open access

Ahead of Print
Review paper
Published online: 2022-12-29
Get Citation

Influence of selected factors on serum AFP levels in pregnant women in terms of prenatal screening accuracy — literature review

Joanna Glowska-Ciemny1, Marcin Szymanski1, Jakub Pankiewicz1, Zbyszko Malewski21, Constantin von Kaisenberg3, Rafal Kocylowski1
DOI: 10.5603/GP.a2022.0148
·
Pubmed: 36597745
Affiliations
  1. PreMediCare New Med Medical Center, Poznan, Poland, Poland
  2. Division of Perinatology and Women’s Diseases, Poznan University of Medical Sciences, Poznan, Poland, Poland
  3. Department of Obstetrics and Gynecology, Hannover Medical School, Germany, Germany

open access

Ahead of Print
REVIEW PAPERS Obstetrics
Published online: 2022-12-29

Abstract

Alpha-fetoprotein (AFP) is one of the biochemical components of the triple (T-3) and quadruple (T-4) test used so far in prenatal screening mainly for trisomy 21 (T21) and neural tube defects (NTDs). Based on many years of experience and data collected during these studies, a variety of factors have been identified that can affect a pregnant woman's serum AFP level, and thus the risk assessment of trisomy 21 (T21) and neural tube defects. These include both unaccounted for purely medical data (e.g., from baseline information about the patient, assisted reproduction methods used, comorbidities and emerging pregnancy pathologies) and errors made during statistical analysis. Since the triple or quadruple test is usually performed between 15 and 20 weeks of pregnancy, most scientific studies are based solely on results from this period of pregnancy — limited data are available for the first and third trimesters of pregnancy. In the era of new improved screening tests, AFP has the potential to become an independent marker for pregnancy well-being evaluation.

Abstract

Alpha-fetoprotein (AFP) is one of the biochemical components of the triple (T-3) and quadruple (T-4) test used so far in prenatal screening mainly for trisomy 21 (T21) and neural tube defects (NTDs). Based on many years of experience and data collected during these studies, a variety of factors have been identified that can affect a pregnant woman's serum AFP level, and thus the risk assessment of trisomy 21 (T21) and neural tube defects. These include both unaccounted for purely medical data (e.g., from baseline information about the patient, assisted reproduction methods used, comorbidities and emerging pregnancy pathologies) and errors made during statistical analysis. Since the triple or quadruple test is usually performed between 15 and 20 weeks of pregnancy, most scientific studies are based solely on results from this period of pregnancy — limited data are available for the first and third trimesters of pregnancy. In the era of new improved screening tests, AFP has the potential to become an independent marker for pregnancy well-being evaluation.

Get Citation

Keywords

prenatal screening; false positive/negative; triple/quadruple test; alpha-fetoprotein; AFP MoM; trisomy 21; neural tube defects

About this article
Title

Influence of selected factors on serum AFP levels in pregnant women in terms of prenatal screening accuracy — literature review

Journal

Ginekologia Polska

Issue

Ahead of Print

Article type

Review paper

Published online

2022-12-29

Page views

93

Article views/downloads

61

DOI

10.5603/GP.a2022.0148

Pubmed

36597745

Keywords

prenatal screening
false positive/negative
triple/quadruple test
alpha-fetoprotein
AFP MoM
trisomy 21
neural tube defects

Authors

Joanna Glowska-Ciemny
Marcin Szymanski
Jakub Pankiewicz
Zbyszko Malewski
Constantin von Kaisenberg
Rafal Kocylowski

