian, what did you think about this?

Adrianne Rahde Bischoff

I mean, these numbers are really high, especially compared to just a preterm population in general. But it is really fascinating to see that almost all these kids — more or less — are gonna come out with some kind of structural injury on a scan.

Nim Goldshtrom (06:02.488)

But what does this mean for them going long term?

Adrianne Rahde Bischoff

Yeah, I was gonna ask you that specific question because this is not a population that I have a lot of exposure to, and I definitely have no experience in follow-up of these kids. But I was wondering what your perspective is when you do see these kids — I don't know if you see them yourselves, or what your colleagues who do follow-up say about how these kids do when they come to clinic. Because I think it's important to put it in perspective, because the numbers look very doom-and-gloom.

But does it actually matter? And what impact does that really have on the quality of life and the true outcomes that families really care about — which is something we've been talking about here, and in many different forums, the last couple of years: what are outcomes that are clinically meaningful, not just for us? Yeah, it's important to know that there's, you know, like a "ditzel" there — abnormal on the MRI — or maybe a couple more than just a few ditzels.

But what do the families really care about, and how does that impact their child and their happiness going on? So what's your perspective? What do you guys see when these kids come back?

Nim Goldshtrom

So this is probably the most important question that you could possibly ask, right? And the reality is follow-up for this population can be challenging. But the data on neurodevelopmental outcomes — at least let's start with the first level, which is the two-year Bayley scores — most of these kids, at around the two-year mark, are going to show about one standard deviation, on average, lower Bayley scores than the general population.

Nim Goldshtrom (07:42.008)

So most of them, in the three domains — cognitive, behavioral, motor — you're gonna see somewhere in the high eighties or low nineties for most of these kids, which isn't bad, but it's also not great. It's also skewed a lot by the most severe lesions — the single ventricles are gonna have the lower scores, the kids who land up on ECMO (extracorporeal membrane oxygenation), the more premature, the SGA (small for gestational age) and growth-restricted. And one standard deviation is not great, but it's also not the most terrible thing.

But we still have not had strong associations in studies that show these kinds of findings — that these anatomical or structural findings on things like MR imaging are correlated with the incidence of these developmental follow-up outcomes. And this is where we have to be very careful. So some of the limitations of this specific study that we have to really hedge about — regarding the findings this paper points to, which is a lot of structural findings of ischemic injury —

which is, first of all, there was not a lot of preterm population in this group. So think of this as a term study, and they excluded genetic conditions. So you really have to caveat this to the non-genetically-diagnosed, full-term infant who is going to have these findings. We know from a lot of other great work that these kids are already at risk for this at baseline — that a full-term, 40-week CHD neonate has a brain the size of a 36-weeker,

compared to non-congenital-heart kids. Their brains are growing smaller, specifically the left side of the brain in certain kids — there's papers on this as well. Again, this study did not look at the association between NDO (neurodevelopmental outcomes) and ischemic brain injury. And I want to point out to readers who go through this article that they suggest these findings — because of MRI findings — may change parents' desires about how to pursue surgery. And I take strong exception to that statement in the discussion.

These findings, in my opinion, should not be the controlling factor of whether to proceed to surgery. The global rate of survival from neonatal critical congenital heart disease has been staggeringly improving — meaning things are getting better, we're able to help these kids survive longer — and all the NDO data shows, you know, one standard deviation. And there's not yet a very strong correlation that these injuries are the things definitively associated, depending on their grade,

Nim Goldshtrom (09:56.738)

with these kinds of developmental outcomes. So I'd be very careful to take this data and apply it to mean this impacts and means your child will definitely have some kind of these problems. And we also know from the five- and eight-year studies that the early problems you see in motor, cognitive, and behavioral aspects at two years differ and translate, as a child with CHD grows to five, eight, and school age, into maybe more problems of executive functioning, emotional regulation. And the problems you see at two are not the problems you see at five and eight. So we really need better studies that can

cover this arc of time and do a better job, because these are really interesting and fascinating findings, but the link isn't perfectly there yet. The one very fascinating thing they did find in this study is the association with age. And if readers go to specifically Figure 3 in the paper, they'll see that age at surgery — in the first two weeks of life — was associated with the findings of

white matter injury, but not in the way you'd expect. Usually you'd think that the longer you're sitting and waiting, the more you're at risk of, you know, ductal physiology — PDAs (patent ductus arteriosus) kept open, more hemodynamic instability. But actually, these kids were found to have a higher incidence of white matter injury the earlier they went to surgery. So day four, five, and six have a higher prevalence rate of injuries, and day seven through eleven have a lower prevalence rate.

And so this might be a little bit due to bias — why are kids getting surgery at day four and five? Are they sicker? It's not completely uniform who's getting it. But it was really fascinating to see that this link is a little different than what you'd expect from other studies. And the sex difference ultimately got washed away by lesion type, which is not unexpected. We know that males are slightly more prone to certain types of lesions, like left-sided lesions — aortic stenosis, coarctation, and TGA (transposition of the great arteries). So it's not completely unexpected that the sex difference gets washed out by these differences. So really,

interesting work. I think this clearly points to us doing more longitudinal connections — centers doing MRI studies that have great follow-up programs. It would be great to see these kinds of connections — how do those MRI findings, operative course, post-operative course, and then outpatient follow-up link together? What kind of services are they getting, what kind of engagement with families are they getting? It would be great to link these two things together. But an interesting observation —

Nim Goldshtrom (12:12.546)

be very hesitant to make strong recommendations about how this should impact care right now, but it can and should drive more research.

Adrianne Rahde Bischoff

So let me ask you a different question then. Do you think routine MRI — whether pre, post, or both — should become the standard of care? I bet we'd get a very wide range of answers if you put one of my colleagues from neurocritical care here versus some of the more skeptical folks, saying, well, if this doesn't really correlate with what we see in the kids later on, is it actually beneficial to have this information? Does it just

add stress to the system, stress to the families about knowing this is there, when it's not something they can change or that might actually cause anything? What's your take on that?

Nim Goldshtrom

So I have two opinions that are hopefully driven by the data. You're right — the logistics of getting an MRI in most places is not easy. Moving a child who is critically ill, or who is pre- or post-operative, is not a simple thing — on PGE (prostaglandin E1, used to keep the ductus arteriosus open), or having just recently had surgery. So what is the gain? The gain would potentially be there if, let's say, as a program, you're noticing that certain lesion types, certain surgery exposures, certain procedures are ending up with new post-operative white matter injury.

