First-trimester Combined Screening for Trisomies 21, 18, and 13 by Three Closed Chemiluminescence Immunoassay Analyzers (an Experiment on Iranian Pregnant Women)

Document Type : Original Article

Authors

1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Biochemistry, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Reference Health Laboratory, Ministry of Health and Medical Education, Tehran, Iran

Abstract

Background: Pregnancy-associated plasma protein-A (PAPP-A) and free β-human chorionic gonadotropin (free β-hCG) as valuable biochemical biomarkers are used to screen down syndrome, Edwards syndrome, and Patau syndrome in the first trimester of pregnancy. Closed immunoassay analyzers are regarded as sophisticated platforms to measure biochemical biomarkers. This study compared the performance of three chemiluminescence analyzers when used for combined screening.
Methods: The present cross-sectional study was conducted on 371 pregnant women within the age range of 20-47 years during 11+0 to 13+6 weeks of pregnancy referring to Dena laboratory in Tehran, Iran, during July 2018 and August 2018 using random selection. The biochemical biomarkers of PAPP-A and free β-hCG were assayed on Cobas, Immulite, and Maglumi analyzers. Benetech software as a commercial screening software was used to calculate the risks of trisomy 21 (T21), trisomy 18 (T18), and trisomy 13 (T13). Deming regression, nonparametric spearman analysis, analysis of variance, and Chi-square test were performed to analyze the data.
Results: For the screening population, although the three systems well correlated to PAPP-A and free β-hCG, the values of Maglumi were slightly higher than those reported for Cobas and Immulite. The multiples of the median (MoM) of PAPP-A and free β-hCG had a significant correlation on three platforms. There were no significant differences between the calculated risks of T21, T18, and T13 on the three systems. The sensitivity for all systems was reported as 50%. In addition, specificity and negative predictive value (NPV) were higher than 99% and 95%, respectively. Positive predictive value (PPV) was reported as less than 50%.
Conclusion: The obtained results of the present study demonstrated that there were significant correlations between three different systems in terms of PAPP-A and free β-hCG values and MoMs. The sensitivity of all systems for all trisomies was 50%; however, the specificity of all systems was almost the same. The best PPV and NPV for T21 were on Cobas, Immulite, and Maglumi, respectively. The PPV and NPV of all systems for T18/13 were almost the same.

Keywords

References

1. Spencer K. Second trimester prenatal screening for Down's syndrome using alpha‐fetoprotein and free beta hCG: a seven year review. BJOG. 1999;
106(12):1287-93.
2. Spencer K, Aitken D. Factors affecting women's preference for type of prenatal screening test for chromosomal anomalies. Ultrasound Obstet Gynecol. 2004; 24(7):735-9.
3. Spencer K, Macri JN. Early detection of Down's syndrome using free beta human choriogonadotropin. Ann Clin Biochem. 1992; 29(3):349-50.
4. Spencer K. Aneuploidy screening in the first trimester. Am J Med Genet Part C. 2007; 145(1):18-32.
5. Bonno M, Oxvig C, Kephart GM, Wagner JM, Kristensen T, Sottrup-Jensen L, et al. Localization of pregnancy-associated plasma protein-A and colocalization of pregnancy-associated plasma protein-A messenger ribonucleic acid and eosinophil granule major basic protein messenger ribonucleic acid in placenta. Lab Invest. 1994; 71(4):560-6.
6. Oxvig C, Sand O, Kristensen T, Gleich GJ, Sottrup-Jensen L. Circulating human pregnancy-associated plasma protein-A is disulfide-bridged to the proform of eosinophil major basic protein. J Biol Chem. 1993; 268(17):12243-6.
7. Tabor A, Alfirevic Z. Update on procedure-related risks for prenatal diagnosis techniques. Fetal Diagn Ther. 2010; 27(1):1-7.
8. Ekelund CK, Jørgensen FS, Petersen OB, Sundberg K, Tabor A. Impact of a new national screening policy for Down’s syndrome in Denmark: population based cohort study. BMJ. 2008; 337:a2547.
9. Ekelund CK, Petersen OB, Skibsted L, Kjærgaard S, Vogel I, Tabor A, et al. First‐trimester screening for trisomy 21 in Denmark: implications for detection and birth rates of trisomy 18 and trisomy 13. Ultrasound Obstet Gynecol. 2011; 38(2):140-4.
10. Spencer K, Spencer CE, Power M, Moakes A, Nicolaides KH. One stop clinic for assessment of risk for fetal anomalies: a report of the first year of prospective screening for chromosomal anomalies in the first trimester. BJOG. 2000; 107(10):1271-5.
11. Bindra R, Heath V, Liao A, Spencer K, Nicolaides KH. One‐stop clinic for assessment of risk for trisomy 21 at 11–14 weeks: a prospective study of 15 030 pregnancies. Ultrasound Obstet Gynecol. 2002; 20(3):219-25.
12. Spencer K, Spencer CE, Power M, Dawson C, Nicolaides KH. Screening for chromosomal abnormalities in the first trimester using ultrasound and maternal serum biochemistry in a one‐stop clinic: a review of three years prospective experience. BJOG. 2003; 110(3):281-6.
13. Rossier MF, Beloeil N, Hediger-Bonfantini J, Dahoun S, Stricker R, Dayer E, et al. Validation of the Cobas/Ssdw system for trisomy 21 screening in the
first trimester of pregnancy: Comparison with the Kryptor/FastScreen combination. Clin Chem Lab Med. 2012; 50(5):1-19.
14. Tørring N, Aulesa C, Eiben B, Ferri MJ, Nicolaides KH, Ortiz JU, et al. Performance characteristics of Elecsys free βhCG and PAPP-A for first trimester trisomy 21 risk assessment in gestational weeks 8+ 0 to 14+ 0. Lab Med. 2016; 40(1):21-9.
15. Engell AE, Carlsson ER, Jørgensen FS, Sørensen S. Comparison of two immunoassay systems for hCGβ and PAPP-A in prenatal screening for trisomy 21, 18, and 13 in the first trimester. Pract Lab Med. 2017; 9:18-23.
16. Malone FD, Canick JA, Ball RH, Nyberg DA, Comstock CH, Bukowski R, et al. First-trimester or second-trimester screening, or both, for Down's syndrome. N Engl J Med. 2005; 353(19):2001-11.
17. Snijders R, Thom E, Zachary J, Platt L, Greene N, Jackson L, et al. First‐trimester trisomy screening: nuchal translucency measurement training and quality assurance to correct and unify technique. Ultrasound Obstet Gynecol. 2002; 19(4):353-9.
18. Spencer K. First trimester maternal serum screening for Down's syndrome: an evaluation of the DPC Immulite 2000 free β-hCG and pregnancy-associated plasma protein-A assays. Ann Clin Biochem. 2005; 42(Pt 1):30-40.
Iranian Journal of Neonatology
Volume 11, Issue 3
August 2020
Pages 71-79

Files

Share

How to cite

Statistics