Transient and Controversial Findings in Fetal Sonography - SD

Introduction

I am Beryl.
Raf. I'm from Boston, Massachusetts,
and I work at Harvard university,
school of Medicine.
I'm gonna be talking today about the transient,
findings in fetal ultrasound
and what to do with these borderline or transient findings.
During this lecture, we're going to talk about
some of the transient
and controversial findings in fetal ultrasound
and what to do about them.
Specifically, we're gonna be talking about some
of the findings, such as a thick
nuchal translucency when the karyotype is normal.
Choroid plexus cyst,
the echogenic intracardiac focus,
a borderline ventricular magaly, a mild ectasis,
hyperechoic bowel
and calcifications in the liver,
single umbilical artery and a nuchal cord.
The question is, when we see some of these findings,
what is the workup that's necessary?
What do we tell the patient?
Are the chances
that the baby is gonna be abnormal or normal?
And can we quantify those chances?

Thickened Nuchal Translucency

Let's talk about a fetus
who has a thickened nuchal translucency.
Now, we all know that a thickened nuchal translucency is
associated with an increased risk
for chromosomal abnormalities, in particular down syndrome,
and trisomy 18.
Clearly when the nuchal translucency is thick
and the risk is up, an amniocentesis
or chorionic villus sampling is necessary.
At least we should offer it once that comes back negative.
What is the next step?
Can we say the baby is gonna be normal,
or what should we do to investigate?

First of all, I think it's important
to get a very good structural survey at 18
to 20 weeks when we can observe all of the fetal anatomy,
make sure that there are no malformations
because in particular, malformations of the heart,
are associated with an increased,
nuchal translucency.
Perhaps even an echocardiogram would be helpful.
And also,
to see whether
or not the nuchal translucency is still thick
or the nuchal fold in that case is still thick.
But in general, once we have
excluded chromosomal abnormality, the outcome
is normal in 90% of survivors, and I say survivors
because there is an increased risk
that the fetus won't survive the pregnancy,
and that depends on how thick,
the nuchal translucency is.
In this study, which encompassed 1,080
survivors, there were 60 that were abnormal.
But, and you can see that it depended on the thickness
of the nuchal translucency.
If it was very thick, greater than six millimeters,
then the survivors were only 31%.
Whereas if it was 3.5, 3.0 to 4.4
millimeters, then the survivors were 86%.
The long-term survival,
or the long-term outcome with,
children born
after a thick
nuchal translucency with a normal karyotype
really depends on a careful evaluation as the baby gets,
as the fetus gets,
further along,
either a good structural survey at 16 to 18 weeks
with perhaps an echocardiogram
or maybe,
another look at 22 to 24 weeks.
And this was a study that looked at doing this
along with a pediatric evaluation at two days,
1, 4, 9, and 24 months,
and showed,
that, 72.2%
with normal karyotype, had a normal outcome.
And if you look at what happened to the others,
10% had a abnormal ultrasound,
five had a fetal demise,
and one each had an SAB
and, an elective,
an elective abortion.
And 162 out
of 179 90% who had a normal scan.
Let's see what happened to them.
87.7% had a normal outcome and 18
or 11% had an abnormal outcome.
And you can see,
that
these abnormal outcomes included some cardiac defects,
high post staus, hip dysplasias, Noonan syndrome
and so forth and so on.
Two out of the 164,
with development delays at two years.
Generally speaking, when we think of
a thickened nuchal translucency
after a normal karyotype, generally speaking,
if you have a normal ultrasound
and a normal echocardiogram, it is very likely
that the baby is going to be okay,
with a still a slightly increased risk of abnormalities,
but for the most part, a close
to 90% chance of a normal outcome.

