Elevated maternal alpha-fetoprotein (AFP)

• produced by the fetal liver and crosses the placenta to enter the maternal circulation.
• Any defect that causes a breech in fetal skin can result in increased levels of AFP in the maternal circulation
• These fetal defects include:
  • open neural tube defects
  • anencephaly
  • omphalocele
• Maternal serum AFP (MSAFP) levels also can be increased in
  • twin pregnancies
  • fetal demise
  • fetus has congenital nephrosis.
• Because the measurement of MSAFP is simple and inexpensive, the American College of Obstetricians and Gynecologists, the American Society of Human Genetics, and the American Academy of Pediatrics recommend offering MSAFP screening to all pregnant women at 16 to 18 weeks of gestation.
• However, such screening should be undertaken only if there is adequate counseling, access to high-quality laboratory services, and appropriate facilities for follow-up testing (ie, qualified diagnostic centers that offer conventional and high-resolution ultrasonography and amniocentesis).
•  additional biochemical markers have been added to this screening test to permit the identification of pregnancies at increased risk for chromosomal abnormalities, most notably trisomy 21.
  
   
• Cutoff is usually 2 to 2.5 times the median value for gestational age
• MSAFP screening detects most fetuses that have open neural tube defects.
• However, because it is a screening test, MSAFP results are abnormal in approximately 1% to 5% of pregnant women with normal babies
• Because the incidence of open neural tube defects is generally 1 in 1,000 or less, most findings of elevated MSAFP are due to other reasons:
  • incorrect dating of the pregnancy (most common reason for false +)
  • other congenital anomalies
  • intrauterine growth retardation
  • multiple gestations
  • fetal demise
• If the dating of the pregnancy is changed by ultrasonography, the MSAFP value should be recalculated
• If the dating is correct, the patient should be offered high-resolution fetal ultrasonography to search for anomalies.
• If ultrasonography does not provide an explanation for the abnormal result (as occurs in about 50% of cases), amniocentesis should be offered to measure amniotic fluid AFP (AFAFP).
• In general, second samples should be obtained only if the initial MSAFP concentration is minimally elevated and there is sufficient time for processing a second specimen. 

Folic Acid

• In one trial, administration of 4 mg of folic acid daily beginning at least 1 month before conception through the first trimester reduced the recurrence risk of neural tube defects from 3.5% to 1.0%.
• trials in women who have not had a prior affected pregnancy also have shown a beneficial effect.
• It is now recommended that all women of childbearing age take folic acid supplements to prevent the occurrence of neural tube defects.
• All women still should undergo MSAFP screening because there is no evidence to suggest that folic acid supplements can prevent all neural tube defects. 

Notes:

• chorionic villus sampling is used to determine fetal karyotype
• elevated MSAFP levels are associated primarily with open neural tube defects, which usually do not result from chromosome abnormalities
• And, AFP cannot be measured in chorionic villi.
• Open neural tube defects are among the most common birth defects, occurring in approximately 1 in 1,000 pregnancies.
• In most cases, there is no family history, although those who do have a positive family history may be at increased risk over the general population. There is no association of neural tube defects with maternal age.

References:
American Academy of Pediatrics Committee on Genetics. Maternal serum
alpha-fetoprotein screening. Pediatrics. 1991;88:1282-1283
American College of Obstetricians and Gynecologists.
Alpha-fetoprotein. In: ACOG Technical Bulletin: An Educational Aid to
Obstetricians-Gynecologists. Washington, DC: American College of
Obstetricians and Gynecologists; 1991:No. 154
Centers for Disease Control and Prevention. Recommendations for the
use of folic acid to reduce the number of cases of spina bifida and
other neural tube defects. MMWR Morb Mortal Wkly Rep.
1992;41(RR-14):1-7
Werler MM, Shapiro S, Mitchel AA. Periconceptional folic acid exposure
and risk of occurrent neural tube defects. JAMA. 1993;269:1257-1261