Alpha fetoprotein (AFP) is a 69,000 kD single chain polypeptide which is similar in size and structure to human serum albumin. In human embryos, AFP is first made in the yolk sac and later in the fetal liver. By the end of the first trimester, nearly all AFP is produced by the fetal liver. The concentration of AFP peaks in fetal serum between 10 and 13 weeks gestation. AFP passes by diffusion from fetal serum through fetal glomeruli into the fetal urine and then into the amniotic fluid. Amniotic levels peak in the first trimester and are 100 times lower than fetal plasma levels.
AFP appears in maternal serum by transplacental transfer. During pregnancy, maternal serum AFP levels rise steadily from a nonpregnant level of 0.2 ng/mL to a peak of approximately 250 ng/mL at 32 weeks of gestation. Thereafter, maternal serum AFP levels decline until term.
Screening of pregnant women for increased AFP serum levels is a routine method of detecting neural tube defects of the fetus prior to birth. Neural tube defects (NTD), such as spina bifida and anencephaly, result from the incomplete closure or functional incompetence of the neural tube. This results in leakage of fetal AFP into the amniotic fluid and increased levels in maternal sera. Screening for NTD is most useful and accurate when performed between 15-20 weeks gestation because there is a greater spread in normal values with advancing pregnancy.
An maternal serum AFP screening program detects approximately 88% of fetuses with anencephaly and 77% of those with open spina bifida. Other fetal abnormalities can also result in elevated maternal serum AFP levels: omphalocele, gastroschisis, congenital kidney disease, and esophageal atresia. Increased levels are also seen with multiple pregnancy, fetal distress and intrauterine death.
Decreased levels of AFP are associated with trisomy 21 (Down Syndrome) and trisomy 18 (Edwards syndrome). Prenatal AFP screening detects 20% of affected fetuses in women less than 35 years of age. Abnormal AFP levels are not diagnostic for neural tube defect or Down Syndrome, but define a population that requires further testing.
AFP is measured in maternal serum and the value is compared to the median AFP value in an unaffected population to obtain a multiple of the median (MoM). The reference range is 0.25 - 2.50 MoM. An AFP MoM of <2.5 is reported as a negative result. An MoM >2.50 does not confirm a diagnosis of neural tube defect, but indicates the need for further evaluation.
Specimen requirement is one SST tube of blood.
Maternal serum AFP is often measured as part of a quadruple screen, including estriol and human chorionic gonadotropin, and inhibin A.
References
Christensen RL, Rea MR, Kessler G, Crane JP, Valdes R Jr. Implementation of a screening program for diagnosing open neural tube defects: selection, evaluation, and utilization of alpha-fetoprotein methodology. Clin Chem. 1986;32(10):1812-1817.
American College of Obstetricians and Gynecologists: Practice Bulletin No. 163: Screening for Fetal Aneuploidy. Obstet Gynecol. 2016;127(5):e123-137
How to resolve AdBlock issue?