What is the Quadruple Screen Test?

Quadruple Screen Test

Prenatal screening tests are designed to help expectant parents evaluate the risk of a potential genetic disorder or birth defect.  One example of an extremely common prenatal screening test is an ultrasound, which uses sound wave imaging to look for physical characteristics that are indicative of a developmental abnormality.  Many other prenatal screening tests involve the collection of a sample from the mother, such as blood or amniotic fluid, to measure the levels of certain hormones and proteins.

What markers make up the quad screen test?

You may have heard of the triple screen test, a common genetic test that measures the levels of three substances – alpha fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol – in the mother’s blood.  The quadruple (or “quad”) screen tests the mother’s blood for the three compounds  above along with one additional substance, inhibin A, between 15 and 20 weeks of pregnancy.

  • AFP is a protein that produced by the liver and found in extremely high concentrations in fetal blood – up to a million times higher than in adult blood! AFP levels fluctuate in a mother’s blood throughout pregnancy, but higher than normal levels can be indicative a neural tube defect, while low levels could point to a higher risk of Down syndrome or trisomy 18.
  • hCG is a hormone that is produced by the placenta. It is a common component of pregnancy tests, as the hormone is present in the urine of pregnant women but not in women who are not carrying a baby.  Levels of hCG in maternal blood increase approximately 100,000-fold during pregnancy.  Levels higher than the normal range could indicate Down syndrome, while low levels of hCG are associated with trisomy 18.
  • Unconjugated estriol is a substance made by the fetus and placenta. Hormone levels steadily rise throughout gestation, with a sharp rise generally preceding the onset of labor.  Low levels of the hormone could suggest Down syndrome or trisomy 18.
  • Inhibin A is a substance that is made by the placenta. Abnormally high levels might be indicative of hypoxia or maternal hypertension, along with Down syndrome.  The addition of inhibin A to the triple screen improves the prediction accuracy for Down syndrome from 69% in the triple screen to 81% in the quad screen.

How accurate are the results?

It’s important to remember that screening tests are exactly that – they screen for an elevated risk of a developmental abnormality, but a positive result does not provide a 100% positive diagnosis.  In fact, the quad screen has a >5% false positive rate, meaning that 5% of test results will come back positive when there are in fact no developmental abnormalities.  Atypical results on more than one test have a higher predictive validity than an abnormal value on just one of the tests.  Some factors to keep in might that will influence test results include a pregnancy of multiples, other medications taken by the mother during pregnancy, and a miscalculation of the gestational age of the baby.

If you do have a positive result on one or more of the tests, your healthcare provider can recommend follow-up testing, such as an amniocentesis, or an appointment with a genetic counselor in order to obtain a more definitive diagnosis.

Deciding to have the quad screen test

The American College of Obstetrics and Gynecology (ACOG) recommends that all pregnant women be offered prenatal genetic testing by their healthcare provider.  Some mothers opt out of any prenatal elective testing while others choose to collect as much information as possible about their new arrival – but at the end of the day, the choice is up to you.

References:

ACOG – https://www.acog.org/Patients/FAQs/Screening-Tests-for-Birth-Defects

An J, Ji H, You J, Woo S, Choi S, Oh S, Roh C, and Kim J.  Introduction of a nomogram for predicting adverse pregnancy outcomes based on maternal serum markers in the quad screen test.  Archives of Gynecology and Obstetrics.  292(3), 589-594, 2015.

Dugoff L, Hobbins JC, Malone FD, Vidaver JMA, Sulliavn L, Canick JA, Lambert-Messerlian GM, Porter TF, Luthy DA, Comstock CH, Saade G, Eddleman K, Merkatz IR, Craigo SD, Timor-Tritsch IE, Carr SR, Wolfe HM, and D’Alton ME.  Quad screen as a predictor of adverse pregnancy outcome.  Obstetrics and Gynecology, 106(2): 260-7, 2005.

Schieving JH, de Vries M, van Vugt JMG, Weemaes C, van Deuren M, Nicolai J, Wevers RA, and Willemsen MA.  Alpha-fetoprotein, a fascinating protein and biomarker in neurology.  Eur J Paed Neurol, 18(3), 243-248, 2014.

Kristen Hollinger
Dr. Kristen Hollinger has a Ph.D. in molecular and cellular biology from Pennsylvania State University. She currently resides in Maryland and works as an Instructor in the Departments of Psychiatry and Neurology at Johns Hopkins University School of Medicine. Her research focuses on neurological diseases including depression and multiple sclerosis.

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