That's an actionable item — getting the pre-op scan, especially, let's say, with TGA patients, who are very high risk for pre-operative brain injury from balloon atrial septostomies, shows you whether your program is somehow one that is either not able to mitigate, or not meeting standards, or somehow experiencing children with new injuries — that's a quality-improvement angle. So you can argue there's value in doing it and learning about your program — is it in certain surgeries, certain conditions, certain bypass or perfusion techniques — that's one thing. And the second is,

Nim Goldshtrom (13:58.954)

if this is what it takes to argue, or to defend, or to help families get data to say, "my child is at risk," and as an outpatient, if they may be getting pushback or difficulty getting insurance to support early intervention services — these could be the added tools that help us show it. Here is the objective evidence — MRI data that can get these kids plugged in and give parents more

tools, and more of a sense of why we want them to get into early intervention, to come back to our clinics — which can sometimes be very difficult to keep up in follow-up, because "my child seems to be doing fine, they're full term, we had the heart surgery, so everything could be fixed." That's sometimes a lot of the message they hear, but it's not really reflecting the baseline of the child — when we bring them in for a developmental evaluation and look closely, we see they're kind of slightly behind in certain domains. And to that end, if systematically you can create those kinds of

support systems, it's probably worthwhile to consider. But, you know, getting an MRI on every neonate or every small child is not an easy thing. You have to really weigh the benefits and the cost to your system. But it can be a tool that supports both improvement at your center and long-term follow-up opportunities for your families.

Adrianne Rahde Bischoff

Is there a role for a pre-operative MRI to preclude a baby from getting surgery?

Nim Goldshtrom

I think very significant neurological injury would probably preclude it, because if you have something that's already really significant — either a bleed or a hypoxic-ischemic injury — first of all, if that were to happen, you'd probably have a clinical picture that matches it. Subtle brain abnormalities, or subtle ischemic or white matter changes, are not going to manifest with a situation that severe. I'll give you one example. Several years ago we had an emergency rescue

Nim Goldshtrom (15:52.972)

for a total anomalous pulmonary venous return (TAPVR) child born at another hospital. We brought them in at eight hours old, and they were extremis — we could not get the sats up. We got an echo, and we ended up putting them on ECMO first to rescue the child physiologically. We did that, we stabilized the child, we got an EEG — there was completely attenuated activity and seizures — and ultimately got head imaging and continued EEG that basically showed there was near brain death. And that dissuaded us

from wanting to do surgery on the child, because it was not going to help. But the clinical picture correlated with that consequence. These mild findings, again, in my opinion, should not be the things that are discouraging, because the clinical outcomes we're currently seeing do not match this prevalence of 70%, knowing that neurodevelopmental outcomes are, at best, maybe one standard deviation off. And most parents would take that in a minute, if they knew their child could have a potentially long life, or a long enough life that is meaningful to them and their family.

Adrianne Rahde Bischoff

Thanks. That was actually quite helpful. I know we can't extrapolate this to preterm neonates, but we do, every once in a while, have preemies here in our NICU with congenital heart disease. So it's helpful to get that perspective from term infants — which obviously is not the same — but I appreciate that.

Nim Goldshtrom

No, that's why I found it fascinating to give a landscape review of where the data is. I think this is a great systematic review to give us a cross-section — here's where we are, but we certainly have a ways to go to connect the dots. This is just one slice of the picture, and the clinical and functional aspects we see in these children at two, five, eight, and preteen years doesn't completely line up with what we see early on. But I guess that's a good thing, right — to have services and to be able to connect the dots over time.

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Nim Goldshtrom (00:01.954)
This second article is going to review "National Trends and Disparities in Congenital Heart Disease Mortality in the United States from 1999 to 2024," in Pediatric Cardiology. First author is Sandesh Raja, and last author is Mohammed Alfaifi. This is a group cohorted primarily in Saudi Arabia. And before getting into the background, which I'm sure a lot of our audience is already familiar with, I'm going to run everyone through a little exercise to think about it. The primary outcome measure that this paper focuses on is what's called age-adjusted mortality rate, or AAMR. Age-adjusted mortality is a comparison metric for death risk that lets you compare across different populations with different age structures.

So you standardize it to a reference population — in this case, most commonly the U.S. standard population from the year 2000 — and express it as the number of deaths per 100,000 people. So for context: the number-one killer of adults is ischemic heart disease, or cardiovascular heart disease, and that number is anywhere from about 150 to 200 deaths per 100,000 people. As an analog, diabetes is only about 20 deaths per 100,000

people. Adrian, take a guess: prematurity — how much? More than diabetes? Less than diabetes?

Adrianne Rahde Bischoff (01:18.954)
Less than diabetes?

Nim Goldshtrom (01:23.954)
It is quadruple the amount of diabetes — 80 deaths per 100,000. Prematurity is no joke.

Adrianne Rahde Bischoff (01:33.954)
No joke.

Nim Goldshtrom (01:38.954)
And for example: number-one unfortunate mortality indicators for children and teens — unintentional injury is around 10 per 100,000 kids, and about 35 per 100,000 teens. So those are the metrics — heart disease in adults almost 200, diabetes down to 20, prematurity around 80. So while I'm introducing this article and going through the methodological steps, I want everyone listening to think: if you had to guess a number for the age-adjusted mortality risk for infants with congenital heart disease, what do you think that number is? You've got 20 for diabetes, 80 for prematurity, almost 200 for heart disease — you can play "The Price Is Right" rules, up to you guys.

Hold that number, we'll get to it in a second. So we know congenital heart disease remains the most common birth defect, and a major contributor to mortality around the world. But things have gotten tremendously better — medical, surgical, intensive care, all the services feeding through to adult congenital care. So these authors wanted to evaluate long-term national mortality trends in the U.S. — to look at demographic, geographic, and socioeconomic disparities related to deaths, and see if there are opportunities for optimization.

So they used something very cool called the CDC WONDER database (Wide-ranging Online Data for Epidemiologic Research), a wide-ranging online database for epidemiological research. They looked at trends from '99 to 2024 using ICD-10 (International Classification of Diseases, 10th Revision) codes for congenital heart disease. And again, they used age-adjusted mortality rates using the standard population from the year 2000, then used something very interesting called Joinpoint regression — developed by the National Cancer Institute — to try to identify temporal changes: where trends changed over time, and at what time point.

