Get the facts about Down syndrome prenatal testing

In effort to clear up the widespread confusion about non-invasive prenatal screening (NIPS), also known as cell free DNA testing, the National Society of Genetic Counselors (NSGC) has issued a fact sheet. Get the facts about this testing.

The NSGC provides a comprehensive review of what NIPS results mean in its fact sheet, which can be viewed and downloaded at this link. Some key points with links to posts from this blog further expounding on the points made:

• NIPS tests cell free DNA:

All individuals have their own cell free DNA in their blood stream. During pregnancy, cell free DNA from the placenta (predominantly trophoblast cells) also enters the maternal blood stream and mixes with maternal cell free DNA.   The DNA of the trophoblast cells usually reflects the chromosomal make-up of the fetus

• NIPS is NEVER positive

Abnormal results indicate an increased risk for the specified condition. However, an abnormal result is not diagnostic and confirmatory testing is recommended.

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A >99% risk score does notmean there is a greater than 99% chance that the pregnancy is affected with a condition.  A “Positive” or “Aneuploidy Detected” does not mean the fetus definitively has a chromosome condition.

• Positive predictive value (PPV) is the number that matters

In order to determine the chance for a high risk result to be a true positive, one must calculate the positive predictive value.

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Positive predictive value (PPV) is the proportion of positive results that are true positives. In other words, PPV answers the question: “What is the chance an abnormal NIPT means the fetus has this condition?”

[None of the labs, however, report out the PPV for their test results]

• A CVS may be just as inaccurate as NIPS

I’m quoting this section of the fact sheet in full because this may be the most news worthy information, in the sense that I have not seen this point highlighted in other statements: because CVS tests the same material as NIPS it can be just as inaccurate and may still report a false positive just as NIPS can report false positives:

Confirmatory testing via CVS or amniocentesis should be offered to all women with an abnormal NIPT result. Patients electing to have CVS for confirmation should be counseled regarding the limitations of this technology since confined placental mosaicism may explain the abnormal NIPT and may be detected with CVS, especially when aneuploidy FISH is ordered. Trophoblast cells are the primary source of cell free DNA in maternal blood and are also the cells analyzed for aneuploidy FISH testing. Confined placental mosacism may cause an abnormal NIPT result and abnormal CVS FISH and/or karyotype result. Cells analyzed by amniocentesis are not typically affected by confined placental mosaicism since they are primarily derived from the fetal skin and genitourinary tract.

Because this paragraph is chock-full of medical-speak, I hope I can further translate. If you scroll up, you’ll see the first point is that NIPS tests cells from the developing placenta, not necessarily from the fetus itself. As a result, a screen-positive NIPS could be the result of a placental cell having an extra 21, 18, or 13 chromosome, but that the fetus would be unaffected. Similarly, CVS tests the same cells that NIPS tests, and, therefore, a CVS could report a positive based on placental cells with an extra chromosome but the fetus may still be unaffected. Only amnio provides a clearer diagnosis because it is testing actual fetal cells.

• Ask for genetic counseling following a NIPS result

This is my formulation of the final point made by the NSGC. Perhaps being too modest, the fact sheet simply concludes with how patients can locate a genetic counselor.

A genetic counselor can be located using the “Find a Genetic Counselor” link on the nsgc.org website.

But, professional guidelines from ACMG, ACOG, and NSGC all recommend post-test counseling and ideally from a genetic counselor. Given the non-intuitive biological material that NIPS is actually testing and then the complex statistical analysis to then understand even what NIPS results mean for PPV, patients should ask for a consult with a genetic counselor following a test result.

When considering NIPS or after receiving your results from MaterniT21, Harmony, verifi, Panorama, InformaSeq, or another NIPS result, get the facts on what those results mean from the NSGC fact sheet.