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Second Trimester Maternal Serum Screening

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Also known as: AFP Maternal; Maternal Serum AFP; MSAFP; msAFP; Triple Screen; Triple Test; Quad Screen; Quadruple Marker Test; 4-marker Screen; Multiple Marker Test
Formal name: Maternal Serum Screen

Were you looking instead 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 a fetus having certain chromosomal abnormalities, such as Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18), and open neural tube defects, such as spina bifida

When to Get Tested?

Usually between the 15th and 20th weeks of pregnancy

Sample Required?

A blood sample drawn from a vein in your arm

Test Preparation Needed?

None

The Test Sample

What is being tested?

Maternal serum screening, or the multiple marker test, measures several substances in a blood sample in order to screen a pregnant woman in the second trimester of pregnancy. Evaluation of the pattern of results from measuring the level of these substances can be used to determine the risk that the fetus has a chromosomal abnormaility or neural tube defect. (For more detail, see the "What does the test result mean?" section.)

These substances include the following, listed below; when the first three substances are measured together, it is called a triple screen; when the fourth substance, inhibin A, is added, it is called a quad 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. With certain problems affecting a baby, an increased amount of AFP leaks into amniotic fluid and then into the mother's blood. As such, an AFP test is used to screen for neural tube defects such as spina bifida and may be performed as part of the triple or quad screen or by itself, especially when risk for chromosomal abnormalities (Down syndrome (trisomy 21) and Edwards syndrome (trisomy 18)) have already been assessed using First trimester screening. According to the American College of Obstetricians and Gynecologists (ACOG), the AFP test detects neural tube defects in 80% of the cases.
  • 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. In pregnancies where the fetus is carrying the chromosomal defect that results in Down syndrome, hCG tends to be high whereas in pregnancies where the fetus has the chromosomal defect that results in Edwards syndrome, hCG tends to be low.
  • 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. In pregnancies where the fetus has Down syndrome or Edwards syndrome, uE3 tends to be low.
  • Inhibin A is a hormone produced by the placenta. Inhibin is a dimer (has two 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. Levels tend to be high in pregnancies where the fetus has Down syndrome.

Including the fourth marker, inhibin A, increases both the sensitivity and specificity of the screen for Down syndrome. According to ACOG, the triple screen detects Down syndrome in 69% of the cases while the quad screen detects it in 81% of the cases.

It is important to remember, however, that screening tests are not diagnostic of a fetal abnormality; they indicate a normal or increased risk. Of all women who have positive screening results, only a very small number of them have babies who actually have a neural tube defect or chromosomal abnormality.

How is the sample collected for testing?

Blood is drawn from a vein in the arm. For the quad screen, 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

Common Questions

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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

Trisomy 18 Foundation. What is Trisomy 18? Available online at http://www.trisomy18.org/site/PageServer?pagename=whatisT18_whatis through http://www.trisomy18.org. Accessed February 2013.

March of Dimes. Birth defects: Down syndrome. Available online at http://www.marchofdimes.com/baby/birthdefects_downsyndrome.html through http://www.marchofdimes.com. Accessed February 2013.

Centers for Disease Control and Prevention. Folic Acid Recommendations. Available online at http://www.cdc.gov/ncbddd/folicacid/recommendations.html through http://www.cdc.gov. Accessed February 2013.

Centers for Disease Control and Prevention. Birth Defects, Diagnosis. Available online at http://www.cdc.gov/ncbddd/birthdefects/diagnosis.html through http://www.cdc.gov. Accessed February 2013.

ACOG. Screening for Birth Defects. Available online at http://www.acog.org/~/media/For%20Patients/faq165.pdf?dmc=1&ts=20130213T1410405774 through http://www.acog.org. Accessed February 2013.

KidsHealth.org. What is the Multiple Marker Test? Available online at http://kidshealth.org/parent/system/medical/triple_screen.html through http://kidshealth.org. Accessed February 2013. 

MayoClinic.com. Quad screen. Available online at http://www.mayoclinic.com/health/quad-screen/MY00127 through http://www.mayoclinic.com. Accessed February 2013.

ARUP Laboratories. Maternal Serum Screen, Alpha Fetoprotein, hCG, and Estriol. Available online at http://www.aruplab.com/guides/ug/tests/0080108.jsp through http://www.aruplab.com. Accessed February 2013.

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.

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.

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