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) 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, weight, race, and diabetic status are used to determine a numeric risk for Down syndrome and for a few other chromosomal abnormalities such as 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 positive or increased.

The test is usually ordered between the 15th and 20th weeks of pregnancy.

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. Screens are not diagnostic of a fetal abnormality; they indicate a normal or increased risk. If a screen is positive, more definitive tests 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.

Not all fetal abnormalities will give positive test results. 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.

The test result is also 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 trisomy 18 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.