References (66)
  1. Conde-Agudelo A, Kafury-Goeta AC. Triple-marker test as screening for Down syndrome: a meta-analysis. Obstet Gynecol Surv. 1998; 53(6): 369–376.
  2. Wald NJ, Hackshaw AK. Advances in antenatal screening for Down syndrome. Baillieres Best Pract Res Clin Obstet Gynaecol. 2000; 14(4): 563–580.
  3. Wald NJ, Rodeck C, Hackshaw AK, et al. SURUSS in Perspective. Semin Perinatol. 2005; 29(4): 225–235.
  4. Glowska-Ciemny J, Pankiewicz J, Malewski Z, et al. Alpha-fetoprotein (AFP) - new aspects of a well-known marker in perinatology. Ginekol Pol. 2022 [Epub ahead of print].
  5. O'Brien JE, Dvorin E, Drugan A, et al. Race-ethnicity-specific variation in multiple-marker biochemical screening: alpha-fetoprotein, hCG, and estriol. Obstet Gynecol. 1997; 89(3): 355–358.
  6. Krantz DA, Hallahan TW, Carmichael JB. Screening for open neural tube defects. Clin Lab Med. 2016; 36(2): 401–406.
  7. Lagiou P, Samoli E, Lagiou A, et al. Levels and correlates of alpha-fetoprotein in normal pregnancies among Caucasian and Chinese women. Eur J Cancer Prev. 2007; 16(3): 178–183.
  8. Bredaki FE, Wright D, Akolekar R, et al. Maternal serum alpha-fetoprotein in normal pregnancy at 11-13 weeks' gestation. Fetal Diagn Ther. 2011; 30(4): 274–279.
  9. Brossard P, Boulvain M, Coll O, et al. Swiss HIV Cohort Study, Swiss HIV Mother and Child Cohort Study. Is screening for fetal anomalies reliable in hiv-infected pregnant women? A multicentre study. AIDS. 2008; 22(15): 2013–2017.
  10. Bredaki FE, Sciorio C, Wright A, et al. Serum alpha-fetoprotein in the three trimesters of pregnancy: effects of maternal characteristics and medical history. Ultrasound Obstet Gynecol. 2015; 46(1): 34–41.
  11. Dashe JS, Twickler DM, Santos-Ramos R, et al. Alpha-fetoprotein detection of neural tube defects and the impact of standard ultrasound. Am J Obstet Gynecol. 2006; 195(6): 1623–1628.
  12. Bredaki FE, Poon LC, Birdir C, et al. First-trimester screening for neural tube defects using alpha-fetoprotein. Fetal Diagn Ther. 2012; 31(2): 109–114.
  13. Ren F, Hu YU, Zhou H, et al. Second trimester maternal serum triple screening marker levels in normal twin and singleton pregnancies. Biomed Rep. 2016; 4(4): 475–478.
  14. O'Brien J, Dvorin E, Yaron Y, et al. Differential increases in AFP, hCG, and uE3 in twin pregnancies: Impact on attempts to quantify Down syndrome screening calculations. Am J Med Genet. 1997; 73(2): 109–112, doi: 10.1002/(sici)1096-8628(19971212)73:2<109::aid-ajmg1>3.0.co;2-p.
  15. Watt HC, Wald NJ, Georg L. Maternal serum inhibin-A levels in twin pregnancies: implications for screening for Down's syndrome. Prenat Diagn. 1996; 16(10): 927–929, doi: 10.1002/(sici)1097-0223(199610)16:10<927::aid-pd972>3.0.co;2-0.
  16. Muller F, Dreux S, Dupoizat H, et al. Second-trimester Down syndrome maternal serum screening in twin pregnancies: impact of chorionicity. Prenat Diagn. 2003; 23(4): 331–335.
  17. Chen Y, Yang F, Shang X, et al. A study on non-invasive prenatal screening for the detection of aneuploidy. Ginekol Pol. 2022; 93(9): 716–720.
  18. Urato AC, Quinn R, Pulkkinen A, et al. Maternal smoking during pregnancy and false positive maternal serum alpha-fetoprotein (MSAFP) screening for open neural tube defects. Prenat Diagn. 2008; 28(8): 778–780.
  19. Crossley JA, Aitken DA, Waugh SML, et al. Maternal smoking: age distribution, levels of alpha-fetoprotein and human chorionic gonadotrophin, and effect on detection of Down syndrome pregnancies in second-trimester screening. Prenat Diagn. 2002; 22(3): 247–255.
  20. Beratis NG, Varvarigou A, Christophidou M, et al. Cord blood alpha-fetoprotein concentrations in term newborns of smoking mothers. Eur J Pediatr. 1999; 158(7): 583–588.
  21. Rudnicka AR, Wald NJ, Huttly W, et al. Influence of maternal smoking on the birth prevalence of Down syndrome and on second trimester screening performance. Prenat Diagn. 2002; 22(10): 893–897.
  22. Odendaal HJ. Effects of alcohol, cigarettes, methamphetamine and marijuana exposure during pregnancy on maternal serum alpha-fetoprotein levels at 20-24 weeks’gestation. J Pediatr Neonatal Care. 2018; 8(1): :00314. Epub 2018.
  23. Mueller VM, Huang T, Summers AM, et al. The effect of fetal gender on the false-positive rate of Down syndrome by maternal serum screening. Prenat Diagn. 2005; 25(13): 1258–1261.
  24. Lehavi O, Aizenstein O, Evans MI, et al. 2nd-trimester maternal serum human chorionic gonadotropin and alpha-fetoprotein levels in male and female fetuses with Down syndrome. Fetal Diagn Ther. 2005; 20(3): 235–238.
  25. Thornburg LL, Knight KM, Peterson CJ, et al. Maternal serum alpha-fetoprotein values in type 1 and type 2 diabetic patients. Am J Obstet Gynecol. 2008; 199(2): 135.e1–135.e5.
  26. Sancken U, Bartels I. Biochemical screening for chromosomal disorders and neural tube defects (NTD): is adjustment of maternal alpha-fetoprotein (AFP) still appropriate in insulin-dependent diabetes mellitus (IDDM)? Prenat Diagn. 2001; 21(5): 383–386.
  27. Huttly W, Rudnicka A, Wald NJ. Second-trimester prenatal screening markers for Down syndrome in women with insulin-dependent diabetes mellitus. Prenat Diagn. 2004; 24(10): 804–807.
  28. Shenhav S, Gemer O, Sherman DJ, et al. Midtrimester triple-test levels in women with chronic hypertension and altered renal function. Prenat Diagn. 2003; 23(2): 166–167.
  29. La Montagna G, Baruffo A, Buono G, et al. False positivity of prenatal Down's syndrome and neural-tube tests in SLE. Lancet. 2000; 356(9236): 1194–1195.
  30. Mizejewski GJ. Levels of alpha-fetoprotein during pregnancy and early infancy in normal and disease states. Obstet Gynecol Surv. 2003; 58(12): 804–826.
  31. Frank M, Maymon R, Wiener Y, et al. The effect of hereditary versus acquired thrombophilia on triple test Down's syndrome screening. Prenat Diagn. 2013; 33(2): 191–195.
  32. Fialová L, Malhoban I, Mikulíková L, et al. Antibodies against beta 2-glycoprotein I (beta 2-GP I) and their relationship to fetoplacental antigens. Physiol Res. 2002; 51(5): 449–455.
  33. Derbent AU, Yanik FF, Inegöl Gümüş I, et al. Impact of inherited thrombophilias on first and second trimester maternal serum markers for aneuploidy. J Matern Fetal Neonatal Med. 2012; 25(11): 2177–2181.
  34. Björklund NK, Evans JA, Greenberg CR, et al. The C677T methylenetetrahydrofolate reductase variant and third trimester obstetrical complications in women with unexplained elevations of maternal serum alpha-fetoprotein. Reprod Biol Endocrinol. 2004; 2: 65.
  35. Hong SY, Kim SY, Kim JH, et al. Predictive value of quad serum markers for adverse pregnancy outcome in antiphospholipid antibody syndrome. Lupus. 2021; 30(6): 981–990.
  36. Ochshorn Y, Kupferminc MJ, Eldor A, et al. Second-trimester maternal serum alpha-fetoprotein (MSAFP) is elevated in women with adverse pregnancy outcome associated with inherited thrombophilias. Prenat Diagn. 2001; 21(8): 658–661.
  37. Salameh M, Lee J, Palomaki G, et al. Snoring and markers of fetal and placental wellbeing. Clin Chim Acta. 2018; 485: 139–143.
  38. Räty R, Anttila L, Virtanen A, et al. Maternal midtrimester free beta-HCG and AFP serum levels in spontaneous singleton pregnancies complicated by gestational diabetes mellitus, pregnancy-induced hypertension or obstetric cholestasis. Prenat Diagn. 2003; 23(13): 1045–1048.
  39. Rana S, Lemoine E, Granger JP, et al. Preeclampsia: pathophysiology, challenges, and perspectives. Circ Res. 2019; 124(7): 1094–1112 [Erratum in: Circ Res. 2020 Jan 3;126(1):e8.].
  40. Türkmen GG, Timur H, Yilmaz Z, et al. Effect of intrahepatic cholestasis of pregnancy on maternal serum screening tests. J Neonatal Perinatal Med. 2016; 9(4): 411–415.
  41. Monte MJ, Morales AI, Arevalo M, et al. Reversible impairment of neonatal hepatobiliary function by maternal cholestasis. Hepatology. 1996; 23(5): 1208–1217.
  42. Tayyar AT, Tayyar A, Atakul T, et al. Could first- and second-trimester biochemical markers for Down syndrome have a role in predicting intrahepatic cholestasis of pregnancy? Arch Med Sci. 2018; 14(4): 846–850.
  43. Peled Y, Melamed N, Krissi H, et al. The impact of severe hyperemesis gravidarum on the triple test screening results. J Matern Fetal Neonatal Med. 2012; 25(6): 637–638.
  44. Bartha JL, Omar KM, Soothill PW. The relationship between maternal serum alpha-fetoprotein and maternal haemoglobin. Prenat Diagn. 2004; 24(8): 609–612.
  45. Bartha JL, Harrison G, Kyle PM, et al. Fetal serum alpha-fetoprotein in alloimmunised pregnancies. Prenat Diagn. 2003; 23(11): 917–920.
  46. Räty R, Virtanen A, Koskinen P, et al. Serum free beta-HCG and alpha-fetoprotein levels in IVF, ICSI and frozen embryo transfer pregnancies in maternal mid-trimester serum screening for Down's syndrome. Hum Reprod. 2002; 17(2): 481–484.
  47. Gupta S, Fox NS, Rebarber A, et al. Biochemical screening for aneuploidy in patients with donor oocyte pregnancies compared with autologous pregnancies. J Matern Fetal Neonatal Med. 2014; 27(14): 1418–1421.
  48. Lam YH, Yeung WS, Tang MH, et al. Maternal serum alpha-fetoprotein and human chorionic gonadotrophin in pregnancies conceived after intracytoplasmic sperm injection and conventional in-vitro fertilization. Hum Reprod. 1999; 14(8): 2120–2123.
  49. Hui PW, Lam YH, Tang MH, et al. Maternal serum hCG and alpha-fetoprotein levels in pregnancies conceived after IVF or ICSI with fresh and frozen-thawed embryos. Hum Reprod. 2003; 18(3): 572–575.
  50. Dondik Y, Pagidas K, Eklund E, et al. Levels of angiogenic markers in second-trimester maternal serum from in vitro fertilization pregnancies with oocyte donation. Fertil Steril. 2019; 112(6): 1112–1117.
  51. Huang T, Boucher K, Aul R, et al. First and second trimester maternal serum markers in pregnancies with a vanishing twin. Prenat Diagn. 2015; 35(1): 90–96.
  52. Katiyar R, Kriplani A, Agarwal N, et al. Detection of fetomaternal hemorrhage following chorionic villus sampling by Kleihauer Betke test and rise in maternal serum alpha feto protein. Prenat Diagn. 2007; 27(2): 139–142.
  53. Knott PD, Chan B, Ward RH, et al. Changes in circulating alphafetoprotein and human chorionic gonadotrophin following chorionic villus sampling. Eur J Obstet Gynecol Reprod Biol. 1988; 27(4): 277–281.
  54. Kumbak B, Sahin L. Elevated maternal serum alpha-fetoprotein levels in patients with subchorionic hematoma. J Matern Fetal Neonatal Med. 2010; 23(7): 717–719.
  55. Colpaert RM, Ramseyer AM, Luu T, et al. Diagnosis and management of placental mesenchymal disease. A review of the literature. Obstet Gynecol Surv. 2019; 74(10): 611–622.
  56. Bartels HC, Postle JD, Downey P, et al. Placenta accreta spectrum: a review of pathology, molecular biology, and biomarkers. Dis Markers. 2018; 2018: 1507674.
  57. Celik OY, Obut M, Keles A, et al. Outcomes of pregnancies diagnosed with circumvallate placenta, and use of uterine artery pulsatility index and maternal serum alpha-fetoprotein for prediction of adverse outcomes. Eur J Obstet Gynecol Reprod Biol. 2021; 262: 57–61.
  58. Sieroszewski P, Wierzbicka D, Bober L, et al. Association between uterine leiomyomas and the biochemical screening test results in the first and second trimester of pregnancy: a pilot study. J Matern Fetal Neonatal Med. 2011; 24(7): 904–906.
  59. Le Meaux JP, Tsatsaris V, Schmitz T, et al. Maternal biochemical serum screening for Down syndrome in pregnancy with human immunodeficiency virus infection. Obstet Gynecol. 2008; 112(2 Pt 1): 223–230.
  60. Djeha A, Money D, Trottier H, et al. The association between antiretroviral therapy and early placental function: a cohort study. J Matern Fetal Neonatal Med. 2021; 34(5): 683–689.
  61. Curtin WM, Menegus MA, Patru MM, et al. Midtrimester fetal herpes simplex-2 diagnosis by serology, culture and quantitative polymerase chain reaction. Fetal Diagn Ther. 2013; 33(2): 133–136.
  62. Pekarek DM, Chapman VR, Neely CL, et al. Medication effects on midtrimester maternal serum screening. Am J Obstet Gynecol. 2009; 201(6): 622.e1–622.e5.
  63. Wiener Y, Frank M, Neeman O, et al. Does low molecular weight heparin influence the triple test result in pregnant women with thrombophilia? Isr Med Assoc J. 2012; 14(4): 247–250.
  64. Besimoglu B, Öcal FD, Sinaci S, et al. Effect of antiepileptic drugs on serum biochemical marker levels of first and second trimester screening tests. J Obstet Gynaecol Res. 2022; 48(7): 1607–1612.
  65. Evans MI, Llurba E, Landsberger EJ, et al. Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values. Obstet Gynecol. 2004; 103(3): 474–479.
  66. Nix B, Wright D, Baker A. The impact of bias in MoM values on patient risk and screening performance for Down syndrome. Prenat Diagn. 2007; 27(9): 840–845.

Regulations

Important: This website uses cookies. More >>

The cookies allow us to identify your computer and find out details about your last visit. They remembering whether you've visited the site before, so that you remain logged in - or to help us work out how many new website visitors we get each month. Most internet browsers accept cookies automatically, but you can change the settings of your browser to erase cookies or prevent automatic acceptance if you prefer.

By VM Media Group sp. z o.o., ul. Świętokrzyska 73, 80–180 Gdańsk
tel.:+48 58 320 94 94, faks:+48 58 320 94 60, e-mail:  viamedica@viamedica.pl