Choroid Plexus Cysts

Now moving on to choroid plexus cyst.
CPC cysts are these small cystic areas within
the choroid plexus.
You can see here,
and you can see them in this other view as well.
They're considered a normal variant.
They are for the most part transient
and go away with the,
advancing pregnancy.
But they are associated with an increased risk
of trisomy 18.
In fact, we know that approximately a third of fetuses
with trisomy 18 have CPC cysts.
But because trisomy 18 is so rare, the majority of fetuses
with CPC cyst do not have trisomy 18.
The CPC cysts are well-defined cysts,
you can have spongy appearing choroids
and these are not what we call CPC cyst.
And if you look at,
the association
with Trisomy 18, as I said, 30% of fetuses
with trisomy 18 have choroid plexus cysts,
but 90 to 80% of fetuses
with trisomy 18 also have major congenital abnormalities.
And considering that trisomy 18 is a very rare
occurrence, when we see these choroid plexus cysts
as isolated findings, the baby is almost always normal.
And the kinds of abnormalities that we see with trisomy 18,
you can see here with they have a heart defect right here
we have a strawberry shaped skull.
We have,
foot abnormalities, clubfoot
or rocker bottom feet here are the club feet in 3D as well.
If you look at the literature, you find,
meta-analysis on isolated choroid plexus cysts.
And I think everybody will agree
that if the choroid plexus cysts are associated
with other findings, then the risk
of trisomy 18 goes way up.
But if the choroid plexus cysts are isolated
and there are no other findings, then the risk
of trisomy 18 is quite low.
And in this meta-analysis of 13 studies, the incidence
of trisomy 18 in fetuses
with isolated CPC cyst was only a fourth of 1%
and did not warrant invasive testing.
Another important fact is that the risk
of down syndrome did not increase with the presence
of isolated CPC cyst, which means
that if you see these choroid plexus cysts,
the fetus can have trisomy 21,
but that would be completely unrelated to the presence
of choroid plexus cysts, so
that these cysts should not increase the risk of Trisomy 21.
One of the largest studies done on choroid plexus cyst
as shown here on more than 12,000 patients,
of which 366
or 2.9% had CP cysts.
It turns out that there were 43 cases
with CP cysts, with no other finding,
and none of them had trisomy 18.
So that the conclusion here was
that isolated choroid plexus cyst were not an indication
for invasive testing.
The recommendation is if you see a choroid plexus cyst,
first of all, correlate with maternal age and prior screen.
'cause nowadays many of these fetuses have had
NT translucency and biochemistry in the first trimester
and perhaps even in the second trimester for screening
for down syndrome.
And trisomy 18 do a detailed sonographic
evaluation that includes the heart, the face, the brain,
the extremities, very important to make sure
that the hand is open
because fetuses with trisomy 18 are not able
to open their hand normally.
And then an amniocentesis is really not recommended
for patients,
who have this finding
as an isolated finding and who are otherwise at low risk.
Just to show you an example, on one side you have a fetus
with trisomy 18, with the hands are clenched
and the overlapping index finger is seen.
Whereas on the other side, you have a normal hand,
which opens up and is typically a stance that the fetus
with trisomy 18 cannot,
do.

