Quad Marker Screening Test Uses, Accuracy, Results, and False Positive

The quad marker screening test (quad screen) is a blood test administered in pregnancy, typically between the 15th and 20th weeks of gestation. Similar to the triple screen, the quad marker screen provides information about whether there is an increased risk for certain birth defects in the baby.

The test is simple and involves taking a blood sample as for any other routine blood test. The quad marker test is a screening test, meaning that it gives information about risk, but it does not allow the definitive diagnosis of any conditions. It can only signal that further testing should be done to confirm a diagnosis. There is no risk to the baby from the test.

The quad screen looks at the three substances also measured in the triple screen (alpha-fetoprotein, human chorionic gonadotropin, and estriol) test plus one additional substance, inhibin A.

• Alpha-fetoprotein (AFP) is produced by the liver of the fetus
• Human chorionic gonadotropin (hCG) is a hormone made by the placenta
• Estriol is an estrogen made both by the placenta and the liver of the fetus
• Inhibin-A is another hormone made by the placenta

Looking at levels of these four substances in the mother's bloodstream allows an estimation of risk for neural tube defects and certain chromosomal abnormalities, like Down syndrome.

The test is a screening test only, and is not 100% accurate. It can predict about 85% of open neural tube defects, problems with the development of the baby's brain and spinal cord. It predicts about 80% of fetuses with Down syndrome in women over age 35 and about 75%  in younger women. The fact that it is not 100% accurate means that not all women who have a positive high risk result on the quad screen will have a fetus with a birth defect, and the test may also be normal even in the presence of birth defects.

For example, about 50 women out of every 1,000 will have a result on the quad screen that indicates an increased risk of a birth defect, but only one to two of those women will actually have a baby with an open neural tube defect. About 40 women out of 1,000 will have a result indicating an increased risk of Down syndrome, but only one to two of these women will have a baby with Down syndrome.

As with any screening test, an abnormal result does not mean that the fetus definitely has a birth defect or genetic condition. It only means that the blood levels of these four substances suggest that a woman's risk is increased of having a baby with certain conditions. Women who have a result suggesting increased risk are typically offered further testing. This can include repeating the quad screen and/or having a high definition ultrasound examination to look for signs of birth defects or abnormalities in the developing baby. If this testing is abnormal, the mother may be offered the choice to undergo amniocentesis. Amniocentesis involves withdrawing a sample of amniotic fluid for genetic and chromosome testing, and it can definitively establish the diagnosis of genetic and chromosomal problems in most fetuses. Amniocentesis carries a small risk of miscarriage (fewer than 1% of fetuses tested).