Discovering Prenatal Genetics

TRANSCRIPT for Podcast Episode with the title Discovering Prenatal Genetics

Voiceover [00:00:02]:

Welcome to the Results Are In from Quest Diagnostics. Conversations with diagnostics industry leaders who enable optimized care pathways for patients.

Lisa Demers [00:00:08]:

Hi, I'm Lisa Demers, Director of Genetics Strategy and Solutions at Quest Diagnostics and your host for today's episode of The Results Are In. In my 20 plus year career as a genetic counselor, I've worked closely with clinicians, patients, health systems and laboratories to help incorporate prenatal genetic screening to improve patient care. So I've seen firsthand how these tools are transforming pregnancy management. These tests have reshaped how we approach pregnancy, offering vital insights that can help guide care before and during pregnancy.

Today, we're diving into prenatal genetic screening with my friend and colleague, Paul Kezmarsky, Director of Genetics Strategy and Solutions and a genetic counselor by trade. Paul brings deep experience in prenatal genetics and has helped drive innovation and access for tests like cell free DNA screening and carrier screening. Paul and I are going to take a look back at the evolution of prenatal genetic screening, discuss the impacts of these tests on patients and providers, as well as the key features to look for when choosing a lab for prenatal genetic screening.

Lisa Demers [00:01:24]:

Hi, Paul, welcome.

Paul Kezmarsky [00:01:25]:

Hi, Lisa. Thank you. I'm really glad to be here. You know, it's been amazing to watch prenatal genetics evolve over my career. I actually started as a prenatal genetic counselor right around the time of cell free DNA screening when it was first introduced. And seeing how it transformed prenatal care from the very beginning really shaped my path as a genetic counselor and eventually led me to working for laboratories in this space really over the past decade, before joining Quest earlier this year.

Lisa Demers [00:01:52]:

Yeah, sounds a lot like my own career path. And you and I can talk about prenatal screening all day, but can you, for our listeners, provide some background about prenatal screening and what it's looked like over the years?

Paul Kezmarsky [00:02:04]:

Yeah, screening tests, as you know, have always been about identifying which patients might need a close might need closer attention in prenatal care. We started Screening for trisomy 21 or down syndrome decades ago with biological biochemical markers, which became the triple screen and then the quad screen, et cetera. And these screening tests were decent.

They provided a numerical risk for having a baby with trisomy 21. But these tests had a 5% screen positive rate, meaning that 5% of all patients having the test were told that they had an increased risk for their baby to have trisomy 21. And as you know, the vast majority of them did not. And then it was in 2011, there was this new screening test that hit the market, one that looked directly at fetal or more specifically placental DNA that was in maternal circulation. I remember that this testing was initially called noninvasive prenatal diagnosis, but that quickly shifted to noninvasive prenatal testing, or NIPT as we call it.

Paul Kezmarsky [00:03:06]:

And actually it was Quest with QNatal that was among the first to adopt the terminal non invasive prenatal screening, which is actually a more accurate way to describe the test.

Lisa Demers [00:03:16]:

Yeah, I remember that first excitement of a test that could theoretically replace diagnostic testing by amniocentesis. But we, you know, in the prenatal genetics community very quickly self-corrected and were sure to strongly and effectively define NIPT as a screening test. And, and I think the greatest excitement stemmed from the fact that we were no longer confined to the statistics of biomarker screening, where a defined number of samples were considered outliers.

This new cell-free DNA screening had a much higher sensitivity than any other screening for aneuploidy. So, we can't eliminate the need for diagnostic testing, but we certainly reduced a significant number of unnecessary diagnostic tests, for sure.

Paul Kezmarsky [00:04:03]:

The excitement didn't stop there. It's been said that NIPT was the fastest growing genetic test, maybe the fastest growing test of any kind in medical practice. And whether or not that's accurate or not, it certainly felt like it was.

Remember, when NIPT was first launched, it was primarily offered to higher risk pregnant patients, those that were over 35, or other clinical risk factors. Over time, though, more and more average risk patients were offered the test.

And this shift really solidified in 2020 during the pandemic when ACOG updated their guidelines and recommended offering cell free DNA screening to all pregnant patients, regardless of age or regardless of risk. It's remarkable to see how quickly this test became integrated into standard prenatal care. It's funny, many providers today don't even know a world without cell free DNA screening.

Paul Kezmarsky [00:04:55]:

Even this testing has truly reshaped how we think about prenatal care.

Lisa Demers [00:04:59]:

Oh, it absolutely has. It's totally different than it was 10, 20 years ago. So, switching gears a bit, but sticking with the evolution of prenatal genetics, can you define carrier screening and describe how it has evolved over the same time period?

Paul Kezmarsky [00:05:15]:

Sure. Carrier screening is genetic testing that checks whether a person carries a gene variant for a recessive or X linked condition that could be passed on to their children. Early available carrier screening was limited though, and was often tied to one's ancestry or country of origin.

Over time, there's been more of a shift to a pan ethic approach for carrier screening, making it more meaningful and equitable for all patients. Technology has also advanced in this time, allowing us to screen for more and more conditions more and more accurately. Today, carrier screening panels, they range from small numbers of conditions all the way up to hundreds of conditions, and that supports a panethic and equitable approach for patients overall. I would say the biggest change, though, in the past five years has been this shift to a pan ethnic approach to carrier screening.

