These tests are used to screen pregnant women in the first trimester of their pregnancy to assess the risk that the fetus they are carrying may have a chromosomal abnormality such as Down syndrome (trisomy 21) or Edward’s syndrome (trisomy 18). The first trimester screen has not been as widely used as the triple/quad screen that is offered in the second trimester, but it has begun to gain acceptance as the medical community has pursued ways to screen women for Down syndrome earlier in their pregnancy. When utilized, first trimester screening is usually ordered between 10 weeks, 4 days and 13 weeks, 6 days of pregnancy. These tests do not replace the triple/quad screen because first trimester screening cannot evaluate the fetus’s risk of developing neural tube defects (such as spina bifida).

There are several approaches to screening depending on what technology is available and when the woman first comes in for prenatal care.

First trimester screening followed by a maternal AFP and/or a fetal ultrasound in the second trimester to check for neural tube defects

Second Trimester screening (Triple or Quad Screen)

Integrated screening – performing both first and second trimester testing and not releasing the results until all testing is completed

Stepwise sequential screening – perform first trimester screen. If positive, woman is offered a diagnostic procedure. If negative, woman is offered the second trimester screen and both first and second trimester results are used in the final risk assessment.

Contingent sequential screening – perform first trimester screen. If positive, the woman is offered a diagnostic procedure. If negative, no further testing is done. If intermediate, second trimester screening is offered and both first and second trimester results are used in the final risk assessment.

About 1 in 1000 babies are born with Down syndrome, a condition that causes mild to moderate mental retardation and is associated with congenital heart defects and other developmental anomalies. The risk of having a child with Down syndrome or other chromosomal abnormality (such as trisomy 18) increases with the age of the mother. Although the risk of having an affected baby is significantly greater in those older than 35, the majority of Down syndrome babies (about 70%) are born to those under 35 because this age group has the greatest number of children. For this reason, The American College of Obstetricians and Gynecologists has recently recommended that all pregnant women be offered a screening test for Down syndrome.

The test is usually ordered between 10 weeks, 4 days and 13 weeks, 6 days of pregnancy.

A mathematical calculation using the results obtained from the PAPP-A, hCG, and nuchal translucency ultrasound is used to determine a numeric risk of a chromosomal defect 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.

In pregnancies where the fetus is carrying a chromosomal defect, such as the extra chromosome material that results in Down syndrome (trisomy 21) or trisomy 18, the levels of PAPP-A tend to be decreased, the levels of hCG are significantly increased, and the space at the fetus’s neck is larger than normal.

The interpretation of these results should be provided by a genetic counselor or clinician who can explain the meaning of the results and offer choices about follow-up. Screening tests are not diagnostic of fetal abnormalities but indicate a normal or increased risk. If a screen is positive, more definitive tests are needed to determine and confirm a diagnosis. These may include a diagnostic test such as a chorionic villus sampling (CVS) in the first trimester or amniocentesis in the second trimester. While these two procedures are more accurate than first or second trimester screening, they are also invasive and carry a small risk of injury to the fetus or miscarriage.

Studies have shown that the first trimester screen can detect more than 85% of Down syndrome cases and up to 95% of fetuses with trisomy 18. About 5% of women will have an abnormal screen, but only about 2-3% of the women whose results show an increased risk will actually have a baby with a chromosome abnormality. Screening will not detect all cases of fetal abnormalities.

Test results are very dependent on nuchal translucency techniques and the 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 (twins, triplets, etc.), calculation of the risk of Down syndrome or trisomy 18 can be difficult because the amount of PAPP-A and free beta-hCG is increased. The nuchal translucency ultrasound, however, does not appear to be affected by multiples. Patients with a multiple gestation pregnancy should consult their doctor about their options.

There is still some controversy surrounding first trimester screening. Many fetuses with Down syndrome are spontaneously aborted, with only about one-fourth surviving to term. Although first trimester testing may detect more cases of Down syndrome, some argue that these extra cases may be not need to be diagnosed as most will not be born.