First Trimester Down Syndrome Screen
First Trimester Screen [Pregnancy-associated plasma protein-A (PAPP-A), human chorionic gonadotropin (hCG) as either free beta subunit or total hCG, and nuchal translucency ultrasound]
Second Trimester Maternal Serum Screening; hCG Pregnancy; Amniotic Fluid Analysis; Chromosome Analysis
Why Get Tested?
To assess the risk of a fetus having a chromosomal abnormality, such as Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18)
When to Get Tested?
Usually between 11 and 14 weeks of pregnancy
A blood sample drawn from a vein in your arm or a blood spot collected on special paper from a finger stick; a nuchal translucency requires a special ultrasound exam.
Test Preparation Needed?
You may be instructed to have a full bladder when having the nuchal translucency ultrasound performed.
How is it used?
The combination of tests for PAPP-A, hCG and nuchal translucency that are included in the first trimester screen are used to assess the risk that the fetus a pregnant woman is carrying has a chromosomal abnormality such as Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18).
The first trimester screen has not been as widely used as the 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 for Down syndrome earlier in pregnancy. The first trimester screen does not, however, assess risk of neural tube defects, such as spina bifida, which can be done with the quad screen.
There are several approaches to screening depending on what technology is available and when the woman first comes in for prenatal care. For more information, see Common Questions #4.
When is it ordered?
The test is usually ordered between 11 and 14 weeks 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 (e.g., probability of 1 in 300 or higher), 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.
While the first trimester screen can correctly identify approximately 85% of women carrying a fetus with Down syndrome and up to 75% of those with Edwards syndrome, about 5% of normal pregnancies will have a false-positive result.
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.
Is there anything else I should know?
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.
What is being tested?
The first trimester screen is a combination of two blood tests and a special ultrasound that are used to assess a pregnant woman's risk of carrying a baby with Down syndrome (trisomy 21) or Edwards syndrome (trisomy 18). Performing and evaluating them together, along with the woman's age, increases both the sensitivity and specificity of the screening results.
- Pregnancy-associated plasma protein A (PAPP-A) is a protein produced first by the outer layer of the developing pregnancy (trophoblast) and then by the growing placenta. During a normal pregnancy, levels of this protein increase in the pregnant woman's blood until delivery.
- Human chorionic gonadotropin (hCG) is a hormone produced by the developing pregnancy and then produced in large quantities by the placenta. Either free beta subunit or total hCG can be used in first trimester screening. Levels of both usually rise rapidly in the pregnant woman'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 measurement made by ultrasound. The ultrasonagrapher measures the fluid collection 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.
If the results of first trimester screening are cause for concern, further screening tests (e.g., quad screen) or diagnostic tests (e.g., amniocentesis or chorionic villus sampling (CVS)) may be recommended.
How is the sample collected for testing?
Blood is drawn from a vein in the woman's arm or collected from a finger stick. The nuchal translucency ultrasound may be performed from outside the abdomen (transabdominally) or the probe may be inserted into the vagina (transvaginally).
NOTE: If undergoing medical tests makes you or someone you care for anxious, embarrassed, or even difficult to manage, you might consider reading one or more of the following articles: Coping with Test Pain, Discomfort, and Anxiety, Tips on Blood Testing, Tips to Help Children through Their Medical Tests, and Tips to Help the Elderly through Their Medical Tests.
Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.
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.
- What is Down syndrome?
About 1 in 700 babies are born with Down syndrome (trisomy 21) each year in the U.S. The condition causes mild to moderate mental retardation and developmental problems and is associated with congenital heart defects, respiratory and hearing problems, leukemia, and thyroid disorders, although many of the complications of Down syndrome can be treated and the lifespan of those affected has greatly increased in recent years. 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 80%) 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 recommended that all pregnant women be offered a screening test for Down syndrome.
- What is Edwards syndrome?
Edwards syndrome (trisomy 18) is a condition in which there are three copies of chromosome 18. As with Down syndrome, the risk of carrying a fetus with Edwards syndrome increases with maternal age. Edwards syndrome is associated with multiple abnormalities and is usually fatal, with live-born infants rarely living beyond one year of age. The frequency of this abnormality is much less than Down syndrome, occurring in only 1 in 6,000 live births. For more information, see the Trisomy 18 Foundation web site.
- Are there other non-invasive screening tests for these disorders?
There is a newer test called cell-free fetal DNA (cffDNA) that only requires a blood sample from the pregnant woman and can be used to screen for certain fetal chromosomal abnormalities, including Down syndrome, Edwards syndrome, and Patau syndrome (trisomy 13). It can be performed as early as the tenth week of pregnancy. Several organizations support its use in pregnant women at high risk of having a child with a disorder caused by an abnormal number of chromosomes. However, invasive diagnostic tests, such as chorionic villus sampling (CVS) and amniocentesis, are still needed to confirm the results. The test is also still seen as experimental by many insurance companies, so the test may not be a covered expense, and it may not be available everywhere. For more information, see New Blood Test for Detecting Fetal Abnormalities Gaining Interest.
- I am pregnant; will I have both the first trimester screen and a quad screen performed?
There are several approaches to screening depending on what technology is available where you are and when you first visit your OB for prenatal care. Options include:
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 (quad screen) to assess risk for chromosome abnormalities and neural tube defects; this may be the only testing done, especially in the case of women who do not visit their health practitioner until the second trimester.
Typically, if first trimester screening has been performed, then a quad screen in the second trimester is not performed because the risks for Down syndrome and Edwards syndrome have already been assessed. However, if you and your health practitioner 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 screen indicates increased risk for Down syndrome or Edwards syndrome, a diagnostic procedure such as chorionic villus sampling is offered. If the screen does not indicate increased risk, then a quad screen in the second trimester is offered and results from both the first and second trimester screens are used in the final risk assessment.
© 2017 American Association for Clinical Chemistry, republished from Lab Tests Online.*
Descriptions of clinical laboratory tests were originally prepared for use on Lab Tests Online, an award-winning patient education website on clinical laboratory testing. Lab Tests Online is produced by the American Association for Clinical Chemistry (AACC), a global scientific and medical professional organization dedicated to clinical laboratory science and its application to healthcare. The Lab Tests Online website is developed in collaboration with other laboratory professional societies and is funded in part through corporate sponsorships.