Alpha-Fetoprotein (AFP): Definition and Clinical Significance
Alpha-fetoprotein (AFP) is an alpha globulin protein primarily produced by the fetal liver that serves as an important biomarker for various clinical conditions, with abnormal values indicating potential fetal anomalies, liver disease, or certain malignancies. 1
What is AFP?
AFP is a glycoprotein molecule with similarity to albumin, synthesized initially by the yolk sac and later predominantly by the fetal liver during early development. It passes into the fetal bloodstream and through the kidneys into the amniotic fluid, with small amounts crossing into maternal circulation. 1, 2
Key characteristics of AFP include:
- Major protein in fetal serum during development
- Measured in international units or mass units (nanograms or micrograms)
- Replaced by albumin shortly after birth
- Present in maternal serum at much lower concentrations than in amniotic fluid
Normal AFP Values
In Fetuses and Newborns
- AFP is present in high concentrations in fetal serum (up to 5,000 μg/L) 3
- Reference interval at birth (umbilical cord blood): 15.7-146.5 μg/mL (95% CI) 4
- Median value at birth: 48.3 μg/mL 4
- AFP levels decrease to 9.7-111.9 μg/mL (95% CI) by 60±24 hours after birth 4
- A significant negative correlation exists between AFP levels and gestational age 4
In Adults
- Normal adult values: approximately 0.5-15 μg/L from age 2 years onward 3
- AFP should be virtually undetectable in healthy adults
Clinical Significance of AFP Values
Elevated AFP Levels
Pregnancy-Related Conditions:
Liver Disease:
Malignancies:
- Hepatocellular carcinoma (primary liver cancer)
- Germ cell tumors
- Yolk sac tumors
- Some gastrointestinal cancers
Neurological Disorders:
- Four neurodegenerative disorders characterized by cerebellar ataxia, abnormal ocular movements, and neuropathy show elevated AFP 3
Low AFP Levels in Pregnancy
- May indicate Down syndrome or other chromosomal abnormalities 1, 5
- Complete AFP deficiency is extremely rare (estimated 1/105,000 newborns) 5
Interpretation Considerations
Gestational Age: AFP values must be interpreted in the context of accurate gestational age, as levels vary significantly throughout pregnancy 1
Demographic Factors: The distribution of maternal serum AFP (MSAFP) is influenced by:
- Race
- Maternal diabetes status
- Maternal weight
- These factors may require separate normative values 1
Monitoring Trends: For conditions like HCC or tyrosinemia type I, the trend of AFP values over time is often more important than a single measurement 1
False Positives: Elevated AFP in maternal serum can occur with multiple gestations, incorrect gestational age dating, or fetal demise 1
Screening vs. Diagnostic: AFP is a screening test that requires follow-up diagnostic testing when abnormal 1
AFP in Disease Monitoring
Hepatocellular Carcinoma: AFP is a key surveillance marker for HCC in high-risk populations, though its sensitivity and specificity are debated 1
Tyrosinemia Type I: In patients with this metabolic disorder, AFP is an important marker for monitoring disease progression and treatment efficacy. Levels should decrease continuously throughout the first year of treatment with NTBC therapy 1
Pregnancy Screening: AFP is part of maternal serum screening programs for neural tube defects and Down syndrome 1
Important Caveats
AFP alone has limited sensitivity and specificity as a screening biomarker for HCC, with elevated levels found in <20% of early-stage HCC patients 1
Normal AFP values do not guarantee the absence of HCC 1
In newborns, the wide range of normal values requires cautious interpretation 4
AFP levels in maternal serum must be interpreted with consideration of demographic and clinical factors 1