“Neurodevelopmental Outcomes of Children with Congenital Heart Disease” by Jane Newburger

December 27, 2019

Welcome to World
Shared Practice Forum. I’m Dr. Jeff Burns,
Chief of Critical Care at Boston Children’s
Hospital and Harvard Medical School. We’re very pleased to have with
us today Dr. Jane Newburger. Dr. Newburger is
the Associate Chief of Cardiology at Boston
Children’s Hospital and the Commonwealth
Professor of Pediatrics at Harvard Medical School. Jane, welcome. Thank you, it’s
great to be here. Dr. Newburger, you’re known
for your academic work over the last several decades
on neurodevelopmental outcomes after congenital heart repair
and congenital heart disease, and I wonder if you
could tell us where– where had the field
been, what do we know, and where are we going? Sure, a pleasure. So we have had
improving outcomes in every form of
congenital heart disease from the ’70s through,
you know, the current time, so that we now expect
babies to survive, and that is very different
from how it was 40 years ago. And with that
improving survival, it’s become evident
that we have a problem with neurodevelopmental outcomes
in many of our patients. So actually behavioral,
developmental, and neurologic abnormalities
are the most common morbidity that’s associated with
congenital heart disease. And it’s more common
in the CHD population than late sudden death,
significant exercise limitations,
significant arrhythmias, unplanned re-operations in
endocarditis all together. And if we look at the complexity
of congenital heart disease, that is highly associated
with the likelihood of having neurodevelopmental challenges. Children with the mildest forms
of congenital heart disease are the least likely to
have neurodevelopmental impairment, whereas
those who are the most severe or
palliated newborns have the greatest
proportion with neurodevelopmental impairments. The highest prevalence
of all, not surprisingly, is in children with
genetic abnormalities. So, Jane, what are
the risk factors for neurodevelopmental problems? So there are many. The first lie in
the genetic sphere. Up to a third of forms
of congenital heart disease are now recognized to
be caused by genetic variants, and these can be
aneuploidies where you have a whole
extra chromosome, like down syndrome,
microduplication, or microdeletion
syndromes like DiGeorge or velocardiofacial syndrome. And then single gene disorders– we recently found that de
novo point mutations actually contribute up to 10% of severe
congenital heart disease in whole exome analyses. We also know that other
congenital abnormalities occur in almost 14% of children who
have congenital heart defects, and if you look at the
likelihood of having excess pro-bands with de novo– with these de novo variants– whereas controls maybe
1% of us have these, and it’s the luck of the
draw where they fall. So in the Pediatric Cardiac
Genomics Consortium, we did whole exome sequencing
in over 1,200 trios of parents and children, and these
damaging de novo mutations were seen in 20% of children
with congenital heart disease, neurodevelopmental
abnormalities, and congenital anomalies,
compared to just 2% in children with isolated
congenital heart disease. And those findings suggest that
these problems have a shared genetic contribution. Another very
important cause that is a hot topic of
investigation, are derangements in
fetal circulation or fetal cerebral hemodynamics. In a study that was done
here at Boston Children’s by Kathy Limperopoulos in 2010,
pregnant women underwent scans, so the fetuses had brain MRIs
at multiple points in time, and those fetuses had either
congenital heart disease or they were unaffected by
congenital heart disease. And what we saw was that
total brain volume did not increase as quickly in the
congenital heart population. So there– although it’s
a cross-sectional study, there seemed to be
slower brain growth. In doing spectroscopy, the
n-acetyl aspartate to choline ratio, which ordinarily has,
kind of, an exponential curve in the third trimester, also
did not increase as rapidly. And the children with
the most impaired values were those that didn’t
have any antegrade arch flow, like what you see
in hypoplastic left heart syndrome. We know that after
birth, children have more dismature brains. So a study that was
done by Dan Licht compared the total maturation
score of the brain at birth by MRI in children
with transposition of the great arteries and other
severe congenital anomalies, to normal total brain
maturation at term. And what he found was
that these children were about a month behind on
average, so their brains are actually dismature. And they start this
out before they even undergo any interventions,
so about a month behind. Then, of course, there are the
sequelae of congenital heart disease itself. Chronic severe cyanosis
is a risk factor for developmental delay. A lot of our children
