Genetic Counseling in the NIPT Age: Quality Patient Care Through Transparency


Concerns regarding the utility and clinical relevance of non-invasive prenatal screening (NIPS) continue to grow and have become more aggressive as new cases of false positive results come to public light. Moreover, recent reports on this technology have been pointed, while also offering lackluster explanations of the test itself.

Regardless of the medical test, any technology will have its benefits, risks, and limitations. Medical guidelines regarding NIPS have recommended that laboratories offering this test be as transparent as possible with patients and doctors by providing clear information about the results and performance of the test on reports.

Here at Recombine, the patient is the first priority. With this post, our goal is to provide clear information on all aspects of NIPS in the hopes of ensuring all couples are able to better understand the utility of the technology as well as their personal results. In doing so, we aim to give individuals the knowledge they need to make the most informed personal decisions for their pregnancy.

What Exactly is NIPS?

NIPS is a relatively new technology that has only been available clinically for approximately four years. This technology improves upon traditional maternal serum screening (MSS) for fetal chromosome abnormalities, like Down syndrome. Unlike MSS, which measures hormone levels associated with different chromosome abnormalities, NIPS analyzes pieces of fetal DNA in a maternal blood sample, thus providing a higher potential for accurate answers. NIPS has been proven to outperform MSS in all women when detecting pregnancies affected with chromosome abnormalities.

How Does NIPS Measure Up?

Sensitivity and Specificity

When trying to determine how beneficial a test is, a logical question to ask is, “how often does this test detect what it’s designed to detect?” To answer this question, we would refer to the sensitivity of the test. In the context of NIPS, sensitivity would be defined as the proportion of pregnancies that receive an abnormal result and are truly affected with a chromosome abnormality. When discussing sensitivity, specificity (the proportion of truly unaffected pregnancies that are correctly identified as such) is also an important piece of information to have.

When a test is designed, the goal is to have high sensitivity and specificity. However, even when sensitivity or specificity is at 99% (as with NIPS for Down syndrome), since it is a screening test and NOT a diagnostic test, there will still be false positives and false negatives. This is an important distinction to make since some may confuse a NIPS result as a definitive answer, which is not the case. Regardless of how accurate a screening test may be, a screening test will only be able to give clarity as to whether there is a high or low chance for a condition to be happening in a pregnancy. If a patient is seeking definitive, diagnostic information, then they must pursue an invasive, diagnostic prenatal procedure, such as amniocentesis.

False Positives and False Negatives

When questioning a test’s validity, the question to ask, therefore, is not if false positives or false negatives occur, but how often do they occur? In context, false positive rate refers to the percentage of abnormal results that are being reported for healthy pregnancies. A false negative would refer to a low risk result being called for a pregnancy that is actually affected with a chromosome abnormality. If either false positives or false negatives are found to occur too frequently, then we can question the validity of a screening technology.  

So, false calls can occur, and are expected to occur a minimal portion of the time with these technologies. While it would be better if false calls never happened, because NIPS and MSS do properly identify the majority of pregnancies affected with a chromosome abnormality, these are screening options you can trust.

PPV: The Next Big Thing

Given the chance for false positive and false negative results from a screening test, how can providers and patients comfortably assess the accuracy of a result? This is where Positive predictive value, or PPV, comes into play. PPV is the probability that a pregnancy which receives an abnormal result truly has the condition in question. With an abnormal NIPS result, PPV takes sensitivity and specificity into account, while also considering the frequency at which that given condition occurs in the pregnancies of women at the patient’s current age. So, PPV goes one step further than sensitivity and says “for this specific woman, at her specific age, this positive result has an XYZ% chance of actually being right.” In the chart below, you can see just how much the prevalence of a condition (first column) can affect the PPV for common chromosome abnormalities.

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PPV really puts the relevance of an abnormal result into perspective. If a patient knows the PPV of a result for a condition is 15%, they would be far less likely to get extremely concerned, in comparison to a result with a PPV of 50% or greater, where it would be far more pressing to diagnostically confirm this result.

PPV is a valuable piece of information to share with a patient and their doctor, but regardless of what the PPV is for an abnormal result, it is still abnormal. PPV is the first step in a long conversation about what the patient wants to do with this result. While PPV can be useful, it does not replace any other part of the recommended management for an abnormal result on a chromosome abnormality screen. If anything, PPV should help a patient better engage in a medical management conversation. As providers, whether we are the doctor ordering the test, the laboratory genetic counselor looking over the result, or the clinical genetic counselor speaking with the patient face-to-face, we need to be ready and willing to support a patient with an abnormal result in the decision-making process.

Educating the Patient

The goal of any screening test during pregnancy is to identify a potential risk as early in the pregnancy as possible. This ensures that the patient can use that information to pursue whatever option she feels would be best for her family, without the added stressor of a time crunch. Based on medical guidelines, any type of chromosome abnormality screening, but especially NIPS, needs to be offered to patients with adequate availability of prenatal genetic counseling and invasive diagnostic prenatal testing. If genetic counseling is not available prior to coordinating the test to discuss all potential outcomes of the test and available next steps, then the onus is put upon the patient’s provider. In addition, either a genetic counselor or a provider should be available to discuss the result in the full context of a patient’s medical history (other screening tests, ultrasound, pregnancy history, etc) as well as compare and contrast the risks, benefits, and limitations of pursuing further screening or diagnostic testing options.

Here at Recombine, we have a protocol in place to help doctors handle all abnormal results. Each abnormal NIPS report contains PPV information on the first page, and all abnormal results are called out to the doctor’s office prior to release. During this call, a genetic counselor has an in-depth conversation with a doctor or nurse in order to ensure the patient has all of their follow-up options available (genetic counseling, ultrasound, invasive diagnostic testing), while also empowering the clinic with pertinent information about the result.

All doctors also have the option to have the patient counseled by a Recombine genetic counselor regarding the abnormal result, and if the clinic declines this option, the genetic counselor will ensure that the patient is being referred appropriately to a genetic counselor, Maternal-Fetal Medicine Specialist, or Perinatologist for proper follow-up. When a patient does have genetic counseling through Recombine, they have a comprehensive genetics consultation, including a discussion regarding 1) NIPS technology, 2) age-related risk for chromosome abnormalities, 3) all of their options for additional screening and diagnostic testing, 4) a detailed family history, and 5) recommended follow-up. After a session, a letter is sent to both the patient and provider, outlining the conversation and the next steps the patient decided upon.

By no means is this a perfect science, but our abnormal NIPS results protocol was created to ensure that no patients fall through the cracks. Every patient deserves the same amount of dedicated care, and at Recombine we do our best to facilitate this. As laboratory genetic counseling becomes more commonplace, we hope that Recombine will not only prove an example to others, but also motivate others to take every step in their power to create transparency throughout the testing process.                 


About Author

Nicholas Paolino

Nicholas Paolino is a board-certified genetic counselor at Recombine. In addition to providing genetic counseling services to Recombine’s patients, Nicholas is also responsible for overseeing the quality control and internal operations of Recombine’s ChromoMap test, a non-invasive prenatal screening technology. Nicholas has a background in high-risk perinatal and reproductive genetic counseling, previously working at Rutgers Robert Wood Johnson Medical School in the Division of Maternal Fetal Medicine. Nicholas received his B.S. in pre-med biology from the University of Scranton and his M.S. in human genetics and genetic counseling from Sarah Lawrence College. He is a licensed genetic counselor in the states of New Jersey and California.