Pregnancy has a lot of checkpoints. Even a single visit to an OB-GYN can mean wrestling with a catalog of acronyms that your doctor wants you to get tested for. One is AFP, which stands for alpha fetoprotein. Getting AFP levels tested is routine rather than particular to high risk pregnancies. So why is everyone getting tested for AFP levels? And is this the best test for its purpose?
To start off, what even is AFP? It’s a protein created in the embryonic yolk sac and in the later fetal liver. After birth, AFP levels in children and adults are low. According to the National Library of Medicine, in non-pregnant people, high levels of AFP serve as a tumor marker—helping to screen for or diagnose cancer. For pregnant people, however, AFP can be detected because the developing fetus makes this protein. According to Scandinavian Association of Obstetricians and Gynaecologists, in utero this AFP permeates into the maternal blood through the placenta or into amniotic fluid, which surrounds the baby as it grows in a protective sac within the uterus. While scientists may not know the exact effect of abnormal AFP levels on the fetus, they do know that these abnormalities are linked with genetic disorders and birth defects.
The National Down Syndrome Society describes lower than normal levels of AFP as an indicator of an increased risk of Down Syndrome. Typically humans have two copies of each chromosome, but an individual with Down Syndrome has an extra copy of chromosome 21. This can manifest in physical traits, heart defects and intellectual disabilities.
The National Library of Medicine describes higher than normal levels of AFP as an indicator of an increased risk of a neural tube defect. Proper formation of the neural tube in a developing fetus is important because it precedes the development of the brain and spinal cord later on in gestation, thus making up the fetus’ central nervous system. The process begins with an open neural plate and concludes with it closing into the neural tube, so any deviation from this process can give rise to serious defects. Some of the defects include spina bifida, wherein the spinal cord does not properly close and the part that remains open leaves spinal nerves exposed. Another neural tube defect is anencephaly, wherein incomplete closure of the neural tube does not allow the skull to form properly. Typically, its formation and closure help join parts of the brain. The National Library of Medicine specifies that in anencephaly the fetus has an underdeveloped brain and degenerating central nervous system—the baby dies shortly after birth.
Essentially, a lot of things can go awry during pregnancy, so patients say “yes” to acronymed tests that their OB-GYN suggests, like the AFP test. This test was developed to help assess a pregnancy’s risk of a genetic disorder or birth defect. The Mayo Clinic cautions that when it comes to patients of advanced maternal age (35 years or older), there is an increased risk of the fetus having Down Syndrome because older eggs are more likely to experience a mistake in cell division that leads to an extra copy of a chromosome. AFP testing serves as a tool for doctors to provide counseling on the risks of a fetus having a genetic disorder.
Getting a routine AFP test is simple. During the second trimester of a pregnancy, specifically between 14 to 22 weeks of gestation, the doctor draws maternal blood to send out and gets a report on whether or not the detected AFP levels fall within the expected range. This method is specifically called maternal serum AFP (MSAFP). If results are abnormal, the doctor may suggest amniocentesis—drawing a sample of amniotic fluid—to get a more accurate measurement of AFP levels.
But is AFP testing the best tool for screening and potential diagnosis? In the case of neural tube defects, which can be fatal, it is indeed a matter of life or death. The Western Journal of Medicine discusses that the trouble lies in the high rate of false positives, which leads women to believe that their fetus has a neural tube defect—AFP levels may be abnormal for a variety of reasons that do not necessarily indicate a birth defect. The Cleveland Clinic describes how further testing, through methods such as amniocentesis and ultrasonography, which uses high-intensity sound waves to visualize internal structures, gives a more accurate look at the fetus. The additional testing often determines that the fetus is actually healthy. On the other hand, false negatives are just as problematic because they lead women into a false sense of security–only later to discover that their baby may have a birth defect.
The American Pregnancy Association highlights that an additional complication to using AFP as a marker for genetic disorders and defects is that AFP levels depend on gestational age. When determining if AFP levels from the fetus found in the maternal blood sample lies within the normal range, the AFP levels are compared to expected values for a given gestational age. This is why accurate dating is important. An incorrect calculation of gestational age can thus lead to false positives or negatives. Sometimes the presence of another fetus can affect AFP levels, so it is also important to note a pregnancy with multiple fetuses.
AFP testing is complicated. So is it the optimal method of screening for something as grave as a neural tube defect? A study from the journal Obstetrics & Gynecology shows that using ultrasonography in addition to AFP testing increases the likelihood of accurately identifying neural tube defects. Another study from the journal General Obstetrics and Gynecology shows that even in low risk pregnancies, use of ultrasonography improves detection. An additional study from the Journal of Prenatal Medicine consolidates that AFP tests are only well grounded when coupled in this way, so AFP testing alone is not the best tool. Greater emphasis should be on other methods, like ultrasonography, or a holistic approach of analyzing AFP levels in conjunction with other tests.
In some respects, AFP testing is even obsolete. The field of maternal fetal medicine has seen the evolution of new technologies and tests since the AFP test was first discovered in 1956 and widely used in the 1970s—those of which can replace the AFP test as part of routine pregnancy care. Maybe one day the AFP acronym will no longer be a routine test at a visit to an OB-GYN.