What is Serum Alpha-Fetoprotein?
Serum alpha-fetoprotein (AFP) is an alpha globulin protein synthesized initially by the yolk sac and later by the fetal liver during early fetal development, which passes into fetal bloodstream, is excreted into amniotic fluid, and appears in maternal blood at much lower concentrations. 1
Biochemical Characteristics
AFP is an oncofetal glycoprotein that serves as the major serum protein during fetal life, most closely resembling albumin, which replaces it shortly after birth. 2, 3
The protein can be measured in international units or in mass units such as nanograms or micrograms. 1
AFP passes from fetal bloodstream through the kidneys into urine, then is excreted into amniotic fluid (designated as AFP), and crosses into maternal circulation at concentrations much lower than in amniotic fluid. 1
Normal Physiological Patterns
During human fetal development, serum AFP concentration falls with increasing gestational age, and 4-5 weeks after birth, AFP is detectable only in low serum concentrations (10-20 ng/ml in normal adults using sensitive radioimmunoassay). 4
During pregnancy, AFP serum concentrations rise physiologically up to 500-550 ng/ml in maternal circulation. 4
In newborn rats (translatable to humans), AFP production is abruptly terminated at approximately 4 weeks of age, closely associated with cessation of liver cell proliferation. 5
Clinical Applications in Pregnancy
Maternal serum AFP (MSAFP) screening between 15-20 weeks gestation detects open neural tube defects with 95% sensitivity for anencephaly and 75-90% sensitivity for open spina bifida using a 2.0 MoM cutoff level. 6, 7
Elevated maternal serum AFP is strongly associated with open neural tube defects, ventral wall defects (gastroschisis, omphalocele), or incorrect gestational dating. 8, 7
Low AFP values may be associated with chromosomal abnormalities including Down syndrome. 1, 6
The distribution of MSAFP results is influenced by race, insulin-dependent diabetes mellitus (IDDM), and maternal weight, requiring separate normative values for accurate interpretation. 1, 6
Clinical Applications in Oncology
Nonseminomatous germ cell tumors are strongly associated with elevated AFP levels, and AFP >20 ng/ml in adults requires thorough evaluation to rule out malignancy. 8
Hepatoblastoma in children, particularly those with Beckwith-Wiedemann syndrome, is strongly associated with elevated AFP. 8
AFP elevation above 2 microgram/ml occurs in primary liver cell carcinoma, hepatoblastoma, and teratoblastoma containing yolk sac tissue due to AFP synthesis in tumor cells. 4
The approximate half-life of AFP is 5-7 days, making it useful for monitoring treatment response and detecting early relapse in testicular cancer and hepatocellular carcinoma. 8, 9
Non-Malignant Elevations
Increased AFP levels signify severity of hepatic destruction and subsequent regeneration, commonly observed in acute and chronic liver conditions, cirrhosis, and virus hepatitis. 2, 4
AFP production recurs in adult rats following reinitiation of hepatic DNA synthesis induced by partial hepatectomy or hepatotoxic chemicals, with replicating hepatocytes producing AFP. 5
Hereditary disorders including congenital tyrosinemia and ataxia-telangiectasia can cause AFP elevation. 4
Critical Interpretation Considerations
AFP results must be interpreted in context of patient age, gestational age (in pregnancy), clinical history, and trend over time rather than single values. 8, 6
Extremely elevated AFP levels (>10,000 ng/mL) in pregnancy raise concern for germ cell tumor requiring oncologic evaluation. 7
False-positive results may occur due to incorrect gestational dating or multiple gestation. 6