don’t have good nutrition if they’re in chronic
heart failure. Cardiac arrests occur,
significant arrhythmias, and all of these can
impact development. We did a study– I’m embarrassed to
say was in the ’80s– in which we analyzed old
data from the Regional Infant Cardiac Program,
which was instituted in New England in the ’70s
where all the medical data was gathered about
children, and then a wonderful psychologist
named Annette Silbert who was then working here
went out to each center and tested the children before
they entered kindergarten. And this was the
same era in which children with transposition
were undergoing the Mustard procedure
at different ages depending on their center. And what we found is that
the later you were repaired, the worse your IQ and each
of the components of your IQ. And that was highly
significant even when you adjusted for social
class and other variables. So chronic cyanosis, we
know, is an important factor. Dr. Newburger, I wonder if
I could pause and ask you, could you remind the audience
what a Mustard procedure was? And still is– And still is in some places. So a Mustard
procedure is done in– was done in children
with transposition of the great arteries in which
the pulmonary artery comes off the left ventricle and the aorta
comes off the right ventricle. So uncorrected you have
to two circulations that are happening in
parallel rather than series. In the modern day, we
do an arterial switch in which we do-si-do the
two great arteries, so they come off the correct ventricle. But in the early days
of cardiac surgery, the technology to do
that wasn’t available. And so a Mustard procedure is
what’s called an atrial switch procedure where you place
a baffle in the atrium, so all the blood coming
back from the IVC and SVC is funneled to the mitral
valve, and blood coming back from the pulmonary veins
goes around that baffle and out into the right ventricle
as shown in the figure. We also know that children
with congenital heart disease can have silent strokes
or overt strokes, and sometimes when a child
comes in with an acute stroke and you do a scan, you
see multiple other areas that were affected and nobody
actually ever knew about it. We know that the
interventions that we do, such as cardiac
surgery and cardiac cath are each associated
with sequelae. They’re necessary. Janet Soul some years
ago looked at brain MRIs in one of our studies and
was the first to describe these little
hemosiderin lesions. So about, depending
on the lesion, a quarter to a third
of children who have open heart
surgery in infancy have these tiny little
microhemmorhages that actually look
a lot like what you get with a shaken baby,
and they’re associated with how long you’re on
the heart-lung machine and also how many cardiac
catheterizations you have. So the cardiologists don’t get
off scott free here either. We know that the duration of
being on the heart-lung machine or bypass is a risk
factor that the longer you’re on the
heart-lung machine– as beautifully
demonstrated by John Beca– the longer you’re
on, the greater– the greater the prevalence of
white matter injury, and that especially goes up when
you get to very long time, since severe injury
becomes more common. We also know– and
fascinating information– that if you have a less mature
brain going into surgery, you have a higher likelihood
of white matter injury. So we know that you’re born
with some white matter injury. Maybe 20% of newborns have white
matter injury before they ever go to the operating room. And about 40% have new white
matter injury after surgery. But the children who have
the most dismature brains to start with are the ones
who are most at risk for this. And that actually
has implications in terms of the timing
of elective delivery. So sometimes obstetricians
feel that it’s better to do a planned
delivery, and they do a c-section or a
induced delivery early, but that has implications
that are adverse for how the brain handles surgery. And so we have a
advocacy role in trying to keep those babies inside
for as long as we can. So millions of
dollars of NIH funding have gone into studying
intraoperative conduct, because it’s the most modifiable
risk factor that we have. The surgeon can manipulate
the heart-lung machine. But we’ve recently
come to realize that a huge source
of neurologic injury actually occurs after
surgery, and this relates to a time
period when you have significant post-operative
hemodynamic instability. When one uses hypothermic
bypass techniques, an infant will lose the
ability to autoregulate their cerebral
vascular circulation, and they don’t have normal
reactivity to carbon dioxide. So in that first 24 hours
they’re exquisitely vulnerable to hypotension and also to
decreased cardiac index. And that’s led to
a tremendous focus on brain monitoring,
which I’ll come back to. We also know from the Boston
Circulatory Arrest Study where children
