Genetic Screening: A Case Based Approach - HD

Introduction

My name is Dolores Pretorius.

I'm from the University of California in San Diego.

I'm gonna talk today about genetic screening, a case-based approach, how we're doing it.

Today I'm gonna talk about genetic screening and I'm gonna do this from a case-based approach.

But first I'm gonna go through a couple slides about what are the blood tests we're doing today to do genetic screening for our prenatal patients.

Prenatal Genetic Screening Tests

We have the first trimester specimen that is testing for Pap A and HCG.

And then we have a second trimester blood specimen that is testing for analytes alpha-fetoprotein beta, HCG, estriol and inhibit.

Screening Options in California

Now I come from California and we have a statewide program for prenatal screening and our state offers to all of our pregnant patients a first trimester screening, which is the first trimester blood test, plus a nuchal translucency ultrasound.

Or we can do a serum integrated screening, which in first and second trimester blood specimens, but there's no NT ultrasound.

Then there's the full integrated screening that is a first and second trimester blood specimen, plus the NAL translucency ultrasound.

And then some patients who don't come in early enough end up with just the quad marker screening, which is the second trimester blood specimen.

So the second trimester specimen is drawn between 15 weeks and 20 weeks.

And this gives us an assessment for trisomy 2118 neural tube defects and slots, which is Smith Lily syndrome.

It uses the second trimester blood specimen of the four analytes that we just talked about and it detects about 80% of trisomy 21 and 67% of trisomy 18.

And we pick up about 80% of the neural tube defects.

If we do the full integrated screening test, we get first the first trimester blood test with the ultrasound nt.

We give that preliminary risk and then we go on, they get a blood test for quad screen in the second trimester.

So now they have the six analytes from the first day and the second trimester plus the NT and we give them a risk for trisomy 2118 and neural tube defects.

Among all the screening options, the full integrated screening option, which is this one, provides the best detection rate for trisomy 21, which is 90% and trisomy 18, which is 81%.

Now the first trimester screening is the blood test and that's drawn between 10 weeks and 13 weeks, six days.

And then the NT is performed someplace between 11 weeks, two days and 14 weeks, two days.

This first trimester screening only gives risk for 21 and 18, doesn't give risk for our neural tube defects.

Cell-Free DNA Testing (NIPT)

And then the last thing that's come in really in the last two years is cell-free DNA blood testing, which is also known as NIPT in the literature and noninvasive prenatal testing.

And this is when we can get fetal cell-free DNA fragments which are present in the maternal plasma blood.

And this identifies an overrepresentation of targeted fetal chromosomal fragments.

This picks up 98.6 to a hundred percent of trisomy 21, with a false positive rate of about 0.03 to 0.2%.

So this is a simple blood test which many families are taking, but it's still a screening test.

It's not a definitive test like an amnio where you're growing your own cells.

The American College of Obstetrics and Gynecology has suggested that cell-free DNA testing be used to screen women at high risk for aneuploidy.

That includes women over 35 women with concerning ultrasound findings, women with a positive biochemical screening test and women who have an affected child or a personal genetic alteration.

Case Studies

Case One: Trisomy 18

So let's go through case one.

This patient comes in, she's at 18 weeks, five days by her clinical age, by her menstrual age, but she's 17 and four by her ultrasound.

So it's a little bit small and you can see that it's small in multiple of the parameters here.

When we look at the fetal head, we see this picture and these little cystic areas measure about 4.7 millimeters and the nuchal fold is 2.7 and look at the shape of this head.

This is a picture through the abdomen with gray scale at the cord insertion site.

And here's another picture with color flow in the same patient.

This is a picture of the hands on both hands and then a picture through the four chamber view of the heart with the two atria here and the two ventricles here, what is your diagnosis in this patient?

Well, this was a 39-year-old who was referred for a positive trisomy 21 and trisomy 18 screen.

Her risk for trisomy 21 was 1.1 in 47 and her risk for trisomy 18 was greater than one in 10.

And that's based on these laboratory values.

She had an ultrasound at 18 weeks and five days, which you've just seen the critical images which showed multiple choroid plexus cysts, clenched hands, and em falle, A VSD and IUGR with the estimated fetal weight at the ninth percentile.

And she had an amnio which confirmed trisomy 18.

So what do we see in trisomy 18?

We often see clenched hands and some series are as high as 95%.

