Maternal serum triple or quadruple screen

The maternal serum triple test (triple screen) measures the amounts of alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and estriol (uE3) in your blood. When a test for inhibin A is added, it is called a quadruple screen. The amounts of these substances help estimate the risk that your fetus may have certain defects, such as Down syndrome, spina bifida, or anencephaly. This screening is usually done around 15 to 20 weeks of pregnancy.

Each substance tested in a triple or quadruple screen gives you different information about possible fetal problems. Together, these results give the best information. Substances tested are:

  • Alpha-fetoprotein (AFP), a substance naturally produced by the fetus's liver. The level of AFP in the mother's blood increases steadily during pregnancy.
    • An abnormally high AFP level can be a sign of a neural tube defect.
    • An abnormally low AFP level can be a sign of Down syndrome.
  • Human chorionic gonadotropin (hCG), a hormone produced by the placenta when a woman becomes pregnant. The level of hCG steadily increases during the first 8 to 12 weeks of pregnancy, typically peaks around the 10th week, and then gradually decreases. Abnormally high hCG can be a sign of Down syndrome.
  • Estriol, a form of estrogen that increases during pregnancy. It is produced in large amounts by the placenta. Estriol can be detected in the blood as early as the 9th week of pregnancy and continues to increase until delivery. Abnormally low estriol can be a sign of Down syndrome.
  • Inhibin A, a protein produced by the fetus and placenta. Abnormally high inhibin A can be a sign of Down syndrome.

When considering your triple or quad screen results, consider that this test only identifies chances of a possible problem, not a diagnosis of a problem. But it can help you decide whether to have diagnostic testing, such as an amniocentesis, that can tell you for certain whether a birth defect is present.

How accurate are triple and quadruple screen results?

With the triple or quad screen, there is a chance of getting a false-positive test result. This means that test result suggests a possible birth defect when one is actually not present. A false-positive test result is increasingly likely as you approach age 40. It can cause undue stress and lead to unnecessary invasive testing (such as amniocentesis).

Of women whose AFP level is high (suggesting a neural tube defect), only 1 in 16 to 1 in 33 actually has a fetus with this defect.1

Of all women who have positive triple screen results, the vast majority are actually carrying a healthy fetus. Similarly, negative test results can occasionally be wrong. But the triple screen does detect most Down syndrome fetuses, particularly in women who are older than 35. In this age group, at least 80% of fetuses that have Down syndrome are detected using triple or quadruple screen. The older you are, the more likely it is to be accurate.1

In one large study of more than 23,000 women, the quadruple screen detected almost 86% of all Down syndrome cases. Based on this study, the quadruple test is more likely to pick up Down syndrome and less likely to be false-positive than the triple screen.2


Your age and an accurate fetal age are necessary for interpreting serum screen results. If your test results are abnormal, your doctor may use a fetal ultrasound to make sure the fetal age, and therefore your screen results, are as accurate as possible. An ultrasound can also be up to 99% accurate in detecting cases of neural tube defects.1

If your serum screen estimates that your risk of carrying a fetus with Down syndrome is higher than the average risk for your age, you may choose to have amniocentesis. (Ultrasound can't detect all cases of Down syndrome.) Amniocentesis provides amniotic fluid that can be tested for Down syndrome and other chromosome abnormalities.


  1. Cunningham FG, et al. (2005). Prenatal diagnosis and fetal therapy. In Williams Obstetrics, 22nd ed., pp. 313–339. New York: McGraw-Hill.
  2. Benn PA, et al. (2003). Incorporation of inhibin-A in second-trimester screening for Down syndrome. Obstetrics and Gynecology, 101(3): 451–454.

Last Updated: November 28, 2008

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