Commentary: The Right Way to Use Noninvasive Prenatal ‘Tests’

Margaret B. Menzel, MS


February 03, 2015

Editorial Collaboration

Medscape &

Not long ago, I met with a patient who had undergone noninvasive prenatal testing (NIPT) that was reported as negative for trisomy 21, 18, and 13. The fetus had a few subtle ultrasound abnormalities but nothing concerning enough to cause her to want to pursue diagnostic testing.

At birth, her baby was diagnosed with trisomy 18 and, sadly, died within 24 hours. The family was understandably shocked and devastated. When I called the ob/gyn, who was not present at the delivery, to tell him of the diagnosis for the child, he said, "That is impossible. The patient had a negative NIPT screening."

This patient's experience, unfortunately, is not as uncommon as you may think.

These past 10-15 years have proven to be a period of exponential growth in the world of genetic testing.[1] Most of these advances, including NIPT, are beneficial to patients and to society at large. A well-known example is genetic testing for mutations in the BRCA1 or BRCA2 genes. Women or men who choose to pursue BRCA mutation testing, when counseled appropriately, will have information about their own cancer risks that will empower them in their medical decision-making.

The problem we are seeing with NIPT screening, however, relates to the lack of appropriate counseling, both by the lab to the physician and by the physician to the patient. Beth Daley provides examples of these misperceptions among patients and providers in her recent Boston Globe article, "Oversold Prenatal Tests Spur Some to Choose Abortions."[2] In the article, Daley gives examples of cases where patients were told about abnormal NIPT results but did not receive adequate counseling about the benefits and limitations of the screen.

"Tests" Are Just Screens

In 2007, the American College of Obstetricians and Gynecologists published practice guidelines recommending that all pregnant patients, regardless of age, be offered screening for Down syndrome.[3] At that time, first-trimester screening was the most reliable and earliest screen for Down syndrome as well as for trisomy 18 and 13. This screening is done in the first trimester and combines an ultrasound measurement of the back of the neck of the fetus along with blood work to provide a risk assessment for the likelihood of trisomy 21, 18, or 13. The laboratory reports for these screens usually say "screen positive" or "screen negative" and provide a risk assessment number (1 in 50, or 2%) on the report, which is then discussed with the family by the provider.

In my experience, there was not the perception with first-trimester screening among patients or providers that this was a screen designed to replace chorionic villus sampling (CVS) or amniocentesis. To diagnose Down syndrome or trisomy 18 or 13, one would have to pursue CVS (99% detection) or amniocentesis (99.9% detection).

Like first-trimester screening, NIPT is a screen, not a diagnostic test. However, because of the way it has been marketed (using the word "test" in its title, for example), many patients believe that it is a test that can replace CVS or amniocentesis. When a screen is marketed with a "99% detection for Down syndrome," even providers make the mistake of thinking that it's close enough to 100% that it might as well be considered diagnostic.

The first thing to understand is that 99% does not apply to an individual's result but rather to the entire population screened. The test is correct 99% of the time for all women in the screening population. High-risk women (over 35, previous pregnancy with chromosome abnormality, etc.) have a higher a priori risk, and, therefore, the positive predictive value (the chance that a "positive" test result is a true positive) is higher for them than it is for a woman who is at low risk. One recent study from Wang and colleagues[4] looked at follow-up karyotype information of 109 positive NIPT results from four different labs and found that of 41 pregnancies with positive NIPT results for Down syndrome, only 38 women were carrying a fetus with Down syndrome (93%). The positive predictive value was even lower for trisomy 13 and 18.

This type of statistical information is not transparent on the laboratory reports and is not something that the laboratory representatives will walk you through when they drop off the blood cards in your office. However, it is information that the patient must understand prior to pursuing testing and, of course, once she receives the test results. Patients and providers need to understand that there can be a "normal" NIPT result and there could still be a baby with Down syndrome. If not having a definitive answer one way or another is okay with the patient, then the screening may be enough. If it isn't, she should be counseled about diagnostic testing options.

Time and Expertise Required

No ob/gyn or maternal-fetal medicine doctor that I know has 30 minutes built into his or her day to discuss all of the complexities of NIPT screening. And, for most of us, statistics was not fun. Without looking it up, do you remember what a positive predictive value is? If so, can you explain it to your patient in relation to her NIPT screening results?

Genetic counselors are board-certified professionals who are schooled in medical genetics, statistics, and counseling. Our job is to clearly explain medical information to different patient populations. As a physician, if you have access to a genetic counselor, you should use one. Unfortunately, the number of patients who need genetic counseling is much greater than the number of genetic counselors available. As of 2012, according to the Bureau of Labor Statistics, there were only 2100 genetic counselors in the United States. This number is expected to grow by at least 49% by the year 2022, but that barely brings us to 3000 within the next decade or so.[5]

Physicians who don't have easy access to a genetic counselor may consider looking on the National Society of Genetic Counselors website to find one in their area. Many maternal-fetal medicine practices and hospitals have genetic counselors on site, and it is worth referring to them even if somewhat out of the way for the patient. Other options include requesting that the participating laboratory provide complimentary access to their genetic counseling services. Some local and community hospitals now provide telemedicine genetic counseling consults, and some genetic counselors will do phone consultations. It may be worth arranging for a genetic counselor to come to your office once a week for half a day and do a "group" counseling session with a follow-up phone call for results. Genetic counselors are good at being creative in how they see and bill for patients, so it is worth exploring options that may not seem feasible at first.

NIPT screening does not have to be as overwhelming as it seems. Better education and communication between laboratories and providers will allow for better patient care. Leaving the counseling to genetic counselors will ultimately benefit your practice and the patient.


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