So it's very important to go get open hands if you have a quad plexus cyst to screen for this, we sometimes see shortened forearms.

Cardiac cardiac anomalies are present in all the chromosomal abnormalities, so you should always look at the heart.

Rock or bottom, feet and club feet, single umbilical arteries, IUGR choroid plexus cysts which this patient had, falle which this patient had.

Micrognathia cystic ky Romas.

And then some things like we don't have numbers for strawberry head and and large NCLE folds.

So if we go back over the slides now you see this very small emale which does not have any liver in it, so it is bowel only.

And when you have bowel out only in emale there's an 80% chance of a karyotype abnormality.

Notice that you can get a normal looking cord insertion so you have to scroll up and down scanning that cord in order to find these small empha seals.

Here are the multiple choroid plexus cysts and this is a strawberry head with a kind of slight protuberance.

Here in the parietal areas.

I just wanted to show you why they called that a strawberry head.

Here are the clinched hands that we see they did not ever open out.

And here is A VSD, this is the Fino Valley in this patient.

Now what is good enough to call a clenched hand?

Generally trisomy 18 hands have the index finger crossing over the other digits like there like here and like on this 3D picture.

In order to call a normal, we need to have the three PHA Gs and at least three of the fingers in order to say there's no clenching of those hands.

So here we happen to have gotten them in both kids at the same, both hands at the same time.

Now other findings that we can see with trisomy 18 that were not seen in this patient, number one is micrognathia.

Look at that chin, look at that micrognathia.

That's a normal for comparison.

So you can see the difference in this.

Also known as mandibular hypoplasia rocker bottom foot.

And that's in comparison to this nice normal, sagittal view of a normal foot.

And here's a club foot both on 2D and on 3D.

To show you the difference, you should not be able to see the sole of that foot with the long axis.

You should only see it in perpendicular like we do here on fall seals.

We've already talked about the smaller one with bowel out only is 80% abnormal karyotypes, but any one with a large emal seal that has liver out the karyotype abnormalities is 40%.

So pretty high.

So asking you a question, which of the following images should be obtained to rule out trisomy 18 and a fetus at increased risk?

And the answer is open hands.

Case Two: Trisomy 21

Okay, now we're gonna go on to case two.

So look at these gestational ages.

She comes in with 20 and five and her ultrasound is 21 and zero.

So the numbers are pretty good.

We look down here.

Do you see anything abnormal?

Here's the head on the left with the anterior part of the head here.

This is a fetal abdomen with the spine over here.

This is a profile and this is a picture of amniotic fluid with a pocket that measures looks like about eight to nine centimeters.

These are the cardiac pictures and here is a four chamber view with the spine over here.

This is a left ventricular outflow tract with the aorta here and the two ventricles there.

And this is the R-V-O-T-V with the spine back here.

What is your diagnosis?

Well this PO patient was 38 years old.

She presented at 20 weeks and five days and she was referred for a positive trisomy 21 screen with a risk of one in 14.

This is partially because her beta HCG is elevated here as is her inhibit

Now on her ultrasound, the size was equal to dates but the femurs were short.

When you look at the measurements overall, there was a Danny Walker malformation, a double bubble picture, a picture suggesting Tetrology of fall low and we'll go over that on those cardiac pictures.

Echogenic bowel, poly hydrous and an absent nasal bone.

She had an amniocentesis and was firm firmed to have trisomy 21.

So if you look at her abnormal serum and analytes at UCSD, we use these as our go-tos for a low pap A is 0.3 mol bands and MOM is multiples of the median.

We use 2.5 as the cutoff for A A FP and estriol.

Point three is the cutoff to be low and the HCG we use three in the hi and we use two.

Now this patient was referred because of this risk of one in 14 and she has an elevated HCG and an elevated in hi and she follows the rules.

So this downs baby, the way we remember this is what is high in downs in down syndrome.

It's the HCG and it's the in Hi hi that are both high and the others are low.

Now what are the findings that we look for on tri for trisomy 21.

Now these are the markers that we've used to RA change our risk ratios and an absent nasal bone.

If it's found in the first trimester, we increase the risk approximately 30 times and if it's found in the second trimester, we would, we increase the risk 10 times.

Nuchal folds, we raise it 9.8 times humerus, 4.1 short femur 1.6, hydronephrosis 1.0 echogenic focus in the heart, 1.1 echogenic bowel 3.0 and a major defect 5.2.

