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Expert Perspectives on NIPT: Rethinking the Standard of Patient Care CME / ABIM MOC
Expert Perspectives
on NIPT
Rethinking the Standard of Patient Care
CME / ABIM MOC
Supported by an independent educational grant from Illumina, Inc.
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Target Audience
This activity is intended for obstetricians & gynecologists and primary care physicians.
Goal
The goal of this activity is to enhance physicians’ knowledge of the benefits and limitations of various methods of noninva-
sive prenatal testing (NIPT), as well as interpreting test results.
Learning Objectives
Upon completion of this activity, participants will:
• Have increased knowledge regarding the
• Key data for different NIPT screening methodologies in the general population
• Have greater competence related to
• Interpreting NIPT results
• Demonstrate greater confidence in their ability to
• Differentiate between the benefits and limitations of various screening methodologies
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Disclosures
Moderator
Lorraine Dugoff, MD
Professor of Obstetrics and Gynecology
Director, Division of Reproductive Genetics
Divisions of Reproductive Genetics and Maternal-Fetal Medicine
University of Pennsylvania
Philadelphia, Pennsylvania
Disclosure: Lorraine Dugoff, MD, has disclosed the following relevant financial relationships:
Received grants for clinical research from: Progenity
Panelists
Anthony R. Gregg, MD, MBA

Chair, Obstetrics and Gynecology
Chief, Maternal Fetal Medicine
Baylor University Medical Center
Dallas, Texas
Disclosure: Anthony R. Gregg, MD, MBA, has disclosed no relevant financial relationships
Editors
Pakinam Aboulsaoud, PharmD

Scientific Director, Medscape, LLC
Disclosure: Pakinam Aboulsaoud, PharmD, has disclosed no relevant financial relationships.
CME Reviewer
Amy Bernard, MS, BSN, RN-BC