Did that trend occur? What they found was that over this 25-year period, over 120,000 CHD-related deaths occurred during the study period. Mortality was highest among — our favorite — infants under one year of age. The other interesting finding is that overall mortality actually declined for the first about 15 years, from 1999 to 2014, but then started to increase back up over the last 10 years.

Higher mortality was also observed in males, slightly, and in non-Hispanic Black and American Indian/Native American populations. And there were also a lot of sociodemographic and regional disparities, such as rural and Midwestern regions having higher mortality rates. So the age-adjusted mortality — for all CHD deaths, across the entire lifespan, from infant to ripe old age above 80 — the age-adjusted rate was 1.6 per 100,000.

Adrianne Rahde Bischoff (04:11.524)
That's for all comers — the entire age spectrum.

Nim Goldshtrom (04:18.954)
Age-adjusted for infants under one year: 54. So basically almost half, or more, of those deaths are happening in our population. And then every other age group has anywhere from one to three, depending on the age group. You see there's been a decrease up to 2024, and then a slight increase in this age-adjusted mortality. There's a growing adult congenital population — they have double the prevalence of comorbidities as the pediatric congenital population — adults who make it with congenital heart disease.

They have added modifiable risk factors. There's also potentially a shortage of specialized workforce, which probably is contributing to the deaths seen at the higher end of the age range. The other interesting finding here is that most deaths actually happen in medical facilities, then at home, then followed by other locations — showing how this is very different from the general population, suggesting that a lot of these individuals, no matter the age group, are dying after some kind of acute exacerbation

that brings them into a medical facility — something like acute heart failure, arrhythmia, some issue potentially related to either the direct morbidity of congenital heart disease or a comorbidity around it. And the fascinating stuff is, again, the slight male predominance of disease burden for mortality, and the regional discrepancies — there are wonderful heat maps here showing much higher mortality rates in the Midwest and West than, let's say, the coasts and the South.

So really suggesting the limits of things like tertiary care centers, the longer travel folks in the Midwest have to take, the lower socioeconomic status of some of these places, and that rural areas are faring much worse than non-rural areas — suggesting a resource-availability issue, not just access to care, but insurance coverage too — suggesting that our system of care in the United States may partly be why there are discrepancies and disparities in congenital heart disease across the country, less so than about the biology of which conditions necessarily. So a fascinating study on the landscape of where we are, but still showing that the highest-risk period is the one we work in. Again, suggesting that our neonatal and pediatric intensive care colleagues caring for these kids have the biggest job in the world — figuring out how to get these kids through the first year as best we can, when the risk is as high as it can possibly be. Thoughts, Adrian, on this?

Adrianne Rahde Bischoff (07:28.954)
I just thought it was interesting how there was a rise after around 2014, even though it was declining before that. Do you have any thoughts on that?

Nim Goldshtrom (07:43.954)
It's really interesting, because they represented that data as all comers — everybody pooled together. Again, I think we're both biased because we see these kids right when they first come out, rather than during the other periods of their lives. So I was curious — is it an upswing proportionally throughout all the years? We don't necessarily have that data, because the

age-adjusted mortality of 54 is unbelievably high. Has that gotten better? Because there are other studies suggesting overall mortality is getting better in neonates. So it could have been worse in 1999, and this is the average over 25 years, and the neonatal numbers are actually improving. And because there are now many more adults, and in the next 10 years there's probably going to be a larger population of adults living with congenital heart disease than pediatric patients — for the first time in the condition's history.

So are we just seeing the progressive morbidities of our inability to keep up with that reality? There's likely a shortage of physicians who specialize in and understand the comorbid conditions and added risk burden of adults with congenital heart disease. The fact that most of them are dying, or experiencing mortality, at a healthcare facility suggests they're waiting for some kind of acute decompensation before getting there.

That there's just not enough palliative care services, or a good way to engage with things like hospice care, the way we do for the general adult population with, say, cancer or other life-limiting conditions when they reach that point. There's also the disparity — the article mentions many times — that East Coast and West Coast centers do not experience the kind of losses, or the kind of significant risk, seen more in the middle of the country, suggesting some of this is not equally distributed across the United States, but concentrated in higher-risk areas  which really raises the question of whether we're bringing the same resources to the entire country. And that's clearly not the case. So there's probably a lot of work to do now that we've done such a good job with the early parts of life, in figuring out how to help these individuals as they become young adults, older adults, adults with families, and toward the end of their life — figuring out how to make that part of their life not as difficult, because that's probably where a lot of the gains are. My personal bias, though, is to focus on the neonatal and infant period — with such a high mortality rate, if we achieve even half an improvement in that rate, we're going to increase that surviving population even more. So the authors do suggest an inability to provide adequate services for aging adults with this disease, and I'm fascinated to figure out what we're missing — is it the preterm infants who are driving this? Is the preterm mortality that much higher? It clearly shows we have a lot of potential gains still to be made, and we don't know if we will make them, right? Single ventricles will always be single ventricles for now, until we have some kind of technological breakthrough. And genetics in single-ventricle disease is a very difficult comorbidity to live with. But it's a fascinating slice of where we are right now with this condition.

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Nim Goldshtrom (00:00.000)
So the next one I wanted to talk about is called "Linking Maternal and Neonatal Circulation in Preeclampsia," which I thought was interesting because it's a kind of novel domain for me, where you're looking at both the moms and the babies. First author is Piani, second author Annesi.

Adrianne Rahde Bischoff (00:31.510)
Great.

Adrianne Rahde Bischoff (00:34.516)
Senior author is Martini, and this paper was published now in 2026 in the American Journal of Physiology-Heart and Circulatory Physiology. So this was a prospective observational pilot study that enrolled 13 mother-and-baby dyads affected by early-onset preeclampsia. And what they did that was kind of unique,

at least from my perspective, was that they looked at maternal cardiovascular function using echo within three weeks before delivery, and then neonatal cardiovascular adaptation in the first 72 hours postpartum using electrical cardiometry. So, in terms of summary — I'm not going to go into the methodology in too much detail — key findings: they found an inverse association between maternal systolic function and neonatal cardiac output.