with transposition were randomly assigned to either
deep hypo– predominant deep hypothermic circulatory arrest
or predominant low flow bypass. And in that study
we meticulously, exhaustively
collected every piece of data, everything that
happened to the child during that hospitalization. We then– when they returned
courtesy of the NIH at age eight years– looked at the effect of length
of stay in the cardiac ICU on their IQ. And what we found is that there
was a linear decrease in IQ with each quartile of
longer length of stay. So verbal IQ went down,
full scale IQ went down, and because this
was an exhaustively done prospective
study, we also were able to adjust for all the
potential confounders or effect modifiers. And even when we adjusted
for the known predictors of longer CICU stay, like
sepsis, and other variables, like social class,
that are universally predictive of your
developmental outcome, this was still highly
statistically significant. And really in the
range of effect between the first versus
fourth quartile of what you might see with
lead poisoning. If you deleted the top 5%
of length of stay patients, so the real outliers,
then each CICU day lead to a reduction of 1.4
points in full scale IQ and 1.6 points in
math achievement just to give you an idea. Lest you think that this is
only a factor for transposition, another great study
was done by Bill Mahle, involved four centers. And their question was
whether IQ is better, whether developmental
outcomes were better if one had a primary transplant
versus staged palliation strategy for children under– with hypoplastic
left heart syndrome. So “Did you go down the
Norwood to Fontan pathway, or did you go down the
transplant pathway?” And it turned out not
to make a difference. But what– the only thing
that really mattered was longer length of stay
at the first surgery. So, and the same finding
has been reproduced in every study pretty much. So Dr. Newburger,
I have to ask you. I’m sure many of my
colleagues around the world are wondering the
same thing I am, and that is cyanosis
as a risk factor for neurodevelopmental
outcomes– Is there a saturation or
a saturation and duration that in your head when you see
that you think, “Oh, dear, I’m worried,” whereas a saturation
above X, you’re less worried? The studies on the effect of
cyanosis under development were done in unoperated
transposition patients, and those children had
saturations in the 60s and 70s. We don’t have any studies that
are modern that really tell us where the cut-point
is and whether having a saturation of 85%, for
example, is just fine. We don’t know for sure. In general, for reasons
of hemodynamic stability, we get pretty uncomfortable
if a saturation is below 75%. And ideally we like
it to be above 80%. From a neurodevelopmental
view point, if you could wave the magic wand
and make everybody completely pink with no adverse effects of
the treatment, then, of course, we would make everybody pink. But what we do is, kind of,
the “teeter totter” method of decision making,
which is we balance the risks of intervening
against the benefits. And so the effect of cyanosis
on the brain is one of the risks that we consider, but we also
consider what kinds of effects the therapies that
we might initiate could have on the brain. So can I ask as a
followup, do you worry about oxygen
saturations in the 80s? Nobody has studied the
effect of saturations in the 80s on neurodevelopment
or brain injury. We all have anecdotal
impressions. I, certainly, know
lots of very smart kids with saturations in
the mid-to-high 80s, but nobody has actually
scientifically studied it. Dr. Newburger, I wonder
if I could ask, again, cardiopulmonary bypass
as a risk factor as you’ve just described it. So I can’t help but be sitting
here thinking and remembering how I would be giving the report
the next morning on rounds and talking about the
circ. arrest time, and is there a number
in the literature, or do you have a cut-point
from your vast experience where you start to
think, “Oh, dear, that was a long bypass run,
that circa rest time was just a little too long,”
and you start to worry? I don’t think there is
any specific hard and fast cut-point. There are a lot of unknowns. We know, in general, a
good and fast operation is much better for the brain
than a slow and bad operation. That’s pretty obvious that we– and part of that is we want
the hemodynamic stability after surgery to be
good with a good repair. And so there’s a lot of
variability in times and speed. There’s also
variability in the ways that you support the brain from
the time you go on bypass ’til the time you come off. Some individuals, we usually
cool the temperature down. How cold that
temperature gets is– there’s tremendous
operator dependence with some people taking
the temperature down to 18 degrees centigrade
and others to 25 centigrade. When we use deep hypothermic
circulatory arrest, what you do is you cool the body