Lead Nurse Planner, Medscape, LLC
Disclosure: Amy Bernard, MS, BSN, RN-BC, has disclosed no relevant financial relationships.
Lorraine Dugoff, MD: Hello. I am Dr Lorraine Dugoff, Professor of Obstetrics and Gynecology and Chief of the Division
of Reproductive Genetics at the University of Pennsylvania in Philadelphia. Welcome to this program entitled Expert
Perspectives on NIPT: Rethinking the Standard of Patient Care.
Joining me today is Dr Tony Gregg, who is Chair of Obstetrics and Gynecology and Chief of Maternal-Fetal Medicine
at Baylor University Medical Center in Dallas, Texas. Welcome, Tony.
Anthony Gregg, MD, MBA, FACOG, FACMG: Thank you, Lorraine.
The discussion today is on non-invasive prenatal testing. I just want to make the point before we move on that there are
2 acronyms and 1 other phrase that is used to describe non-invasive prenatal testing. First is the acronym NIPT. In 2013,
the American College of Medical Genetics and Genomics suggested that the acronym NIPS might be more appropriate,
the S standing for screening. More recently, it has become accepted that cell-free fetal DNA be used to describe this
technology.
Let us start by asking the question: What is fetal aneuploidy?
Aneuploidy is a term that represents abnormal numbers of chromosomes in that early conceptus. You will recognize that
non-invasive prenatal testing, at least in its initial inception, was used to screen for aneuploidy.
Lorraine, what is the source of DNA in non-invasive prenatal testing or NIPT?
Dr Dugoff: Some people use the term cell-free fetal DNA, and I just wanted to mention that as a bit of a misnomer, because
what we are looking at is cell-free placental DNA.
During the formation of the placenta, some trophoblast cells, including mostly syncytiotrophoblast cells, will undergo
apoptosis, and the cell-free DNA will be fragmented. The apoptotic trophoblast will migrate into the maternal circulation
passing into the intervillous space, which is filled with maternal blood. That is how we get this placental cell-free DNA
in the maternal circulation.
Can you elaborate a little bit on the mosaicism image? You described aneuploidy, but I think it is really relevant to cell-free
DNA screening to talk about mosaicism.
Dr Gregg: Another really important aspect to the background of this technology and how it is used clinically is not only
to understand what aneuploidy is but what mosaicism is. If we think about that early conception, what happens is that
a proportion of the cells in the developing zygote go on to form the placenta. That is called the outer cell mass in early
embryonic Paralens.
The inner cell mass, those cells in that inner portion of the blastocyst, eventually go on to form the fetus. When there
are 2-cell populations in a single placenta-fetal combination, and the 1-cell population carries an abnormal number of
chromosomes, the other of normal chromosomes, we say that there is mosaicism. We are referring to the term mosaicism
as meaning that there are 2 different populations of cells. They are different because they have a different constitution of
chromosomes.
Lorraine, how common is aneuploidy?
Dr Dugoff: The autosomal trisomies increase with advanced maternal age. A woman who is 35 years old has about a 1
in 378 risk for having a fetus with Down syndrome. Her total chromosome or abnormality risk is elevated again due to
the increased risk of other autosomal trisomies. A 35-year-old has a risk of about 1 in 190 of having a fetal chromosomal
abnormality.
This risk increases pretty dramatically as a woman ages especially starting at the age of 40. A woman who is 40 years
old has about a 1 in 100 risk for having a fetus with Down syndrome and about a 1 in 60 risk for having a fetus with any
chromosomal abnormality.
One important point to make is that younger women really do not have a very high risk for having a fetus with a trisomy,
including a fetus with Down syndrome. Younger women and all women, actually, have about a 1 in 180 (a 1.2%) risk for
having a fetus with a copy number variant, which is either a microdeletion or a microduplication.
I think it is really important when thinking about aneuploidy screening to keep this in mind and just really keep in mind that
this risk is higher in younger women.
Dr Gregg: We talk about copy number variants as age-independent. Is that correct?
Dr Dugoff: That is correct.
Dr Gregg: The issue of a common aneuploidy seems to have relevance or prevalence in more advanced-aged women. Is
that correct?
Dr Gregg: Sometimes, what we ask is: What is the value of prenatal aneuploidy screening in patients? At least in my
experience, patients want to know. They want to know so that they can educate themselves about their expectation for the
pregnancy and later for their child going forward.
They have the opportunity prior to birth to become acquainted with any medical needs of a child or raising a child with a
particular disability. They can also early on become an advocate for their child rather than go down a diagnostic odyssey
later in life. They might also avail themselves of social resources.
Again, they can also begin to prepare for where they are going to deliver their child, knowing that a child is at risk for having
a heart defect, for example. It might require a little bit more follow-up throughout the pregnancy (ultrasound follow-up
following the fetus through development). It might also require that there is a healthcare team immediately available at the
time the child is born.
Some patients decide that they are going to go through various reproductive choices including adoption or pregnancy
termination depending on the information that they receive from this kind of aneuploidy screening.
