You may have heard of this test referred to as the triple marker screen, the triple test, expanded AFP or simply "maternal serum screening." A board-certified Genetic Counselor explains a little bit more about this test, and what positive and negative results may mean.
Allison Gregory, MS, CGC

About the screening test
Most women are offered a maternal serum screening test during the second trimester of pregnancy to estimate the risk for certain birth defects. This requires a small specimen of blood. The test may vary slightly among different states, regions, or even physician offices and is most often called a triple marker screen or triple screen. (In California, it is called an Expanded AFP test.)

Maternal serum screening tests are designed to identify which pregnant women have an increased risk to have a baby with one of three different birth defects. The test, being a screening test and not a diagnostic one, simply provides an estimate of this chance; further testing is necessary to learn more about the possibility. A positive test result indicates that the risk is increased beyond what would normally be expected. Most positive results are later learned to be "false positives," meaning the unborn baby does not have one of the birth defects in question.

The test usually measures three substances in the mother's blood that are produced by the unborn baby or placenta. These substances, called alpha-fetoprotein (AFP), human chorionic gonadotropin (hCG), and unconjugated estriol (uE3), are normally only present in the blood during pregnancy. The levels of AFP and uE3 typically rise during the second trimester, while hCG decreases. Measuring all three levels gives information about the risk for birth defects.

When the test is performed, usually between 15 and 20 weeks of pregnancy, it is important to know the gestational age of the unborn baby, the age of the mother, her weight, her ethnicity, whether she is diabetic, and whether it is a twin pregnancy. If any one of these factors is reported inaccurately, a false positive or false negative result may occur.

What does the test look for?
The test determines if there is an increased risk for Down syndrome, neural tube defects, and/or trisomy 18.

Down syndrome is caused by a change in the baby's chromosomes. These are the rod-shaped structures in the cells of the body that contain all the genes, or instructions for development. Most babies with Down syndrome have an extra copy of the 21st chromosome. Individuals with Down syndrome usually have mild to moderate mental retardation and a typical facial appearance. Heart defects, abnormalities in the digestive system, and frequent infections are also common. The risk for Down syndrome is increased when AFP and uE3 levels are low and the hCG level is high.

Neural tube defects are a class of birth defects that occur in the spine and head. Spina bifida describes an opening in the spine, which can cause nerve damage. Anencephaly refers to an opening in the back of the head and incomplete formation of the brain, which is not compatible with life after birth. The risk for neural tube defects is increased when the AFP level is elevated. The neural tube defect risk is not affected by the levels of hCG and uE3.

Trisomy 18 occurs when the baby has an extra copy of the 18th chromosome. This causes severe mental retardation, heart defects, and other birth defects that are also usually not compatible with life. The risk for trisomy 18 is elevated when AFP, hCG, and uE3 levels are all low.

What does a positive result mean?
A positive result can occur for several reasons. Most often, it is found to be a false positive result, meaning that the baby does not have any of the conditions described above. A false positive frequently occurs because the woman is earlier or later in her pregnancy than was previously thought. Having an ultrasound can decide the gestational age of the baby most accurately. If a significant change is found, the test results may be calculated again or a new blood specimen may need to be drawn. Also, ultrasound will determine if it is a twin pregnancy, which can make the AFP level appear falsely high.

If the result remains positive after an ultrasound is done and the test results are reviewed to assure that accurate information was used, then an amniocentesis will most likely be recommended. Amniocentesis diagnoses Down syndrome and trisomy 18 with extremely high accuracy. Amniocentesis and ultrasound together can identify most cases of neural tube defects. Many other abnormalities are also detectable with these tests.

What does a negative result mean?
A negative result is very reassuring, although it does not mean it is impossible for the baby to have one of these conditions. Typically, in addition to indicating if the test is positive or negative, the laboratory report will give more specific information about the risk for these birth defects. If you are concerned about your results, ask your healthcare provider to review them with you in more detail. The risk for birth defects also depends on the mother's age and the unborn baby's family health history, so be sure to mention any concerns to your

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Kitty December 24, 2012
Hi there, Please can you shed some light, I am 27 years of age, Indian, Wieght of 50.3kg, no diabetes and 16 weeks pregnant (according to my gynae) with my first baby. I have been for a triple marker screen, and my results have come back showing I have a 1:59 risk of Down syndrome, Age calculated risk of 1:1179... I am only due to see the fetal specialist in 3 weeks but I am extremely worried even though these tests have a high rate of false positives.
Is it possible that that AFP and Hcg taken early show high risk?