down to below 18 degrees, and then you basically
exsanguinate that baby into a venous reservoir,
remove the cannulae. You’re operating on a
totally clean, bloodless, cannula-free field, and
it’s great for visibility. If you can do that surgery
in less than half an hour, the shorter period,
the better, but I think once you get to 30 or
40 minutes, in all likelihood that risk goes up somewhat. And when the times get
very long, for example, to over an hour, then we
become very concerned. It isn’t as cut and
dry as you would think, because there are many other
factors about how you regulate the heart-lung machine, whether
you put in carbon dioxide or not when you’re cooling,
what the hematocrit is, and such that can
affect brain protection. And so it really is an
extraordinarily complex field in and of its own. What I would say is that we just
did a study of 1,700 children from multiple countries
who had already been part of either published
or in a couple of cases not yet published series
and looked at surgical risk factors. And although we looked at every
aspect like circulatory arrest time and regional
cerebral perfusion time where you’re perfusing the brain
at a lower rate during surgery, we found that they’re all
highly related to each other, and no variable did better
than total support time, meaning the time
you go on the pump ’til the time you
come off the pump. So, Jane, could I
push a little further? After your paper came out in the
New England Journal of Medicine about comparing the outcomes
of deep hypothermic circulatory arrest to other
forms of bypass, did the use of deep hypothermic
circulatory arrest decrease? It did. It decreased around the
country, in general. But importantly, there were
some operations like the Norwood procedure where one can’t
continue flow to the whole body during the operation. And there, I would
say investigators are very interested
in the trade-offs of deep hypothermic circulatory
arrest where there’s no flow compared to
regional cerebral perfusion where there is antegrade flow
of blood just to the brain. And very conflicting
data regarding which one is better with a
lot of true belief on both sides of the equation. Most of the data,
as I mentioned, suggested that the total
support time may be the most important risk factor. In summary then, risk
factors for adverse outcomes include patient factors. Examples are genetic variants,
in-utero environment, and cerebral hemodynamics
or family environment. Second, medical or surgical
management, for example, your procedural
methods during surgery, complications,
instability after surgery, and then finally sequelae
of the heart disease itself like cyanosis,
malnutrition, or cardiac arrest. We recommend that all
children with congenital heart disease who undergo either
reparative or palliative procedures should be
presumed to be at increased neurodevelopmental risk unless
there is convincing evidence otherwise. Also, increased
neurodevelopmental surveillance should be a routine
part of follow up of children with
congenital heart disease, and the reason for this is so
that emerging difficulties can be identified and of course,
appropriate supportive interventions implemented. Dr. Newburger, that’s
a fascinating overview of the risk factors. So now I’m sure I speak for
my colleagues when I ask: what is the phenotype? How do they manifest these
neurodevelopmental delays? The areas of weakness in
congenital heart disease patients have been
really well studied. First of all, there
often are delays in motor skills both gross
motor and fine motor, and in infants– in children who have had
infant heart surgery, they have apraxia of speech. And if you think about the
area of the brain that’s developing the most
rapidly in a newborn, it’s the oral-motor function. They have to suck, and so the
motor planning part of speech can be affected. Visual-spatial skills
are another area of concern, vigilance and
sustained attention, higher order language. So not so much “Can
you talk,” but “Can you tell a story when you’re
shown a number of pictures?” And then extremely important
is executive function, so working memory, the ability
to hold on to information and perform operations on
it, hypothesis generation and testing, organizing
and carrying out complex, kind of multi-step tasks,
and applying principles to solve problems. We know that in
our transposition study in the Boston
Circulatory Arrest Study, we brought children back,
again, courtesy of the NIH, at age 16 years, and we tested
their memory with something called the Children’s
Memory Scale. And compared to normative
values and a comparison healthy population
within Boston, these children had worse
attention/concentration, worse learning, and
worse general memory. We also had a survey
called the BRIEF, which is a Behavior Rating Inventory
of Executive Function that was completed by parents,
the children, and teachers that also showed worse
