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The alpha-fetoprotein (AFP) or fetal alpha globulin is thought to function in the fetus in a similar role to that of serum albumin postnatally. AFP is synthesised in both the fetal liver and the yolk sac.

The AFP test is a test that is performed during pregnancy of maternal blood or fetal amniotic fluid at 16-19 weeks of gestation. The amniotic test (Amniocentesis) is more invasive than the maternal blood test. The protein is synthesized by yolk sac and liver of the fetus and is also expressed in the adult in some liver cancers and is a member of a multigenic family encoding albumin, alpha-albumin, and vitamin D binding protein.

Low levels of AFP normally occur in the blood of a pregnant woman. Abnormal amounts of the protein may indicate genetic or developmental problems in the fetus. High levels may indicate neural tube defects (spina bifida, anencephaly), the neural tube defect allows AFP to leak through into the amniotic fluid. May also be an indicator of embryo ventral wall defects and abnormal placental structure.[1] This test can also be used in non-pregnacy testing of clinical conditions, including liver disease.[2]

Diagnosis Links: Prenatal Diagnosis | pregnancy test | amniocentesis | chorionic villus sampling | ultrasound | Alpha-Fetoprotein | Pregnancy-associated plasma protein-A | Fetal Blood Sampling | Magnetic Resonance Imaging | Computed Tomography | Non-Invasive Prenatal Testing | Fetal Cells in Maternal Blood | Preimplantation Genetic Screening | Comparative Genomic Hybridization | Genome Sequencing | Neonatal Diagnosis | Category:Prenatal Diagnosis | Fetal Surgery | Classification of Diseases | Category:Neonatal Diagnosis

Some Recent Findings

Trisomy 21 newborn
  • The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome[3] "Low maternal serum levels of pregnancy-associated plasma protein A (PAPP-A) measured in the first trimester and high levels of alpha fetoprotein (AFP) measured in the second trimester have been associated with adverse pregnancy outcomes reflective of placental insufficiency, and there is a synergistic relationship between the two. We investigated the utility as a screening test of a simple ratio of maternal serum AFP to PAPP-A (AFP:PAPP-A) measured in the first trimester. We studied 4057 nulliparous women with a singleton pregnancy from the Pregnancy Outcome Prediction (POP) study. ...An elevated maternal AFP:PAPP-A ratio in the first trimester is associated with placentally-related adverse outcomes in a cohort of unselected nulliparous women."

first trimester maternal serum alpha fetoprotein is associated with ischemic placental disease[4] |Elevated first trimester msAFP is associated with ischemic placental disease, fetal growth restriction, and preterm birth. This suggests that elevated msAFP may help to identify high risk pregnancies as early as the first trimester of pregnancy. Future studies are necessary to determine if addition of first trimester msAFP to existing algorithms can improve the early detection of ischemic placental disease.}

  • second trimester Prenatal Screening for Down's Syndrome (DS) in Mainland Chinese Subjects using Double-Marker Analysis of α-fetoprotein and β-human Chorionic Gonadotropin Combined with Measurement of Nuchal Fold Thickness ( NT)[5] "Second trimester prenatal screening using double-marker analysis for AFP and β-hCG combined with measurement of NT is effective for the detection of DS in Mainland Chinese pregnancies."
More recent papers  
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Search term: Alpha-Fetoprotein | Alpha-Fetoprotein Test

Older papers  
These papers originally appeared in the Some Recent Findings table, but as that list grew in length have now been shuffled down to this collapsible table.

See also the Discussion Page for other references listed by year and References on this current page.


  • Protein first identified in the 1950's.[6]
  • AFP Levels - normal values for males or non-pregnant females is less than 10 micrograms/millilitre.
  • Member of the albuminoid gene superfamily which includes, serum albumin, vitamin D binding protein and alpha-albumin (afamin).[7]
  • Screening has low sensitivity for fetal hydrocephalus and is rarely elevated in isolated cases.[8]
    • When fetal hydrocephalus is detected, elevated AFP levels indicate that the fetus is at significant risk to have additional malformations.
  • Serum alpha fetoprotein (AFP) has also been used as a tumor marker in the adult for liver cancer (Hepatocellular carcinoma, HCC).[7]
  • Stem cell researchers have used AFP expression as an early marker to identify differentiation of endoderm germ layer in embryoid bodies.[9]

Female Function

  • In knockout KO Mice, essential for female fertility and for expression of normal female behaviors.[10]
    • sequestrates estrogens
    • protects the female developing brain from deleterious (defeminizing/masculinizing) effects of these hormones.[11]
    • mice suffer from anovulation

Trisomy 21

Alpha-fetoprotein combined with other markers was part of a second trimester serum screening for Trisomy 21 syndrome.[12]

  • triple test - (alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG) and unconjugated estriol)
  • quadruple test - (alpha-fetoprotein (AFP), human chorionic gonadotrophin (HCG), unconjugated estriol), and inhibin A.
Links: Trisomy 21

Postnatal Diagnostic Uses

  • Serum α-fetoprotein (AFP) level is used as a tumour marker for the diagnosis and detection of hepatocellular carcinoma.
    • elevated AFP level (≥ 200 ng/dL)
  • Some patients have hereditary persistence of AFP and also have persistent abnormal AFP.