Now this comes from these three papers.

It is obvious to me that in different centers they use different likelihood ratios.

So I know someone on the east coast that uses three for an echogenic focus and one for echogenic bowel.

So it really depends upon which papers you're going to use.

And these are just estimates.

Now what are some of the abnormalities that we look for?

Cardiac abnormalities in 40 to 50% absent nasal bone in 20% short femur or humerus in about a quarter GI anomalies and up to 10% and CNS anomalies, four to 8%.

So what are some of these anomalies?

We always look for atrial ventricular canals, VSDs, tetrology of fallot, duodenal atresia and esophageal atresia.

So when, when you look at this picture of the dating, notice that the femur length is 19 and six and the BPD is 21 and five.

We always compare the length of the femur to the bial diameter rather than to the gestational age.

And the reason we do that is because babies with tri only 21 have brachycephaly big heads.

So notice that the head is bigger than our gestational age and that's you have a better sensitivity with your femur length shortening if you will look at that.

So the percentiles don't help us that much, it's really this internal comparison that is helpful.

Now the other findings that this fetus had was first it's posterior fossa was dilated here and it looked like a Danny Walker malformation.

That's in comparison to this nice normal that we have down here showing the dumbbell shape of the cerebellum.

And this has the keyhole appearance going through it it here there is ventricular magaly in comparison to this patient who has normal size ventricles.

So we use 10 millimeters as our cutoff for ventricular magaly.

This is a patient with the double bubble sign that we saw initially and that is often seen with duodenal atresia as in this patient and poly hydros

here is echogenic bowel that is often seen in patients with chromosomal abnormalities.

Not specific for trisomy 21 but it is certainly can be seen with 21.

Now the cardiac pictures are difficult.

The VSD that you see right here, sometimes this can be artifactual and you have to come at it from different angles.

You also can turn color on.

And in this LVOT view where we see the aorta, we can see that it is overriding these septum on both of these.

And you see that VSD as well.

Now the RVOT picture is right here.

This is a nice normal for comparison where we see the valve and we see the bifurcation with the aorta in the center and the spine back here on our case the pulmonary artery is very small.

You can see the bifurcation and there's the aorta and it's very small in comparison.

And that is a sign worrisome for pulmonic stenosis.

You put those together and that's tetrology of fall flow.

Here's the absent nasal bone that was on the first image I showed you and here's a nice normal nasal bone for comparison.

This is an increased nuchal translucency of 4.7 millimeters and here's a nice normal for comparison 1.7.

Now someplace around three, anything above three is gonna be abnormal.

Really do have to look at it to gestational age as well.

Here's an atrial ventricular canal and another patient, a hole in the center of the heart.

There's a nice normal four chamber view for comparison.

You can see on color there's flow crossing over and it's predictable.

So this is very important when we look at an AV canal during diastole, when the valves are open, do open, they often have this hole but if the valves are closed they can almost look normal.

So it's very important to slow down your clip when you're looking for an AV canal and see what you can see.

Here's another patient with an isolated VSD and our nice normal for comparison.

You can see it right here as well.

Now a teaching question for you which heart disease should be ruled out in a fetus at increased risk for trisomy 21 V-S-D-A-S-D, AV canal or Tetrology of fallot.

And the answer is all of them and we showed you pictures of all of them in this case presentation.

Case Three: Turner's Syndrome

Okay, we're going on to case number three.

So let's see what you think about this.

The menstrual dates here are 16 and six and the ultrasound age is 15 and three.

So look at all these numbers and what do you think you go on?

You look at the fetal neck and this is what we see and the neck itself is right here.

This is a picture through the thorax with the spine over here to the right and this is a picture through the abdomen.

These two pictures are through the abdomen and transverse with the spine right here.

What's your diagnosis?

This was a 20-year-old referred for evaluation of cystic MNE on an outside ultrasound.

She had two normal children and she had a sonogram at 14 weeks and six days which showed a 2.2 centimeter cystic hydroma pleural effusion, an echogenic bowel and a possible hypoplastic left heart.

She had an amniocentesis and her karyotype came back Turner's syndrome or 45 xo.

So what do we look for in turner's?