What are alternatives to prenatal screening for aneuploidy, Lorraine?
Dr Dugoff: First of all, it is important to recognize that screening is completely voluntary. There are certain patients who
may not be interested in pursuing genetics screening or prenatal diagnostic testing which is the other option. As far as
diagnostic testing goes, it is important I think for patients to recognize that screening is screening. It is not a diagnostic test.
If patients really are interested in a definitive diagnosis, they should consider either CVS, which can be formed in the first
trimester between about 10 and 13 weeks’ gestation, or amniocentesis, which is generally performed between 15 and 20
weeks gestation.
Dr Dugoff: There are various screening options. How have they changed over time?
Dr Gregg: They were focused around Down syndrome primarily, the screening test for aneuploidy. Again, the test metric
that was most often considered was: How does the test perform from a detection rate perspective? In the case of Down
syndrome, we have known for many years that age is a really good screening test for Down syndrome. On the one hand, it
is really good. But when we think about that test metric, it only picks up about 30% of the cases of Down syndrome overall.
Dr Dugoff: Maybe, it is not really good.
Dr Gregg: That is right. People look for other ways to approach Down syndrome and to screen for Down syndrome. 30%
is not good and, as you will see, it is not very good when we think about the other options available. In the early 1980s,
maternal serum AFP was recognized to be reduced in cases of Down syndrome. When you added maternal serum AFP
with maternal age, you came up with detection rates that were about 50%. You gained about 20% detection by adding this
analyte detected in maternal blood, called maternal serum alpha-fetoprotein.
As we advanced through the 1980s and into the 1990s, we added first 2 analytes to call this, then a triple screen, maternal
serum alpha-fetoprotein, estriol, and free beta hCG. These 3 analytes made up the triple screen. Dimeric inhibin A was
added in the mid-1990s to late 1990s to make up the quadruple screen or quad screen as it was known. Those were the
primary analytes in the second trimester, which was referred to then as analyte screening.
In the mid-1990s, ultrasound markers became predominant and in particular, the most common use was the nuchal
translucency, measured somewhere between 10 and 14 weeks in the pregnancy.
This ultrasound marker was incorporated with age. When an ultrasound marker with age is used alone, the detection
rate is 64% to 70%. Remember, the quadruple screen was about 80%, the triple screen about 65% to 70%. Still, nuchal
translucency, though in first trimester screening, gives you something in the 70% detection rate window.
Dr Dugoff: We are saying nuchal translucency in first trimester, but that is without the markers, right? If you consider the
markers -- so, low PAPP-A and elevated hCG level -- beta hCG level does increase your detection rate.
Dr Gregg: Now, we are up to about 80% or 85% when we are talking about adding markers with ultrasound or up at a
detection rate that is in the 80% to 85% range depending on the study quoted. Then, if we look at first trimester markers
including the ultrasound and include some second trimester markers, and combinations of these, and report these in
different ways, by 20 weeks’ gestation, we can, really, by incorporating various combinations, get up to about 90% to 95%,
that is, with analytes and ultrasound together.
In 2011, non-invasive prenatal screening was introduced into the obstetric care environment. What we arrived at were
detection rates that were above 95%. Ninety-eight percent to 99% are typically quoted detection rates for non-invasive
prenatal testing or non-invasive prenatal screening. What we talked about was really going from a detection rate of 30%
in over a 20- to 30-year period, establishing detections that are 98% to 99%. Are there any other important test metrics in
screening? The answer is, of course, that we have to be mindful of false positive rates.
Lorraine, can you tell us a little bit about false positive rates?
Dr Dugoff: Sure. With conventional screening. So, for their first trimester screening or the quad screen or a combination
of both with sequential screening, the false positive rate is about 5%. With cell-free DNA with NIPT, the false positive rate
screening for trisomy 13, 18, and 21 is somewhere in the 0.2% range. It is really significantly lower.
I wanted to take a little bit of time and just review some of the causes associated with false positive rates and NIPT, because
I think it is important for physicians to know about these and for patients to be counseled that these are potential outcomes
when they undergo screening. The first one you have already described, which is confined placenta mosaicism. What
makes sense from a biological point of view is that this could cause a false positive.
Another important thing is Vanishing Twins or if you have a co-twin demise. Vanishing Twins we know are more likely to
result from aneuploidy, or there is an increased risk for being aneuploic. I will be shutting cell-free DNA into the maternal
circulation. For that reason, we do not recommend that they have screening with NIPT.
Another interesting association has been underlying maternal tumors, so, maternal cancers… so, leukemias, breast cancer,
colon cancer. A variety of underlying malignancies have been associated with false positives.
Organ transplants, we know, shed cell-free DNA and can cause false positives, and then just sample mix-ups, so, human
error if a wrong sample is evaluated by a lab.
