Noninvasive Prenatal Screening: A Genetics Counselor's Perspective

Laura A. Stokowski, RN, MS; Katie Stoll, MS


November 08, 2013

Editor's Note:
Noninvasive prenatal screening provides the ability to detect certain fetal chromosomal abnormalities even earlier than current methods. However, there are still many uncertainties about this type of screening, such as what type of counseling interested patients should receive before they get the test.

Medscape spoke with Katie Stoll, MS, a genetics counselor at Group Health Cooperative in Seattle, Washington, about the many questions that can arise from noninvasive prenatal screening.

Medscape: As a genetics counselor, what information do you disclose in the informed consent process before a woman undergoes noninvasive prenatal screening?

Ms. Stoll: The decision to undergo any prenatal genetic screening, including noninvasive screening, is very personal and should be based on individual needs and values. This type of testing should not be presented as routine or recommended,and women should understand that it is okay to accept or decline the screening. They should have some understanding of why some individuals undergo this testing and some do not.

For instance, some women may do this testing because they believe that having information about chromosomal conditions before the birth of their baby will help them feel more prepared. Some choose this screening because they know that they would consider pregnancy termination if a chromosomal condition was identified.

On the other hand, some women feel that this information is of little value to them because they consider that the chance of a chromosomal condition is low or they recognize that a positive result would cause worry and uncertainty. For women who plan to continue their pregnancy regardless of the screening result, the stress accompanying a positive result may be unwelcome.

It is critical that the clinician help the patient look ahead and consider what getting a positive result might feel like. How would they feel about finding out that they have a high probability of a chromosomal condition? How would they feel about the possibility of receiving results that are uncertain?

Patients need to understand that noninvasive prenatal screening is not diagnostic, and that false-positive and false-negative results can and do occur. If a woman feels that she needs to know with certainty about chromosomal conditions, diagnostic testing through amniocentesis may be the best choice for her. For women who know they would never consider invasive testing but also know that they are not comfortable with uncertainty, noninvasive prenatal screening may cause undue stress.

Another critical part of informed consent for noninvasive prenatal screening should include a discussion of the conditions included in the screen as well as some basic information about those conditions. Trisomy 18 and trisomy 13 are associated with many health and developmental problems and a shortened life expectancy. Although both are rare conditions, the vast majority of affected fetuses will be picked up on second-trimester ultrasonography.

On the other end of the spectrum are the sex-chromosome conditions, such as 47,XXY, 47,XXX, and Turner syndrome. These conditions are more common, and the associated health and developmental concerns much less severe. In fact, many people who have an extra X or Y chromosome are never diagnosed as having a chromosomal condition at all and don't have any significant health or developmental concerns. It is important for patients to realize that the conditions screened for are highly variable.

Medscape: Do you find that women who have positive screening results are making pregnancy termination decisions without confirmation by invasive testing?

Ms. Stoll: We do not have published outcomes data yet to show us what women are doing with the results of noninvasive prenatal screening, but without a doubt, some women are making pregnancy termination decisions on the basis of screening results alone. One laboratory presented some preliminary outcomes data at a genetics meeting recently showing that some women were terminating on the basis of noninvasive screening results alone. Hopefully, patients who are adequately counseled about the limitations of this testing will wait to make decisions until they have undergone diagnostic testing.

But I imagine that in areas where maternal/fetal medicine and genetic counseling services are not available, and gestational age limits for pregnancy termination are restricted to the first or early second trimester, women feel a lot of pressure to act quickly and may be more likely to make decisions on the basis of noninvasive screening results without following up with ultrasonographic or genetic counseling. Hopefully, we will see more research looking at how individuals are using this information.

Medscape: How are the screening test results reported? Are result reports consistent for all 4 tests currently available?

Ms. Stoll: All of the laboratories report the results in slightly different ways. One laboratory use the terms "aneuploidy detected" or "aneuploidy suspected." One uses "positive" or "negative." Another reports "high risk" or "low risk" and gives a probability, such as > 99% or < 1 in 10,000.

