The Controversy Behind Alpha-Fetoprotein Screening in Pregnancy

Genetic Screening for Neural Tube Defects and Down Syndrome

Young woman with pipette in the laboratory.
Credit: Hans Verleur Photo & Film/Stone/Getty Images

Genetic testing of any sort typically brings with it a large debate. The alphafetoprotein (AFP) test, also sometimes done as part of a triple screen, quad screen or penta screen, is no exception.

What Is the Alphafetoprotein Test?

The AFP test is a blood test done to check the levels of a pregnant woman's AFP, a protein secreted by the fetal liver and excreted in the mother's blood. It is generally used as an indicator for neural tube defects, but it can also indicate abdominal wall defects, esophageal and duodenal atresia, renal and urinary tract anomalies, Turner syndrome, low fetal birth weight, and placental complications.

A low level of AFP could also indicate Down Syndrome.

The triple screen option measures not only AFP, but also beta-hCG and unconjugated estriol (uE3). This test has been shown to be more accurate, and to screen. for additional genetic problems. For these reasons, it is beginning to replace the standard AFP.

Generally speaking, any combination of these tests will identify 60 percent of the babies with Down Syndrome and 80-90 percent of the babies with neural tube defects.

In addition to the substances screened in the triple screen, the quad screen checks the level of the hormone inhibin A. The penta screen looks for those four substances as well as Invasive Trophoblast Antigen (ITA). Which screening test you have will depend on which lab is available to you. If you had the first trimester screening along with the nuchal fold translucency ultrasounds, it is recommended that you use the same lab.

So Where Does the Controversy Come In?

The controversy in these tests lies in many places, one of which is the accuracy of the screenings. While some claim that they have only a 5 percent "false positive" rate, most research finds that there is actually an 80+ percent rate of positive tests where the baby has been unaffected.

These false positive rates are affected by many factors, including appropriate gestational age, maternal age, weight, and the presence of diabetes.

There are also followup tests done that carry risks, like amniocentesis or chorionic villus sampling (CVS), which does carry a 1 - 2 percent rate of fetal loss. The standard is usually to just repeat the AFP or triple screen. Another positive screen will then go to the Level II Ultrasound. Ultrasound can even be used to detect some of the anomalies associated with Downs Syndrome. If the ultrasound doesn't find a mix-up in gestational age, or a multiple pregnancy, an amniocentesis is generally the next step.

There is a possible benefit of identifying neural tube defects before birth, because it can alter care, and even the mode of delivery. For example, it is generally considered safer for a baby with spina bifida to have a cesarean delivery

But of the positive test results, some research shows that 90 percent of these babies will not actually have any anomalies.

In fact, the test results are generally given as either positive/negative, or with a risk ranking. It is important to remember that being at an increased risk does not mean your baby has the defect. You should ask your practitioner to explain the results in detail to you.

What Does the American College of Obstetricians and Gynecologists (ACOG) Recommend?

ACOG guidelines recommend that this test be offered to all pregnant women, regardless of maternal age. However, many women are made to believe the testing is mandatory. Those who refuse the test are asked to sign waivers. 

Given the fact that amniocentesis and CVS have the ability to cause pregnancy loss, some women choose not to use these invasive tests. Some women feel that no matter what the test shows, they wouldn't terminate the pregnancy. So why bother? Whether or not to have the test is a tough decision and a very personal one. 

Sources:

Hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen) immunoassay: A new basis for gestational Down syndrome screening. Clin Chem. 1999 Dec;45(12):2109-19.

Integrated serum screening for Down syndrome in primary obstetric practice. Prenat Diagn. 2005 Dec;25(12):1162-7.

New Robin J.R. Blatt, Prenatal Tests, England Journal of Medicine 323, No. 9, Aug 30, 1990.

Reproducibility of risk figures in 2nd-trimester maternal serum screening for down syndrome: comparison of 2 laboratories. Clin Chem. 2006 Nov;52(11):2087-94. Epub 2006 Sep 21.

Benn PA, Makowski GS, Egan JF, Wright D.

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