Meaning that the worse the cardiac output, ejection fraction, and tissue Doppler velocities in the mom, the higher the neonatal cardiac output. And that held even after adjusting for PDA and inotropic support. They reported minimal neonatal vascular adaptation. Even though maternal ejection fraction was positively associated with neonatal systemic vascular resistance in some adjusted models,

this effect actually weakened after PDA adjustment. The other finding was that neonates appeared to compensate for maternal hemodynamic impairment primarily by increasing cardiac output, but not really by altering vascular tone, which I think is interesting — not necessarily surprising, but interesting. So this is, to some extent, the first study to quantify maternal and neonatal hemodynamic coupling in early-onset preeclampsia.

So some of the things they did well: obviously this was a very novel study with a clinically meaningful question. It addresses a high-impact and underexplored area, where maternal cardiovascular adaptation directly influences neonatal hemodynamic transition — which has major implications we absolutely do not talk about these days for individualized neonatal care, and will just make our lives even more complicated if, besides looking at the baby, we also have to think about

Adrianne Rahde Bischoff (02:56.940)
the mom — besides what we typically do in a very broad stroke, like whether they have chorioamnionitis, diabetes, preeclampsia, and so on. They also used more robust physiologic measurements — they did maternal echo, which is essentially the gold standard for non-invasively assessing cardiac function, and then electrical cardiometry, which provides continuous, non-invasive neonatal data.

Nim Goldshtrom (03:50.240)
Yeah, so here's what I want to ask you, as our resident echo expert. In reading the methods section, it seems the methodology for the maternal echo was pretty standard — they performed LV (left ventricular) function and output assessments. I'll talk about electrical cardiometry in a second, but they did say they performed transthoracic echo in the babies, in the methods section, during those 72 hours, which is really interesting.

Nim Goldshtrom (03:54.656)
And I wanted to make sure I was reading that correctly a few times, because I kind of wonder why they would say that and only report the non-invasive data. Because if you do an echo on a baby — and this is where I need your expertise — how hard is it to get, you know, LV and RV output and ejection fraction in preterm infants, with either method? Honestly speaking, what's your experience?

Adrianne Rahde Bischoff (04:07.500)
It's not hard once you're trained, but it's not standard, right? And it's not standard to obtain quantitative measurements — specifically of output — in the cardiology world. We know it's feasible to train people, and we are part, here in Iowa, of the Echo Core Lab for a pivotal PDA trial, meaning we provided training for echo labs

Nim Goldshtrom (04:30.180)
That's standard, okay.

Nim Goldshtrom (04:33.784)
Sure, sure.

Adrianne Rahde Bischoff (04:48.994)
throughout the country as part of this multicenter study, to help obtain the measurements we use in our PDA severity score. As part of our PDA score, it does include measurements of left ventricular output and right ventricular output. So we know it's feasible — people can do it once they're trained. There's still technique

finessing that we provide feedback on, even to this day, as we're about 75% through enrollment. But it has gotten a lot better, and it is feasible — it's just not routinely acquired. So I'm not sure why that wasn't reported.

Nim Goldshtrom (05:21.400)
Sure.

Nim Goldshtrom (05:24.780)
This is great perspective, because on page seven, in the middle, they clearly say concomitant daily echocardiographic assessments were performed to assess neonatal cardiac function and ductal status. So I have to wonder — they did the echoes, they put on the electrical cardiometry monitor, and they only reported the electrical cardiometry data, which is interesting to me. So my second question for you — I go down to the end of the table, I think it's Table 1.

Adrianne Rahde Bischoff (05:48.900)
Ha, ha, ha.

Adrianne Rahde Bischoff (05:49.345)
Yeah.

Nim Goldshtrom (05:53.760)
And I look at some of the numbers there for cardiac output, stroke volume, SVR (systemic vascular resistance) — that cardiac output, 280 mL per kilogram per minute — is that what you'd expect for preterm infants? Is that — and in which direction is that? Too low? Too high? What are you seeing there?

Adrianne Rahde Bischoff (06:10.300)
Absolutely not.

Adrianne Rahde Bischoff (06:11.966)
It's definitely higher than what I'm used to. I will say, if the baby has a PDA that is hemodynamically significant, it's not completely out of the realm — but even then, in the first 72 hours of life, that's still higher than what I typically see. Most often, preterm infants — obviously it depends on gestational age, but most often preterm infants with a hemodynamically significant PDA are not able to mount

Nim Goldshtrom (06:20.150)
Yeah, correct.

Nim Goldshtrom (06:21.688)
Correct, correct — which a lot of these kids had, I think, from the reporting, yeah.

Adrianne Rahde Bischoff (06:41.440)
a much higher pre-ductal cardiac output. What happens is they end up with a lower post-ductal cardiac output, but they don't have such a high pre-ductal cardiac output. But we do know that's method-based — when we look at studies comparing non-invasive cardiac output measures with echo, we know they're discrepant. The value I find, at least to this day, is in using non-invasive methods as a trend —

Nim Goldshtrom (07:02.600)
Correct.

Adrianne Rahde Bischoff (07:10.198)
Right. If you have a baseline and it goes up or down, you can use it that way — not as an absolute value, which is kind of what they were reporting here.

Nim Goldshtrom (07:17.050)
Mm-hmm, correct.

Nim Goldshtrom (07:18.924)
So I'm so glad we're having this discussion, and I'm glad we picked this article, because it walks through the whole cascade of what I was hoping would be a teaching point, and I hope the audience appreciates it. I really hope the premise of this paper ends up being true — that preeclamptic mothers, with placentas under strain, show some kind of adaptive mechanism in the baby, and that this can help us understand certain maladaptive mechanisms — that when a

preterm baby comes out after being exposed to preeclampsia, seeing those expected changes in cardiac output and SVR may actually help us — if we're seeing those kids being either hypotensive or having high blood pressure, similar to what we see with HIE (hypoxic-ischemic encephalopathy) populations who have RV (right ventricular) failure or LV (left ventricular) dysfunction — that would totally make sense. However, based on everything you've just described in the study, this is not the study to establish that. So, my biases and problems with this —

on the Incubator site, we're going to also post these articles alongside another article which, in my opinion, describes exactly the problem here. So Anup Katheria and his group recently published a great paper called "Multimodal Approach to IVH (intraventricular hemorrhage) Using Echocardiography, NIRS (near-infrared spectroscopy), and Electrical Cardiometry in Preterm Infants." And the reason I mention it is that they highlight a problem this paper perfectly exhibits: electrical cardiometry is a great technology — it uses electrical impedance, the same as the telemetry leads we put on kids to get heart rate,

and then a proprietary technology, using equations that take the EKG signal and break it apart to give you the stroke volume under each QRS complex, essentially, with some adjustment for control variables, to give you an estimate of cardiac output. However, in data looking at infants, neonates, small children, and adults, the group with the worst confidence intervals and the most extreme bias and limits of agreement is neonates.

