1st Trimester Screening plus 2nd Trimester QUAD Test

Background

In November, 2005, a large, multicenter study was reported in the New England Journal of Medicine in which several questions were examined regarding the best approach to be used in screening for the fetus with Down syndrome. One portion of the study examined the interaction between first-trimester screening techniques combined with the second-trimester QUAD screen. The authors of this study reported that the highest detection rates for Down syndrome occurred when a combination of first-and second-trimester tests were combined. This section explores each of these options.

Serum Integrated Screening

This technique does not require the patient to undergo a first-trimester ultrasound to measure the nuchal translucency. Since measurement of the nuchal translucency requires specific skills and certification by the physician or sonographer performing the test, it is problematic in that not all patients who would desire this test could have access to the ultrasound component. For this reason, the Serum Integrated Screening test was developed.

  

This test requires blood to be drawn between 11 weeks and 13 weeks 6 days to measure PAPP-A, followed by a second trimester blood sample in which the QUAD test is performed. From these two tests a risk for Down syndrome is provided to the patient in the second trimester. This combination of blood tests detected between 85% and 88% of fetuses with Down syndrome, with a 5% screen positive rate (screen-positive rate is the number of patients informed that their test is abnormal, thus a recommendation would be made to undergo an amniocentesis). The detection rate for Down syndrome was almost identical to the combined first-trimester test in which maternal serum PAPP-A, free beta hCG, and the nuchal translucency were measured (82-87%). The following table compares the detection rates for the first-trimester combined test and the Serum Integrated Screening test with a 5% screen positive rate. The table illustrates that the earlier in the first-trimester the blood is drawn, the higher the detection rate for Down syndrome.

 

Screening Test Used to Detect Down Syndrome

PAPP-A Blood Drawn at 11 weeks

PAPP-A Blood Drawn at 12 weeks

PAPP-A Blood Drawn at 13 weeks

Combined Test: Blood Test plus Nuchal Translucency Measurement

87%

85%

82%

Serum Integrated Test: PAPP-A + QUAD

88%

86%

85%

 

The authors' of this study did not analyze their data as a function of maternal age. This means that the detection rates for Down syndrome may have been lower for women less than 35 years of age compared to women 35 years of age and older. The benefit of this approach is that it is more cost-effective than first-trimester combined screening, but does not allow the patient to obtain early results regarding her risk for Down syndrome.

 

Fully Integrated Test

This test measures the nuchal translucency from the fetus and the PAPP-A from the maternal serum in the first-trimester of pregnancy, followed by the second-trimester QUAD test (15-18 weeks).

 

Using this approach, the detection rate for Down syndrome is between 94% and 96%. The disadvantage of this approach is that the patient must wait until the second-trimester to receive her results.

 

Screening Test Used to Detect Down Syndrome

PAPP-A Blood Drawn at 11 weeks

PAPP-A Blood Drawn at 12 weeks

PAPP-A Blood Drawn at 13 weeks

Combined Test: Blood Test (PAPP-A + B-hCG) plus Nuchal Translucency Measurement

87%

85%

82%

Fully-Integrated: (1st Trimester Nuchal Translucency and PAPP-A plus 2nd trimester QUAD serum screening test)

96%

95%

94%

 

 

Stepwise Sequential Screening

This approach allows the patient to realize the benefit from first and second trimester screening.

 

For example, all patients undergo the combined test (nuchal translucency plus PAPP-A and beta hCG). Those with a high risk for Down syndrome are notified of the test results and offered chorionic villus sampling. Patients with a negative test return at 15 weeks for the QUAD test. The final risk for Trisomy 21 is computed from the combination of first and second trimester tests and the final risk then given to those patients who tested negative following the first trimester test. Using this approach the detection rate for Down syndrome varies between 91% and 97%, with a screen positive rate of 4.9%.

Genetic Ultrasound

Irrespective of which of the tests a patient elects to undergo, the addition of Genetic Ultrasound increases the overall detection rate for Down syndrome, as well as other chromosomal defects. In addition, Genetic Ultrasound may identify other birth defects that the above tests may miss.

Which Test Should You Undergo?

The following graph, published in the British Medical Journal in 2001, illustrates that the most cost-effective screening test for society for detection of Down syndrome involves first-trimester screening. Any test above the blue line is less cost-effective than those on the blue line.

 

Your selection of a test specifically for you depends upon your needs, the affordability of the testing scheme you choose, and what you would do if the screening tests were abnormal. Lets examine several scenarios. In a recent study in which over 1,000 British women were interviewed, the majority selected a first-trimester screening option.

Scenario 1: If personal cost were an issue, then the FULLY INTEGRATED test would be the best option. You would not have to pay for a first-trimeter ultrasound or the free-beta hCG blood test. The only problem would be that if the final test were abnormal, you would undergo an amniocentesis after 16 weeks. However, this is not such a bad option since most patients in the United States undergo genetic amniocentesis as their first option. The only question that you would want to ask your health care provider is the detection rate for this test for your specific age, as well as the screen-positive rate. If you are younger than 35, the detection rate for Down syndrome may be lower. If you are over 35 the detection rate for Down syndrome may be higher, with a higher screen-positive rate. In another study of women in the United States, 95% found the integrated serum screening as an option they would consider. In addition, this approach detects over 90% of fetuses with Trisomy 18, a lethal chromosomal defect.

Scenario 2: If personal cost was not a consideration, then STEPWISE SEQUENTIAL SCREENING plus Genetic Ultrasound has the highest detection rate for Down syndrome. The advantage of this approach is that if there is a high risk for Down syndrome discovered in the first-trimester, then the patient is offered chorionic villus sampling. If the risk is not high, then the second trimester QUAD test is offered, coupled with a Genetic Ultrasound. If the risk, following these tests is low, then the risk for Down syndrome has been reduced by over 97%. If, however, the test is positive, then the patient is offered genetic amniocentesis.