The afp Test
The AFP (alphafetoprotein) test (also called the “quad” screen - quad means 4 separate tests are done) allows us to screen the fetus for possible spina bifida (a birth defect of the fetal brain and/or spinal cord), Down's Syndrome and for other even more rare disorders. In California, it is the law that every pregnant woman be offered the AFP test. (Some of my patients think that the law says that they actually have to do the AFP test! Big Brother hasn't gone that far, yet.)
This blood test is usually done about 16-18 weeks gestational age. Results can take another week or two. Thankfully, most of the time (98% of the time!), the results are normal. It is the abnormal report that is the source of so much concern and misunderstanding.
In my experience, the counseling of patients regarding this test and its possible results is more difficult than for any other routine pregnancy issue. Many patients are afraid of this test because it causes false positives. The purpose of this article is to explain the value of the AFP test, and why false positives are actually not a bad thing.
What is afp?
AFP stands for alpha-fetoprotein. This is a serum protein circulating in the bloodstream of every fetus. Small amounts of this protein normally leak into the amniotic fluid and then even smaller amounts leak from the amniotic fluid into the mother's bloodstream. By testing thousands of pregnant patients for their blood level of AFP and documenting their pregnancy outcomes, we have learned a tremendous amount about using AFP levels to help try and detect many different but rare birth defects. This is also we determined what a low, normal or high level really is.
Causes of Elevated afp
What can cause a "high" level of AFP in the mother's blood? Any condition where the fetal skin is not intact, since intact fetal skin prevents excess AFP leakage from the baby into the amniotic fluid.. This is why a neural tube defect known as spina bifida can be the cause of a high AFP. With a neural tube defect the brain or spinal cord is partly outside the body without a skin covering, so lots of AFP leaks out from the baby into the fluid, and thus the level in the mother's blood is detected as high. However, most patients with a high AFP level (and thus a possible chance of fetal spina bifida) have a perfectly normal baby. The higher the "high" level is, the more chance there is of finding something wrong.
Another possible result is a "low" AFP. This is more challenging to explain. When the data from thousands of pregnancies was analyzed, there was an unexpected finding. Statistically, there were more babies with Down's syndrome born to mothers whose AFP levels were lower than average. This finding was duplicated, further analyzed, and is now the most useful aspect of the AFP test.
The low AFP by itself has no significance. We don't even know why the level is lower when Down's syndrome is present. Furthermore, this result is not 100% reliable. Most patients with a low AFP level (and thus a possible chance of Down's syndrome) have a perfectly normal baby. But some will have a baby with Down's.
Reasons for abnormal afp
In the real world, the most common reason for an abnormal AFP result (either high or low) is improper pregnancy dating. The due date must be accurately known for this test to be useful. Undiagnosed twins can cause an abnormally high result. So can undiagnosed miscarriage, fetal swallowing problems, fetal intestinal disorders, fetal cystic fibrosis, and other even more rare conditions.
The Next Step
The KEY to understanding this entire issue is this: what is supposed to be done when the AFP is either high or low? First the due date must be confirmed if there is any doubt. An ultrasound should have been done to rule out the common causes of abnormal afp such as twins or an undiagnosed miscarriage.
Next, the patient is referred to a genetic testing center for an amniocentesis. With a genetic amniocentesis, the AFP level in the amniotic fluid is determined, and the fetal chromosomes are analyzed. Additionally, a detailed ultrasound is performed. Only with these tests can it be definitively determined if the baby has spina bifida or if the baby has Down's Syndrome.
The ONLY value of the AFP test is in identifying patients who might benefit from having an ultrasound and amniocentesis, when otherwise there would have been no reason to have one!
The “fire alarm” concept - false alarms are common
Think of the abnormal AFP result as your "fire alarm" going off. The investigation of the ringing alarm is the only way to tell for sure if it was a "false alarm" or if there was a real problem. We depend on our alarms to be sensitive so we don't accidentally get hurt. We expect this and we demand this. The same is true for the AFP test, and for many, many other medical tests. However, the price to be paid for having a reliable, sensitive alarm is that invariably, there will be false alarms!
If you want to minimize or eliminate false alarms you only have two choices. You can turn off the alarm, but then you completely lose the benefit of having it. Or, you can turn down the sensitivity of the alarm (use a different cut-off for defining low and high AFP levels). But doing this could also be dangerous, because then the alarm might not go off when it was supposed to. A perfect alarm would only go off when there's a fire, and never go off otherwise. Tell me where to buy one.
A perfect test is when a normal result means with 100% certainty that everything is okay, and an abnormal results means that there is 100% chance that something bad has been found. The amniocentesis is close to being a perfect test but the AFP is not. If the amniocentesis could be easily and routinely performed on all pregnant women with zero degree of risk, it might very well become a routine test, and there would be no need for the AFP test.
Who should consider having the afp test done
The AFP test is not for everyone. If the patient is going to be over 35 by the due date, the amniocentesis is often advised. The AFP test is usually offered to patients under age 35, who would otherwise not be candidates for amniocentesis. In my opinion, neither an AFP test nor an amniocentesis should be done at all if the patient's belief system would prohibit pregnancy termination under any circumstance.
When counseling patients about drawing their blood for the AFP test, I tell them that they do not have to decide whether or not they would terminate, they just have to know if it is a possible option that they would consider if the results came back positive for a severe birth defect. Also, I would not advise an AFP blood test if the patient is already over 35. The test results take into account the mother's age, and usually will come back suggesting an increased risk for Down's, not because the blood test was abnormal, but because the computer looked at the patient's birthday.
AFP testing has allowed a greater ability to detect severe birth defects. Perhaps new technology will one day render it obsolete. For example, one day we will be able to isolate fetal cells from the mother's bloodstream, which can then be chromosomally analyzed. Additionally, we now have 3-D ultrasound that might allow for 100% detection of spina bifida without an amniocentesis. But until these tests are widely available and proven to be reliable, we have to depend on the AFP "fire alarm."
And thank goodness in the great majority of situations, "where there's smoke", doesn't mean there's a fire.