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Triple test
AFP Maternal
Quad Screen
4-marker screen
Nome formal
Triple Screen [with AFP (alpha-fetoprotein), hCG (human chorionic gonadotropin) and uE3 (unconjugated estriol)]; Quadruple Screen [with the addition of inhibin A]
Este artigo foi revisto pela última vez em
Este artigo foi modificado pela última vez em 10 de Julho de 2017.
At a Glance
Why Get Tested?
To assess the risk of carrying a fetus with abnormalities, such as Down syndrome, trisomy 18 (Edward's syndrome), and open neural tube defects during the second trimester of pregnancy
When To Get Tested?
Women in the 15th to 20th week of pregnancy
Sample Required?
A blood sample drawn from a vein in the arm
Test Preparation Needed?
What is being tested?
The triple screen is a group of three tests that are used to screen pregnant women in the second trimester of pregnancy. The quad screen adds a fourth test to the group. Each test that is performed measures a different substance found in the blood: AFP, hCG, unconjugated estriol, and with the quad – inhibin A. The newest marker, inhibin A, increases both the sensitivity and specificity of the screen.

  • Alpha-fetoprotein (AFP) is a protein produced by fetal tissue. During development, AFP levels in fetal blood and amniotic fluid rise until about 12 weeks, and then levels gradually fall until birth. Some AFP crosses the placenta and appears in the maternal blood.
  • Human chorionic gonadotropin (hCG) is a hormone produced by the placenta. Levels in maternal blood rise for the first trimester of pregnancy and then fall to less than 10% by the end of pregnancy.
  • Unconjugated estriol (uE3) is a form of estrogen that is produced by the fetus through metabolism. This process involves the liver, adrenals, and the placenta. Some of the unconjugated estriol crosses the placenta and can be measured in the mother’s blood. Levels rise around the 8th week and continue to increase until shortly before delivery.
  • Inhibin A is a hormone produced by the placenta.  Inhibin is a dimer (has 2 parts) and is sometimes referred to as DIA or dimeric inhibin A. Levels in maternal blood decrease slightly from 14 to 17 weeks gestation and then rise again.

In pregnancies where the fetus is carrying the chromosomal defect that results in Down syndrome (trisomy 21), the levels of AFP and unconjugated estriol tend to be low and hCG and inhibin A levels high.

In pregnancies where the fetus has trisomy 18, unconjugated estriol and hCG levels are low and AFP levels can be variable.

A baby with an open neural tube defect has an opening in its spine, head, or abdominal wall that allows higher-than-usual amounts of AFP to pass into the mother’s blood. The other markers are not used in the evaluation of risk for carrying a fetus with a neural tube defect.

How is the sample collected for testing?

Blood is drawn from a vein in your arm. All four tests (AFP, hCG, unconjugated estriol, and inhibin A) can be done on the same tube of blood.

Is any test preparation needed to ensure the quality of the sample?

No test preparation is needed.
Accordion Title
Common Questions
  • How is it used?
    The triple or quad screen is used as a screening test in the second trimester of pregnancy. It is ordered to help evaluate the risk that a fetus has certain abnormalities, including Down syndrome (trisomy 21) and neural tube defects such as spina bifida or a condition called anencephaly.

    These tests have been established as a triple or quad screen because their power lies in their use together. A mathematical calculation involving the levels of these 3 or 4 substances (AFP, hCG, unconjugated estriol, and, sometimes, inhibin A) and considerations of maternal age, weight, race, and diabetic status are used to determine a numeric risk for Down syndrome and for a few other chromosomal abnormalities such as trisomy 18 in the fetus. This risk is compared with an established cut-off. If the risk is higher than the cut-off value, then it is considered positive or increased.

  • When is it ordered?
    The test is usually ordered between the 15th and 20th weeks of pregnancy.
  • What does the test result mean?
    The interpretation of a test result should be provided by a genetic counselor or clinician who can explain the meaning of the results and offer choices about follow-up. Screens are not diagnostic of a fetal abnormality; they indicate a normal or increased risk. If a screen is positive, more definitive tests are needed to determine and confirm a diagnosis. These include high-resolution ultrasound and perhaps amniocentesis followed by chromosome analysis. These follow-up tests are used to help women and their doctors make decisions about the management of their pregnancies.
  • Is there anything else I should know?
    Not all fetal abnormalities will give positive test results. Of all women who have positive triple or quad screening results, only a very small number of them have babies who actually have a neural tube defect or chromosomal abnormality.

    The test result is also very dependent on accurate determination of the gestational age of the fetus. If the gestational age of the fetus has not been accurately determined, the results may be either falsely high or low.

    In multiple gestation pregnancies, calculation of the risk of Down syndrome or trisomy 18 is difficult. For twin pregnancies, a “pseudorisk” can be calculated comparing results to normal results in other twin pregnancies. For higher gestation pregnancies, risk cannot be calculated from these tests.

    Evaluation of the risk of open neural tube defects in twin pregnancies can be determined, although it is not as effective as in singleton pregnancies.

  • What is Down syndrome?
    Down syndrome (DS) is a chromosomal abnormality, also called trisomy 21, which affects about 1 in 800 live births. Patients with DS have an extra copy of part or all of chromosome 21. Most affected children have some retardation of growth and development. The risk of carrying a fetus with Down syndrome increases with the mother’s age, especially in women over 40 years old. For more information, visit the National Down Syndrome Society.
  • What is a neural tube defect?
    Neural tube defects are serious birth defects: the brain, spinal cord, or their coverings do not develop completely. There are 3 kinds of neural tube defects:

    • Anencephaly: incomplete development of the brain and the skull.
    • Encephalocele: a hole in the skull through which brain tissue protrudes.
    • Spina bifida: the most common neural tube defect, in which the spine does not close properly during early pregnancy. (For more information on spina bifida, visit the Spina Bifida Association of America.)
  • What is trisomy 18?
    Trisomy 18 or Edwards Syndrome is a condition in which there are 3 copies of chromosome 18. The risk of carrying a fetus with trisomy 18 also increases with maternal age. Trisomy 18 is associated with multiple abnormalities and is usually fatal, with live-born infants rarely living beyond one year of age. The frequency of this abnormality is much less than Down syndrome, occurring in only 1 in 3000 live births. For more information, see the Trisomy 18 Foundation website.
  • What can I do to help prevent formation of a neural tube defect?
    The U.S. Public Health Service recommends that all women of childbearing age should take 0.4 mg of folic acid daily.
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