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'Alpha-fetoprotein' ('AFP') is a molecule produced in the developing embryo and fetus. In humans, AFP levels decrease gradually after birth, reaching adult levels by 8 to 12 months. Normal adult AFP levels are low, but detectable; however, AFP has no known function in normal adults. In normal fetuses, AFP binds the hormone estradiol. AFP is measured in pregnant women, using maternal blood or amniotic fluid, as a screening test for a subset developmental abnormalities, principally open neural tube defects. It is also measured in pregnant women, other adults, and children, to detect a subset tumors, principally endodermal sinus tumors.

Contents

Structure and levels

History

AFP in normal infants

AFP tests

Maternal serum

Tumor marker

References

See also

External links

Structure and levels

AFP is a glycoprotein of 590 amino acids and a carbohydrate moiety that is normally produced by the fetal yolk sac, the fetal gastrointestinal tract, and eventually by the fetal liver. Levels of AFP in fetal serum rise until the end of the first trimester of gestation and then fall. Because the fetus excretes AFP into its urine, amniotic fluid levels of AFP tend to mirror fetal serum levels. In contrast, maternal serum levels of fetal AFP are much lower but continue to rise until about week 32.

History

LabCorp, a large US clinical laboratory testing company, began offering AFP screening tests in the early 1980s.^[1]

AFP in normal infants

The normal range of AFP for adults is variously reported as under 50, under 10, and under 5. At birth, normal infants have AFP levels 4 or more magnitudes above^{[2][3][4][5][6][7]} the normal range for adults,^[8][9] decreasing to adult levels over the first year of life. Correct evaluation of ''abnormal'' AFP levels in infants must take into account this normal pattern.
Very high AFP levels may be subject to 'hooking', resulting in a false low level.^[10]

AFP tests

There are two categories of AFP tests: tests performed on serum (blood plasma), and tests performed on
amniotic fluid. Tests performed on serum are further categorized by the reason for performing the test: maternal serum, adult tumor marker, and pediatric tumor marker.
===Tests performed on serum===
For these tests, the patient visits a phlebotomy lab to have a blood sample drawn. Usually, this requires that the patient (or guardian) first obtain a written order from the patient's physician. In the US, an alternative is to use MyMedLab.
The standard is a quantitative test, reporting a measured concentration of AFP in the sample, but there is also a less expensive qualitative test, reporting only that the concentration is normal or high. The qualitative test is appropriate only in some circumstances.
The resulting test report should specify the assay method and equipment used, and the report of a quantitative test should also provide a reference range for the test result. Many laboratories report reference ranges that are based on all other samples tested in that laboratory, necessarily including samples with abnormal AFP concentrations due to disease. Superior reference ranges are produced by research on healthy subjects.

Maternal serum

Maternal serum AFP tests need to be interpreted according to the gestational age, as levels rise until about 32 weeks gestation. Typically, such measurements are done in the middle of the second trimester (14-16 weeks). Elevated levels are seen in multiple gestation as well as in a number of fetal abnormalities, such as neural tube defects including spina bifida and anencephaly, and abdominal wall defects. Other possibilities are errors in the date of the gestation or fetal demise. In contrast, low levels of maternal serum AFP are associated with Down syndrome and trisomy 18. Diabetic patients also have lower levels. Patients with abnormal levels need to undergo detailed obstetric ultrasonography. The information is then used to decide whether to proceed with amniocentesis.
Maternal serum AFP may be measured as part of a routine prenatal screening test:

★ Triple test: AFP, hCG and estriol

★ 'Quad test': AFP, hCG, estriol, and Inhibin

★ Genetic counseling usually is offered when the screening test result is positive.

Tumor marker

Like any elevated tumor marker, elevated AFP by itself is not diagnostic, only suggestive. Tumor markers are used primarily to monitor the result of a treatment (e.g. chemotherapy), if levels of AFP go down, the tumor is not growing. A short term increase in AFP immediately following chemotherapy may indicate the tumor is not growing but rather paradoxically shrinking (and releasing more AFP as a result). AFP-L3, an isoform of AFP which binds ''Lens culinaris'' agglutinin, can be particularly useful in early identification of aggressive tumors associated with hepatocellular carcinoma (HCC).
AFP is the main tumor marker (along with HCG) used to monitor testicular cancer and teratoma in any location: values of AFP over time can have significant effect on the treatment plan.
AFP is normally elevated in infants, and because teratoma is the single most common kind of tumor in infants, several studies have provided reference ranges for AFP in normal infants.^[11][12][13]. Perhaps the most useful is this equation: log Y = 7.397 - 2.622.log (X + 10), where X = age in days and Y = AFP level in nanograms per milliliter.^[14]
=== Tests performed on cerebrospinal fluid (CSF) ===
In normal infants, AFP in CSF is^[15]:

★ median 61 kIU/L (5th-95th centile: 2-889 kIU/L) in infants -69 to 31 days old

★ median 1.2 kIU/L (5th-95th centile: 0.1-12.5 kIU/L) in infants 32 to 110 days old
Levels of AFP in CSF decline with gestational age in proportion to levels of AFP in serum^[16]

References

1. LabCorp 2004 Annual Report
2. Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age., Blohm ME, Vesterling-Hörner D, Calaminus G, Göbel U, , , Pediatric hematology and oncology, 1998
3. Alpha-fetoprotein (AFP) levels in normal children., Ohama K, Nagase H, Ogino K, ''et al'', , , European journal of pediatric surgery : official journal of Austrian Association of Pediatric Surgery ... [et al] = Zeitschrift für Kinderchirurgie, 1997
4. Serum alpha-fetoprotein in normal Chinese infants., Lee PI, Chang MH, Chen DS, Lee CY, , , Zhonghua Minguo xiao er ke yi xue hui za zhi [Journal]. Zhonghua Minguo xiao er ke yi xue hui, 1988
5. Plasma alpha fetoprotein reference ranges in infancy: effect of prematurity., Blair JI, Carachi R, Gupta R, Sim FG, McAllister EJ, Weston R, , , Arch. Dis. Child., 1987
6. Alpha-fetoprotein in the early neonatal period--a large study and review of the literature, Bader D, Riskin A, Vafsi O, ''et al'', , , Clin. Chim. Acta, 2004
7.
8. Alpha-fetoprotein levels in normal adults, Ball D, Rose E, Alpert E, , , Am. J. Med. Sci., 1992
9. Mean alpha-fetoprotein values of 1,333 males over 15 years by age groups, Sizaret P, Martel N, Tuyns A, Reynaud S, , , Digestion, 1977
10. The hook effect: a need for constant vigilance., Jassam N, Jones CM, Briscoe T, Horner JH, , , Ann. Clin. Biochem., 2006
11. Serum alpha fetoprotein (AFP) levels in normal infants
12. Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age
13. Alpha-fetoprotein in the early neonatal period--a large study and review of the literature
14. Serum alpha-fetoprotein levels in normal infants: a reappraisal of regression analysis and sex difference
15. Coakley J, Kellie SJ, Nath C, Munas A, Cooke-Yarborough C. Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants. Ann Clin Biochem. 2005 Jan;42(Pt 1):24-9. PubMed abstract
16. Alpha-fetoprotein in human fetal cerebrospinal fluid

See also

★ Tumor marker

External links

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