Topic: Information Point: Screening Copy

Screening Tests for Down syndrome

First Trimester Screening Tests

The patient in this video had a first trimester
screening involving the assessment of the levels of one or more analytes
(PAPP-A and typically free beta HCG) and a measure of “nuchal translucency”
through the use of ultrasound. The nuchal translucency is simply a normal
aspect of the fetal anatomy, which is determined in the neck and under a very
carefully controlled set of anatomic and technical circumstances. The
sensitivity of first trimester nuchal translucency in conjunction with analytes
is thought to be in the range of 82 to 87%, set for a false positive rate of 5%
(ACOG, 2016).

Non-Invasive Prenatal Screening Tests

There are also newer non-invasive prenatal screening tests
that can be done after 9 or 10 weeks. These tests have the highest detection
rates among all screening tests for Down syndrome, Edward syndrome, Patau
syndrome, and the sex of the fetus, specifically for women who have already
learned their pregnancy has greater chances for a genetic condition. These
tests look at pieces of genetic material from the placenta in the woman’s blood
to find chromosome conditions. These tests are still considered screening tests
because false negatives and false positives do occur. The accuracy is improved
but varies depending on the condition, so diagnostic testing is recommended for
patients who want to know with certainty. In addition, these tests do not
detect many other genetic conditions or factors that might be present in a
pregnancy. These tests also might not be as reliable in some situations, such
as with twins or multiples. ACOG (2016) has thus noted that pregnancy
management decisions should not be made on the basis of these screening tests
alone.

Testing companies note that non-invasive prenatal screens have both high levels of sensitivity and specificity (> 99%).  However, sensitivity and specificity are not the same thing as positive predictive value (PPV), which is an estimation that the baby actually has the condition being tested for, and is of course, the primary screening result patients have asked to know. To see how positive predictive value can vary by both condition and maternal age, you can refer to the NIPS PPV calculator: https://www.perinatalquality.org/Vendors/NSGC/NIPT/

For example, for a sensitivity set at 99.2% and a specificity
set at 99.91% for a 30-year-old patient whose NIPS test is positive for Down
syndrome, the PPV is calculated at 61%.  This
means that there is a 61% chance that the fetus actually does have Down
syndrome.  Further diagnostic testing is
available to determine the actual presence of the condition. PPV varies with
maternal age and tested condition, and PPV is generally less for younger
patients and for rarer conditions.

Reference:

American College
of Obstetricians and Gynecologists (2016, May). 
Practice bulletin 162: Prenatal
diagnostic testing for genetic disorders. 
Washington, DC: American College of Obstetricians and Gynecologists.

For accessible explanations
of prenatal screening and ultrasound for patients, see the following online
resources:

  1. Maternal Serum Screening (MSS) by the Washington State Department of Health and Genetic Support Foundation:  https://youtu.be/TOdEbBlhIgU?list=PL82Z-swK0-4lq6SaKF_lCRquP15gJ3VG0               
  2. Ultrasound in the Second Trimester by the Washington State Department of Health and Genetic Support Foundation: https://youtu.be/b9Ug23X0voc?list=PL82Z-swK0-4lq6SaKF_lCRquP15gJ3VG0 

For a discussion of cell-free DNA screening suitable for
both medical providers and patients, you can view this short video from the
Washington State Department of Health and the Genetic Support Foundation.

Prenatal Cell-Free DNA Screening (cfDNA Screening):  https://www.youtube.com/watch?time_continue=64&v=e86_l_UqecU&feature=emb_logo