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What is alpha-fetoprotein testing, anyway?

At Kamm McKenzie, we offer fetal screening tests in the first and second trimesters to all of our
patients. One test that I have found raises a great deal of confusion is the blood test for alpha
fetoprotein (AFP). In the past, AFP was used as one of multiple markers in the Quad and Tetra
screens which evaluated for the likelihood of chromosomal abnormalities such as Down’s
syndrome. Now, we almost universally screen for chromosomal abnormalities with cell-free DNA
(cfDNA) testing. With the widespread use of cfDNA, we now use AFP on its own for a different
screening indication – to assess the risk of fetal structural or anatomic defects.


AFP is a protein produced in the fetal liver and gastrointestinal tract during pregnancy – so I like
to think of it as an inside protein. When more AFP is outside of the fetus, and we therefore see
elevated levels in the maternal blood, it could indicate a defect in the fetus – something that lets
this inside protein out. We offer expecting patients a blood test for AFP between 15 and 20
weeks, and in this gestational age range, AFP levels usually fall between 10 ng/ml to 150 ng/ml.
Because the expected value is dependent on the exact gestational age and some maternal
factors, the result is reported in multiples of the median (MoM). An AFP test result is considered
abnormal when it is greater than 2 MoM, i.e. more than two times the “average” level of AFP
you’d expect to see at that point in pregnancy.


So, what could make an alpha-fetoprotein testing result abnormal?
Well, things like open neural tube defects (such as spina bifida, anencephaly), abdominal wall
defects (like omphalocele, gastroschisis), abnormalities of the renal system (think urinary
obstruction, polycystic or absent kidneys), or even some placental and bone issues.


But won’t my anatomy ultrasound show these kinds of problems?
Yes, and this is why most patients forego the test. An ultrasound is far more sensitive at discovering an abnormality than the AFP test. The potential benefit that I see with the AFP test comes down to timing and index of suspicion. The AFP blood test can be done as early as 15 weeks, and results return within a week. If the test returns abnormal, the patient is referred for a detailed ultrasound and consultation with Maternal Fetal Medicine specialists at that time. Without the AFP test, a low risk patient would have a routine anatomy ultrasound at 18-20 weeks. With the AFP test, an otherwise low risk patient could find out important information about their pregnancy up to 4 weeks sooner. But because all tests have a false positive rate, the potential downside is unnecessary anxiety if the AFP test is positive, but subsequent ultrasound and workup ends up being normal.

Full disclosure, I am a tester. I like to have all of the information possible. So for me, the AFP test has value. Not everyone feels the same way that I do though, and that’s okay! I just want the possible utility and implications of this test to be well understood by my patients, which is why I wrote this blog.


Written by Dr. Buckheit


Check out more on the topic of prenatal screening here: https://www.kmobgyn.com/fetal-defect-
screening-tests/

And here: https://www.acog.org/womens-health/faqs/prenatal-genetic-screening-tests

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