Down Syndrome Screen
Down Syndrome Screen
- PAPP-A is a protein produced first by the trophoblast (outer layer of the developing pregnancy) and then by the growing placenta. During a normal pregnancy, levels of this protein increase in the mother's blood until delivery.
- hCG is a hormone produced by the trophoblast and then created in large quantities by the placenta. Either free or total hCG can be used in First Trimester Screening. Concentrations of both usually rise rapidly in the mother's circulation for the first 8 to 10 weeks, then decrease and stabilize at a lower level for the remainder of the pregnancy.
- Nuchal translucency is an ultrasound that measures the space (thickness) between the spine and the skin at the nape of the fetus's neck. It is a procedure that requires a specially trained radiologist, proper alignment of the fetus, and careful measurement. It is not a routine ultrasound, and it is not a procedure that is available at every hospital or health facility.
How is the sample collected for testing?Blood is drawn from a vein in the arm. The nuchal translucency ultrasound may be performed transabdominally (from outside the abdomen) or transvaginally (the probe is inserted into the vagina).
Is any test preparation needed to ensure the quality of the sample?You may be instructed to have a full bladder when having the nuchal translucency ultrasound performed.
How is it used?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.
When is it ordered?The test is usually ordered between 10 weeks, 4 days and 13 weeks, 6 days of pregnancy.
What does the test result mean?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.
Is there anything else I should know?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.
How does Down syndrome affect a person?Those with Down syndrome usually have mild to moderate mental retardation and may have congenital heart defects, respiratory and hearing problems, leukemia, and thyroid disorders. Many of the complications of Down syndrome can be treated, and the lifespan of those affected has greatly increased in recent years.
What is trisomy 18?Trisomy 18 or Edwards Syndrome is a condition in which there are three copies of chromosome 18. Trisomy 18 is associated with multiple abnormalities and is usually fatal shortly after birth. This chromosomal defect occurs about in about 1 in 3000 live births.