From the Guidelines
Alpha fetoprotein (AFP) is a crucial biomarker used in prenatal screening and cancer detection, with elevated levels indicating potential neural tube defects or liver diseases, and low levels suggesting Down syndrome or other chromosomal abnormalities. During pregnancy, AFP is measured between 15-20 weeks gestation to assess the risk of neural tube defects, Down syndrome, and other chromosomal abnormalities 1. The optimal time for neural tube defect screening is at 16 to 18 weeks gestation, with a cut-off level of 2.0 to 2.5 multiples of the median (MoM) in singleton pregnancies, and 4.0 to 5.0 MoM in twin pregnancies 1.
Key Points to Consider
- Elevated AFP levels may indicate neural tube defects like spina bifida, while abnormally low levels can suggest Down syndrome 1.
- In non-pregnant adults, AFP is normally present only in very small amounts, with a normal range of less than 10 ng/mL 1.
- Elevated AFP levels in adults can indicate liver diseases, particularly hepatocellular carcinoma (liver cancer), as well as certain testicular and ovarian germ cell tumors 1.
- Regular monitoring of AFP levels is recommended for patients with chronic liver disease to detect early liver cancer development when treatment options are more effective 1.
Clinical Guidelines
- Maternal serum screening has been modified during the past 25 years and is now widely utilized during the second trimester to identify women at risk for fetal open neural tube defects (ONTDs), anencephaly, and trisomies 21 and 18 1.
- The American College of Medical Genetics (ACMG) recommends using a second trimester Down syndrome cut-off risk of 1 in 270, with a combination of maternal age, MSAFP, hCG, uE3, and INH-A detecting approximately 75% of Down syndrome cases in women who are younger than 35 years with a positive screening rate of 5% 1.
From the Research
Alpha Fetoprotein Overview
- Alpha fetoprotein (AFP) is a protein produced by the fetal liver and is the major protein of fetal serum, resembling albumen which replaces it shortly after birth 2.
- It passes into the amniotic fluid via fetal urine and a small amount crosses into the maternal circulation.
Clinical Significance
- Elevated levels of AFP in amniotic fluid or maternal serum can indicate fetal demise or abnormalities such as neural tube defects 2, 3.
- Maternal serum AFP measurement can be used as a screening procedure to identify neural tube defects, but requires a rigorous protocol including laboratory-established normal ranges, reliable assays, and access to genetic counseling and expert sonography 2.
Screening and Diagnosis
- Second-trimester anatomical sonography, first-trimester sonographic screening, maternal serum alpha-fetoprotein, and prenatal magnetic resonance imaging are recommended for screening neural tube defects 4.
- Diagnostic amniocentesis with chromosomal microarray and amniotic fluid alpha-fetoprotein and acetylcholinesterase can be used for genetic testing 4.
- Amniotic fluid acetylcholinesterase measurement can be used in conjunction with AFP measurement for prenatal diagnosis of open neural tube defects, with a high detection rate and low false-positive rate 5.
Interpretation of Results
- Concentrations of maternal serum alpha-fetoprotein can be adjusted for variables such as maternal weight, race, residence, and gestational age to provide predicted risks of fetal conditions 6.
- Clinical laboratories can report results of assays of maternal serum alpha-fetoprotein in terms of predicted risks to facilitate understanding by physicians and patients 6.