Why so many Down syndrome screening tests?

Throughout pregnancy, women have to make lots of decisions.  Two of those are “Do I want to have a screening test to see if my baby has an increased risk of Down syndrome?” If the answer to that is yes then the logical next question would be “What tests can I choose from?”  That is not an easy question for most women to answer without some guidance from their doctors and it’s not easy for many doctors to help provide that guidance.  Why?  Simply put, there are many tests from which to choose.

Let’s be clear on an important concept up front.  Screening tests are not diagnostic tests.  A test that screens for Down syndrome doesn’t identify if a baby has Down syndrome; it identifies babies that are at increased risk of having Down syndrome.  Women with abnormal or positive screening test results can undergo additional tests that can be used to confirm if their baby does or does not have Down syndrome but the screening tests cannot do that. 

All Down syndrome screening tests require a blood sample from the mother.  Biochemical markers in the blood are measured in the laboratory and the results used to calculate the risk that the baby has Down syndrome.  Those biochemical markers include:

  • Alpha-fetoprotein (AFP)
  • Human chorionic gonadotropin (hCG)
  • Unconjugated estriol (uE3)
  • Dimeric inhibin A (DIA)
  • Pregnancy-associated plasma protein A (PAPP-A)

Some screening tests also include the measurement of nuchal translucency (NT) that is obtained by an ultrasound scan of the fetus.  The NT is the width of the space between the spine and skin at the fetus’ neck.

All together, these 5 biochemical markers and 1 ultrasound marker can be used in various combinations to create the different Down syndrome screening tests.  There are 6 to choose from:

Table

Some, like the Triple (3 markers) and the Quad (4 markers) tests are performed on a blood sample collected during the 2nd trimester and don’t require the NT ultrasound measurement.  The Combined test (so called because it “combines” the biochemical and ultrasound tests) is performed only in the 1st trimester.  All the other tests use two different blood samples (one collected from the mother in the 1st and the other in the 2nd trimester) and may or may not also include the NT measurement.  No wonder this is confusing!

Why are there so many different tests?  Two reasons: first because Down syndrome screening tests evolved over many decades (and continues to evolve) and second because the medical community is often slow to change its habits.

In the not so distant past, one “test” was used to determine Down syndrome risk: the age of the mother.  We actually still use the mother’s age in determining Down syndrome risk.  The risk of having a baby with Down syndrome increases as the age of the mother increases.  We now use this age-based risk as a starting point; a risk that is the modified by the results of the screening test.

In 1988, the Triple test was introduced as a way to adjust the age-based risk using the measured concentrations of AFP, hCG, and uE3 in the mother’s blood.  A few years later, the Triple test turned it into the Quad test when it was discovered that the addition of DIA to the Triple test improved the Down syndrome detection rate.  However, the Triple test didn’t disappear and labs simply continued to offer it as well as the Quad test.

The Combined test appeared in 1999 and had a Down syndrome detection rate that was similar to that of the Quad test.  Unlike the Quad test, however, the Combined test provided women a way to get Down syndrome screening test results many weeks sooner.  So, it was added to the menu along with the Triple and the Quad tests.

It wasn’t long before someone thought to “integrate” the Combined test with the Quad test and thus was born the Integrated test.  And, for those women without access to the specialized equipment needed to perform the ultrasound NT measurement, the Serum Integrated test required only the mother’s blood samples to be tested.  While both of these tests provide the greatest Down syndrome detection rates, the need for the second blood sample collected in the 2nd trimester means that early risk-assessment is not possible.

And finally, the Sequential test developed as a modification of the Integrated test.  While the Integrated test delivers its results in the 2nd trimester after all testing has been completed, the Sequential test offers women results in the 1st trimester only if the risk of Down syndrome is very high.  In the absence of a high risk, results are provided only after the test is completed in the 2nd trimester.

Because it’s a test with a lot of history and experience behind it and because it’s well known to the doctors that order Down syndrome screening tests, the Quad test still leads the pack in terms of test usage.  The Triple test is slowly falling out of favor (as it should) and the Combined, Integrated, and Sequential tests are gaining more traction, albeit slowly.  As I said earlier, old habits are slow to change.

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