Medscape: A criticism of noninvasive prenatal screening has been that the manufacturers have not reported data for positive predictive value (PPV) and negative predictive value (NPV). How does this affect the interpretation of the results and patients' understanding that this is a screening test and not a diagnostic test?

Ms. Stoll: There is a lot of concern that the reports may mislead patients and providers into thinking that these results are diagnostic or near-diagnostic. It may be difficult to recognize that a "positive" result or a result that states "aneuploidy detected" is not definitive.

Furthermore, there is a tendency to confuse the sensitivity with PPV. Whereas a test may detect > 99% of pregnancies with Down syndrome, a positive result does not mean that there is > 99% chance that the pregnancy is affected with Down syndrome. The PPV is the probability that a positive result is a true-positive result, and this is really dependent on the existing probability of the condition in the individual patient.

In the case of aneuploidy, this is generally based on age. For younger, lower-risk women, the likelihood of a false-positive result may be higher than a true-positive result when you consider the results for all chromosomal conditions detected.

Medscape: Whole fetal genome/whole fetal exome sequencing may be possible with cell-free DNA technology. Whether advances in testing are targeted or nontargeted, how should clinicians prepare for rapid advances in tests being offered noninvasively and marketed to consumers?

Ms. Stoll: I am concerned that our technology already has outpaced our ability to offer this testing in a way that empowers truly informed decisions and meaningful information for our patients. There are so many genetic variations that we do not know how to interpret even when we find them in pediatric and adult patients. Is a variant of uncertain significance harmful or beneficial? We often do not know.

Having this level of genetic information prenatally, when we understand so little of what it means, is bound to cause confusion, anxiety, and fear. When used in a way that supports individual needs and values, prenatal testing is incredibly powerful. However, as it becomes more routine and, at the same time, more complex, we run the risk of burdening patients with information that may do more harm than good.

Medscape: Guidelines suggest that both pre- and post-test genetic counseling be provided, either with the obstetric clinician or a genetic counselor.[1,2] Why should clinicians refer to genetic counselors rather than just reviewing the results with the patient?

Ms. Stoll: It isn't mandatory for genetic counselors to review results of noninvasive prenatal screening with patients. Many obstetric clinicians can do a fine job of following up these test results. The difficulty may be in the amount of time available during a brief clinical encounter to discuss these test results, answer questions, and make a plan for follow-up. Genetic counselors may have had more experience with the conditions that are being tested for and can give patients information about these conditions and, in some cases, may be able to help patients connect with resources and support organizations that may be helpful if a test result indicates a high probability of a chromosomal condition.

The NPV of noninvasive prenatal screening is very good, indicating that false-negative test results are rare. But false-negative results do occur, and when providers are disclosing negative test results to patients, they should be clear about this small possibility and inform patients that this test only screens for specific chromosomal conditions, not all genetic conditions or other factors that can affect health or development.

With a positive result, I would encourage clinicians to refer patients on for formal consultation to review the results with a genetic counselor or perinatologist. I am concerned that the laboratory reports often make this testing sound more diagnostic than it is and that some women are making pregnancy termination decisions without confirming the diagnosis. In some cases, the chance of a false-positive result is much higher than people expect.

Sometimes I hear that a patient was not referred for genetic counseling because she knew she was continuing the pregnancy. No matter what a woman plans to do with the information, genetic counselors can provide support and resources that can be extremely valuable.

Medscape: If clinicians largely choose to refer patients to genetic counselors, are there enough to meet the demand?

Ms. Stoll: It is hard to say. Currently, genetic testing options are growing at a rapid pace. We need to look at some alternative service delivery models and consider how genetic counselors can better support clinicians as we try to support the growing demand for genetic counseling services.

Some of the work that I have been focused on is ways to support obstetric providers and patients through prescreening decision-making and in post-test counseling. I find that there are a lot of untapped opportunities in this area that we hope to expand on. I would encourage obstetric providers to reach out to genetic counselors in their communities and find out how they can support them in their practice.


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