And the Katheria study perfectly summarizes that — the most modern study — showing that the values from electrical cardiometry, compared to LV and RV output by transthoracic echo and neonatal echocardiography, were much lower than electrical cardiometry's numbers. Electrical cardiometry often overestimates cardiac output, particularly in the neonatal population. So I was very suspicious when they said they performed echoes every single day on these kids

Nim Goldshtrom (09:43.320)
for function and ductal status, and then only wanted to report the electrical cardiometry data. And the value was so high, as you expertly told us, that there's something fishy here. It still might be true, and I hope it is, but this is not the study for that right now, in its current conception, without a more gold-standard comparison. There are reasonable limits of agreement for electrical cardiometry in neonates — it gets worse as cardiac output gets higher, but electrical cardiometry will consistently overestimate in the neonate. So

if you use it, use it as a trend marker, just like NIRS. NIRS is not a perfect point estimate, but it's a great trend marker. I personally haven't found that electrical cardiometry is a perfect trend marker either — maybe we're just not using it in the right populations. But this is why I wanted to discuss this article: a great concept, a great idea, not executed the way I'd think is best, statistically and methodologically. So it's wonderful to go through, and I hope the audience appreciates the nuances there.

Sounds good, all right. Have you guys ever used electrical cardiometry at all, tested it, studied it?

Nim Goldshtrom (11:01.388)
Yeah, yeah.

Adrianne Rahde Bischoff (11:13.408)
Only in research settings. We talk about some scenarios where we wonder if it would be helpful — in the preterm baby, for example, in the transitional period, we screen all our babies to look for a hemodynamically significant duct that we do treat pretty early on. But there are many babies where, by the time we do the screening echo, they still haven't quite transitioned — they have kind of a transitional physiology, still a bidirectional shunt, and we'll scan them again the next day, but sometimes we wonder — is this duct going to become an issue within six hours, within twelve hours, when we're not scanning? And perhaps if we had that trend of pre-ductal cardiac output, it would be a trigger to say, well, this baby's probably already transitioning — maybe we should do the echo sooner rather than later, or start therapy sooner rather than later. But it's all speculative — we don't actually use it in routine practice.

Nim Goldshtrom (11:47.200)
Same here. I did an early study several years ago, trying it on the congenital heart disease group after surgery — same problem. A lot of overshoot, not a lot of variance. So we use, again, NIRS — especially renal NIRS — as our early-warning indicator, because it just moved... it moved, but not to the same degree that renal NIRS does, in terms of being a good early-warning predictor. So I hope either technology gets better, or the ability to combine them gets better, but yeah — echo is still the gold standard.

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Adrianne Rahde Bischoff (00:00.000) And the next paper is "Echocardiographic Markers of RV Diastolic Dysfunction in Neonates and Infants with Congenital Heart Disease." First author is Massimiliano Cantinotti. And it was published in the Journal of Clinical Medicine, now in 2026. I will say, even though Nim said, "well, this is your domain, TnECHO (Targeted Neonatal Echocardiography)" — this is not TnECHO, because this is in congenital heart disease, which is not my population, but I'm still interested — it's a disease we talk about all the time in a theoretical standpoint, but we haven't really done a lot of studies in the normal-heart population on diastolic function.

Nim Goldshtrom (01:10.234) That's okay. I was hoping we'd join forces again on this paper, because RV failure can be such a big problem for us. So using your expertise, understanding how to think about this paper, I'm curious to hear your thoughts — please.

Adrianne Rahde Bischoff (01:22.234) So they decided to look at RV diastolic function, which is obviously very complex to assess in any baby, because the RV has its unique geometry. There's respiratory variability, which impacts the right side much more than the left side. There are obviously developmental changes that happen as the PVR (pulmonary vascular resistance) is changing, and the physiologic inversion you'd expect of the E/A ratio — the early-to-atrial-filling ratio of the right ventricle. And what we know from adult Doppler data is that it obviously doesn't translate to infants — pediatric normative data is pretty limited in our population. So what the authors of this paper wanted to do was understand what the tricuspid inflow patterns look like in infants who have RV pressure overload after interventions for pulmonic stenosis or tetralogy of Fallot. So they enrolled 57 babies prospectively, and did uniform post-intervention timing, at 12 to 48 hours after either surgery or catheter-based therapies. They compared those to 134 matched healthy controls — roughly twice as many — to try to validate a normative dataset. And the primary focus was the tricuspid E and A wave with the E/A ratio and the E-wave deceleration time, which is something that we obtain images for, but haven't explored, at least locally, in the targeted neonatal echo world.

Nim Goldshtrom (03:19.234) Do you do anything else for diastolic dysfunction, just out of curiosity?

Adrianne Rahde Bischoff (03:20.234) Yes. Theoretically, you could look at tissue Doppler or strain imaging — strain rate, specifically — but we just don't know what to make of it yet. We're still in a fairly simplistic world of looking at the direction of the atrial-level shunt and things like that, and guessing. We don't routinely assess this, mostly because we don't even know what normal is. So it's hard to say what would be abnormal, and even if you find something abnormal, what do you do about it? Anyway, what they found was that these babies with congenital heart disease and RV pressure overload had a consistent pattern where they had, first of all, markedly reduced beat-to-beat variability, which is interesting. And anecdotally, I've noticed this in neonates — the well, spontaneously breathing babies have more variability, which is part of why we're kind of skeptical about measuring this, because you'd have to average out many, many beats, while babies who are vented and muscle-relaxed and so on tend to have less beat-to-beat variability. They have a higher A velocity — meaning the atrial kick contributes more to right ventricular filling — and therefore a lower E/A ratio, and the inversion of the E/A ratio was essentially universal in this population, as opposed to about 50% of the controls. And there was minimal correlation between any of these findings and systolic indices, suggesting these diastolic abnormalities seem to be an independent phenomenon. So I thought it was good that it was prospective, with a very clearly defined population, a pretty large sample size actually, with a control dataset. They emphasized beat-to-beat variability, which I think is very important when looking at right-sided, especially inflow, markers. They had pretty good reproducibility, with good inter-rater correlation coefficients. But the main question — first of all, this was obviously a pretty narrow disease spectrum, which matters when you're trying to validate something —but you can't generalize this to pulmonary hypertension, cardiomyopathies, and other complex heart diseases. And also, the assessment at 12 to 48 hours is a pretty broad, and very dynamic, hemodynamic period. So some of these findings could reflect transient physiologic adaptation rather than truly intrinsic diastolic function, from my standpoint. And then, obviously, they didn't look at more advanced techniques like tissue Doppler, atrial strain, or ventricular strain, which could potentially enhance the understanding of true RV diastolic function. So those are my main thoughts — ask me your questions now.

