More NIPGS = More Misdiagnoses and Risk

AutonomyNIPTA new study reports on the impact of noninvasive prenatal genetic screening (“NIPGS”) on referrals for diagnostic testing. It finds plummeting diagnostic testing and more. 

Study results

In the April issue of the American Journal of Obstetrics & Gynecology (AJOG), a team lead by John Williams, III report on their findings of the impact of NIPGS’ introduction into clinical practice.

The team reviewed the cases of all women referred for genetic counseling and prenatal testing at the Cedars-Sinai Prenatal Diagnosis Center from January 1, 2010 – December 31, 2011, the two years preceding NIPGS, and January 1, 2012 – December 31, 2013, the two years following NIPGS.

The full article can be reviewed here (subscription required). Here are the highlights:

  • Pre-NIPGS, 3,944 women were referred for genetic counseling and diagnostic testing; Post-NIPGS, 2,824, a reduction of 28.4%.
  • Pre-NIPGS, 26.2% of women declined diagnostic testing; post-NIPGS, 31%.
  • There was a 48% reduction in the number of procedures performed in 2013 as compared to the number performed in 2010.
  • Pre-NIPGS, 467 women not candidates for NIPGS were referred for genetic counseling and diagnostic tesing; post-NIPGS, 285, a reduction of 38.9%.
  • Of the women who had CVS during study period, NIPGS would not have identified 32.4% of the aneuploidies identified due to NIPGS’ limited scope of conditions.

The authors note that there was no difference in the referral rate for genetic counseling and diagnostic testing based on first-trimester combined or second trimester quad-screen results, suggesting a greater reliance on the accuracy of NIPGS than traditional screening. Further, there was no apparent decrease in the overall birthrate to account for the reductions in referrals post-NIPGS.


From the report, the authors draw the following conclusions and concerns:

  • The decrease in referrals for genetic counseling is not consistent with the American College of Obstetricians & Gynecologists and Society for Maternal-Fetal Medicine joint statement recommending informed pretest counseling prior to accepting NIPGS.
  • “Genetic counseling has been shown to identify additional significant genetic risks in 35.6% of women. As fewer women are being referred for genetic counseling, the potential for missing additional risks for genetic orders is likely to increase.”
  • “An even greater concern” is women at an increased risk for fetal aneuploidy and single gene conditions not detectable by NIPGS relying only on NIPGS results and not having these conditions identified through prenatal testing.

This concern of NIPGS’ limited scope missing a significant number of other conditions has been noted in other studies, which the graphic with this post illustrates.

Williams et al. further are concerned about the reduction in diagnostic testing due to the appeal of NIPGS being noninvasive and therefore not carrying a risk of miscarriage. They note that:

[I]nvasive diagnostic procedures (CVS and amniocentesis) have been shown to be relatively safe, particularly in the hands of experienced operators. In experienced hands, both have been reported to carry procedure-related loss rates of approximately 1 in 400.

To their credit, the authors recognize the impact decreased invasive procedures will have on increasing the risk of those procedures:

[A]s the number of referrals for diagnostic testing continues to decline, some CVS and amniocentesis practitioners may lose their technical skills. … It is possible that practitioners who were able to perform enough diagnostic procedures to maintain competency prior to the introduction of [NIPGS] into clinical practice may not be able to maintain their skills.

(I wrote about this inverse relationship between the number of procedures and the risk of invasive testing for a presentation at the 2013 American College of Medical Genetics & Genomics annual conference).

Finally, Williams et al. make an observation that may not be appreciated by the laymen or their professional colleagues.

The “greater concern” noted above, of women with single-gene conditions not being referred for diagnostic testing, the authors postulate could be due to a misunderstanding on the limitations of NIPGS by patients and clinicians. Williams et al. suggest that future studies assess patient and clinician “understanding of the differences between prenatal screening and diagnostic tests.”


NIPGS is resulting in fewer women being referred for genetic counseling and diagnostic testing due to an apparent reliance on the accuracy of NIPGS which may be misplaced, particularly for conditions not detected by NIPGS. This reduction may lead to more misdiagnoses, i.e. women not being diagnosed who otherwise would have but for relying on the limited scope of NIPGS, and an increased risk for invasive testing due to the plummeting number of procedures. As a result, the article’s final sentence is suitable for ending this post as well:

In addition, with the current and future complexities of diagnostic genetic testing, genetic counseling should be offered to all patients considering any type of genetic screening or diagnostic testing.


2 thoughts on “More NIPGS = More Misdiagnoses and Risk

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