Echogenic Intracardiac Focus

Now going on to the next subject
of the echogenic intracardiac focus,
the echogenic intracardiac focus is a little bright dot,
which has to be as bright
as bone usually in the left ventricle of the fetal heart.
This is seen in about 5% of all second trimester fetuses,
but it is seen in 18% of fetuses with down syndrome.
This finding carries a fourfold increased risk for trisomy,
21, when you look at all cases.
But if you look at the echogenic intracardiac focus
as an isolated finding with no other findings,
it only doubles the risk
of the prior risk of down syndrome.
Now going back to 1992,
it was shown in the pathology literature long
before it was ever shown by ultrasound that fetuses
that were examined pathologically
and that had down syndrome.
And also Trisomy 13 had an increased incidence of
microcalcifications in the papillary muscle.
And in fact, they found these calcifications in 16%
of fetuses with Trisomy 21,
as opposed
to 2%
of normal controls.
This is very similar to our study where we had 18%
of fetuses with trisomy, 21
and 4.8% of normal controls who had this findings.
Now, we also found that the Asian population seems
to have a higher incidence
of the echogenic intracardiac focus almost four times
more likely than women that are not of Asian background.
And so,
it is important to,
not
over-diagnose this finding in fetuses of Asian descent
and not over-interpret,
the meaning of this finding.
And in fact, we don't usually change the risk
of down syndrome for the Asian population.
I think what's important to realize is
that the implication
of these markers is very different if you're dealing
with a high risk or a low risk patient.
There are two studies in low risk patients that have found
that if you see an isolated echogenic intracardiac focus,
it is likely not to mean anything.
Here it was found in only one of 626
down syndrome fetuses from among
more than 21,000 patients.
And so that both of these studies concluded
that an isolated echogenic focus was not a marker
for down syndrome in the low risk patients, patients
who have tested at low risk in their early risk assessment.
Another study found only one fetus with Down syndrome in 141
fetuses that had echogenic intracardiac focus,
but she was 38 years old
and she was at increased risk due to her age.
Now here's another study,
in a low risk population.
It was a 16 year study of,
62
plus thousand patients.
In 2,223 fetuses
with echogenic intracardiac Focus.
Trisomy 21 occurred in 218 patients,
about a third of 1%.
The echogenic focus
and other markers together with other
findings was associated
with a 4.4 likelihood ratio
of Trisomy 21.
But on the other hand, the isolated echogenic focus was not
associated with a statistically increased risk
for Trisomy 21 in patients who were below age 35
and those who did not have an abnormal serum screen.
In other words, those that were at low risk,
it is far less likely for an isolated echogenic focus
to indicate a fetus with down syndrome
in a patient population who has already undergone screening.
'cause when you think about it,
when a patient population undergoes the first trimester
screening, about 80 to 90% of fetuses
with down syndrome are already identified.
So in that case, the incidences of down syndrome in
what remains of the population
that have not been identified is very, very low.
In one study from Britain,
there were almost 17,000 pregnancies, all
of whom were offered NT translucency
and mid trimester serum screen.
And none of these fetuses
who had an isolated EIF had down syndrome.
It's important,
that
that we not do more harm than good.
Ultrasound soft markers are responsible
for a 4% increased detection, which is very low
of anomalies, but unfortunately a 12 fold increase in false
positive rate,
if we apply it to everybody.
And because the soft markers,
can occur in up to 10
to 15% of patients,
and in fact the echogenic focus occurs in at least 5%
of normal fetuses.
But if the population that we're dealing
with has already tested very low in probability
for down syndrome,
that must be considered.
And those patients,
should not panic.

Borderline Ventricular Megaly

Now going on to the borderline ventricular magaly
or only slightly increased,
width
of the lateral ventricles, you can see
that the lateral ventricle here
is measured at the atrium right at the place
where the choroid plexus ends.
And that measurement remains constant throughout the second
and third trimester.
The mean is 7.6 millimeters
and it needs to be less than 10 millimeters to be normal.
What happens if the lateral ventricle measures between 10
and 12 millimeters?
This is really mild or borderline ventricular magaly.
In a study that we did in our lab of 44 fetuses
with exactly that, 12% of them had abnormal karyotypes
and most of these were down syndrome.
Eight fetuses died or were electively terminated.
So 26 out of the 36 live born
or 72% were developing normally,
but there were 10 that were handicapped.
Now it makes a difference whether these fetuses had other
anomalies or whether it was just the ventricular magaly.
39% of fetuses had other anomalies
and 50% of them are developing normally, whereas
those that did not have other findings, 80%
of those are developing normally.
When we see borderline ventricular magaly
as an isolated finding, we need
to do a very detailed structural survey, make sure
that we can identify the other features of the brain such
as the corpus callosum, consider an echocardiogram
because there's an increased risk for down syndrome.
Consider amniocentesis for karyotype
and also consider that this can be secondary
to congenital infections such as CMV.
And so perhaps an fetal MRI would be helpful to
evaluate,
the brain in a way
that ultrasound is often not able to.
The MRI can show abnormalities that are not seen
by ultrasound such as,
migrational abnormalities
and,
cortical gyral,
findings.
And we have actually learned from MRI how to see some
of those now by ultrasound, for example, this is a fetus
that had periventricular heterotopia.
And we learned from MRI that you can find these
by ultrasound by seeing these little,
irregular
echogenic foci right here along the lateral aspect
of the ventricular wall.
You can see them here. And instead
of seeing a nice smooth wall, you see an irregular,
wall that,
is not nice and smooth.
This is a sign of periventricular heterotopia,
that do not have a good prognosis.
Early on, it is sometimes very difficult
to diagnose agenesis of the corpus callosum,
but that also is very important.
And that may not necessarily give you a,
borderline ventricular magaly
because the ventricle may actually measure normal
or if it measures,
more, it'll be only slight.
But what you have to look at here is the distance
between the two frontal horns.
Here, the frontal horns are too far away
and there is no cavum septum lucidum, which is
that little square box that occurs,
in
between the lateral horns.
And if you look at a coronal view
and you see the frontal horns here of the,
lateral ventricles, you'll see
that there is no corpus callosum.
There is no cavum septum.
There are just lines going through here
with no interruption.
When we talk about ventricular magaly, we also have
to realize that there is a difference between boy
and girl fetuses.
The normal male fetus has ventricles
that are slightly larger than the normal female fetuses.
So boys with a borderline ventricular measurement
of 10 in utero tend to be more often normal children
than do girls with the same borderline
ventricular measurement.
This is something to consider.
And if you see a measurement of 10
and you notice that the fetus is a boy,
I think it is easier to reassure.
The parents said this is probably a normal variant.

