Also known as: Triple/quadruple test; total hCG
Name: First trimester screening [pregnancy-associated plasma protein A (PAPP-A), human chorionic gonadotrophin (hCG), both free beta and total, and nuchal translucency]
Related tests: Prenatal screening, hCG
Why get tested?
To assess the risk of a fetus having chromosomal abnormalities, such as Down syndrome and trisomy 18
When to get tested?
Usually between 10 weeks and 4 days and 13 weeks and 6 days of pregnancy.
Sample required?
A venous blood sample and a special ultrasound scan.
Is any test preparation needed?
You may be asked to have a full bladder for the nuchal translucency measurement.
What is being tested?
First trimester screening is a combination of two blood tests and a special ultrasound scan used to screen women in the first trimester of pregnancy. Each test measures a different factor that is altered in a fetus with chromosomal abnormalities such as Down syndrome or trisomy 18. Carrying them out and assessing them together increases both the sensitivity and the specificity of the screening results.
• PAPP-A is a protein produced first by the trophoblast (the outer cell mass of the blastocyst) and then by the growing placenta. During a normal pregnancy, levels of this protein in the mother’s blood rise until delivery.
• hCG (human chorionic gonadotrophin) is a hormone produced by the trophoblast and then in large amounts by the placenta. Both free and total hCG can be used in first trimester screening. Levels of both usually rise rapidly in the mother’s circulation for the first 8-10 weeks, then fall and settle at a lower level for the rest of the pregnancy.
• Nuchal translucency measures the space or thickness between the spine and the skin at the back of the fetus’s neck. The procedure requires a specially trained sonographer, exact positioning of the fetus and accurate measurement. It is not a routine ultrasound scan and is not available in every hospital or healthcare facility.
How is the sample collected for testing?
Blood is taken from a vein in the arm. Nuchal translucency can be measured transabdominally (from outside the abdomen) or transvaginally (with a probe inserted into the vagina).
Is any preparation needed to ensure the quality of the sample?
You may be asked to have a full bladder for the nuchal translucency measurement.
How is it used?
When is it requested?
What does the test result mean?
Is there anything else I should know?
How is it used?
These tests are used to screen women in the first trimester of 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). First trimester screening has not been used as widely as the triple/quadruple test recommended in the second trimester, but it has started to gain acceptance as the medical community has moved towards screening women for Down syndrome earlier in pregnancy. When used, first trimester screening is usually requested between 10 weeks and 4 days and 13 weeks and 6 days of pregnancy. These tests do not replace the triple/quadruple test, because first trimester screening cannot assess the fetus’s risk of neural tube defects (such as spina bifida).
There are several approaches to screening, depending on which technology is available and on when the woman first presents for antenatal care.
• First trimester screening followed by maternal AFP and/or fetal ultrasound in the second trimester to check for neural tube defects
• Second trimester screening (triple/quadruple test)
• Integrated screening: both first and second trimester tests are carried out, and results are not reported until all tests have been completed
• Stepwise sequential screening: first trimester screening is carried out. If positive, the woman is offered a diagnostic procedure. If negative, the woman is offered second trimester screening, and both first and second trimester results are used for the final risk assessment.
• Contingent sequential screening: first trimester screening is carried out. If positive, the woman is offered a diagnostic procedure. If negative, no further tests are carried out. If intermediate, second trimester screening is offered, and both first and second trimester results are used in the final risk assessment.
About 1 in 1,000 babies is born with Down syndrome, a condition that causes mild to moderate intellectual disability and is associated with congenital heart defects and other developmental abnormalities. The risk of having a baby with Down syndrome or other chromosomal abnormalities (such as trisomy 18) increases with the mother’s age. Although the risk of having an affected baby is significantly higher in women over 35, most babies with Down syndrome (about 70%) are born to mothers under 35, because this age group has the most babies. For this reason, the American College of Obstetricians and Gynecologists has recently recommended that all pregnant women be offered screening for Down syndrome.
When is it requested?
The test is usually requested between 10 weeks and 4 days and 13 weeks and 6 days of pregnancy.
What does the test result mean?
A mathematical calculation based on the PAPP-A, hCG and nuchal translucency results is used to determine a numerical 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, the result is considered positive or increased.
In pregnancies in which the fetus has a chromosomal defect, such as the extra chromosomal material that results in Down syndrome (trisomy 21) or trisomy 18, PAPP-A levels tend to be lower, hCG levels are significantly higher, and the tissue at the back of the fetal neck is thicker than normal.
These results should be interpreted by a genetics expert or clinician who can explain what they mean and offer choices about what to do next. Screening tests do not diagnose fetal abnormalities but indicate a normal or increased risk. If a screen is positive, more precise tests are needed to establish 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. While these two procedures are more accurate than first and second trimester screening, they are also invasive and carry a small risk of harm to the fetus or miscarriage.
Is there anything else I should know?
Studies have shown that first trimester screening 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 women whose results show an increased risk will actually have a baby with a chromosomal abnormality. Screening will not detect all cases of fetal abnormality.
The test results depend heavily on nuchal imaging techniques and on accurate determination of the fetus’s gestational age. If gestational age has not been determined precisely, results may be falsely high or low.
In multiple pregnancies (twins, triplets, etc.), calculating the risk of Down syndrome or trisomy 18 can be difficult because the amounts of PAPP-A and free beta hCG are increased. Nuchal translucency, however, does not seem to be affected by multiple pregnancies. Patients with a multiple pregnancy should discuss the possible options with their doctor.
First trimester screening is still somewhat controversial. Many fetuses with Down syndrome miscarry spontaneously, and only about a quarter survive to the end of the pregnancy. Although the first trimester test can detect more cases of Down syndrome, some argue that there is no need to diagnose these extra cases because many will not be born anyway.
1. What is a person with Down syndrome like?
2. What is trisomy 18?
1. What is a person with Down syndrome like?
People with Down syndrome usually have mild to moderate intellectual disability and may have congenital heart defects, breathing and hearing problems, leukaemia and thyroid problems. Many of the complications of Down syndrome can be treated, and life expectancy has increased considerably in recent years.
2. 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 in about 1 in 3,000 live births.