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Triple Screen or Quad Screen

Also known as: Triple test; AFP Maternal; Maternal serum AFP; msAFP; Quad Screen; 4-marker screen
Formal name: Triple Screen [with AFP (alpha-fetoprotein), hCG (human chorionic gonadotropin) and uE3 (unconjugated estriol)]; Quadruple Screen [with the addition of inhibin A]
Related tests: hCG; Estrogen; First Trimester Down Syndrome Screen; Amniotic Fluid Analysis; Chromosome Analysis

Were you looking for AFP tumor markers, used to help diagnose and monitor therapy for certain cancers of the liver, testes, or ovaries?

At a Glance

Why Get Tested?

To assess the risk of carrying a fetus with abnormalities, such as Down syndrome, Edwards syndrome (trisomy 18), and open neural tube defects during the second trimester of pregnancy

When to Get Tested?

Women in the 15th to 21st week of pregnancy

Sample Required?

A blood sample drawn from a vein in the arm

Test Preparation Needed?

None

The Test Sample

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 fourth marker, inhibin A, increases both the sensitivity and specificity of the screen for Down syndrome (trisomy 21).

  • 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. An AFP test may be performed by itself to test for neural tube defects, especially when risk for chromosomal abnormalities (Down syndrome and Edwards syndrome) have already been assessed using First trimester screening.
  • Human chorionic gonadotropin (hCG) is a hormone produced by the placenta. Levels in maternal blood rise for the first trimester of pregnancy and then decrease during the remainder of the 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.

Results of each of these tests are considered together to determine the risk that the fetus has a chromosomal defect or an open 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.

NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

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

No test preparation is needed.

The Test

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), Edwards syndrome (trisomy 18), 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, family history, weight, race, and diabetic status are used to determine a numeric risk for Down syndrome and for a few other chromosomal abnormalities such as Edwards syndrome (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 a positive screening test or increased risk exists for carrying a fetus with one of the discussed abnormalities.

An AFP test may be performed by itself and not as part of a triple or quad screen, especially when First Trimester Screening has already been used to assess the risk for chromosomal abnormalities. The AFP is used to help determine the risk of neural tube defects.

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When is it ordered?

The test is usually ordered between the 15th and 21st weeks of pregnancy.

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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. It is important to remember that screening tests are not diagnostic of a fetal abnormality; they indicate a normal or increased risk. 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.

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 Edwards syndrome (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.

If a screen is positive, tests that are more definitive 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.

The triple screen can detect about 70% of fetuses affected by Down syndrome while the quad screen can detect about 80%. Either screen can detect about 75-80% of those affected with spina bifida and 95% cases of anencephaly.

Not all fetal abnormalities will give positive test results.

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Is there anything else I should know?

The test result is 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 Edwards syndrome 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.

If you have had a First Trimester Screen, then a triple/quad screen (second trimester screening) is not performed because the risks for Down syndrome and Edwards syndrome have already been assessed. However, if you and your doctor wish to use the results of both first and second trimester screening to assess the risk of chromosome abnormalities, then integrated or sequential screening may be employed. For more on these, see the article on First Trimester Screening.

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Common Questions

1.  What is Down syndrome?

Down syndrome (DS) is a chromosomal abnormality, also called trisomy 21, that affects about 1 in 800 live births. People 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.

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2.  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 three 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.)

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3.  What is Edwards syndrome?

Edwards syndrome (trisomy 18) is a condition in which there are 3 copies of chromosome 18. The risk of carrying a fetus with Edwards syndrome also increases with maternal age. Edwards syndrome 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 3,000 live births. For more information, see the Trisomy 18 Foundation web site.

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4.  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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Article Sources

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

Sources Used in Current Review

Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. Burtis CA, Ashwood ER, Bruns DE, eds. St. Louis: Elsevier Saunders; 2006, Pp 2167-2173.

(April 9, 2010) Singh D. Prenatal Diagnosis for Congenital Malformations and Genetic Disorders. Medscape article. Available online at http://emedicine.medscape.com/article/1200683-overview through http://emedicine.medscape.com. Accessed September 2010.

(2008 November). Maternal Blood Screening for Birth Defects. March of Dimes [On-line information]. Available online at http://www.marchofdimes.com/professionals/14332_1166.asp through http://www.marchofdimes.com. Accessed September 2010.

Clarke, W. and Dufour, D. R., Editors (2006). Contemporary Practice in Clinical Chemistry. AACC Press, Washington, DC, Pp 416-418.

(September 2009) American Pregnancy Association. Triple Screen Test: Multiple Marker Screen and Quad Screen. Available online at http://www.americanpregnancy.org/prenataltesting/ through http://www.americanpregnancy.org. Accessed September 2010.

(June 30, 2010) Mayo Clinic. Quad Screen. Available online at http://www.mayoclinic.com/health/quad-screen/MY00127 through http://www.mayoclinic.com. Accessed September 2010.

Trisomy 18 Foundation. Available online at http://www.trisomy18.org. Accessed September 2010.

Barclay, L. and Lie, D. (Reviewed 2008 January 3). New Guidelines Recommend Universal Prenatal Screening for Down Syndrome. Medscape Medical News [on-line CME]. Available online at http://www.medscape.com/viewarticle/550256 through http://www.medscape.com. Accessed September 2010.

Sources Used in Previous Reviews

Thomas, Clayton L., Editor (1997). Taber's Cyclopedic Medical Dictionary. F.A. Davis Company, Philadelphia, PA [18th Edition].

Pagana, Kathleen D. & Pagana, Timothy J. (2001). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO.

Shirley L. Welch, PhD, DABCC, FACB. Director of Chemistry, Kaiser Permanente, NW, Portland, OR.

Barkai G, Goldman B, Ries L, Chake R, Zer T, Cuckle H. Prenatal Diagnosis 13: 843-850 (1993).

Lambert-Messerlian GM, Saller DN, Tumber MB, French CA, Peterson CJ, Canick JA. Prenatal Diagnosis 18: 1061-1067 (1998).

Cuckle H, et al. Prenatal Diagnosis 10: 71-77 (1990).

(2006 January). Healthy Pregnancy, The Second Trimester. WomensHealth.gov [on-line information]. Available online at http://www.womenshealth.gov/pregnancy/pregnancy/2nd.cfm through http://www.womenshealth.gov. Accessed 2/25/07.

Barclay, L. and Lie, D. (2007 January 4). New Guidelines Recommend Universal Prenatal Screening for Down Syndrome. Medscape Medical News [on-line CME]. Available online at http://www.medscape.com/viewarticle/550256 through http://www.medscape.com. Accessed 2/25/07.

Pagana, Kathleen D. & Pagana, Timothy J. (2007). Mosby's Diagnostic and Laboratory Test Reference 5th Edition: Mosby, Inc., Saint Louis, MO. Pp. 47-49, 416-419, 651-652.

Ashwood, E. et. al., Reviewed (2007 January). Prenatal Screening and Diagnosis. ARUP Consult [on-line information]. Available online at http://www.arupconsult.com/Topics/Perinatal_Disease/Prenatal_Screening_and_Diagnosis.html through http://www.arupconsult.com. Accessed 2/17/07.