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

Serum Screening Tests

Now numerous serum screening tests (blood tests) are available during pregnancy that estimate your chance to have a baby with Down syndrome and other chromosome problems. 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 these serum screening tests.

About Free Beta HcG and PAAP-A

During the first trimester, two substances -- free beta HcG and PAPP-A -- found in mom’s bloodstream, are measured and used to give a chance for the baby to have Down syndrome or trisomy 18. The chance estimate is based on the levels of these substances in your blood, your age, your weight and how far along you are in the pregnancy. Typically this blood test is done between 10 to 14 weeks of pregnancy. This test only screens for Down syndrome and trisomy 18.

Results are reported as “screen negative” or “screen positive” and only give an estimate of your chance to have a fetus with a chromosome condition. Serum screening tests cannot diagnose Down syndrome and other chromosome abnormalities.

“Screen negative” results mean that your chance to have a fetus with these disorders is low and no follow-up testing is offered.

It is 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 such as CVS or amniocentesis. You will also be offered another serum screening 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 meaning that the chance for the fetus to have one of these chromosomal conditions is higher than usual and follow-up testing such as CVS or amniocentesis is offered. And a “screen positive” result does not mean that the baby has a birth defect. In fact, most women with “screen positive” results will have normal healthy babies.

How Accurate is First Trimester Serum Screening for Down Syndrome

Serum screening tests do not give you a diagnosis but do give you an estimate of your chance. While the accuracy of the testing varies somewhat from lab to lab, in general, first-trimester serum screening will detect about 80% of Down syndrome and trisomy 18. 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% of pregnancies with Down syndrome and trisomy 18, it will “miss” 20% (about 1 in 5) pregnancies with these conditions.

More about HCG and PAPP-A

Free beta HCG (Free beta human chorionic gonadotropin) - is a hormone made by the placenta. Very early in pregnancy, it is the substance used in pregnancy tests. HCG is used in both first-trimester and second-trimester screening tests to screen for Down syndrome and trisomy 18. Pregnancies in which the fetus has Down syndrome tend to have higher levels of HCG than other pregnancies. Pregnancies in which the fetus has trisomy 18 tend to have lower HCG levels.

PAPP-A (Pregnancy Associated Plasma Protein A) - PAPP-A - a protein that is measured in a blood test to determine the chance of having a baby affected with Down syndrome or trisomy 18. Women with low blood levels of PAPP-A at 10 to 14 weeks of gestation have an increased chance for the fetus to have Down syndrome and trisomy 18. Unexplained very low levels of PAPP-A may also indicate an increased chance for intrauterine growth restriction, premature delivery, preeclampsia, and stillbirth.

Screening Analyte Results

Screening analyteLevel for trisomy 21 (Down syndrome)Level for Trisomy 18
HCGHighLow
PAPP-ALowLow

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 consider normal or “screen negative” and a nuchal translucency measurement of over 3 mm is considered abnormal or screen positive. Nuchal translucency ultrasound screening screens for Down syndrome, trisomy 18, other chromosome problems, and heart defects. 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.

What if I Am Too Late for First Trimester Serum Screening?

First trimester serum screening and nuchal translucency are done early in a pregnancy. If you miss the timing cutoff for these tests, you may want to consider second trimester serum screening and/or a genetic ultrasound.

The Bottom Line

First trimester serum screening can give you an estimate of your chance to have a baby with Down syndrome or trisomy 18. While screen negative results are reassuring, they are not a guarantee that the baby does not have these condition. A screen positive indicates you have a slightly higher than average chance to have a baby with these conditions and should be offered follow-up diagnostic testing such as CVS or amniocentesis.

While they indicate that your chance may be slightly higher than average, it is important to remember that most women who have screen positive results, have perfectly normal healthy babies.

Sources:

Benn PA (2002). Advances in prenatal screening for Down syndrome: I. General principles and second trimester testing. Clin. Chim. Acta 323 (1-2): 1–16.

Ball RH, Caughey AB, Malone FD, et al (2007). First- and second-trimester evaluation of chance for Down syndrome. Obstet Gynecol 110 (1): 10–7.

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