They have coarctation of the aorta in 45% of cases they have other cardiac abnormalities in 20 to 40 abnormal ductal flow, 75% hypoplastic left heart in 15%, cystic hydroma 60% and then some of them will go on to have non-immune hydros, often called congenital lymph ectasia and horseshoe kidneys.

Something we look for in children with turner syndrome.

So this is the very large cystic hygroma that's pretty classic through the posterior aspect of the neck.

Here we see the skin thickening or edema often referred to as Annas Sarka with a stomach.

Over here on the through the thorax we can see the bilateral pleural effusions and here we have a slightly smaller left ventricle than a right ventricle.

And on this sagittal view you can see large bilateral effusions that are consistent with this non-immune hydro hydros or congenital lymph anacasia.

These pictures I think they're hard.

This is the horseshoe kidney of tissue that's coming from the left side to the right side and you see more of it right here.

The kidneys are a little bit more displaced anteriorly in the belly and that's a nice normal kidney For comparison.

Here we have coarctation of the aorta with narrowing right after the takeoff of the third vessel to the neck.

And when we look at the heart the first clue for CoARC tends to be right left disproportion with the right heart being larger than the left heart.

And you can see this on the right outflow tract view as well that the right pulmonary artery is larger than the aorta.

This is a rib shadowing here, this is a hypoplastic left heart.

The spine is here and the chamber closes to the spine is the left atrium, that's the left ventricle.

This is the right ventricle in the right atrium and you turn on color and there's flow here on the right but very little flow on the left.

And here's another picture of this hypoplastic left heart in comparison to a nice normal of what we should be seeing.

Case Four: Trisomy 13

Okay, next case.

Here we go.

Comes in at gestational age of 18 weeks one day and her ultrasound is 17 weeks, five days.

And look at these parameters here when we look at the fetal head, this is the anterior aspect of the head and this is the posterior aspect of the head.

Same for this picture.

What do you think?

This is actually superior and this is the spine coming down into the chest.

These are pictures of the hands and these are pictures of trying to get the four chamber view.

These are pictures of the kidneys in coronal at 18 weeks and they measured 2.1 and 2.2 and these are transverse images with mild renal separation.

Okay, these are pictures of the brain and the face.

What's your diagnosis?

Well this was a 33-year-old who was referred for a positive 21 screen.

You can see that her hiin hiin is a little bit elevated and on her ultrasound we found holo cephalic with an absent cavem septum ity We have absence of one of the orbits, the right orbit, syn actally and clenched fingers and enlarged echogenic kidneys and a hypoplastic left heart.

She had an amniocentesis and was found to have trisomy 13.

So what do we look for in trisomy 13?

Well they get cardiac abnormalities, particularly hypoplastic left heart like in our case holo pro cephalic, a very common finding.

Club feet, facial abnormalities, polydactyly that's one of the times when we look and actually count digits.

And then multicystic echogenic kidneys that are enlarged and IUGR.

So this patient had ho LoPro cephalic with a mono ventricle and no cavem septum lucidum as you can see in this nice normal for comparison.

This patient also has fused thalami with this mono ventricle which is well known to go with ho LoPro cephalic.

I wanted to show another classic appearance of ho LoPro cephalic with this nice mono ventricle and the fused thalami here as well because not all of 'em are easy.

This one's much more classic.

The last one is a little bit harder I think.

Okay we also look for polydactyly and you can see in this hand that we've counted these digits and so there are six digits on both hands and also sandact with fusion and classic fusion of the third and fourth is suggestive of a chromosomal abnormality.

Hypoplastic left heart.

Sometimes they're hard to decide because you think you're just technically not able to get it but if you go back and forth and move your transducer you should be able to get that.

Four chambers.

So this was a hypoplastic left.

These are the kidneys which are enlarged and echogenic.

These kidneys measured 21 and 22 and in general a kidney should be the same as the gestational age.

So this fetus was at 18 weeks.

It should have had kidneys around 18 millimeters.

There we go.

There's the kidneys that are echogenic as well and notice what they should be.

For comparison, this fetus had only one orbit so you could see this side but we could never see the other side and there's a nice normal for comparison of what you're supposed to see.

Now another finding that's often seen with trisomy 13 and holo pro cephalic is hypo tism or even cyclops with a single orbit.

But more commonly see this hypo tism and then the SCUs, that fleshy mass that comes in above the orbits.

So it's not the nose, it's just sort of a nose like structure.

