Category Archives: Nuchal Translucency

Nuchal Translucency

Choosing a screening test for Down syndrome


Last month I wrote about the many different tests used for Down syndrome screening.  Today, there are 6 different screening tests that a woman can choose from should she opt for any testing at all.  Selecting one can't be an easy task for most women and, given the relatively short time that most physicians have to spend with patients today, many simply follow their doctor's advice and don't truly understand their options.

The choice of which Down syndrome screening test to have depends on the answers to a few questions:

  • When during pregnancy does the patient first seek obstetrical care for her pregnancy?

Some screening tests are performed in the first or the second trimester while other tests are performed in both first and second trimesters.  If a woman first seeks obstetrical care after the 14th week of pregnancy then only the second trimester tests can be offered.  That means either the Triple or the Quad tests.  If she presents earlier then all screening tests can be considered.

Nuchal translucency (NT) is an ultrasound measurement of space under the skin behind the fetal neck and is performed only during the first trimester.  An increased NT is strongly associated with Down syndrome and other chromosomal abnormalities.  It's a component of the Combined test, the Integrated test, and the Sequential test.

Chorionic villus sampling (CVS) is the removal of a small piece of placental tissue in order to obtain fetal cells in order to obtain the fetal karyotype.  The karyotype will identify the number of chromosomes the fetus has inherited and is usually only performed after an abnormal Down syndrome screening test.  This procedure is performed in the first trimester because amniocentesis can't be performed this early in pregnancy.

If CVS is not available then options include the Integrated, the Triple, or the Quad test.  If the NT is not available then the choice of screening tests is limited to the Serum Integrated test, the Triple test, or the Quad test (the same is true if both NT and CVS are not available).

  • When does the mother want the results of the screening test?

If the woman wants the earliest assessment of the risk of carrying a fetus with Down syndrome then she should opt for the Combined test.  The test is performed only in the first trimester and results are available sooner than with any of the other test options.  However, the test doesn't perform as well as some of the other tests.  On average, the Combined test detects about 85% of all Down syndrome fetuses at a 5% false-positive rate.

If she's willing to wait until the second trimester for the test results then the best screening test is the Integrated test.  This test gives the highest Down syndrome detection rate (about 95%).  The test can also be performed without an NT (the Serum Integrated test) and will provide the same detection rate with a slightly higher false-positive rate.

If the patient desires early risk assessment but is willing to wait for test results if needed, then the Sequential test may be appropriate.  The Sequential test reports results in the first trimester only if the risk of having a Down syndrome fetus is very high.  If the risk is not high, then results are not reported until the second trimester test is completed.

The table below summarizes the performance of the 6 different Down syndrome screening tests.  The "detection rate" (DR) is the percentage of Down syndrome pregnancies that are correctly identified by the test and the "false positive rate" (FP) is the percentage of unaffected pregnancies identified as abnormal.

Performance of maternal serum screening tests

Selecting a test for Down syndrome screening doesn't have to be complicated.  Patient's should be informed about the pros and cons of each test (and screening tests in general).  It's often said that information is power and, when it comes to Down syndrome screening, women should be empowered to choose the test that is right for them.

      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.