New choices in prenatal screening for Down syndrome
A FASTER trial investigator discusses first-trimester combined screening, integrated screening, and findings from the trial
TABLE
5 screening approaches: What the SURUSS and FASTER trials reveal
| TEST | NUCHAL TRANSLUCENCY MEASURED? | METHOD OF PRENATAL DIAGNOSIS | DETECTION RATE (%) AT 1% FALSE-POSITIVE RATE | DETECTION RATE (%) AT 5% FALSE-POSITIVE RATE | FALSE-POSITIVE RATE* (%) TO ACHIEVE: | |||
|---|---|---|---|---|---|---|---|---|
| SURUSS | FASTER | SURUSS | FASTER | 85% DETECTION | 95% DETECTION | |||
| 2nd-trimester triple marker | No | 2nd-trimester amniocentesis | 56 | 45 | 77 | 70 | 14 | 32 |
| 2nd-trimester quad marker | No | 2nd-trimester amniocentesis | 64 | 60 | 83 | 80 | 7.3 | 22 |
| 1st-trimester combined | Yes | 1st-trimester chorionic villus sampling | 72 | 73 | 86 | 87 | 3.8 | 18 |
| Serum integrated test | No | 2nd-trimester amniocentesis | 73 | 73 | 87 | 88 | 3.6 | 15 |
| Full integrated test | Yes | 2nd-trimester amniocentesis | 86 | 88 | 94 | 96 | 0.6 | 4 |
| FASTER=First- and Second-Trimester Evaluation of Risk[1]; SURUSS=Serum, Urine, and Ultrasound Screening Study.2 | ||||||||
| *Based on data from FASTER trial only. | ||||||||
Clinical considerations
Integrated screening
A number of considerations are important:
Tell the patient screening for neural tube defects is included in the integrated test, since it spans the first and second trimesters and includes AFP as one of the markers measured. Thus, women having the integrated test will also be screened for open spina bifida and anencephaly, in addition to Down syndrome.
Hold individual measurements until all results are in. First-trimester nuchal translucency and PAPP-A results are the first to become available. After these tests are performed, a waiting period of about 2 to 5 weeks is required to allow for second-trimester testing, tabulation, and integration into a single risk estimate.
In the case of ultrasound imaging, it is important for the sonographer to explain what is being measured without conveying special import regarding the nuchal translucency measurement—whether it is large or small. If asked, the sonographer should explain that nuchal translucency is only 1 of 6 measures that will determine the patient’s risk.
Advise the patient that definitive diagnosis will not occur until the second trimester. Because the integrated test is reported after the second-trimester serum sample is drawn and assayed, any follow-up diagnostic testing will not be available any sooner than is typical for second-trimester screening (ie, 16–18 gestational weeks).
A very large nuchal translucency measurement may be cause for concern and points to the need for early diagnosis. If a woman having the integrated test is found to have a nuchal translucency measurement of 3 to 4 mm or more (or any cystic hygroma), a clinically reasonable strategy is to offer immediate prenatal diagnosis by CVS rather than continue with the screening test.
Nuchal translucency values of 3 or 4 mm or more are seen in fewer than 1% of women scanned, and are associated with a very high risk of fetal aneuploidy and adverse pregnancy outcomes.
If nuchal translucency ultrasound is not available in your region, the integrated test using serum markers will provide better screening performance than any other serum-only test.
First-trimester combined screening
Offer it as early as possible. The benefit of first-trimester screening is the prospect of early prenatal diagnosis. Therefore, the earlier the test is offered within the accepted time frame of 11 to 13 completed weeks, the more apparent the benefit.
Early screening requires nuchal translucency measurement. First-trimester screening involves the measurement of serum analytes and ultrasound measurement of nuchal translucency. Serum markers without nuchal translucency or nuchal translucency without serum markers provide insufficient screening. If nuchal translucency is unavailable, offer the serum-only form of the integrated test or the second-trimester quad marker test.
Early diagnosis is requisite. Patients who are screen-positive in the first trimester should have CVS as an option for the earliest possible diagnosis. If amniocentesis at 15 weeks or beyond is the only invasive diagnostic procedure available, first-trimester combined screening is not appropriate.
An additional screen for neural tube defects is needed. First-trimester combined screening does not test for risk of open neural tube defects. Most commonly, a second-trimester serum AFP measurement is recommended for all women who have had first-trimester screening. Alternatively, a second-trimester ultrasound scan for fetal anomalies is highly indicative of neural tube defects if it includes the cranial lemon and cerebellar banana signs.
Even newer choices
Within the past year, 2 new screening methods have been proposed: sequential testing and contingent testing.15,16 They are essentially hybrids of the first-trimester and integrated tests. Both identify a very small, very high-risk group based on first-trimester nuchal translucency and serum markers. This group (eg, women having a risk of 1 in 25 and higher) would account for less than 1% of the total screened population and would ultimately be found to have more than 50% of Down syndrome cases.
In sequential testing, all women whose risk is less than the high-risk cutoff (eg, a possible cutoff of less than 1 in 25 or higher) would go on to have the full integrated test. In contingent testing, a second group would be identified as very low-risk based on first-trimester markers (eg, a possible risk cutoff of 1 in 2,000 or lower). Such low-risk women would have a small chance of having their results become high-risk based on the completed integrated test; therefore, they would be identified as screen-negative early and would not have to go on to integrated testing. In contingent testing, only the intermediate group (eg, those between, say, 1 in 25 and 1 in 2,000) would complete the integrated test.