Mild Ectasia

Now going on to mild ectasis
and ectasis at all, when do we call it ectasis
and when do we pass it as being normal?
And how much fluid should be allowable in the,
the renal pelvis before you actually call it abnormal?
Here is a renal pelvis right here.
Can see a nice kidney around it,
a little bit of fluid in here.
And the question is, is that normal or not?
Here is some fluid here in this
collecting system over here and the one over there.
And this is a coronal view of the kidneys,
whereas the other one is the longitudinal view.
You measure the renal pelvis
from front to back and that is the measurement
that we're going to use.
The method really is measuring from front to back
or back to front, and there's this distance
that makes a difference.
Now there's also, in this particular case, some blunting
of the calyces, which makes it more than just ectasis.
The blunting of the calyces here indicates
that there is a more severe,
abnormality
of the kidney here than just a little fullness,
of the collecting system.
What is the measurement in the absence
of any blunting of the calyces?
What is the normal measurement,
of the kidneys?
We did a study a while back that showed that
if you measure the renal,
pelvic diameter at
about five millimeters, we could draw a line
that separated the patients that,
the fetuses
that went on to postnatal surgery from the ones that didn't.
And that was between 15 and 20 weeks, between 20
and 25 weeks or 20 and 30 weeks.
Sorry, that line was at eight millimeters and between 30
and 40 weeks, the line was at 10 millimeters.
And you can see the yellow dots here are the
ones that went to surgery.
Since then, we have revised this line
to be four millimeters.
So our threshold,
between 15
and 20 weeks is four millimeters,
which is,
what we typically use in our current practice.
When the renal pelvis is very dilated as it is here,
you can see a very large dilated renal pelvis
and you can see it here as well.
And here you see that there are calyces
that are also very dilated.
And sometimes what happens in these calyces is that they will,
they will explode in the sense,
so
that the fluid will come out,
to the periphery of the kidney.
And this is what happens here.
You get a fluid collection,
a perinephric fluid collection
or a perinephric urinoma that
compresses the renal parenchyma really from both sides.
You get it compressed from the outside and from the inside.
And eventually what happens is that the kidney has blown up.
And now most of the fluid
or urine is on the outside pressing,
onto the kidney.
There's only a little bit of fluid in the collecting system
'cause the kidney is no longer making urine.
And eventually, now this is now turned,
upside down,
if you will, collecting system is here, the urinoma is here
and this is all that's left of the renal parenchyma.
And by the third trimester, all you have is a big cyst.
And if you came across this fetus,
for the first time in the third trimester,
you would call this a big renal cyst.
But really what it is is an end stage urinoma
that has actually destroyed the kidney.
When you see a urinoma form, that's
because the pressure was too much within the kidney.
There was a rupture
and the urine started to accumulate outside the kidney.
The kidney does change over time
and that's why you have to repeat the scans when you see a
renal abnormality 'cause things do change.
And here is a,
a kidney,
that has multiple cysts throughout,
throughout the kidney.
This is a multicystic dysplastic kidney.
When this patient came back later on,
it had shrunken to almost nothing.
And this has become a tiny dysplastic kidney.
Eventually these patients may end up,
as a child having really no visible remnant of the kidney
and perhaps being labeled as an adult is having
had renal agenesis.
But really what they had was a kidney
that developed into a multicystic dysplastic kidney
and then collapsed down.
And here's an example of one
that we called a multicystic dysplastic kidney early on
came back in the third trimester
and this turned out to be only in the upper pole.
There was a duplex collecting system with,
the cyst in the upper pole moiety with a lower portion
of the kidney or a lower pole that was actually normal.
Keep in mind when we talk about,
ectasis,
that this is one of the markers that are, is associated
with an increased risk of down syndrome.
It's,
very low on the list of markers for down syndrome.
Likelihood ratio is only 1.5,
but
nonetheless, it,
does raise the risk ever so slightly,
for down syndrome.