executive function in the cardiac population. David Bellinger at
Boston Children’s was the first to describe
deficits in social cognition in children with
congenital heart disease. And social cognition
is the processing of social information,
interpreting social relationships
and social situations that you might be
in, and the ability to read the emotions
of other people and make inferences about
what they’re feeling. And we administered something
called the Mind in the Eyes Test, and as you
see in this example, there are screenshots of
eyes and facial expressions. And there are four choices
for each expression. So in this particular
one you could be aghast, board,
insisting, or cautious, and the answer is cautious. These are really hard
to do, so there’s a bell-shaped distribution with
some very, very smart people not having a lot of skills in
this domain of interpreting facial expressions. But the average
score of children with transposition or
tetralogy of Fallot is way at the lower end of
the bell-shaped distribution. A very hot topic
right now is looking at connections between
areas of the brain and the resting state, and
that’s called the connectome. And we took the same data
from children, adolescents with transposition,
and collaborated with Ashok Panigrahy who
is the Chief of Radiology at Pittsburgh Children’s
Hospital and a neuroradiologist with an interest in this area. And what we found, and you
can see this in the figure, is that you can divide the
brain into subhemispheres. When we study the
resting state, we look at subhemispheres and
the connections within them. For example, anterior,
posterior, right, and left. And then we look
at the connections and the density of connections
between those subhemispheres. And what we found
was that there were more intrahemisphereic,
or sub-network connections in the children with
transposition, but way fewer connections between
these sub-hemispheres or sub-networks, and the
connections themselves were associated with certain
developmental abnormalities. So executive
function, for example, is worse if you don’t
have a lot of connections between sub-networks. Dr. Newburger, of course,
all of these studies, as you well know, because
you’ve explained this to me over the decades,
concerned children who had two ventricles. And, of course,
in the modern era the real challenge
is for the child born with what we call
“single ventricle physiology.” What do we know about their
neurodevelopmental outcome? So as you’re suggesting, this
is the group at highest risk. They have the highest likelihood
of genetic abnormalities. They are– they have
congenital CNS abnormalities, they’re the most likely
to have been in shock, and to be chronically blue, to
have congestive heart failure. Growth is a huge
problem in this group, with somewhere between a half
to a quarter in most series having g-tubes. And they have multiple
catheterizations in operations, so many risk factors. In the Single Ventricle
Reconstruction Trial, which was a Pediatric
Heart Network Study done across 15 centers,
we brought children back at a year– 14 months to be exact– to do the Bayley exam. And the average
population should have a mean score or
median score of 100 with a standard
deviation of about 15. These children on their
psychomotor development score had a median score
of 72, which is almost two standard deviations
below the average scores in the general population. For the mental
development index, which is a, kind of a
pre-cognitive index, the median score was better
at 92 compared to the 100 that it should be. We found that those
scores at 14 months were most related to
innate patient factors, like, having a genetic
syndrome or anomalies, lower maternal education,
and lower birth weight, and also to greater morbidity
in the first year of life. So longer time after the
Norwood in the hospital. So longer length of
stay comes up again, and more complications after
discharge from the Norwood until 12 months. If we fast forward
to three years these children filled out the
Ages and Stages Questionnaire, and 2 and 1/2% should be
found to be at risk in any of the five domains
of communication, gross motor, fine motor, problem
solving, or personal social. Those are the five domains. And in each of those they
were vastly greater percent at risk ranging from about
17% from communication to almost 35% for
fine motor deficits. We administered the Child Health
Questionnaire 50 parent report form to the parents of
adolescents with Fontan and found compared to
the normative population parents reported much greater
percents with attention problems, developmental delay,
learning problems, and speech problems. And we did in-person
testing on those children, and just to highlight some of
the more interesting findings, when the parent, child, and
teacher completed the brief– which is a test of
executive function– what we found was