Another important thing to think about is just the actual way that the test works itself. We know that a fetal fraction, which
is the percentage of placental DNA (cell-free DNA). We know that that needs to be at least 4%, a fetal fraction of at least
4% for a lot of labs really to report a result. The closer a fetal fraction is to 4%, the likelier the chance potentially that a false
positive can be reported out.
Dr Dugoff: Can you tell us a little bit about how NIPT has performed in real-world studies.
Dr Gregg: Sure. We talked a little bit about these test metrics. These test metrics are initially derived out of validation
studies. These validation studies gave us our detection rate and our specificity.
In the CARE trial and NEXT trial, 2 large studies in the United States, there were about 1700 patients or so. When Down
syndrome was looked at, and non-invasive prenatal testing was compared with conventional screening, the detection rate
for non-invasive prenatal screening and conventional screening was about 100% detection in the NEXT trial, which was the
largest trial, and about 78% to 79% in the case of conventional screening. Just what we predicted, though our validation
study is pretty close to what we described earlier in the evolution of these tests.
Positive predicted value, though, was a little bit different. In all comers, the positive predictive value for non-invasive
prenatal testing was about 81%. That was for all comers, patients of all ages. Conventional screening performs much more
poorly, and the positive predictive value there was about 3% to 4%, specifically 3.4%. It means that when patients get a test
result back and they’re positive on a non-invasive prenatal testing report, they are more likely to be true positives after
diagnostic testing compared to those that have had analyte screening or some combination of analyte and ultrasound
marker screening.
It turns out that the positive predictive value as expected would come down if we are talking about a lower risk patient
population. In the NEXT trial, for those patients that were less than 35 years old, it was about 76%. For those that had
already had a screening test result that was negative or those that were at a very young age, the positive predictive value
was about 50%.
We should recognize that the positive predictive value for analyte screening in any of these tests is most often less than
10%. We have been living for 30 years with a screening test that has a very low positive predictive value. One of the values
for non-invasive prenatal testing is that it not only brings a high detection rate but also brings a very much higher (about a
10-fold higher) positive predictive value.
What about trisomy 13 and 18? Do these test metrics bear out similarly for those common aneuploidies, Lorraine?
Dr Dugoff: They do. The detection rates for trisomy 18 and 13 are high just like there are with trisomy 21, and the false
positive rates are low. There is a meta-analysis from Gill that reported detection rates for trisomy 18 at about 98% and
trisomy 13 similar at about 99%, with false positive rates for each at about 0.04%.
One important point, though, that I think is important for providers to recognize, is that although the positive predictive
values are still higher, as they are with conventional screening, they are not nearly as high as they are with trisomy 21. That
just has to do with prevalence. Trisomy 13 and trisomy 18 are not as prevalent as trisomy 21 especially in a younger woman.
Dr Gregg: You mentioned earlier some of the history that we need to take. What are the must-haves in pretest counseling?
Dr Dugoff: There are a number of important points that are important to review. I think it is important that women are
offered the options of screening, of diagnostic testing, as well as no screening or testing. When you are talking about
different screening tests, as well as diagnostic testing, it is important to describe the risks, the benefits, as well as the
limitations associated with each option.
As far as NIPT, in particular NIPS, there are a number of really important pretest counseling issues that need to be reviewed
with the patients before they have the test. One of them is that patients need to understand that this is the most accurate
screening test for trisomy 21, that the test also screens for trisomy 13 and 18, and that it also screens for the most common
sex chromosome aneuploidies.
They need to understand if they are having that screening, that they are having that testing. We have had a number of
patients who have been referred to us with positive screens for sex chromosome aneuploidies, yet they did not even know
they were being screened for those conditions.
Also, patients need to understand that NIPS does not screen for all conditions. Just because they have a normal result, it
does not mean that their fetus does not have any chromosomal abnormality or that their fetus will be “normal.”
Women who desire definitive information about chromosome conditions, including these copy number variants should be
offered the option of amniocentesis, as well as CVS. Again, the false positive and false negative rate associated with NIPS
should be reviewed with the patients. Another important point is that any patients who have a positive screen, they need
to understand again that this is not a diagnostic test. All of these women need to know they will be offered the diagnostic
testing to confirm the result.
Dr Dugoff: We also need to remind women that NIPS does not screen for neural tube defects. Some women may have had
a conventional screening with the prior pregnancy, so they may have automatically been screened for neural tube defects.
It is really important to let them know they need to return at 15- to 16-week gestation for an MASFP.