Hyperechoic Bowel

Now, going on to hyperechoic bowel, you can see here
that there is,
an echogenic,
area in the middle of the fetal abdomen,
that really represents the bowel.
Very echogenic. Sometimes it looks like a clump.
Sometimes it looks like the bowel wall is echogenic.
But either way,
this is associated,
with an increased risk for down syndrome as well
as cystic fibrosis.
And CMV, it's a very subjective marker,
and it varies a lot by the transducer frequency,
the machine settings,
how big the patient is and so forth.
But when we looked at a study,
and we looked at several studies, you, you see
that it is associated, this finding is associated
with down syndrome, cystic fibrosis, CMV
and also growth restriction fetuses with,
hyperechoic bowel can have a very severe early onset
of IUGR or intrauterine growth restriction.
The incidence of this finding is quite low in the general
population, only about a half of 1%
and the sensitivity for down syndrome is between 16 and 20%.
So it's not very high either in down syndrome.
The recommendations when we see hyperechoic bowel is to do
to look at the serum,
screen
and consider that the likelihood ratio
for down syndrome is six.
So you multiply the serum screen result
or prior screening result by six to get a revised risk,
make sure that the parental CF carrier status is known.
Check the,
titers,
viral titers,
the torch titers, and make sure
that there is a follow-up scan planned
for the third trimester for growth.
When a fetus has cystic fibrosis,
the bowel tends to be also not only bright,
but also a little bit dilated
and it tends to be mostly the rim of the bowel.
And you can see these little individual loops
of bowel in here that are dilated.
And so that would be more worrisome for say,
cystic fibrosis than it would be for down syndrome.

Isolated Liver Calcifications

Okay, going on to isolated liver calcifications,
here is a calcification in the liver.
You can see it's shadowing,
it's not in the gallbladder, it's not a gallstone.
What do we do with these?
These are usually innocuous.
They usually don't mean anything
and they're not associated with any adverse outcome.
But in our experience, when we looked at our series
of 25 patients,
that displayed these little calcifications, there was one
that ended up having CMV or cytomegalovirus.
And it was first diagnosed
as a single liver calcifications at 21 weeks
and subsequently came back at 33 weeks
and showed multiple hepatic calcifications and microcephaly.
This fetus ultimately died
and none of the other fetuses had any problems.
Just to show you this particular case here is the
isolated liver calcification at 21 weeks,
you came back at 33 weeks
and you see all of these little calcifications
that,
came up.
The recommendation when we see isolated liver
calcifications, it's certainly to reassure the patient
because there are usually of no clinical significance.
But because of the occasional,
torch infection,
we suggest a follow-up scan as well
as the torch titers,
in maternal blood.

