Quad Screen Test, A Multiplexed Biomarker Assay for Prenatal Screening to Assess Birth Defects: The Columbia University Experience Using the Beckman Access2 Immunoassay Analyzer and Benetech PRA

  • Awet Tecleab
  • Alex K. Lyashchenko
  • Alex J. RaiEmail author
Part of the Methods in Molecular Biology book series (MIMB, volume 1885)


In the prenatal quad screen, the levels of four analytes in maternal serum are used to calculate the risk of serious birth defects. The Beckman Access2 Immunoassay System is an automated analyzer that enables rapid measurement of alpha-fetoprotein, unconjugated estriol, human chorionic gonadotropin, and dimeric inhibin A. The Benetech PRA software package is used to convert maternal serum analyte concentrations to multiples of the median (MoM) and calculates the risks of particular birth defects. The results from this simple and minimally invasive screen determine the need for more sensitive, specific, and usually riskier diagnostic procedures. We present herein some recent data from our experience at Columbia University Medical Center in New York, NY, using the Beckman Access2 immunoassay analyzer and Benetech PRA software package.

Key words

Fetal defect markers Prenatal diagnosis Maternal screening Quad screen 


  1. 1.
    Benn PA (2002) Advances in prenatal screening for Down syndrome: I. general principles and second trimester testing. Clin Chim Acta 323(1–2):1–16PubMedGoogle Scholar
  2. 2.
    Benn PA et al (2003) Incorporation of inhibin-A in second-trimester screening for Down syndrome. Obstet Gynecol 101(3):451–454PubMedGoogle Scholar
  3. 3.
    Wald NJ, Huttly WJ, Hackshaw AK (2003) Antenatal screening for Down’s syndrome with the quadruple test. Lancet 361(9360):835–836CrossRefGoogle Scholar
  4. 4.
    Macri JN, Baker DA, Baim RS (1981) Diagnosis of neural tube defects by evaluation of amniotic fluid. Clin Obstet Gynecol 24(4):1089–1102CrossRefGoogle Scholar
  5. 5.
    Rose NC, Mennuti MT (1993) Maternal serum screening for neural tube defects and fetal chromosome abnormalities. West J Med 159(3):312–317PubMedPubMedCentralGoogle Scholar
  6. 6.
    Combining maternal serum alpha-fetoprotein measurements and age to screen for Down syndrome in pregnant women under age 35 (1989) New England regional genetics group prenatal collaborative study of down syndrome screening. Am J Obstet Gynecol 160(3):575–581CrossRefGoogle Scholar
  7. 7.
    Merkatz IR et al (1984) An association between low maternal serum alpha-fetoprotein and fetal chromosomal abnormalities. Am J Obstet Gynecol 148(7):886–894CrossRefGoogle Scholar
  8. 8.
    Cuckle HS, Wald NJ, Lindenbaum RH (1984) Maternal serum alpha-fetoprotein measurement: a screening test for Down syndrome. Lancet 1(8383):926–929CrossRefGoogle Scholar
  9. 9.
    Palomaki GE et al (1995) Risk-based prenatal screening for trisomy 18 using alpha-fetoprotein, unconjugated oestriol and human chorionic gonadotropin. Prenat Diagn 15(8):713–723CrossRefGoogle Scholar
  10. 10.
    Kjessler B, Johansson SG (1977) Monitoring of the development of early pregnancy by determination of alpha-fetoprotein in maternal serum and amniotic fluid samples. Acta Obstet Gynecol Scand Suppl 69:5–14CrossRefGoogle Scholar
  11. 11.
    Brock DJ, Sutcliffe RG (1972) Alpha-fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet 2(7770):197–199CrossRefGoogle Scholar
  12. 12.
    Wald NJ, Brock DJ, Bonnar J (1974) Prenatal diagnosis of spina bifida and anencephaly by maternal serum-alpha-fetoprotein measurement. A controlled study. Lancet 1(7861):765–767CrossRefGoogle Scholar
  13. 13.
    Penney LL, Klenke WJ (1980) Variability in unconjugated and total estriol in serum during normal third trimester pregnancy. Clin Chem 26(13):1800–1803PubMedGoogle Scholar
  14. 14.
    Bogart MH, Pandian MR, Jones OW (1987) Abnormal maternal serum chorionic gonadotropin levels in pregnancies with fetal chromosome abnormalities. Prenat Diagn 7(9):623–630CrossRefGoogle Scholar
  15. 15.
    Cole LA (2010) Biological functions of hCG and hCG-related molecules. Reprod Biol Endocrinol 8:102CrossRefGoogle Scholar
  16. 16.
    Sturgeon CM, McAllister EJ (1998) Analysis of hCG: clinical applications and assay requirements. Ann Clin Biochem 35(Pt 4):460–491CrossRefGoogle Scholar
  17. 17.
    van Zonneveld P et al (2003) Do cycle disturbances explain the age-related decline of female fertility? Cycle characteristics of women aged over 40 years compared with a reference population of young women. Hum Reprod 18(3):495–501CrossRefGoogle Scholar
  18. 18.
    Wald NJ et al (1997) Antenatal screening for Down’s syndrome. J Med Screen 4(4):181–246CrossRefGoogle Scholar
  19. 19.
    Crandall BF (1981) Alpha-fetoprotein: the diagnosis of neural-tube defects. Pediatr Ann 10(2):38–48PubMedGoogle Scholar
  20. 20.
    Macri JN, Weiss RR (1977) The utilization of alpha-fetoprotein in prenatal diagnosis. Birth Defects Orig Artic Ser 13(3D):191–199PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Awet Tecleab
    • 1
  • Alex K. Lyashchenko
    • 2
  • Alex J. Rai
    • 2
    Email author
  1. 1.Department of Pathology and Laboratory MedicineStaten Island University HospitalStaten IslandUSA
  2. 2.Department of Pathology and Cell BiologyVagelos College of Physicians and Surgeons, Columbia University Irving Medical CenterNew YorkUSA

Personalised recommendations