Protein Sequence

Length 609 Mass (Da) 68,678


Human Albuminoid Family

Other than AFP, all albuminoid family genes are located on chromosome 4 and the proteins are synthesised in the adult liver.

  1. Alpha-fetoprotein (Mr 69K)
  2. Serum albumin (Mr 66K)
  3. Alpha-albumin (Mr 82K)
  4. Vitamin-D-binding protein (Mr 58K)


  1. Smith GC, Shah I, Crossley JA, Aitken DA, Pell JP, Nelson SM, Cameron AD, Connor MJ & Dobbie R. (2006). Pregnancy-associated plasma protein A and alpha-fetoprotein and prediction of adverse perinatal outcome. Obstet Gynecol , 107, 161-6. PMID: 16394054 DOI.
  2. Sultana C, Diţă C, Botescu A, Grancea C & Ruţă S. (2014). SERUM ALPHA FETOPROTEIN, A SURROGATE MARKER FOR LIVER DISEASE PROGRESSION IN CHRONIC HEPATITIS C. Roum Arch Microbiol Immunol , 73, 69-73. PMID: 26201121
  3. Hughes AE, Sovio U, Gaccioli F, Cook E, Charnock-Jones DS & Smith GCS. (2019). The association between first trimester AFP to PAPP-A ratio and placentally-related adverse pregnancy outcome. Placenta , 81, 25-31. PMID: 31138428 DOI.
  4. Dinglas C, Afsar N, Cochrane E, Davis J, Kim S, Akerman M, Wells M, Chavez M, Herrera K, Heo H & Vintzileos A. (2019). First trimester maternal serum alpha fetoprotein is associated with ischemic placental disease. Am. J. Obstet. Gynecol. , , . PMID: 31794723 DOI.
  5. Liu F, Liang H, Jiang X, Zhang Y, Xue L, Yang C, Cheng J, Liu P, Liu Y & Guo X. (2011). Second trimester prenatal screening for Down's syndrome in Mainland Chinese subjects using double-marker analysis of α-fetoprotein and β-human chorionic gonadotropin combined with measurement of nuchal fold thickness. Ann. Acad. Med. Singap. , 40, 315-8. PMID: 21870022
  6. BERGSTRAND CG & CZAR B. (1956). Demonstration of a new protein fraction in serum from the human fetus. Scand. J. Clin. Lab. Invest. , 8, 174. PMID: 13351554 DOI.
  7. 7.0 7.1 Mizejewski GJ. (2004). Biological roles of alpha-fetoprotein during pregnancy and perinatal development. Exp. Biol. Med. (Maywood) , 229, 439-63. PMID: 15169963
  8. Maternal serum alpha-fetoprotein levels in fetal hydrocephalus: a retrospective population based study. Terrence P Szajkowski, Bernard N Chodirker, Karen M MacDonald, and Jane A Evans BMC Pregnancy Childbirth. 2006; 6: 23. Published online 2006 July 7. doi: 10.1186/1471-2393-6-23. PMCID: PMC1526755
  9. Pekkanen-Mattila M, Pelto-Huikko M, Kujala V, Suuronen R, Skottman H, Aalto-Setälä K & Kerkelä E. (2010). Spatial and temporal expression pattern of germ layer markers during human embryonic stem cell differentiation in embryoid bodies. Histochem. Cell Biol. , 133, 595-606. PMID: 20369364 DOI.
  10. De Mees C, Bakker J, Szpirer J & Szpirer C. (2007). Alpha-fetoprotein: from a diagnostic biomarker to a key role in female fertility. Biomark Insights , 1, 82-5. PMID: 19690639
  11. Bakker J, De Mees C, Douhard Q, Balthazart J, Gabant P, Szpirer J & Szpirer C. (2006). Alpha-fetoprotein protects the developing female mouse brain from masculinization and defeminization by estrogens. Nat. Neurosci. , 9, 220-6. PMID: 16388309 DOI.
  12. Morris RK, Cnossen JS, Langejans M, Robson SC, Kleijnen J, Ter Riet G, Mol BW, van der Post JA & Khan KS. (2008). Serum screening with Down's syndrome markers to predict pre-eclampsia and small for gestational age: systematic review and meta-analysis. BMC Pregnancy Childbirth , 8, 33. PMID: 18680570 DOI.