much worse scores– high is bad on this test– but much worse
scores in executive function, in adolescent
Fontans given by the parent, the adolescents
themselves, and their teachers. And worse than both healthy
controls in our study and also worse than
the national norms. This is especially
important, because what we found is that psychosocial
health on the Child Health Questionnaire is
extraordinarily related to executive function
ratings by parents. And the R is the
correlation coefficient– Spearman– is about 0.7. We don’t usually see
anything as high as that in the way of correlation
with psychosocial variables. And I think the reason
is, in adolescence parents become a lot less important, but
how you relate to your friends, your peer group, how
you do in school, how you measure up against other
kids becomes super important. And when you don’t have
good executive function, you can’t organize
your activities, and it really affects
your overall performance. Risk factors when we looked
for executive dysfunction and other forms of worse
neurodevelopmental findings in adolescent Fontans
included having a younger gestational age at birth. So that gets back to
the immature brain and the potential for worse
injury during surgery. Having a genetic
abnormality, being on bypass for longer at the time
of the first operation, having more circulatory
arrest at the time of the first operation,
having more operations in general, more cardiac
catheterizations, more complications, and a
history of seizures, those were all risk factors. We also looked at psychiatric
diagnoses in mental health together with Dave DeMaso,
who’s our Chair of Psychiatry at Children’s, and in
psychiatric interviews, we found that adolescent
Fontans had a 65% lifetime incidence of any
psychiatric diagnosis compared to 22% in our
healthy referent population. Mood disorders
were not different, 13% of our adolescent
Fontans versus 9% of our healthy controls. Anxiety disorders were way
overrepresented, so 35% prevalence during
your lifetime up to adolescence of
an anxiety disorder compared to 7% in
the normal controls. And disruptive
behaviors, largely ADHD, were much more common. So 34% of the adolescent
Fontans met criteria for having ADHD compared to
6% of our normal controls. We did structural brain MRIs
in adolescence on the Fontans as well and found an
11-fold greater likelihood of having any abnormality on
a clinical, structural brain MRI with infarct strokes
found in 13% of the Fontan patients, none of the controls. And among those
13%, about a third didn’t know that they
ever had a stroke until they had a brain MRI. These little
hemosiderin lesions, these microhemorrhages, were
present in more than half of the children. We also did much more
sophisticated research studies on white– on cortical
volume and cortical thickness and found multiple areas where
children with Fontan procedures had less cortical
volume, just lower volume of the cerebral cortex,
and less thickness of the cerebral cortex. In summary, children with
congenital heart disease provide a very distinctive
pattern of deficits. These don’t always
match up very well with categories of
learning disability that the schools are alert to. These children have prominent
deficits in higher order integration skills,
like executive function or attention, and we find
that the severity of problems increases with time as the
demands for such skills increase. They’re more evident, for
example, in high school than they are in kindergarten. And then finally, we see
emerging evidence of deficits in social cognition,
and these could impact social relationships
and psychosocial health later in life. So Dr. Newburger many of the
children who underwent bypass are now into their fifth
decade, and perhaps even a little older. How are they doing as adults? As our congenital
heart disease patients are moving into
adulthood, they’re also developing all the risk factors
for adult type neuro– sort of, neurocognitive issues. They have hypertension. They have obesity and
coronary artery disease. And what that does
is it puts them at risk for the more adult-type
cerebrovascular lesions. So you have– we
think in pediatrics about neurodevelopment,
but that development stops at latest in your mid-twenties. And then you begin developing
more degenerative problems, and how these two risk factors,
these two periods will combine is a great source of concern
in our adult congenital heart disease population. So, Jane, where are we going? So the first question is,
“Are we doing better?” We’ve changed so
many parts of what we do in the operating room,
and how we care for children. And I think the
first question to ask is, “Are we
improving over time?” In the ICCON Study, we did
a retrospective analysis of over 1,700 children
in 22 countries and looked at the Bayley
at 14.5 months on average. And what we found is
that both PDI and MDI are going up slowly. So they’re slowly