Single Umbilical Artery

Now going on to the single umbilical artery
prevalence is just under 1%
and it's easy to make the diagnosis
because you can either look at a cross section
of the free loop of cord
and see that there are only two vessels,
or you can take a look at the vessels that course
around the bladder, typically the umbilical arteries,
and see that there is only one when you turn on the color.
A single umbilical artery is an abnormality,
but if it's not associated with any other abnormalities,
it's not gonna make a difference
because the cord is not a part of the fetus that you keep.
So that,
eventually the cord would be,
tossed and the fetus,
would be normal.
But it is associated because it is an abnormality.
It is associated with renal and cardiac anomalies.
Some people think 13%, some 46%,
somewhere in between there.
But these abnormalities are usually quite visible.
You can see here,
one of these abnormalities
where you have a duplex collecting system
with an upper pole moiety that is dilated,
and,
a very large dilated ureter going
down towards the bladder.
Other isolated findings, the risk
of aneuploidy can be as high as 50%
when you have isolated findings,
not when it's an isolated finding,
but when you have associated findings,
then your risk
of aneuploidy can be quite high.
Here's an example of a dandy walker abnormality right here
in a patient that had a single umbilical artery
and,
an extra digit right here on
that hand in a fetus,
that had trisomy 13.
In the literature,
turns out that about 7%
of fetuses that have seemingly isolated,
single umbilical arteries actually have
abnormalities at birth.
And,
these have been shown to be small VSDs,
TE fistulas, ambiguous genitalia club feet,
and one case of trisomy 18 that was apparently missed.
The recommendations here is a careful anatomic survey,
including very close scrutiny of the heart,
and of the kidneys,
possible increased risk
of stillbirth and IUGR.
So that means follow-up scans for fetal wellbeing
and growth in the,
third trimester.
Although the apriori risk
for down syndrome really does not change
because of the presence of a single umbilical artery.
If we check the vessels,
we certainly do it on,
on every scan that's part of our protocol.
On part of the guidelines,
we do a structural survey looking carefully at the hands,
the outflow tracks all of these difficult areas to look at.
And if there are associated findings,
certainly an amniocentesis is recommended.
And,
keep in mind
that the patient has probably had some testing,
prior to coming in.
And so you might have,
the availability
of the early risk assessment for down syndrome
or trisomy 18,
that the patient has had.

Nuchal Cord

Now going on to the nuchal cord,
the question is always here.
If we see a nuchal cord, should we photograph it?
Should we call it? Should we tell the patient
and the referring physician?
Obviously the referring physicians are reluctant
to hear about this because this makes the patients crazy
and puts a lot
of pressure on the referring physicians to deliver the baby.
But the last thing we need is more premature babies.
And so,
we need to look at this carefully
and try to make an informed decision as to what to do.
The overall incidence of a nuchal cord is 23%.
It's very, very high.
And in this particular study, it was a random event with 60%
of fetuses studied having a nuchal cord in any
one of four exams.
It comes and goes, this study,
done in the second and third trimester had 233 patients
of which 118 had nuchal cord.
So, and there was no statistical difference
with any adverse outcome,
between those
that had the nuchal cord and those that didn't.
And that was a very important study,
to,
consider.
The question is what do you do? If you see a nuchal cord?
We only really report it when we
see multiple loops.
And what I mean by multiple loops is three loops.
And here you have three loops of cord that are
around this baby's neck
and you can even see that this cord is indenting the neck.
So it's pretty tight.
And in this case, we do call it, it happens very rarely.
We see this may be a couple of times a year.
This is a rare occurrence.
It would be,
worth a call at that point.
The patient,
would certainly get a biophysical profile,
a non-stress test, and would be put on the monitor to look
for decelerations and have also some doppler studies.
Here's another example of a triple nuchal cord,
that almost makes the baby look like it has a turtleneck.
And this is that term.
But short of having three loops like this,
what we recommend, certainly for single loops
and even doubles, don't look for it.
If you see a loose nuchal cord with no evidence
of fetal compromise
and no depression like that, don't take a picture
of it and don't report it.
That is now really the consensus.
Certainly in our hospital and our community.
If you see multiple loops of cord with the indentation,
as this image shows, then we do take a picture,
we do report it, and we do ask the obstetrician
for the proper surveillance.
And here's an example,
of a triple nuchal cord
and that that is likely to catch your eye.
I mean, even if you're not looking for
this, you will see it.
The incidence is probably less than a half of 1%.
And this is something that we would in fact call.
And if you wanna know whether
or not there's compression,
you can do a doppler
and if there is cord compression,
you might be able
to see it as a systolic notch in the,
umbilical cord artery waveform that is quite characteristic
of,
some compression,
of the,
cord and compromise of the blood flow.
And that certainly would be another reason
to be concerned about it.

Conclusion

We've come to the end of,
this presentation.
I'm gonna leave you with,
my approach
to scanning a fetus.
First of all, we assume that every fetus is abnormal
until proven otherwise.
However, probably the worst thing you can do in ultrasound
is to call a,
fetus abnormal, who is in fact normal,
that fetus might not survive.
So you have to be very careful what you call abnormal
and what recommendation you give the parents.
'cause we must understand
that life in the uterus is a continuum
and we have to allow for normal variation.
And we have to look at the findings
that they evolve over time,
whether they get better or worse.
And when in doubt, repeat the scan.
Thank you very much for your attention.