Mizejewski GJ. (2011). Review of the putative cell-surface receptors for alpha-fetoprotein: identification of a candidate receptor protein family. Tumour Biol. , 32, 241-58. PMID: 21120646 DOI.

Houwert AC, Giltay JC, Lentjes EG & Lock MT. (2010). Hereditary persistence of alpha-fetoprotein (HPAF P): review of the literature. Neth J Med , 68, 354-8. PMID: 21116028

Yuan W, Chen L & Bernal AL. (2009). Is elevated maternal serum alpha-fetoprotein in the second trimester of pregnancy associated with increased preterm birth risk? A systematic review and meta-analysis. Eur. J. Obstet. Gynecol. Reprod. Biol. , 145, 57-64. PMID: 19457604 DOI.

Terentiev AA & Moldogazieva NT. (2006). Structural and functional mapping of alpha-fetoprotein. Biochemistry Mosc. , 71, 120-32. PMID: 16489915

Mizejewski GJ. (2001). Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp. Biol. Med. (Maywood) , 226, 377-408. PMID: 11393167

Tomasi TB. (1977). Structure and function of alpha-fetoprotein. Annu. Rev. Med. , 28, 453-65. PMID: 67821 DOI.


La'ulu SL, Rasmussen KJ & Roberts WL. (2011). Pediatric reference intervals for serum alpha-fetoprotein. Clin. Chim. Acta , 412, 1695-6. PMID: 21640088 DOI.

Murray MJ & Nicholson JC. (2011). α-Fetoprotein. Arch Dis Child Educ Pract Ed , 96, 141-7. PMID: 21613305 DOI.

De Mees C, Bakker J, Szpirer J & Szpirer C. (2007). Alpha-fetoprotein: from a diagnostic biomarker to a key role in female fertility. Biomark Insights , 1, 82-5. PMID: 19690639

Ball D, Rose E & Alpert E. (1992). Alpha-fetoprotein levels in normal adults. Am. J. Med. Sci. , 303, 157-9. PMID: 1375809

Search PubMed

Search PubMed: Alpha-Fetoprotein


Prenatal Diagnosis Terms

  • blastomere biopsy - An ART preimplantation genetic diagnosis technique carried out at cleavage stage (day 3), excluding poor quality embryos, detects chromosomal abnormalities of both maternal and paternal origin. May not detect cellular mosaicism in the embryo.
  • blastocyst biopsy - An ART preimplantation genetic diagnosis technique carried out at blastocyst stage (day 4-5), removes several trophoblast (trophoderm) cells, detects chromosomal abnormalities of both maternal and paternal origin and may detect cellular mosaicism.
  • cell-free fetal deoxyribonucleic acid - (cfDNA) refers to fetal DNA circulating and isolated from the plasma portion of maternal blood. Can be performed from GA 10 weeks as a first-tier test or as a second-tier test, with women with increased probability on combined first trimester screening offered cfDNA or diagnostic testing.
  • false negative rate - The proportion of pregnancies that will test negative given that the congenital anomaly is present.
  • false positive rate - The proportion of pregnancies that will test positive given that the congenital anomaly is absent.
  • free β human chorionic gonadotrophin - beta-hCG subunit of hCG used as a diagnostic marker for: early detection of pregnancy, Trisomy 21, spontaneous abortion, ectopic pregnancy, hydatidiform mole or choriocarcinoma.
  • multiples of the median - (MoM) A multiple of the median is a measure of how far an individual test result deviates from the median and is used to report the results of medical screening tests, particularly where the results of the individual tests are highly variable.
  • negative predictive value - The probability that a congenital anomaly is absent given that the prenatal screening test is negative.
  • Non-Invasive Prenatal Testing - (NIPT) could refer to ultrasound or other imaging techniques, but more frequently used to describe analysis of cell-free fetal DNA circulating in maternal blood.
  • polar body biopsy - (PB biopsy) An ART preimplantation genetic diagnosis technique that removes either the first or second polar body from the zygote. As these are generated by oocyte meiosis they detects chromosomal abnormalities only on the female genetics.
  • positive predictive value - The probability that a congenital anomaly is present given that the prenatal screening test is positive.
  • prenatal screening sensitivity - (detection rate) The probability of testing positive on a prenatal screening test if the congenital anomaly is present.
  • prenatal screening specificity - The probability of testing negative on a prenatal screening test if the congenital anomaly is absent.
  • quadruple test (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, unconjugated estriol, and inhibin A) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).
  • single nucleotide polymorphisms - (SNPs) the variation in a single DNA nucleotide that occurs at a specific position in the genome.
  • triple test - (maternal serum testing of a-fetoprotein Template:AFP, free B-hCG or total hCG, and unconjugated estriol) is a fetal chromosomal anomaly test usually carried out later in pregnancy (GA 14 to 20 weeks).

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Cite this page: Hill, M.A. (2024, May 25) Embryology Alpha-Fetoprotein. Retrieved from

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