Dr Gregg: Exactly.
Dr Dugoff: I have talked about the false positives, and it is really important for women to understand that although the
chances are low, that it is possible they may have a false positive test that could even lead to a possible diagnosis of a
malignancy.
Dr Gregg: Unlike analyte screening, NIPT can sometimes give us this unusual result. It has been referred to as a no-call
result. I just want to go into, just for a second, some of the causes of no-call and how frequently they are seen. Again, it
depends on the testing platform. There has been described anywhere from less than 1% of cases resulting in a no-call all
the way up to about 10% to 12% of cases resulting in a no-call. Again, this no-call rate seems to depend on the specific
laboratory platform being used.
The causes of no-call fall into several different categories. One of the more commonly talked about is the low fetal fraction.
We mentioned that low fetal fraction in its earliest iteration was defined as being less than 4%. On occasion, and I have seen
it really much less frequently than low fetal fraction, there will be an assay failure, where the DNA could not be extracted
maybe because of the way the sample was handled. By the time it left the patient and arrived in the testing laboratory,
where there was a problem with amplification or sequencing, sometimes, that can lead to a no-call.
Again, sometimes, there is a problem with the shipping aspect or there is a collection error in and of itself. I am sure you
have also a strong belief that the laboratory should be very clear on why the no-call is being reported.
Lorraine, what are the causes then of low fetal fraction?
Dr Dugoff: There are a number of important causes that I think we should review. I think the most important one for
providers to keep in mind is that patients with a low fetal fraction have an increased risk of fetal aneuploidy. I think the NEXT
trial was one of the first studies to report an association between low fetal fraction and fetal aneuploidy. It is associated with
trisomy 13, 18, and triploidy.
A study by Bargman and colleagues also reported that association. They reported an odds ratio of over 9 for fetal
aneuploidy and cases with no result due to a low fetal fraction -- so very important for providers who have that on their
radar when they get a patient with no result due to a low fetal fraction.
There are other causes. In our population, there is a very high prevalence of obesity. Obesity is a big risk factor and has
been associated with no result due to a low fetal fraction. The numbers I keep in mind that tend to be helpful are based on
a study by Ashur et al: they found that women who weighed more than 250 pounds reported an incidence of no result, due
to a low fetal fraction. For women who weighed 350 pounds or more, there was over 50% incidence of no result.
Other issues associated with a low fetal fraction are early gestational age. Particularly, if you are drawing out a sample of
blood at 9 to 10 weeks gestation, you are more likely not to get a result. Lastly, an interesting thing that has been reported
recently is women who are being treated with low molecular weight heparin have a significantly higher chance of not
getting a result due to a low fetal fraction.
Dr Dugoff: Tony, how do professional organizations recommend a no-call result get followed up?
Dr Gregg: First of all, all professional organizations that weigh in on this technology recommend that a low fetal fraction be
followed up with genetic counseling by a genetics professional. That professional could be a genetics counselor. It could be
a trained clinical geneticist. It could be a maternal-fetal medicine subspecialist, but somebody that is really knowledgeable
about what is happening with the low no-calls and low fetal fractions.
The American College of Medical Genetics and Genomics, as do all the other professional organizations, recognized that
we should be offering those patients a diagnostic test. Both the American College of Obstetrics and Gynecology and
the Society for Maternal-Fetal Medicine allow also that patients should be offered ultrasound screening as part of that
counseling visit. Depending on their gestational age, they should be offered the option of a repeat screening test.
What can be determined from analyzing or from analyzing cell-free DNA and maternal circulation other than the common
aneuploidies we mentioned earlier?
Dr Dugoff: All of the labs actually are offering screening for sex chromosome aneuploidy. To the most common sex
chromosome aneuploidies are trisomy X. There is Klinefelter’s which is 47 XXY. Forty-seven XYY is one of the most
common, as well as Turner syndrome, which is monosomy X.
I think that as any provider who is offering cell-free DNA screening or NIPT/NIPS will have patients ultimately who screen
positive. I think it is important for providers to have some background information about these conditions and be familiar
with the incidences.
I just wanted to review briefly the performance characteristics, because they are also quite good associated with sex
chromosome aneuploidy, although the confidence intervals are wider. If you look at the meta-analysis data… because there
have not been as many cases reported in the literature….
For monosomiacs, the overall detection rate is thought to be about 96%. The false positive rates though are higher. From
one meta-analysis, the false positive rate was 0.14%. In a meta-analysis, a recent one, they combined the other 3 sex
chromosome aneuploidies just because there were so few cases that have a wide confidence interval range, the detection
ranging from 83% to 100% with actually a much lower false positive rate of 0.004 - - just something to keep in mind if you
