Alpha-fetoprotein (AFP) is a major plasma protein produced primarily by the yolk sac and the fetal liver during prenatal development. It acts as the fetal counterpart to serum albumin, transporting molecules like fatty acids and hormones. After birth, AFP levels drop significantly, and only trace amounts are found in healthy adults. Measuring AFP levels in the blood, either maternal or adult, is a widely used clinical tool for two different diagnostic purposes.
The Role of AFP in Prenatal Screening
Maternal Serum Alpha-fetoprotein (MSAFP) testing is offered as a screening measure during the second trimester of pregnancy, usually between 15 and 20 weeks of gestation. This blood test assesses the level of AFP that has crossed from the fetal circulation and amniotic fluid into the mother’s bloodstream. The test identifies pregnancies that may have an increased risk for certain birth defects.
To standardize results, AFP values are reported as Multiples of the Median (MoMs). The median is the central AFP value established for unaffected pregnancies at a specific gestational age. A result is considered abnormal if it falls significantly above or below this median, often using a threshold of 2.5 MoM for high results.
Abnormally high MSAFP levels may indicate the fetus has an open neural tube defect (ONTD), such as spina bifida or anencephaly. These conditions allow AFP to leak directly from the fetal cerebrospinal fluid into the amniotic fluid and subsequently into the mother’s blood. High levels can also be associated with abdominal wall defects, placental abnormalities, or the presence of multiple fetuses (e.g., twins).
Conversely, an abnormally low MSAFP level is associated with an increased risk for certain chromosomal abnormalities. Low MoM values may suggest conditions like Down syndrome (Trisomy 21) or Trisomy 18 (Edwards syndrome). MSAFP is a screening tool, not a definitive diagnosis. An abnormal result indicates the need for further, more detailed confirmatory testing, such as a targeted ultrasound or amniocentesis.
AFP as a Biomarker for Cancer Diagnosis and Monitoring
Outside of pregnancy, AFP is utilized as a tumor marker in the management of specific cancers where adult cells re-express this fetal protein. It is primarily associated with Hepatocellular Carcinoma (HCC), the most common form of liver cancer. In non-pregnant adults, AFP levels are normally very low, often below 10 ng/mL, making persistent elevation a potential warning sign.
For HCC, a significantly elevated AFP level, sometimes exceeding 400 ng/mL, suggests the presence of cancer. AFP is used in combination with imaging to aid in initial diagnosis and can help with cancer staging. The protein is also a marker for non-seminomatous germ cell tumors, which frequently arise in the testes or ovaries. These tumors include subtypes like yolk sac tumors and embryonal carcinomas, and often present with extremely high AFP levels.
In patients treated for HCC or germ cell tumors, AFP levels are used for continuous monitoring. A decrease in AFP after surgery or chemotherapy suggests successful treatment, while a rise may indicate recurrence or progression. Moderately elevated AFP levels can also occur in non-cancerous conditions, such as chronic liver diseases like hepatitis or cirrhosis, due to liver cell regeneration. These benign elevations do not reach the high pathological levels seen in active cancer.
Factors Influencing Measured AFP Values
The interpretation of an AFP test result can be complicated by several physiological and technical variables that artificially affect the measured value. Since AFP levels change rapidly throughout the second trimester, the most common source of error in prenatal screening is an inaccurate calculation of gestational age. If the pregnancy is further along than thought, the AFP level will appear artificially high; conversely, if the pregnancy is less advanced, the level will appear artificially low.
Maternal weight systematically influences the measured concentration of AFP in the blood. Heavier pregnant women tend to have lower AFP levels because the protein is diluted in a larger blood volume. To correct for this, laboratory results are adjusted based on the mother’s weight to ensure an accurate MoM calculation.
Racial and ethnic background can influence baseline AFP values, necessitating specific adjustments to the median used for MoM calculations. Other variables, such as diabetes and cigarette smoking, also affect serum AFP levels and must be accounted for during interpretation. These adjustments ensure that the reported MoM accurately reflects the risk level rather than a non-disease-related physiological variation.