The Quad Test

2000, Volume 11, Number 1


David F. Keren, M.D.

What is the new “Quad Test” for prenatal screening?

In the past month, I have received several questions about the new Quad Test for prenatal screening. It is likely to replace the current standard, the Triple test.

The Triple Test has been the main prenatal screening test for detecting women who are at increased risk for carrying a fetus with a neural tube defect, Down syndrome (Trisomy 21), or Trisomy 18 (Edward’s syndrome). It consists of assaying the maternal blood during the second trimester for alpha-fetoprotein, human chorionic gonadotropin (hCG), and unconjugated estriol. The Triple test is far from perfect. But, it is able to detect about 60-65% of Down syndrome cases and about 80% of neural tube defects. We follow-up all screen positive cases as a quality assurance review annually.

Many of the concerns that individuals have about the triple test relate to the false positive rate of the test. Because the risk of Down syndrome increases with the age of the mother, the false positive rate increases with the age of the population being tested. Typical false positive rates using a cut-off of around 1:270 range from 7-9%. In our annual follow-up studies, and in published literature, the rate of chromosomal abnormality detection from our most recent evaluation was 1 per 63.2 screen positive samples with a false positive rate of 7.4%.

New methods that attempt to increase the detection rate and/or decrease the false positive rate appear monthly in the scientific literature. Earlier attempts at improving the detection, such as the addition of alpha hCG have not proven to be useful. However, the addition of Inhibin A to the triple test in several research studies has consistently increased the detection rate an average of 8%. Unfortunately, the assays for Inhibin A have been available only in a research mode. A few commercial assays for Inhibin A suffered from poor reproducibility, thereby obviating their use for prenatal screening.

Fortunately, a promising new Inhibin A assay is now available that soon should attain approval by the Food and Drug Administration. We are evaluating this new assay and anticipate its availability at Warde Medical Laboratory by this summer.

In the interim, for those wishing to offer their patients the Quad Test, Warde Medical Laboratory has arranged with Dr. Cannick (the originator or the Quad Test), to have the Inhibin A assays performed in his laboratory. Please contact our Client Services Department at 800-876-6522 for details on ordering it. When the test is available in-house, we will send a bulletin to you and publish information about the Quad Test on our website (