The ISPD has a serious concern about new prenatal testing for Down syndrome

The International Society for Prenatal Diagnosis (ISPD) issued a policy statement that sets forth its position on prenatal testing for Down syndrome. The policy statement was prompted by the new prenatal testing for Down syndrome called Non-Invasive Prenatal Screening (NIPS), where a mother’s risk assessment is recalculated based on testing cell free DNA in her blood stream. ISPD has a “serious concern” about NIPS. Read on to find out why. 

The new ISPD position statement was preceded by numerous studies on the reliability of the various private laboratories’ brands of NIPS:  Ariosa’s Harmony, Natera’s Panorama, Sequenom’s MaterniT21 Plus, and Verinata’s verify. Though the studies about the new testing had reached a critical mass to justify a new position statement, the ISPD makes a point of spelling out the limitations of the new testing. The identified limitations include:

• The published studies only show reliable NIPS results for trisomy 21 (the cause of most forms of Down syndrome) and trisomy 18. NIPS results for trisomy 13 are not large, and NIPS results for sex chromsome aneuploidy (XXX, XXY, XYY) “is unacceptably low.”
• NIPS has not been shown to be reliable in low risk populations, yet.
• NIPS has not been shown to be useful for pregnancies with more than one fetus.
• Sometimes there is insufficient cfDNA in the mother’s blood sample or the test fails for another reason.
• NIPS may not detect some pregnancies carrying a child with Down syndrome and may report false-positives.
• NIPS has not been shown to be cost-effective, timely and fairly provided to all populations.

It is based on these limitations that the ISPD only considers NIPS as a test to be made available to women already determined to be at high risk. ISPD states (emphasis in original):

Women interested in [NIPS] should receive detailed counseling that explains the benefits and limitations of the test. cfDNA screening should only be provided after they have been informed that these tests are still under clinical development.

And, while all of this sounds like serious concerns, they still are not the serious concern ISPD has about NIPS.

Rather, for the ISPD, “The current absence of specific guidelines for quality control and quality assurance for cfDNA screening is a serious concern.” The laboratories providing NIPS use different testing methodologies and are selective in how they report their results. All of the testing laboratories are largely independent of regulatory oversight. And, as private companies, each laboratory is jockeying for more market share from its competitors–what the ISPD describes as “intense commercial competitive pressures.” Consequently, an apples-to-apples comparison of the various brands of testing is impossible, so there is no evidence-based way to say which test is the optimal test. For all of these reasons, the ISPD states (with emphasis again being in the original):

It is expected that quality control standards will be developed and the ISPD strongly cautions providers to seek out laboratory services that meet national guidelines for quality control and proficiency testing that is the current standard for other molecular tests.

I mentioned in my post on the highlights of the new position statements how the ISPD listing of concerns can be given even greater weight because many of its authors are affiliated with the very testing laboratories that the ISPD statement states it has serious concerns about. Of the sixteen authors of the position statement, seven–or 43%–of them had declared conflicts of interest, either with the testing laboratories or distributors of the NIPS tests. As a result, when the ISPD says it has a serious concern, that includes individuals affiliated with the various NIPS testing laboratories expressing a serious concern about NIPS.

The next post will address the new ACMG policy statement on NIPS. I hope that this series is not overloading you with talk of the new prenatal testing for Down syndrome. If I have not addressed a question you have, please share that in the comments below.