Nim Goldshtrom (05:54.040) So many. The questions I have come from this specific population. Every once in a while you get a kid — not necessarily the tetralogy of Fallot and pulmonic stenosis patients, but like truncus arteriosus, for example, or others who are supposed to be two-ventricle — and you get an RV that's failing. And you want to call it systolic failure, but honestly, a lot of the time it's diastolic failure, and there's just no good way, other than a cath, to figure it out, so you just say, "well, it's probably that." So methodologically, it sounds like all the techniques and measurements they used were standard for what you'd do. Does this finding at all — the lower E/A ratio they found, and the more limited variability — change how you think about this disease, and would it change your practice at all seeing these kinds of findings? Okay, right, it's in the middle. But does it change anything for you? Like, if you measure this, would you be calling these kids, or labeling them, more as at risk? These are populations — tetralogy of Fallot and pulmonic stenosis — where we'd expect these findings, and then they should get better once you fix the disease, do the balloon septostomy, or the pulmonary valve for pulmonic stenosis, or the tetralogy of Fallot repair. I'm curious — if I had a kid with these persistent findings who's at risk for RV failure, can I count on this being enough evidence that I don't need a cath and another invasive procedure on this kid? Is this good enough data? And that's my first question — is this good enough, or does it move us closer to better data for this kind of thing?

Adrianne Rahde Bischoff (07:38.234) I think it's probably not good enough. I think it's all speculative and hypothesis-generating at this point. To really be clear whether this is reliable enough, you'd have to correlate it with cath — you'd need an echo-versus-cath study.

Nim Goldshtrom (07:49.234) That was my next question, which I was wondering — why didn't they do that for this study? I'm not criticizing them, but wouldn't that be the next logical step? You do an echo, either during cath — although that's different, because then they're sedated, paralyzed, and intubated — or right before that, you do the echo in the cath lab, then sedate and paralyze them, get the RVEDP (right ventricular end-diastolic pressure), and try to correlate the pre-anesthetic echo with the cath data. That would be a nice logical step, because otherwise

Adrianne Rahde Bischoff (08:21.234) you'd have to argue that the echo should be done at the same physiologic status as the cath, because the ambient conditions could be different — once anesthetized, you might drop PVR, you might change SVR. So it should be at the same time. We actually have a study that's been very hard to recruit for in the neonatal population — Dr. Audrey Hébert is the PI, she's from Quebec, and she's looking at babies with chronic pulmonary hypertension, usually BPD (bronchopulmonary dysplasia)-related, who do go for diagnostic cath. We take the echo machine at the same time and obtain some of our measurements, to try to validate or at least correlate what we see non-invasively with the cath markers. Which I think is relevant, because it's not uncommon to have a kid you're sure has pulmonary hypertension, and then they come back from the cath lab and it's normal, or mild, or not that big a deal, and you're like —

Nim Goldshtrom (09:08.076) Yeah, correct — subsystemic RV pressures, like...

Adrianne Rahde Bischoff (09:15.234) Yeah, but when they're awake and thrashing around, which is how they actually live, they do show some of that. So I think it's important to do that study, and I hope we'll get some more answers. But this is the trend — this is what should be done for any validation of echo markers, is to validate against the gold standard. So this is a start. I think it's hypothesis-generating — I wouldn't stake my reputation on it that you need to change management. You just might think about it a bit more critically. But it's a single parameter, and you know I preach — we preach — a multi-parametric approach. This is only one of them. So I think it's just a start.

Nim Goldshtrom (10:02.234) But diastolic dysfunction — there are so few variables — you end up sounding like every one of my cardiologists: "I don't know what to do with this. Maybe. I guess it's probably diastolic dysfunction, but none of the variables we have are good enough to assess it."

Adrianne Rahde Bischoff (10:15.234) But more than that, it's how do you handle it? How do you treat it?

Nim Goldshtrom (10:19.234) Well, so here's the thing I have no idea about — we just end up putting them on pulmonary vasodilator therapy for forever, basically. But for me, at least at this stage of care — let's say it's congenital heart disease, and you worry the child isn't making clinical progress, and that's the physiology — obviously we live in an age where you're going to get the cath at some point in most of these centers. But because cath is such a big deal for a lot of these kids in the neonatal period — because if you're going to get one, you're going to get many more. Forget even the single ventricles — but once you start down that road, it's a never-ending road, and the thrombus and clot risk from repeatedly instrumenting those vessels eventually leaves you with limited access if you're doing them too repeatedly. We always want to wait. But if you really have an RV that's failing, in most centers or in most places, you're going to go down the route of: is this the heart for us? How else do we better optimize? Are we ever going to get off respiratory support if part of the reason is intracardiac shunting? And then the idea is: do we have less invasive data that can help us move the needle — not just to adjust therapy, but to adjust expectations and the trajectory, and say, well, "we're stuck on oxygen and pressure support for RV failure" — that doesn't make sense, you shouldn't be on pressure modes for respiratory support, but sometimes you are. And to start opening the conversation of: well, you may not be leaving the hospital sooner, which we might know, but then how do we better support you sooner — when do we get the heart failure and transplant teams involved? And it always ends up being the cath, which is the standard of care, and we don't want to suggest otherwise. I was hoping we'd start to find better, earlier, non-invasive techniques that could help us get that data sooner rather than later. But it seems we're still a little far away. Maybe the other modalities you suggested, like speckle tracking, tissue Doppler, could be the future — but we need better studies, like you said, matching them to gold standards. Fascinating stuff. I always love these talks. These are always great articles that inspire more questions, and sometimes help us understand the landscape of our field.