Case Five: Triploidy

Okay, next case is case five.

Last Minal period is 17 weeks and 15 weeks for the ultrasound age.

And you can see that all of the parameters are low with the abdominal circumference being the lowest.

In addition, we had these findings on the head.

Here's the four chamber view And here's a picture through the urinary bladder and transfers.

When we looked at the spine we got these pictures.

Longitudinal transverse.

What's your diagnosis?

This woman came in 29 years old.

She was referred for low amniotic fluid at 14 weeks she had a positive trisomy 18 risk from her quad screen of one in 10.

Her sonogram at 17 weeks showed ventricular magaly a lemon head sign, a neural tube defect at the lower lumbar spine and echogenic focus in the left ventricle, a two vessels cord and possibly absence of the cavem septum lucidum.

Her amniocentesis was performed and confirmed that this fetus had tripley.

So tripley is three sets of chromosomes generally 69 XXY and about 60% of them XXX and 37% and XYY and 3% CNS lesions are common 60% all across the board.

Ventricular magaly neural tubes, dandy walker malformation of the fourth ventricle, cardiac abnormalities in 42%.

They also get cystic omas and micrognathia.

They get sandact which is classic club feet.

Falle umbilical hernias, hydro nephrosis and single umbilical arteries as well as early IUGR.

So this patient was I thought quite interesting because here's our nice normal posterior fossa for comparison and this one did not look that bad.

More classically a neural tube defect will have the banana sign and a basement of the posterior fossa, but this patient did not Here we also see that she did have dilated ventricles.

We didn't see the cavem septum hallin but it was only 17 weeks.

Here's a nice normal for comparison.

If you don't see it at 17 weeks it could be developmental and they may, it just may not be seen yet.

It may take you up until 18 to 20 weeks to see the cavem septum and we don't go chasing for absence of a cavem, and doing MRI until we get to 20 weeks.

So here we have echogenic focus in the left ventricle a a single umbilical artery where we should have two as you can see here in this nice normal for comparison in comparison to this.

And there's that normal four chamber comparison showing you that echogenic focus.

Here we can see the meninga myelo and long and it should look like this and it doesn't.

And then here's the sack coming off and the splaying through the posterior elements.

And this is a normal lumbar spine for comparison.

So what are the best sonographic clues for triploid e?

Well first early severe asymmetric intrauterine growth restriction.

Second, ventriculomegaly and syn, particularly the third and fourth digits.

Now the placenta may have multiple placenta lucencies if it's a partial mole and classically paternal origin have lucencies in maternal origin are small and more normal looking.

Other findings of tripley in the syn, this is what it looks like pathologically.

Here it is again in this fetus.

You can see there's also club feet here.

These are the lucencies that we see in a partial mole.

This, this pregnancy happened to have a normal fetus in it.

Here's a more normal placenta at 13 weeks for comparison.

This is enlarged and has multiple cystic structures.

This is a large cystic hygroma that you might see in a fetus with triploid E.

And here is a longitudinal showing that cystic lesion going all the way down the spine, often referred to as lymphangiectasia.

Now we always think about thecal lutin cysts in our patients with partial moles and with triploid e but it ends up that they're only seen in about 10% of triploid pregnancies.

So they are being hyperstimulated by the HCG but we don't see it classically in everyone.

Case Six: Increased Nuchal Translucency and Klinefelter's Syndrome

Okay, going on to the next case, case six.

This patient presented at 13 weeks in three days and her ultrasound was 13 and five.

It's right on.

And this is the nuchal translucency image right here that measured 3.6.

And this is the nasal bone picture.

What's your diagnosis?

Well, a 3.6 is always increased and we're gonna give that person an increased risk.

I will show it to you on the next slide.

This one shows that the nasal bone is present, so that's helpful.

Now an increased ncal lucency can be due to an abnormal karyotype.

It can also be due to early heart failure and the imaging findings for people with numbers or measurements that are above the 95th percentile.

We look at this chart.

So in this patient she was 3.7, so we would go to this range here of 3.5 to 4.1 and we would counsel her and tell her that she has a 21% chance of a chromosomal abnormality, a 2.7% chance of death, a 10% chance of a major fetal anomaly and a 70% chance that the fetus will be alive and well at delivery.

Now if the number, if the NAL translucency goes up, you can see that these numbers go up.

