Noninvasive prenatal testing should be a secondary screen

Down Syndrome Prenatal Testing CycleThe headline isn’t my conclusion. Tellingly, it’s the result arrived at by a researcher for one of the Non-Invasive Prenatal Screening (NIPS) labs. And, one of the labs that would prefer if the opposite were the case.

Dr. Mary Norton has been active in the development of prenatal testing for years. Based on her expertise and her interest in the subject, she has received research funding by Ariosa and CellScape, companies developing noninvasive prenatal testing. In Ariosa’s case, its test–called “Harmony”–is already on the market.

Ariosa has a published study of the general population to support its position that it’s Harmony test should be available to all expectant mothers–not just those considered “high-risk” per the majority of professional medical statements on NIPS.

Which is why Dr. Norton’s statements at a meeting in August on pregnancy management in San Francisco are all the more interesting.

Dr. Norton used available data to run three possible testing scenarios based on 2.9 million pregnant women being screened and 5,110 pregnancies with Trisomy 13, 18, or 21 (Down syndrome). The scenarios considered what effect testing the populations using conventional prenatal screening, e.g. Nuchal Translucency, Quad testing; NIPS as a first-level screening, i.e. offered to all women; and, NIPS as a second-level screening, i.e. only to those women who received a result first from conventional screening. The estimated results are reflected in the table at Figure 1:

Norton Screening Protocols and miscarriages

Norton’s numbers reflect much the same that other studies have found: that NIPS can dramatically reduce the number of invasive tests due to its high-detection and low false negative rates. At the same time, NIPS only achieves those high levels of detection and low number of procedure-related miscarriages when used as a secondary screen–not a primary screen.

Significantly, as emphasized in the last column, fewer pregnancies would suffer miscarriage due to invasive testing where NIPS is used as a secondary screen. Where NIPS is used as a primary screen, as compared to just conventional screening, it reduces the number of procedure-related miscarriages by half. But, where NIPS is used as a secondary screen–as recommended by most professional organizations–the number of miscarriages is less than 10% as compared to conventional screening, but the number of miscarriages is also almost 85 percent fewer than where NIPS is used as an initial screen.

The table also reflects why the American College of Medical Genetics & Genomics (ACMG) separated itself from the professional statements on NIPS. The statements of ACOG, NSGC, and ISPD limit NIPS to those mothers considered “high-risk,” typically due to maternal age or for having a conventional screen result. ACMG, however, reasoned that since conventional screening is to be offered to all expectant women, and conventional screening has higher false positives and false negatives than NIPS, then NIPS should be offered to all expectant mothers, as well.

The factor not included in ACMG’s reasoning, but one certainly considered by patients (and insurers), is cost.

Whereas conventional screening can cost well under $500, the least expensive NIPS test (coincidentally the Harmony test), costs just over $700. Therefore, another factor not reflected in Norton’s table would be a column showing the thousands of dollars saved from the healthcare and insurance systems that would otherwise be spent on the thousands of unnecessary tests if NIPS were offered to all expectant women.


  1. […] the last post, I mentioned that one factor often left out in the discussion of prenatal genetic testing is the […]

  2. […] own research corroborating with clinical experience what Dr. Norton’s theoretical models demonstrated: that NIPS is an effective secondary screen, but not as a primary […]

  3. […] a statewide study of California’s screening program, researchers led by Mary Norton found that for women whose screen results showed an increased chance for having a child with Down […]

  4. […] should be given to the authors for asking these fundamental questions. One particularly, Mary Norton, has advised non-invasive prenatal screening laboratories. She, no doubt, understands how these […]

  5. […] the study’s finding could instead support the existing recommendations of using cfDNA as a secondary screen, not a primary […]

Leave a Reply

%d bloggers like this: