Vol 93, No 1 (2022)
Review paper
Published online: 2021-12-21

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Alpha-fetoprotein (AFP) — new aspects of a well-known marker in perinatology

Joanna Glowska-Ciemny1, Jakub Pankiewicz1, Zbyszko Malewski12, Constantin von Kaisenberg3, Rafal Kocylowski1
Pubmed: 35072257
Ginekol Pol 2022;93(1):70-75.


Alpha-fetoprotein (AFP) is a serum protein, which is characteristic of the fetal development period and a well-known oncological marker. The predominance of AFP among serum proteins is common in fetal life, whereas after birthing its functions are gradually taken over by albumins. An understanding of the mechanism of AFP transfer between fetus and mother has led to the development of screening tests for identifying neural tube defects and Down’s syndrome. Currently, the knowledge on patophysiology and the possible importance of AFP in perinatology and fetal medicine extends far beyond those 2 disease states. Throughout the 50 years of research on AFP, there has been dynamic progress of diagnostic techniques, from the qualitative ones that are used solely for scientific studies to the widely used radioimmunoassays and immunoenzymatic assays (enzyme-linked immunosorbent assay, chemiluminescence immunoassay, time-resolved fluorescence immunoassay). Some genetic mutations cause complete inhibition of AFP production by the fetus. This affects the results of screening tests during pregnancy, and also leads to constantly high levels of AFP in adults, which are not linked to oncogenesis.  

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  1. Mizejewski GJ. Levels of alpha-fetoprotein during pregnancy and early infancy in normal and disease states. Obstet Gynecol Surv. 2003; 58(12): 804–826.
  2. Adinolfi A, Adinolfi M. Alpha-feto-protein during development and in disease. J Med Genet. 1975; 12(2): 138–151.
  3. Terentiev AA, Moldogazieva NT. Alpha-fetoprotein: a renaissance. Tumour Biol. 2013; 34(4): 2075–2091.
  4. Murray MJ, Nicholson JC. α-Fetoprotein. Archives of Disease in Childhood - Education and Practice. 2011; 96(4): 141–147.
  5. Li X, Alexander S. Hereditary persistence of alpha-fetoprotein. Pediatr Blood Cancer. 2009; 52(3): 403–405.
  6. Butterstein G, Morrison J, Mizejewski GJ. Effect of alpha-fetoprotein and derived peptides on insulin- and estrogen-induced fetotoxicity. Fetal Diagn Ther. 2003; 18(5): 360–369.
  7. Petit FM, Hébert M, Picone O, et al. A new mutation in the AFP gene responsible for a total absence of alpha feto-protein on second trimester maternal serum screening for Down syndrome. Eur J Hum Genet. 2009; 17(3): 387–390.
  8. Mizejewski GJ. Alpha-fetoprotein structure and function: relevance to isoforms, epitopes, and conformational variants. Exp Biol Med (Maywood). 2001; 226(5): 377–408.
  9. Bartha JL, Illanes S, González-Bugatto F, et al. Maternal serum transformed alpha-fetoprotein levels in women with intrauterine growth retardation. Fetal Diagn Ther. 2007; 22(4): 294–298.
  10. González-Bugatto F, Bailén Md, Fernández-Macías R, et al. Transformed alpha-fetoprotein (t-AFP) levels in women with threatened preterm labor. Gynecol Obstet Invest. 2009; 68(3): 199–204.
  11. Mizejewski GJ, Mirowski M, Garnuszek P, et al. Targeted delivery of anti-cancer growth inhibitory peptides derived from human alpha-fetoprotein: review of an International Multi-Center Collaborative Study. J Drug Target. 2010; 18(8): 575–588.
  12. Mizejewski GJ. The alpha-fetoprotein third domain receptor binding fragment: in search of scavenger and associated receptor targets. J Drug Target. 2015; 23(6): 538–551.
  13. Huai L, Leng J, Ma S, et al. Replacing alpha-fetoprotein with alpha-fetoprotein-l3 increases the sensitivity of prenatal screening for trisomy 21. Am J Ther. 2016; 23(6): e1754–e1757.
  14. Yamamoto R, Ohkouchi T, Tabata K, et al. A study of oligosaccharide variants of alpha-fetoproteins produced by normal fetuses and fetuses with trisomy 21. Acta Obstet Gynecol Scand. 2005; 84(12): 1145–1149.
  15. Chen Y, Wang X, Lu S, et al. The diagnostic accuracy of maternal serum alpha-fetoprotein variants (AFP-L2 and AFP-L3) in predicting fetal open neural tube defects and abdominal wall defects. Clin Chim Acta. 2020; 507: 125–131.
  16. Sharony R, Amiel A, Bouaron N, et al. Congenital deficiency of alpha-fetoprotein and associated chromosomal abnormality in the placenta. Am J Med Genet A. 2003; 121A(2): 113–117.
  17. Schefer H, Mattmann S, Joss RA. Hereditary persistence of alpha-fetoprotein. Case report and review of the literature. Ann Oncol. 1998; 9(6): 667–672.
  18. Hereditary persistence of alpha-fetoprotein: a rare cause for unexplained alpha-fetoprotein elevations in pregnancy. Ct Med. 2013; 77(1): 43–45.
  19. Houwert AC, Giltay JC, Lentjes EGWM, et al. Hereditary persistence of alpha-fetoprotein (HPAF P): review of the literature. Neth J Med. 2010; 68(11): 354–358.
  20. Newby D, Dalgliesh G, Lyall F, et al. Alphafetoprotein and alphafetoprotein receptor expression in the normal human placenta at term. Placenta. 2005; 26(2-3): 190–200.
  21. Crandall BF, Robertson RD, Lebherz TB, et al. Maternal serum alpha-fetoprotein screening for the detection of neural tube defects. West J Med. 1983; 138(4): 524–530.
  22. Yachnin S. The clinical significance of human alpha-fetoprotein. Ann Clin Lab Sci. 1978; 8(2): 84–90.
  23. Liang OD, Korff T, Eckhardt J, et al. Oncodevelopmental alpha-fetoprotein acts as a selective proangiogenic factor on endothelial cell from the fetomaternal unit. J Clin Endocrinol Metab. 2004; 89(3): 1415–1422.
  24. Christiansen M, Høgdall C, Høgdall E. Alpha-fetoprotein in human fetal cerebrospinal fluid. Clin Chim Acta. 2000; 291(1): 35–41.
  25. Seller MJadinolfi M. Levels of albumin, alpha-fetoprotein, and IgG in human fetal cerebrospinal fluid. Arch Dis Child. 1975; 50(6): 484–485.
  26. Coakley J, Kellie SJ, Nath C, et al. Interpretation of alpha-fetoprotein concentrations in cerebrospinal fluid of infants. Ann Clin Biochem. 2005; 42(Pt 1): 24–29.
  27. Blohm ME, Vesterling-Hörner D, Calaminus G, et al. Alpha 1-fetoprotein (AFP) reference values in infants up to 2 years of age. Pediatr Hematol Oncol. 1998; 15(2): 135–142.
  28. Krantz DA, Hallahan TW, Carmichael JB. Screening for open neural tube defects. Clin Lab Med. 2016; 36(2): 401–406.
  29. Toal M, Chaddha V, Windrim R, et al. Ultrasound detection of placental insufficiency in women with elevated second trimester serum alpha-fetoprotein or human chorionic gonadotropin. J Obstet Gynaecol Can. 2008; 30(3): 198–206.
  30. Newby D, Aitken DA, Crossley JA, et al. The pathophysiology of Down's syndrome pregnancies. Early Human Development. 1996; 47: S67–S68.
  31. Spencer K, Khalil A, Brown L, et al. First trimester maternal serum alpha-fetoprotein is not raised in pregnancies with open spina bifida. Prenat Diagn. 2014; 34(2): 168–171.
  32. Hu J, Zhang J, He G, et al. First-trimester maternal serum alpha-fetoprotein is not a good predictor for adverse pregnancy outcomes: a retrospective study of 3325 cases. BMC Pregnancy Childbirth. 2020; 20(1): 104.
  33. Hu JL, Zhang YJ, Zhang JM, et al. Pregnancy outcomes of women with elevated second-trimester maternal serum alpha-fetoprotein. Taiwan J Obstet Gynecol. 2020; 59(1): 73–78.
  34. Wang JJ, Mao JH. The etiology of congenital nephrotic syndrome: current status and challenges. World J Pediatr. 2016; 12(2): 149–158.
  35. RIA. https://www.cisbio.eu/human-alpha-fetoprotein-immunoradiometric-assay-kit-33950.
  36. ELISA. https://www.raybiotech.com/human-afp-iqelisa-kit/?variation_id=73457.
  37. CLIA. https://www.mybiosource.com/human-clia-kits/alpha-fetoprotein-afp/2025401.
  38. TRFIA. https://myassays.blob.core.windows.net/apub/productfiles/pdf/delfia_hafp_a004-201_en.pdf.