rising when you adjust for all risk factors,
but they’re still quite low. So the improvements
are relatively modest. I think what that
points to is that there may be tremendous importance of
genetic and epigenetic factors. Whole exome sequencing,
which is what’s mostly been studied
to date, only accounts for 1% of the genome. And so whole genome sequencing
studies are underway, and I think we may find that
genetic abnormalities explain a lot more than we ever
thought of neurodevelopmental disabilities. And it is even possible
with techniques like CRISPR. It’s no longer science fiction
to imagine that they might even– or some of them– may even be modifiable. And then there’s the “deja
vu” versus “vuja de.” So deja vu is when you
encounter a new situation, and you feel like
you’ve seen it before. But vuja de is when
you go into a situation that you’ve seen
thousands of times before, but you suddenly see it anew. And I think our intensive
care unit is like that. These children are
surrounded by noise, they have frequent
painful stimuli, and they are exposed to
phenols and phthalates, which are plasticizers. We know from the
preemie population that exposure to plasticizers
is found in the urine. Everything that we
know about plasticizers is that they’re not
beneficial for your brain and may be harmful. And I think that
there’s a lot that we can do to modify
the ICU environment and a lot that we can learn
about the environmental toxicities there. I think that we will be
seeing much more science in fetal interventions, whether
it’s maternal hyperoxygenation, progesterone
therapy is now being tested by Bill Gaynor’s group. Pomegranate juice may be
beneficial, and just avoiding early term delivery. So we’re going to
learn a lot more about how to improve the circulation
of the cerebral brain, and how to prot– of the fetal brain,
and how to protect it. All through the country,
people are doing much more work on monitoring the
brain and trying to intervene on the brain
based on those monitoring findings in the ICU. There are great guidelines that
were released by the American Heart Association that
now advise pediatricians and cardiologists to do routine
neurodevelopmental screening and testing of
high-risk children who have congenital
heart disease. And that gives one
the opportunity to intervene at a
much earlier point, and also to educate families
and patients and school systems. Because the phenotype
in congenital heart disease is not one that
the school systems are accustomed to looking out for. We are embarking on a trial here
of the so-called Cogmed Working Memory Intervention in which
we’re randomizing children to have this executive function
and working memory intervention that goes on for five
weeks to see how it– whether it can benefit
school performance, and we’re pretty excited
about doing that. There is tremendous
opportunity in the current era for multi-center collaboration. The Cardiac Neurodevelopmental
Outcomes Consortium, or CNOC, has just been formed with
many centers agreeing to collaborate and collect
relatively similar data. The National Institutes of
Health Pediatric Heart Network is doing neurodevelopmental
studies across centers. The Pediatric Cardiac
Genomics Consortium is just about to embark
on a large study looking at the effect of mutations on
neurodevelopmental outcomes. The Congenital Heart Public
Health Consortium Work Group, a neurodevelopmental, cognitive,
and psychosocial quality of life work group,
that’s a big mouthful, is looking at
advocacy and looking at public policies
for our children, to see ways that the public
can help them do better. And then a great
deal of attention is going into the leveraging
of existing databases like the Society for
Thoracic Surgeons Database and the
PC4ICU database, as well as National
Health Registries. So I think we’re coming into
just a great time for progress in the field. I’m just going to end by saying
that if you take the long view, the advances in
congenital heart disease have really been astonishing. Children didn’t survive
four decades ago. And if you look at the majority
of congenital heart disease patients, they are generally
within normal limits. And in fact, there are more
adult congenital patients with college degrees
than those that didn’t graduate from high school. And I think what we’re
going to do going forward is only going to
make outcomes better. Well, Dr. Jane
Newburger, thank you so much for sharing these
valuable, not insights, but decades of
meticulous research. And on behalf of my
colleagues around the world, I can understand why the
American College of Cardiology asked you to give the
McNamara lecture, which is a very prestigious
lecture on this very subject, which you did. And so thank you for
sharing it with colleagues around the world. Thank you. It’s really been a pleasure.

Leave a Reply

Your email address will not be published. Required fields are marked *