First Trimester Prenatal Serum Screening Tests for Down Syndrome

What are the substances that they look at?

Red blood cells
Red blood cells. K. Fergus/Istockphoto

There are a few serum screening tests (blood tests) available during pregnancy that can estimate your chances of having a baby with Down syndrome.

While these tests vary as to when in pregnancy they are done, and their sensitivity (the likelihood that they give you a correct answer), they all measure substances that are made either by the fetus or the placenta.

The main advantage to serum screening compared to diagnostic testing is that there is no risk of miscarriage associated with them.

First Trimester Screening Test: hCG and PAPP-A

During the first trimester, two substances called hCG and PAPP-A are found in a mother's bloodstream. These substances can be measured (typically between 10 to 14 weeks of pregnancy) and used to indicate a woman's chance of having a baby with Down syndrome (which is trisomy 21).

HCG (Human Chorionic Gonadotropin)

HCG is a hormone made by the placenta. In fact, very early in pregnancy, it's the substance detected in home and doctor office urine and blood pregnancy tests. 

Pregnancies in which the fetus has Down syndrome tend to have higher levels of hCG than other pregnancies. 

PAPP-A (Pregnancy Associated Plasma Protein A) 

Women with low blood levels of PAPP-A at 10 to 14 weeks of gestation have an increased chance for their baby to have Down syndrome. Low levels of PAPP-A may also indicate an increased risk for intrauterine growth restriction, premature delivery, preeclampsia, and stillbirth.

 

Results of First Trimester Serum Screening Tests for Down Syndrome

Results of this blood test for hCG and PAPP-A are reported as “screen negative” or “screen positive” and only give an estimate of your chance to have a baby with either trisomy 21. In other words, this screening blood test does not diagnose Down syndrome.

Screen Negative Results

“Screen negative” results mean that your chance of having a baby with Down syndrome is low. Even so, it's important to remember that a “screen negative” result does not guarantee that there are no birth defects. If you have a “screen negative” result, you will not be offered follow-up diagnostic testing with a CVS or amniocentesis. (These tests can diagnose Down syndrome, unlike the screening blood tests).

On the other hand, you will be offered another screening blood test, done in the second trimester, that measures a substance called AFP. The amount of AFP present screens for open neural tube defects such as anencephaly and spina bifida. 

Screen Positive Results

“Screen positive” results mean that the chance for the fetus to have Down syndrome is higher than usual. So, with this result, follow-up diagnostic testing with CVS will be offered.

It's important to note that a “screen positive” result does not mean that the baby does indeed have a chromosome abnormality. In fact, most women with “screen positive” results will have normal healthy babies.

Accuracy of Screen Positive and Screen Negative Results

To clarify again, serum screening tests do not give you a diagnosis but do give you an estimate of your chance of having a baby with Down syndrome.

While the accuracy of the testing varies somewhat from lab to lab, in general, the first-trimester serum screening test for hcG and PAPP-A will detect about 80 percent of babies with Down syndrome.

This detection rate increases if you use this test in conjunction with an ultrasound screening test called nuchal translucency testing, which is also done in the first trimester.

While first-trimester serum screening detects about 80 percent of pregnancies with Down syndrome, it will “miss” 20 percent (about 1 in 5) pregnancies with these conditions.

More about Nuchal Translucency Ultrasound Screening

Nuchal translucency screening is a specialized ultrasound done in the first trimester that measures the amount of fluid behind the baby’s neck (the nuchal translucency).

This is a specialized and difficult measurement to obtain, and the ultrasound can only be done by someone who has been specifically trained and certified on obtaining this measurement.

In general, a measurement under 3 mm is considered normal or “screen negative” and a nuchal translucency measurement of over 3 mm is considered abnormal or screen positive.

Most often, the nuchal translucency measurement and your first-trimester serum screening values are combined together using a special algorithm or formula, and you are given one set of screening results.

If your nuchal translucency screening is positive, you will be referred to a genetic counselor to discuss your screening results, what they mean, and your diagnostic testing options such as CVS and amniocentesis.

Another First Trimester Screening Test: Cell-Free DNA Blood Test

It's important to note that there is another first-trimester screening test for Down syndrome which detects cell-free DNA in the mother's blood. This test can be done as early as 10 weeks of gestation and detects up to 99 percent of pregnancies affected by Down syndrome. 

The drawback of the test is in about one to five percent or more of the blood samples, no results can be obtained, even after the test is repeated. In addition, the test is costly. That said, women at a high risk of having a baby with Down syndrome generally undergo this test (for example, women who are age 35 years or older at the time of delivery).

In addition, women who have a "screen positive" test for hCG and PAPP-A can choose to undergo a cell-free DNA test in lieu of going ahead with a diagnostic test. If the cell-free DNA test is positive as well, then a CVS or amniocentesis can be performed to make a diagnosis.

On the other hand, if the cell-free DNA test is negative, then the original blood test (the hCG and the PAPP-A) is usually deemed a false positive.

A Word From Verywell

As you can see, there are a number of first-trimester different screening options for Down syndrome including a blood test of hCG and PAPP-A, ultrasound, or a combination of the two. In addition, for high-risk women, there is also the cell-free DNA blood test. 

Choosing which (if any) screening method, as well as the timing (some women choose to wait until the second trimester), is right for you is a very personal decision and requires a close conversation with your doctor and sometimes a genetic counselor. 

Sources:

American College of Obstetrics and Gynecologists. (2014). Screening Tests for Birth Defects. 

Messerlian GM, Palomaki GE. Down syndrome: Overview of prenatal screening. Wilkins-Huag L, ed. UpToDate. Waltham, MA: UpToDate Inc. 

National Down Syndrome Society. (2012). Understanding a Diagnosis of Down Syndrome. 

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