First Trimester
Down Syndrome Screen

The combination of tests for PAPP-A, hCG and nuchal translucency 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 Edwards syndrome (trisomy 18). The first trimester screen consists of:

• A blood test that measures
  • PAPP-A, a protein produced first by the outer layer of the developing pregnancy and then by the growing placenta
  • hCG, a hormone produced by the developing pregnancy and then produced in large quantities by the placenta
• Nuchal translucency, a measurement made by ultrasound; the ultrasonagrapher measures the fluid collection between the spine and the skin at the nape of the fetus's neck.

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 screening for neural tube defects in the second trimester because first trimester screening cannot evaluate the fetus's risk of developing neural tube defects such as spina bifida. A maternal serum AFP level may be measured in the second trimester to assess risk of neural tube defects.

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 for chromosome abnormalities followed by a blood test for maternal AFP and/or a fetal ultrasound in the second trimester to check for neural tube defects
• Second trimester screening (Triple/Quad Screen) to assess risk for chromosome abnormalities and neural tube defects; this may be the only testing done, especially if the woman does not visit her doctor until the second trimester.

Typically, if first trimester screening has been performed, then a triple/quad screen (second trimester screening) is not performed because the risks for Down syndrome and Edwards syndrome have already been assessed. However, if a woman and her doctor wish to use the results of both first and second trimester testing to assess the risk of chromosome abnormalities, then one of the following approaches is used:

• Integrated screening - involves performing both first and second trimester testing and not releasing the results until all testing is completed
• Sequential screening – involves performing a first trimester screen; if the woman screens at increased risk for carrying a baby with Down syndrome or Edwards syndrome, she is offered a diagnostic procedure such as chorionic villus sampling (CVS). If she is not at increased risk, then the woman is offered a triple/quad screen in the second trimester and both first and second trimester results are used in the final risk assessment.

About 1 in 1,000 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 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 Congress of Obstetricians and Gynecologists has 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 a positive screen and the woman may be at increased risk for having a baby with a chromosomal abnormality.

In pregnancies where the fetus is carrying a chromosomal defect, such as the extra chromosome material that results in Down syndrome or Edwards syndrome, 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. It is important to remember that screening tests are not diagnostic of fetal abnormalities but indicate a normal or increased risk.

With the first trimester screening test, about 5% of normal pregnancies will have an abnormal result, but only about 2-3% of the women whose results show an increased risk will actually have a baby with a chromosome abnormality. A positive result on this screen means that there is a 1 in 100 to 1 in 300 chance that the fetus has an abnormality. However, the first trimester screen is useful because studies have shown that it can detect more than 85% of Down syndrome cases and up to 95% of fetuses with Edwards syndrome. You can get a similar rate of detection with the integrated or sequential screens with a lower false positive rate.

If a screening test is positive, more definitive tests are needed to determine and confirm a diagnosis. These may include a diagnostic test such as 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 miscarriage and a rare risk of injury to the fetus.

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 Edwards syndrome can be difficult because the amount of PAPP-A and free beta hCG is increased. The nuchal translucency ultrasound, however, is an assessment that is unique to each fetus and can be done independently with ultrasound. Women 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 and other chromosomal abnormalities 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. In addition, the woman is spared from making decisions about managing her pregnancy because the loss happens spontaneously.