Alpha-fetoprotein (AFP) is a protein produced in large amounts by the yolk sac and the liver of a developing fetus. The protein’s concentration rises in the fetal bloodstream, and some crosses into the mother’s blood during pregnancy. After birth, AFP levels in a healthy individual drop to a very low concentration. The AFP test measures the level of this protein in a blood sample.
Contextualizing the AFP Test
The interpretation of an AFP result depends entirely on the clinical context in which the test was ordered. The test is utilized in two distinct scenarios: as a screening tool during pregnancy and as a marker for certain cancers in non-pregnant adults. The units of measurement also reflect this difference in purpose.
In prenatal screening, the test is often called Maternal Serum AFP (MSAFP) and is typically performed during the second trimester. Results are reported using the Multiples of the Median (MoM), which compares the measured value to the median AFP level for that specific gestational age. In non-pregnant adults, AFP testing functions as a tumor marker, primarily for monitoring treatment or detecting cancer recurrence. These results are usually reported in absolute concentrations, such as nanograms per milliliter (ng/mL) or International Units per milliliter (IU/mL).
Interpreting Elevated AFP Levels
An elevated AFP level holds different significance depending on whether the patient is pregnant or an adult being monitored for disease. In the prenatal context, a high MoM result suggests that a larger-than-expected amount of AFP is passing into the mother’s bloodstream. This elevation is most commonly associated with a potential Neural Tube Defect (NTD) in the fetus, such as spina bifida or anencephaly, where the neural tube fails to close completely.
The high level may also be caused by defects in the fetal abdominal wall, allowing AFP to leak directly from the fetal circulation. However, the most frequent non-pathological reasons for an elevated MoM are carrying multiple fetuses (e.g., twins) or an inaccurate estimation of the pregnancy’s gestational age. Since AFP levels change rapidly week-by-week, being even a week further along than calculated can inflate the result.
For non-pregnant adults, an elevated AFP level, typically above 10 ng/mL, can serve as an indicator for certain malignancies. The most common cancer associated with a high AFP concentration is Hepatocellular Carcinoma (HCC), which is the most prevalent form of liver cancer. Elevated levels can also be seen with non-seminomatous germ cell tumors of the testicles or ovaries.
In the oncology setting, the absolute value is less important than the trend over time. Rising AFP levels can signal disease progression or recurrence following treatment. Conversely, a rapidly decreasing AFP level often suggests a favorable response to therapy, such as chemotherapy or surgical removal of the tumor. Non-cancerous liver conditions, like cirrhosis or chronic hepatitis, can also cause mild to moderate elevations in AFP.
Interpreting Low AFP Levels
A low AFP result is almost exclusively a concern within the context of prenatal screening. When the Maternal Serum AFP (MSAFP) level falls below the established median for the gestational age, it is expressed as a low MoM value. A low AFP is one component of the multiple marker screening tests used to estimate the risk of certain chromosomal conditions.
The most recognized association for a low MoM result is an increased risk for Down Syndrome (Trisomy 21), a condition caused by an extra copy of chromosome 21. Low AFP is often combined with the results of other maternal serum markers, like unconjugated estriol and human chorionic gonadotropin, to calculate a comprehensive risk assessment. The pattern of these markers together provides a more accurate risk profile.
A low AFP level is also associated with Edwards Syndrome (Trisomy 18), a less common but more severe chromosomal abnormality. In this situation, the AFP level is often markedly low, sometimes accompanied by lower levels of the other serum markers. A low AFP result is a screening indicator only; it identifies pregnancies that warrant further investigation but does not confirm a diagnosis.
Next Steps After Screening Results
An abnormal AFP result, whether high or low, should prompt immediate follow-up testing to determine the cause. Because the AFP test is a screening tool, an atypical result indicates an increased risk, not a definitive diagnosis. In the prenatal setting, the first step after an abnormal MSAFP is usually a targeted ultrasound examination.
This imaging can precisely confirm the gestational age of the fetus, which often corrects the initial abnormal reading if the pregnancy was misdated. The ultrasound can also detect structural issues, such as open neural tube defects or abdominal wall defects, or confirm multiple fetuses. If the ultrasound does not provide a clear explanation, a diagnostic test like amniocentesis may be offered, measuring AFP directly in the amniotic fluid for a more conclusive result.
For non-pregnant patients with an elevated AFP tumor marker, additional medical imaging, such as a CT scan, MRI, or PET scan, is typically ordered to locate or assess the size of a potential tumor. If cancer is already diagnosed, the AFP level is tracked to monitor the effectiveness of the treatment plan. A persistent rise in the AFP concentration may signal that the current therapy is ineffective or that the cancer has returned, necessitating a consultation with an oncologist to adjust the treatment strategy.