Alpha-fetoprotein (AFP) is a protein produced primarily during fetal development. A serum test measures the concentration of this protein in the blood. This simple blood draw is used in two distinct medical contexts: prenatal care, where it screens for certain developmental conditions in a fetus, and oncology, where it monitors specific types of cancer.
The Biological Function of Alpha-Fetoprotein
Alpha-fetoprotein is one of the most abundant proteins found in the plasma of a developing fetus. Production begins in the yolk sac and is later taken over by the fetal liver and gastrointestinal tract. AFP functions as a carrier protein, transporting essential materials like fatty acids, hormones, and retinoids to growing cells. Its structure is similar to serum albumin.
The protein also binds estrogen, which may help regulate the fetal hormonal environment. AFP levels are extremely high in the fetus, peaking around the 12th week of gestation, and decline rapidly after birth. By eight to twelve months of age, an infant’s AFP concentration reaches the low levels found in non-pregnant adults, typically less than 10 to 40 nanograms per milliliter of blood.
AFP Screening During Pregnancy
The AFP test is commonly offered to pregnant individuals as a screening tool, typically performed between the 15th and 20th weeks of gestation. This maternal serum AFP (MSAFP) measurement is often included in a multiple marker screen, such as the triple or quad screen, which assesses other placental hormones. The screening estimates a fetus’s risk for certain birth defects and genetic disorders.
High AFP levels in the mother’s blood can suggest the presence of an open neural tube defect (NTD), such as spina bifida or anencephaly. In NTDs, the incompletely closed nervous system structure allows AFP to leak into the amniotic fluid and cross into the mother’s bloodstream. Elevated AFP can also indicate conditions where the fetal skin barrier is compromised, such as abdominal wall defects like omphalocele or gastroschisis.
Conversely, lower than expected AFP levels can signal an increased risk for certain chromosomal abnormalities. Low AFP, often combined with abnormal levels of other markers like human chorionic gonadotropin (hCG) and estriol, may suggest an elevated risk for Trisomy 21 (Down syndrome) or Trisomy 18 (Edwards syndrome). Accurate calculation of gestational age is important for interpreting these results, as AFP levels naturally change significantly throughout the pregnancy.
Using AFP as a Tumor Marker
Outside of prenatal care, AFP is primarily used in non-pregnant adults as a tumor marker. Elevated AFP can signal certain malignancies because these cancers re-activate the gene normally suppressed after infancy. The test is most relevant for the diagnosis and management of primary liver cancer, specifically hepatocellular carcinoma (HCC).
AFP testing, often combined with imaging like ultrasound, is a standard tool for screening individuals at high risk for HCC, such as those with chronic hepatitis or liver cirrhosis. High AFP levels are also associated with certain germ cell tumors originating in reproductive cells (e.g., testicles or ovaries). Monitoring AFP concentration helps track a patient’s response to treatment. A decrease suggests effective therapy, while a rising level indicates tumor growth or recurrence.
Understanding Test Limitations and Follow-Up Steps
The AFP serum test is a screening or monitoring tool, not a definitive diagnosis on its own. An abnormal result simply indicates an increased risk and necessitates further investigation. For example, the most common reason for an elevated AFP during pregnancy is an incorrect estimation of the due date, which skews the interpretation of the protein’s concentration.
Other non-malignant conditions can also cause elevated AFP levels in adults, including non-cancerous liver diseases like cirrhosis, chronic hepatitis, or acute liver injury. Additionally, some individuals with AFP-related cancers may have normal levels, meaning the test cannot completely rule out a malignancy.
For this reason, an abnormal AFP result in a pregnant person often leads to a targeted ultrasound or amniocentesis for a definitive diagnosis. In the oncology setting, an atypical AFP level will trigger additional diagnostic procedures such as CT scans, biopsies, or magnetic resonance imaging to confirm the presence of cancer.