are adding a screening for sex chromosome aneuploidies that will bump up the false positive rate a bit.
There are some clear benefits to screening for sex chromosome aneuploidy. There have been definite improvements
associated with prenatal diagnosis of some of these conditions, especially Turner syndrome as well as Klinefelter’s. Just
having this knowledge prenatally, then, it allows parents and others to screen early for possible developmental delays
and to institute other therapies that can really benefit those individuals later in life who have these sex chromosome
aneuploidies.
Besides sex chromosome aneuploidies, what else can NIPT provide? What other information?
Dr Gregg: You can imagine that there is a panoply of options, because you have DNA now in a tube, and DNA can be
analyzed in many different ways. It turns out that many companies offer aneuploidy screening for autosomes other than 21,
18, and 13, the common aneuploidies that we recognize clinically.
Dr Dugoff: What about microdeletions?
Dr Gregg: Microdeletions and duplications can be detected using non-invasive prenatal screening technologies. In fact,
many companies offer this. The only caution there is that the positive predictive value is lower than it is for the common
aneuploidies. If the positive predictive value is much lower, it means false positives are higher.
Single gene disorders can also be probed in a way using this cell-free fetal DNA and maternal circulation.
What does NIPT not detect that analyte screening or ultrasound might do a better job with, Lorraine?
Dr Dugoff: I mentioned earlier that it is really important to remember to screen patients or discuss screening for neural tube
defects. With conventional screening, ideally, we are drawing a sample in the second trimester at 15 to 16 weeks gestation.
You get a result back then as part of an aneuploidy screening. It is just important to do that using an NIPS. It is really still
important I think to be offering that at 15 to 16 weeks’ gestation, unless your office is performing these earlier ultrasounds.
And then also the other conditions as well that are detectable by ultrasound that can be picked up by an elevated AFP, so
things like ventral wall defects. I think there is a real benefit to still getting that MSAFP at 15 to 16 weeks unless a patient is
having an early ultrasound that could detect those associated anomalies.
Lastly, patients who had abnormal analytes -- so, either low PAPP-A levels, or elevated AFP, hCG, or inhibin A levels -- some
of those patients may have had increased fetal surveillance, because we know that those abnormal analyte levels are
associated with adverse obstetric outcomes. That is another thing that may be missed in the era of NIPS.
Do you think that patients that have NIPT should be offered an early ultrasound say at 12 to 14 weeks? Is there any value for
those patients?
Dr Dugoff: Absolutely. I think there is so much value. This is really important, first of all, for accurate assessment of
gestational age or identification of embryonic gestation. As I have mentioned before, I think it is really important to identify a
Vanishing Twin, because if a Vanishing Twin is present, I think that NIPT/NIPS is not the ideal screening test, because of the
increased risk of a false positive.
Early ultrasounds are also going to identify a fetal demise, detection of multiple gestations, early identification of structural
abnormalities, and even early identification of possible first trimester markers for aneuploidies. If you do an ultrasound and
you have an increased nuchal translucency, or if you identify a cystic hygroma, then that patient really is a better candidate
for diagnostic testing for CVS as opposed to NIPS.
Dr Dugoff: Lorraine, in the real-world environment, should all patients be made aware of non-invasive prenatal testing?
Should they be offered this as one of their screening options?
Dr Gregg: I think that all patients should be offered screening. They should all be offered diagnostic testing. As part of the
screening algorithm, I think that they should definitely be offered NIPT.
Dr Dugoff: We have talked about screening for Down syndrome. NIPT clearly has the highest detection rates and the
lowest positive rates for the detection of trisomy 21. I think that especially for women who are interested in screening for
Down syndrome, it is the best test. I do also think that it is really important that women understand what they are being
screened for and that women are counseled appropriately about what they are at risk for. They should also be offered the
option of diagnostic testing.
Dr Dugoff: What do you think, Tony?
Dr Gregg: I completely agree with you. I offer all my patients non-invasive prenatal testing. The thing that is balanced, I
think, in this whole discussion, though, is that there is a higher cost associated with non-invasive prenatal testing. Again, it
clearly has the highest test metric. If patients really want maximal information choosing a diagnostic testing option might be
most appropriate for them. If they are accepting of some of the most common microdeletion and duplication syndromes,
if they want to know about sex chromosome aneuploidy and common aneuploidies, they might embrace non-invasive
prenatal screening. Again, this whole panoply of options exists for patients. I hope we have been able to elucidate some of
the nuances of this.
Dr Dugoff: Tony, thank you so much for participating in this activity.
Thank you for participating in this activity. Please continue on to answer the questions that follow and complete the
evaluation.
Abbreviations
ACMG = American College of Medical Genetics and Genomics

