Noninvasive prenatal screening: replacing confusion with clarity

Oct. 22, 2015

With so much attention focused on the growth of consumerism in healthcare, it is easy to forget that most medical services are not typical consumer products. Many of the diagnostic test services laboratories provide to physicians on behalf of patients involve complex technologies, advanced science, and results whose interpretation defies easy explanation to lay audiences. The result can be confusion about how to use diagnostic information for clinically appropriate actions. The exploding field of noninvasive prenatal screening (NIPS) with cell-free fetal DNA analysis is a case in point.

NIPS screens for aneuploidies based on analysis of fetal DNA circulating in the maternal bloodstream. It was introduced to the United States from Hong Kong in 2012. NIPS uses a simple blood test to determine the need for follow-up invasive diagnostic procedures such as amniocentesis and chorionic villus sampling (CVS) in pregnant women and has rapidly gained currency with the medical community. (Amniocentesis and CVS are invasive procedures that involve direct sampling of amniotic fluid or a bit of the placenta, and they carry a small risk of miscarriage as well as discomfort.) The American College of Obstetrics and Gynecologists (ACOG) supports the use of these screening tests primarily in high-risk women, which includes those 35 years of age or older or those who have a personal or family history, among other factors, although health plans are beginning to cover NIPS for average-risk women.

However, NIPS is only a screening test, and ACOG recommends that a positive NIPS result be followed up with a diagnostic test such as amniocentesis or CVS. This is an important fact that may not be well understood by all patients—and even providers. A recent survey1 of maternal fetal medicine specialists revealed that 94 percent of respondents currently offer NIPS. About 13 percent of these specialists reported that they offer noninvasive prenatal screening as a diagnostic test, indicating that “education gaps remain among MFM specialists regarding the limitations of NIPT and current professional practice guidelines.” News stories about women who have made family planning decisions based on results of NIPS, alone, also demonstrate a lack of understanding of the difference between screening tests and diagnostic tests.

Another concern regards misunderstanding about a test’s performance characteristics as a gauge of its accuracy in detecting abnormalities. While most NIPS tests available in the U.S. have sensitivity and specificity rates approaching 100 percent, other performance characteristics are important to consider. When a test is used to help detect a condition with a low prevalence—such as is the case with fetal aneuploidies—positive and negative predictive values are critical measures of a test’s reliability.

In August 2014, Genetics in Medicine published a peer reviewed study2 by several of my colleagues at Quest Diagnostics that compellingly illustrates this point. The team of investigators examined the performance of a number of widely used noninvasive prenatal screening tests. They determined that the chance that a positive NIPS test result was actually a false positive could be 50 percent or higher for some aneuploidies.

The experience of NIPS highlights the need to balance the risks inherent to the use of a new technology with the significant health benefits that technology may provide. Fortunately, the medical community can align these competing dynamics to provide innovations responsibly to serve the best interests of patients.

Responsible innovation means providing medical services that are based on the best technology and robust science to produce information that is not just academically informative but clinically actionable. It also means carefully describing the advantages and limitations of a test, including the information it can and cannot provide.

The Perinatal Quality Foundation recently launched an educational and research campaign designed to address these gaps. The campaign will provide women and their healthcare providers with access to educational information about the types of prenatal screening and diagnostic tests, their strengths and limitations, test results interpretation, and actions to consider based on these results.

Another facet of this program is the development of a patient registry to track outcomes of women post-partum to help determine the true predictive values of NIPS from different providers. This effort will help to clarify the true rate of false positives and false negatives for NIPS, thereby reducing one of the limitations of these screening methods.

Clinical laboratories are responsible for more than developing and providing diagnostic innovation. In an age of advanced science and technology, we also have a responsibility to help people make use of the insights provided by our innovations so that they can take actions leading to healthier lives. When provided in a responsible manner, NIPS can advance quality screening and, ultimately, better outcomes for women.


  1. Allyse M, Minear MA, Berson E, et al. Non-invasive prenatal testing: a review of international implementation and challenges. Int J Womens Health. 2015;7:113-126.
  2. Wang JC, Sahoo T, Schonberg S, et al. Discordant noninvasive prenatal testing and cytogenetic results: a study of 109 consecutive cases. Genetics in Medicine. 2015;17(3):234-236.
Douglas S. Rabin, MD, serves as the medical director, women’s health, for Quest Diagnostics. Quest supports the Perinatal Quality Foundation’s prenatal testing education and research campaign.