Adam Wolfberg’s research says don’t offer new testing for Down syndrome to all moms

The Justification for Offering NIPS to All Patients

The basis for offering NIPS to all patients

Actually, Adam Wolfberg recently said just the opposite. But, Wolfberg’s own research doesn’t support his recommendation. 

The newest form of prenatal testing for Down syndrome is based on the mother’s blood to identify cell free DNA. It tests whether the fetus has an extra chromosome, typically Down syndrome, or, more rarely, Trisomy 18 or 13. The American College of Medical Genetics and Genomics pointedly referred to this testing as “Non-Invasive Prenatal Screening” (NIPS) to emphasize it still is not a diagnostic test.

When Sequenom, a publicly-traded company, introduced its version of NIPS in 2011, Wolfberg was ho-hum: “I don’t expect much to change when the test becomes available.” But then, just four months later, he quoted approvingly that “These tests may completely revolutionize what we do.”

At that time, in 2012, Wolfberg acknowledged that the evidence was limited to studies of populations of “high-risk” women, i.e. women already at an increased chance for having a child with Down syndrome. To figure out if these tests would work on low-risk women, Wolfberg concluded it would take “time, big studies, and probably a good deal of prescribing the tests ‘off-label.’”

“Off-label,” means not according to recommended uses. And, this is exactly what Wolfberg now admits to doing just a year after recognizing the need for big studies and despite his own study.

In his recent post, Wolfberg criticizes the “establishment”—the professional medical societies for obstetrics and prenatal diagnosis—for pushing back against offering NIPS to all expectant women, low and high risk. He is responding to an article published in the New England Journal of Medicine (discussed further at this post). That article cautioned against NIPS “drifting into routine practice ahead of the evidence.” Wolfberg instead calls for just this sort of drift despite his own evidence.

In June 2012, Wolfberg was part of a group of researchers that studied whether combining NIPS with a first-trimester ultrasound yielded more reliable results for detecting pregnancies positive for Down syndrome. The study ran for seven months, concluding in January of this year and being presented at the June 2013 conference for the International Society for Prenatal Diagnosis. This makes Wolfberg’s research some of the most recent on the utility of NIPS in the general population. What did Wolfberg and his team find?

The study consisted of 1,228 women. Each were offered first-trimester ultrasound testing, which can have a correlation with the fetus having Down syndrome, and NIPS testing. Of the 1,228 who had the ultrasound, 1,184, or 96.4%, had an ultrasound that did not indicate Down syndrome. Of these low-risk patients, 1,153 accepted NIPS. Only 5 NIPS tests returned a positive result, making 99.5% of the NIPS tests negative. Now, how many of those 5 were actually pregnant with a child with Down syndrome? One. That’s right. Four of the five positive NIPS results of the 1,184 women screened as low risk were false positives. Put another way, 80% of the positive NIPS results in low-risk women were false positives.

Turning to those women with an ultrasound that showed a higher chance, here’s what the study found for them.

There were only 44 women out of the 1,228 patients with an ultrasound indicating Down syndrome. Only 3 of these high-risk patients had NIPS testing: 2 were positive for Down syndrome and one had a false negative for Trisomy 13—meaning the NIPS test came back negative, but the pregnancy was actually carrying a fetus with Trisomy 13. So, of the 3 NIPS tests done of the high-risk population, one-out-of-three was a false negative.

In his column justifying offering NIPS to every patient, he describes the NIPS research as “nothing short of astounding: near-perfect risk assessment of Down syndrome … with a false positive rate significantly below 1 percent.” That is not what his research found. In the low-risk population, 4-out-of-5 positive NIPS tests were false positives. That is not near-perfect.

Why then is Wolfberg plowing ahead, ignoring the professional standard of care and admitting to and arguing for the offering of NIPS testing to all patients? His own research does not even support his recommendation.


  1. Because it is a population screening technique to reduce the birth prevelance of Down syndrome and it uses a “drag net” to get as many as possible. It’s only ever been about reducing birth prevalence, the rest is hyperbole.

    • In my opinion, the false positive rate is tolerable. These results are not presented as gospel, and most people receiving such news will be offered- or ask to have- more diagnostic testing, i.e. amniocentesis or CVS. You act as if people are just waiting for any excuse to absort their unborn baby. That is quite a stretch. It is an agonizing decision to make, not something that anyone wishes to be in the position of having to contemplate.

      I can understand distaste for “wiping out” the population of people with Down Syndrome. But, ultimately, these tests allow those decisions to come earlier in the pregnancy rather than later, at a point when fetal development has not accelerated. From my point of view, that is a more humane time to terminate if you’re going to terminate. While you would not abort period, many parents do not share your view, and this technology probably makes it easier on everyone involved, including the fetus.

      • As a population screening tool it targets a particular group, with the result that it reinforces negative social attitudes towards that group. That is one of the differences of such eugenics programmes, they devalue the lives of all people living with disability. That is why it is in conflict with disability rights. Other groups of human beings are targeted in this way.

        Bear in mind that women being offered antenatal tests have wanted pregnancies, so we are seeing a change here to selecting the type of child. Women who don’t want to be pregnant don’t go to Obstetricians for pregnancy care. The inherent dignity and worth of the wanted child doesn’t change with a diagnosis and neither should the support of that wanted pregnancy.


  1. […] a previous post, I addressed the advocacy by Dr. Adam Wolfberg for offering NIPS to all expectant women, contrary […]

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