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Eli Cahan (00:02.086)

Our next set of articles is about something we're very passionate about and keeping a close eye on here on the news, which is... hepatitis B, not vitamin K. We just talked about vitamin K, hepatitis B — we're passionate about both, but anyway, Freudian slip on that one. Hepatitis B. I think we've talked previously on Neo News about decisions made behind the curtain at federal agencies, and other agencies, that shape the evolving conversation around prenatal, perinatal, and postnatal care in this country. When you think about the conversations that are happening around hepatitis B — we've discussed previously the rhetoric from the government saying that people diagnosed with hepatitis B, known cases of hepatitis B, their infants should get the vaccine, because we know that many, many people in the US who have hepatitis B are not diagnosed. So that's one thing we've talked about in the past — the government's discussion that this should be shared decision making, as if that's not something we were already doing, and whether that introduces new layers into these conversations, as well as doubt in the advice or recommendations of health institutions. Another piece of this conversation, around how the conversation is shifting, is what direction the science is going in around these sorts of vaccines, and what the government is paying for, what they're supporting in terms of the science they're interested in, and the evidence base they're interested in developing. We've spoken previously about the government's initiatives to study more in depth the relationship between vaccines and autism, to much controversy and uproar from various agencies and associations like the AAP (American Academy of Pediatrics), which we won't get into. One of the efforts the government has taken, as it relates to hepatitis B, is the funding — unsolicited, non-competitive funding — of two Danish vaccine researchers, much-maligned Danish vaccine researchers who, and I quote, are best known for pioneering a theory that vaccine opponents have embraced: that vaccines have potentially unknown and nonspecific effects on the immune system. And that while some vaccines that use weakened live viruses can reduce mortality, others using inactivated viruses can increase it. My dear colleague, friend, and mentor, Katherine Eban, wrote about these two researchers for Rolling Stone — she basically used a research outpost in an impoverished West African country, Guinea-Bissau, to look into the relationship between hepatitis B vaccines and all of these outcomes. At one point, Katherine found these two researchers and their project were at a point where they might not be able to continue the research — until they got a financial lifeline at the top level of the US government's scientific establishment, in the form of a $1.6 million grant to fund global health research into the dangers of vaccines. That's the conversation around what the government is paying for — what kind of science, what kind of global health work — when it feels like they won't pay for other forms of global health work. But when it comes to funding a vaccine study in Guinea-Bissau, this is, quote, "a funding priority for CDC (Centers for Disease Control and Prevention) slash HHS (Department of Health and Human Services)," according to a senior advisor at the CDC, and on the heels of these kinds of decisions, there's now emerging data that the doubts and rhetoric around hepatitis B are showing consequences. There's a study that came out in JAMA (Journal of the American Medical Association) Network that found vaccine rates for hepatitis B rose from 67% in January 2017 to a peak of 83% in February 2023, and then declined to 73.2% by August 2025. There's another analysis showing pretty profound economic consequences to a lack of vaccination. So even if you thought, well, this is my decision, and the decision just for my infant doesn't have bearing on anyone else — and by the way, it doesn't really have bearing only on our family — this study, in an analysis of 3.6 million infants, found that delayed vaccination scenarios — these are cases where the infants did get vaccinated eventually, just later — added costs on the order of tens of millions of dollars, due to additional infections in infants who delayed vaccination. So Ben, what do you make of the government's decisions around the science they're paying for, and the consequences of those decisions, as we're seeing there, in the clinical as well as the economic data?

Ben Courchia (05:57.935)

I want to go back to this situation you brought up about the study in Guinea-Bissau, because if you haven't heard about this, it's a case study in medical research ethics. Basically, what you have to understand is that the trial over there was designed to evaluate, quote unquote, the "non-specific effects" of the newborn monovalent hepatitis B vaccine. And the trial was designed by this Danish group, the Bandim Health Project. Listen to this — this is where it gets really... I'm sorry, I'm going to curse, but it gets really fucked up. Their core hypothesis basically states that some vaccines can have broader, non-specific changes to an infant's immune system, potentially increasing all-cause mortality, or contributing to neurodevelopmental and skin conditions. So basically, it's a unique study where they're searching for harm. And unlike other trials, where you'd use a vaccine to try to reduce spread or establish efficacy against a specific pathogen, this study is explicitly structured to hunt for hidden negative side effects of a 40-year-old vaccine that global health bodies long ago established as safe. So how do they go about doing that? They go to Guinea-Bissau, where they're trying to enroll 14,000 newborns. This is an impoverished country in West Africa where the background rate of hepatitis B is exceptionally high — extremely rampant within the population. And the protocol set up a single-blind randomized controlled trial where half of the enrolled infants would have the standard hepatitis B birth dose intentionally withheld or delayed for weeks to serve as the control group. I'm just going to let that sit for a second — this is infuriating. The articles you mentioned highlight emails that leaked between the CDC and these researchers, where the CDC in the US was interested in potentially funding this particular work, because if they could highlight some negative effects associated with the hepatitis B vaccine, it would go along with the desire to change the current practice of giving the hepatitis B vaccine at birth. Now, thankfully, the official halt of this study in Guinea-Bissau came after strong warnings — from whom? From the Africa Centers for Disease Control and Prevention, the Africa CDC. Thankfully, the medical community and public health researchers have all been up in arms about this. Some members of the US Congress thankfully also raised vehement opposition, and the study is no longer taking place. It's not just that you can argue about a study and say "I don't like how this is done" — I think it's important to go over the details: we're talking about taking 14,000 babies in a country that's rampant with hepatitis B, and withholding the vaccine. It's absolutely insane, and it makes me furious. That's number one. And then I think the—

Eli Cahan (09:32.07)

Ben, before you go any further — do you know what people would say about this study if it were happening in Alabama? You know what they'd say if this same study were happening in Alabama? I think they'd say one word.

Ben Courchia (09:45.399)

Yeah. They'd say... yeah, I mean, I think you're talking about the R word.

