What is Alpha-Fetoprotein (AFP) testing done for?

Alpha-Fetoprotein (AFP) Testing: Clinical Applications

AFP testing is primarily done for prenatal screening of open neural tube defects and Down syndrome in pregnant women (maternal serum AFP), and for detection and monitoring of certain malignancies including hepatocellular carcinoma, hepatoblastoma, and nonseminomatous germ cell tumors in non-pregnant patients. 1, 2

Prenatal Screening Applications

Primary Indications in Pregnancy

• Maternal serum AFP (MSAFP) is used primarily to predict occurrence of open neural tube defects in the fetus, including anencephaly and open spina bifida cystica 3
• Abnormal MSAFP levels (both high and low) also predict other adverse pregnancy outcomes including Down syndrome, imminent miscarriages, fetal demise, and eventual prematurity 3
• The optimal screening window is between 16 and 18 weeks of gestation 3, 2

Important Screening Caveats

• MSAFP is a screening test, not diagnostic—both false-negative and false-positive results occur 3
• The test requires a comprehensive program with baseline values, follow-up procedures, counseling, level II ultrasound capability, and amniocentesis availability 3
• MSAFP screening should be voluntary with nondirective counseling provided early in pregnancy 3
• Women with insulin-dependent diabetes mellitus require separate consideration as AFP levels are lower on average in this population 2

Malignancy Detection and Monitoring

Germ Cell Tumors

• Nonseminomatous germ cell tumors are strongly associated with elevated AFP levels, and the National Comprehensive Cancer Network recommends thorough evaluation to rule out malignancy in adults with AFP >20 ng/mL 1
• AFP has an approximate half-life of 5-7 days, making it useful for monitoring treatment response and detecting early relapse in testicular cancer 1
• For suspected intracranial germ cell tumors, both serum and cerebrospinal fluid levels of AFP and human chorionic gonadotropin should be measured 4

Hepatocellular Carcinoma (HCC)

• AFP >200 ng/mL with characteristic imaging features allows HCC diagnosis without biopsy in patients with chronic liver disease 2
• A rising AFP over time in a step-like manner strongly suggests HCC, even if absolute values remain below diagnostic thresholds 2
• Up to 35% of HCC cases have normal AFP levels, even with large tumors, highlighting limited sensitivity as a standalone test 2
• For patients with chronic liver disease or hepatitis B/C, contrast-enhanced CT or MRI should be ordered when AFP is elevated 2

Pediatric Malignancies

• Hepatoblastoma is strongly associated with elevated AFP, particularly in children with Beckwith-Wiedemann syndrome 1
• The American Cancer Society recommends regular AFP monitoring and abdominal ultrasound every 3 months through the child's fourth birthday for children with overgrowth syndromes 1
• Elevated serum AFP after the first two postnatal years usually indicates malignant disease, as AFP is only produced physiologically during fetal development 4

Interpretation Principles

Critical Considerations

• AFP results must be interpreted in context of patient age, clinical history, symptoms, and trend over time rather than single values 1
• In infants under 2 years, serial values should be plotted on a logarithmic chart to ensure appropriate decline with a typical half-life of 5-6 days 4
• The rate of decline after treatment is important in assessing treatment response 1
• Small rises within reference ranges should not trigger additional testing 1

Common Pitfalls

• AFP is not solely a cancer marker—it is the major protein of fetal serum and normally present during pregnancy 5
• Chronic liver disease can cause AFP elevation without malignancy 4
• Some genetic mutations cause complete inhibition of AFP production by the fetus, affecting screening test results 6