ACOG = American College of Obstetricians and Gynecologists
BMI = body mass index
cfDNA = cell-free DNA
CI = confidence interval
CVS = chorionic villus sampling
DR = detection rate
DS = Down syndrome
FPR = false positive rate
hCG = human chorionic gonadotropin
MSAFP = maternal serum alpha-fetoprotein
NIPT = noninvasive prenatal testing
NT = nuchal translucency
ONTD = open neural tube defect
PAPP-A = pregnancy-associated plasma protein-A
PPV = positive predictive value
SCA = sex chromosome aneuploidy
SMFM = Society for Maternal-Fetal Medicine
uE3 = unconjugated estriol
US = ultrasound
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Expert Perspectives on NIPT: Rethinking the Standard of Patient Care CME / ABIM MOC

Supported by an independent educational grant from Illumina, Inc.

This article is a CME / ABIM MOC / ACCENT certified activity.

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Anthony R. Gregg, MD, MBA

Pakinam Aboulsaoud, PharmD

Amy Bernard, MS, BSN, RN-BC

Anthony Gregg, MD, MBA, FACOG, FACMG: Thank you, Lorraine.

Let us start by asking the question: What is fetal aneuploidy?

Lorraine, what is the source of DNA in non-invasive prenatal testing or NIPT?

Lorraine, how common is aneuploidy?

Dr Gregg: We talk about copy number variants as age-independent. Is that correct?

Dr Dugoff: That is correct.

What are alternatives to prenatal screening for aneuploidy, Lorraine?

Dr Dugoff: Maybe, it is not really good.

Lorraine, what are the causes then of low fetal fraction?

Dr Dugoff: What about microdeletions?

Dr Dugoff: What do you think, Tony?

Dr Dugoff: Tony, thank you so much for participating in this activity.

ACMG = American College of Medical Genetics and Genomics

meta-analysis. Ultrasound Obstet Gynecol. 2017;50:302-314.

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