Lisa Demers [00:06:12]:

Yeah, I've been very happy with this change. When I was practicing clinically, my patients would sometimes not know their ancestral origins, so I was stuck with basing clinical decisions on someone's best guess.

Paul Kezmarsky [00:06:24]:

Yeah. And sometimes their best guess wasn't a guess at all. It was what they knew. I remember a patient I had in Poughkeepsie, New York, one time and just asking them what their ancestry was or where they were from, and they replied, Rhinebeck. Rhinebeck's about 20 miles north of Poughkeepsie. But to them, that's where their ancestors were from.

Lisa Demers [00:06:46]:

Yeah. And thankfully now both ACOG and ACMG have provided pretty clear guidance about carrier screening.

Paul Kezmarsky [00:06:52]:

Yeah. And ultimately, while these guidelines do offer direction, there's still flexibility for the providers to counsel their patients about carrier screening and what conditions to screen for and then aid in decision making.

Lisa Demers [00:07:05]:

So let me ask you, do you think there's a sweet spot for these carrier screening panels?

Paul Kezmarsky [00:07:10]:

You know, there could be. The goal, when you think about it, is to offer enough conditions to provide actionable insights while keeping it manageable for both the providers, but more importantly, the patients. For example, our QHEROT carrier screening panels give flexibility to meet a variety of clinical needs without overwhelming everybody with unnecessary complexity.

Lisa Demers [00:07:34]:

Yeah. Yeah. So we've been working together at Quest now for nearly a year, but we have both known about Quest in the genetic space for years. Is there anything that you have learned at your time here about Quest and genetics that has surprised you?

Paul Kezmarsky [00:07:49]:

Yeah, what's really surprised me is the depth of experience here. Quest brings decades of experience in genetic testing, supported by a really robust clinical and operational team. And in prenatal genetics specifically, what we've been talking about today, our QNatal test has been part of cell free DNA screening since the early days, more than 10 years now. And QHerit complements that by providing broad, flexible carrier screening.

Together, they form a comprehensive prenatal genetic test offering. And while this is just screening Quest, we go beyond that. We offer a continuum of care for the patient from start to Finish. From screening to diagnostic testing, offering more answers for patients during their reproductive journey.

Lisa Demers [00:08:32]:

Yeah, well, it's really helpful clinically to be able to offer both screening and diagnostic testing, you know, to complete the clinical picture. And then when it comes to genetic testing, the results are personal and the results can also be very complicated. So in your opinion, what can laboratories do to support providers as they share results with patients?

Paul Kezmarsky [00:08:54]:

The goal really should be to offer clarity and actionability. Results should be designed so the clinician can quickly understand key findings and help patients make informed decisions. That's the ideal. So in my opinion, the ideal report should turn, as we discuss as genetic counselors, Lisa, it should turn this complex genetic information into something meaningful. In this case, something clinically meaningful.

Lisa Demers [00:09:22]:

Yeah. And then beyond the tests themselves and the reports, what other ways can a laboratory support thoughtful and effective genetic testing?

Paul Kezmarsky [00:09:33]:

Well, with any specialty, you want access to subject matter experts. And for genetic testing, those experts are genetic counselors. As genetic counselors ourselves, I think we should highlight the incredible team of genetic counselors.

Here at Quest, we have genetic counselors involved in many areas of our operations, but specifically for providers and patients, we have genomic science specialists. And this team is made up of all board-certified genetic counselors. And they're readily available. They support providers, they support patients with questions about testing and about the results, making sure that guidance is available whenever it's needed.

Lisa Demers [00:10:15]:

Yeah, there is an invaluable part of the team for sure. Even for us, the colleague genetic counselors. We're all reaching out to them all the time. So looking ahead, how do you see prenatal genetics continuing to evolve?

Paul Kezmarsky [00:10:30]:

Well, it's been exciting so far and we're in the middle of exciting times in prenatal genetics. And looking back, you and I both have experienced this in clinic. And now on the industry side, prenatal genetics just continues to evolve rapidly as technology continues to evolve rapidly. And Quest is continually innovating in this space and we're really super excited about future developments.

Lisa Demers [00:10:54]:

Yeah, can't wait. Well, thank you so much for joining me in this conversation today, Paul.

Paul Kezmarsky [00:10:58]:

Thanks, Lisa. It was a pleasure.

Lisa Demers [00:11:00]:

That brings us to the end of today's episode. Once again, thanks to Paul Kezmarsky for joining me today and helping us explore the role of prenatal genetics in patient care. For clinicians, prenatal screening has become an essential tool for providing vital insights and guidance for patients throughout their pregnancy journey.

At Quest, we're proud to offer accessible, affordable and innovative options like QNatal and QHerit, backed by expert support that goes well beyond the test itself. To learn more, visit questdiagnostics.com and explore our resources on prenatal genetic screening. Thanks for tuning in. I'm Lisa Demers, and we'll see you next time on the Results are in by Quest Diagnostics.

Voiceover [00:11:53]:

This podcast was produced in partnership with Amaze Media Labs.