So if the nucle is greater than 6.5 millimeters, we're gonna give her a 64.5% chance of a chromosomal abnormality.

A chance of 46% of a major fetal anomaly and only 15% chance of having a baby that is alive and well at delivery.

So what do we do when we have an increased nuchal translucency?

Well we offer the patient chorionic villa sampling.

Some people will do that, that's usually done before 14 weeks.

Some will come back for an amniocentesis at 16 weeks and occasionally 15 weeks and some families will opt for the blood test cell-free DNA testing.

If the fetus has a normal anatomical study at 16 weeks, many people will do a fetal echocardiogram.

And this is recommended.

The question is when do you do it?

It depends upon your lab.

If you have people who are competent at doing fetal echocardiograms at 14 weeks, you can do it then if you have to wait and do it later, then maybe at 18 weeks.

And if it's a really large patient you may have to wait till 20 weeks.

Just depends.

Now increased nuchal translucency is seen with trisomy 21, 18 13 and other abnormalities.

Most often people will have normal chromosomes, believe it or not.

So that if you look at a group of 95,000 NAL translucencies 4,000 ended up with an increased NAL translucency.

And of those about 234 had trisomy 21.

So of a total of all the trisomy 20 ones in this group, the NT picked up 70% of those or so.

And you can see as you go down, trisomy 18 was the next most common 89 of the cases.

And trisomy 13, they picked up 33 out of this total over here.

So it just gives you perspective on how often is a trisomy 21, how often is it 1813, and then we go down turner's, triploid and then other abnormalities.

If the ultrasound is normal at the 18 week exam and there's a normal karyotype and the nuchal translucency resolves and the fetal echo echocardiogram is normal, then 95% will be normal at delivery, which is really amazing.

Now I know you can't read this slide and you're not supposed to, but there are a ton of abnormalities that are associated with the Eloqua and cardiac is the one we all worry about.

That's why we do a fetal echocardiogram on these patients.

Now this patient had Klinefelter's syndrome XXY and I just wanted to give you a little bit of information about that.

It's about one in a thousand live male births.

It's a non disjunction of sex chromosomes of either parent and they, their presentation is often related to the sim nephros tubules and the light excel damage which leads to small testes and infertility.

These, men often have tall stature and there is an increased incidence of psychiatric and social problems.

Case Seven: Cell-Free DNA Testing Example

Okay, we're moving on to the next case.

Case seven, notice the numbers 17 and five versus 17 and one and look at the numbers as we come down here.

This was a 37-year-old woman, G five P four.

She had a first trimester, blood test and risk with NAL translucency and her NT was 1.9 quite normal.

But her risk because of the blood work was one in 43.

Her second trimester blood test, gave her a risk of one in eight.

We scanned at 16 in weeks, five days and everything looked normal.

There were no sonographic markers for trisomy 21.

So we doubled her risk and changed her risk from one in eight to one in 16 because of the normal ultrasound.

Well, we offered her amniocentesis 'cause we would consider that a relatively high risk, but she declined the amnio and she decided to take the cell-free DNA blood test first.

Well, we've done a study at UCSD where we've looked at 206 of our patients are that had, decided to take the cell-free DNA test just to see who was taking it in our setting.

And we found that 75% of those were from advanced maternal age.

41% had positive aneuploidy screening.

39% had an abnormal ultrasound, either a marker or a congenital abnormality.

And there were two other patients.

This patient pursued cell-free DNA testing and her maternity 21 test was negative.

The patient declined amniocentesis due to this and the outcome was a term female delivered at 39 weeks.

Normally with a birth weight at the 50th to the 85th percentile.

And the physical exam showed no stigmata of Trisomy 21.

So for this patient, the cell-free DNA test was a great test.

Now what have we found out on our positives?

In our group of first group of 200, we found a positive cell-free DNA and six out of the 10 patients opted for amniocentesis or chorionic villus sampling to find out what was going on.

A negative cell-free DNA, only 7% pursued invasive testing.

We have also found that we decreased amniocentesis and CVS by 34% during our study period compared to a similar time period the year before.

So just for actual numbers, our amnios went from two 70 to 1 71 and our CVS went from 42 to 34.

So a significant impact on clinical medicine.

Conclusion

I'd like to thank you very much for listening and I hope you've gotten a few ideas of how to look for chromosomal anomalies in fetuses.

Thank you.