Eli Cahan (09:52.812)

No, I'm talking about the T word — Tuskegee. If we were saying, "hey, let's randomize thousands of people against the thing we know works, and just kind of see how it plays out" — I think,

Ben Courchia (10:10.975)

It's worse than that, Eli. It's worse than that. To me, it's like you're going to a country where, to be honest, they don't have very much going for them — it's an extremely poor country. You take 14,000 babies who've done nothing to anyone and say, "you know what, the pathology that's actually rampant in your country, that we have a vaccine for, we're not going to give you." It's like, what the fuck? This is absolutely crazy. And I think this discussion dovetails very nicely with the other articles, because we don't really always grasp, because we've been vaccinating babies all along, what exactly we're talking about when we talk about babies not being vaccinated against hepatitis B. A few things I want to mention about the vulnerability of our patients: number one, we have to remember something known as age-dependent chronicity. If a newborn gets hepatitis B in their first year of life, they face a 90% risk of developing a chronic, incurable condition, while in adults that risk drops to only 5%. So catching this as a baby is a very, very big deal — it's not the same as catching it as an adult. In terms of lethality, chronic hepatitis B virus is highly destructive for our patient population — 25% of children infected prenatally will die prematurely from cirrhosis or liver cancer. And then the issue we deal with is this horizontal transmission myth — parents will refuse the vaccine and say, "well, I'm negative." But what we tend to forget is that hepatitis B virus survives on surfaces for durations as high as seven days, and it's transmitted via minor skin lesions or shared items, in a household or in daycares. And kids between the ages of one and five carry a 30% risk of lifelong chronic liver disease. So it's an extremely big deal. And when we have patients who refuse the initial birth dose — even if we're not talking about refusing it altogether, because honestly, at my institution, it's hard for me to know what's actually happening, since parents could tell me "we'll do it at the pediatrician," and that's in a couple of days, but I have no idea if these infants actually get it. So if we look at even a two-month delay, which is what was mentioned in the news by the administration, and we assume perfect adherence to that two-month dose, we're looking, according to projections, per single US birth cohort, at 90 additional acute hepatitis B infections, 76 additional chronic hepatitis B virus cases, 29 additional deaths, and $16.4 million in additional healthcare costs. So the burden is there. And I think that, unlike vitamin K, we tend to assume they'll get it done at the pediatrician, who they have an appointment with within, what, 72 hours of birth, or even five days of birth, but I don't know if the hepatitis B vaccine is actually given at that point in time, and that really frightens me.

Eli Cahan (13:36.24)

Yeah. Well, listen, I couldn't agree more with everything you said. By the way, I think the R word is racism. And if I'm not mistaken, there's a C word here too — colonialism. But those points aside, I just think this is when we

Ben Courchia (13:52.309)

We didn't, which, by the way, right — we didn't really get into the fact that Danish researchers are going into the middle of Africa to conduct experiments — human experiments. It's

Eli Cahan (13:55.875)

We didn't. Yeah.

Eli Cahan (14:06.022)

Yeah, no bueno. Long history of that one. Not good. And especially not something the American taxpayer wants to be paying for.

Ben Courchia (14:09.071)

Yeah.

Ben Courchia (14:15.728)

And by the way, this isn't like they applied for this grant — this is unsolicited money being offered to them. I think this idea of a no-bid grant, where basically they went and said, "do you need money to sustain this?" — this is crazy.

Eli Cahan (14:34.418)

Yeah, I think the other — I think the other—

Ben Courchia (14:36.792)

And they could potentially do the study in the US now, since we're delaying the vaccine so much.

Eli Cahan (14:41.202)

Yeah, well, they could do a natural history version of it — I don't know if we'd let them, I don't know what IRB (Institutional Review Board) would approve that here. But again, I think the no-bid piece of this is probably also infuriating to the legions of our colleagues — young investigators, previously NIH (National Institutes of Health)-funded people, who are now getting exceptionally high scores and not getting funded, seeing research projects die, seeing postdocs and postgrads laid off and sent back to the countries they're coming here from, leaving their families because they're so devoted to science, and now they have to go back and do that — or go to European countries that say, "hey, there are a bunch of smart people who are now free agents, let's go get them." I'm sure this is infuriating to all of them. It's not the way the process is even supposed to work on paper, so there are legality questions too. I think the other thing here that struck me about this reporting — Katherine's reporting — and the effects we're seeing now on hepatitis B, obviously not just from the study, but from the broader conversation around hepatitis B, is that these are the kinds of studies people come across when they say, quote, "I've done my own research." These are the studies that pop up, and that

Ben Courchia (15:54.724)

Yeah. And it's very important — that's also why I was mentioning the potential ramifications of delaying by two months. This idea that delaying by two months — myself included, in the beginning — is a safe compromise, "at least they get it eventually" — it's not a safe compromise. It is not safe for these infants to delay their dose by two months. It increases the risk of infection, of chronic disease, of mortality. I think

we need this data to have evidence-based talking points, data to provide families that goes beyond just our opinion, or "the way we used to do things." That's critical, because we need to present the data. We need to be good advocates for evidence-based practices. And delaying the birth dose is not going to cut it.

Eli Cahan (16:48.85)

And we need to be aware of these studies out there on the internet, that maybe an AI chatbot is pulling into its summaries when somebody asks, "should I get the hepatitis B vaccine, are there dangers associated with it?" and it pulls up, "hey, there's a study from West Africa that shows there are dangers associated with it." We have to read these studies, we have to know they're out there, we have to engage with this head on.

We have to say to families, "I understand where you're coming from — we both want the same thing, which is health for your baby, so let's talk about the risks and the benefits." That's something we have to address head on. At the same time, if you're inclined to solve systems-level issues, you can call your Congress people and say, "what's going on with the NIH? Why are we giving out blank checks to unsolicited proposals, while my wonderful colleagues can't get funding to do things that

for years we've decided are important?" Anyway, lots, yeah.

Ben Courchia (17:45.134)

Huh. Yeah. Especially with all the conversation about stopping efforts to fund research outside the US — like a year ago, two years ago, where every initiative outside the US that we were funding was shut down — and now we see that this can continue? Give me a break. And by the way, you can find-

Eli Cahan (18:10.874)

Yeah. Unless you're a Danish couple — then you can get funded. Then we'll pay for it.

Ben Courchia (18:14.136)

Yeah. And the tragic thing for me is, I have some pride in being an American citizen — it took me some time to become a citizen — and it's like, you look at this study in the news, and you'll find it: it's the "Guinea-Bissau, US-funded hepatitis B study." US-funded. Why are we even tied to this? It's just crazy. Anyway, I think that does it for us today, we're over time.

But thank you, thank you, Eli. All right.

Eli Cahan (18:46.588)

Thanks