ADVANCING PRENATAL TESTING: NON-INVASIVE ANEUPLOIDY SCREENING IN HIGH-RISK PREGNANCIES

Main Article Content

Shahida Hashim Marwat
Saima Nadeem
Sumaiya Khan
Madiha Afzal
Uzma Aziz
Kailash Kumar Daseja
Abdulla K. Alsubai
Akashnath Kivalur Ganeshanath
Hafsa Syeda Shuaib
Zacarius William Seit

Keywords

Prenatal testing, non-invasive screening, high-risk pregnancies

Abstract

Introduction: Maternal-fetal health is a critical facet of prenatal care, with advancements in screening technologies continually shaping the landscape of diagnostic approaches. High-risk pregnancies, characterized by factors such as advanced maternal age, necessitate enhanced and non-invasive screening methods to assess the risk of chromosomal abnormalities.


Objective: To study the prenatal testing by evaluating the accuracy and reliability of non-invasive aneuploidy screening in high-risk pregnancies.


Methodology: The study employed a robust methodology, involving the recruitment of high-risk pregnant individuals based on specific criteria, including advanced maternal age, pertinent medical history, and prior pregnancy outcomes. Blood samples collected in early pregnancy underwent detailed analysis using state-of-the-art sequencing technologies, such as Illumina, Ion Torrent, and PacBio. Statistical analyses, including sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and regression analyses, were conducted to provide a comprehensive assessment of the screening method.


Results:  Preliminary results from our non-invasive aneuploidy screening demonstrate a robust sensitivity of 94.2%, specificity of 96.8%, positive predictive value (PPV) of 89.5%, and negative predictive value (NPV) of 97.3%. Comparative analysis with traditional invasive procedures reveals a strong concordance rate of 94.7%, validating the efficacy of the non-invasive approach. In terms of cost-effectiveness, the total test costs amount to Rs. 412,500, with anticipated healthcare savings of Rs. 1,375,000. The overall economic impact, balancing costs and potential savings, stands at Rs. 962,500. Regression analyses identify a significant association between advanced maternal age and positive screening results (p-value = 0.021), providing essential insights for personalized risk assessment in high-risk pregnancies. These findings underscore the effectiveness, economic feasibility, and personalized utility of non-invasive aneuploidy screening in prenatal care.


Conclusion: This study establishes the efficacy and reliability of non-invasive aneuploidy screening in high-risk pregnancies, providing accurate and comparable results to traditional invasive procedures. The findings contribute to personalized risk assessment and support the ongoing evolution of prenatal testing methods. The integration of advanced sequencing technologies and meticulous statistical analyses ensures the robustness of this research, fostering confidence in the potential broader adoption of non-invasive screening in the context of high-risk pregnancies.


 

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References

1. Benn P, Cuckle H, Pergament E. Non‐invasive prenatal testing for aneuploidy: current status and future prospects. Ultrasound in Obstetrics & Gynecology 2013;42:15–33. https://doi.org/10 .1002/ uog.12513.
2. Beta J, Lesmes-Heredia C, Bedetti C, Akolekar R. Risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review of the literature. Minerva Obstetrics and Gynecology 2018;70. https://doi.org/10.23736/S0026-4784.17.04178-8.
3. Suzuki Y, Yamamoto T, Kojima K, Tanemura M, Tateyama H, Suzumori K. Evaluation Levels of Cytokines in Amniotic Fluid of Women with Intrauterine Infection in the Early Second Trimester. Fetal Diagn Ther 2006;21:45–50. https://doi.org/10.1159/000089047.
4. Iwarsson E, Jacobsson B, Dagerhamn J, Davidson T, Bernabé E, Heibert Arnlind M. Analysis of cell‐free fetal DNA in maternal blood for detection of trisomy 21, 18 and 13 in a general pregnant population and in a high risk population – a systematic review and meta‐analysis. Acta Obstet Gynecol Scand 2017;96:7–18. https://doi.org/10.1111/aogs.13047.
5. Gil MM, Quezada MS, Bregant B, Ferraro M, Nicolaides KH. Implementation of maternal blood cell‐free DNA testing in early screening for aneuploidies. Ultrasound in Obstetrics & Gynecology 2013;42:34–40. https://doi.org/10.1002/uog.12504.
6. BUSTAMANTE‐ARAGONES A, RODRIGUEZ DE ALBA M, GONZALEZ‐GONZALEZ C, TRUJILLO‐TIEBAS MJ, DIEGO‐ALVAREZ D, VALLESPIN E, et al. Foetal sex determination in maternal blood from the seventh week of gestation and its role in diagnosing haemophilia in the foetuses of female carriers. Haemophilia 2008;14:593–8. https://doi.org/10.1111/j.1365-2516.2008.01670.x.
7. Scheffer PG, van der Schoot CE, Page-Christiaens GCML, Bossers B, van Erp F, de Haas M. Reliability of Fetal Sex Determination Using Maternal Plasma. Obstetrics & Gynecology 2010;115:117–26. https://doi.org/10.1097/AOG.0b013e3181c3c938.
8. Hui L. Non‐invasive prenatal testing for fetal aneuploidy: charting the course from clinical validity to clinical utility. Ultrasound in Obstetrics & Gynecology 2013;41:2–6. https://doi.org/10.1002/uog.12360.
9. Ashoor G, Syngelaki A, Wagner M, Birdir C, Nicolaides KH. Chromosome-selective sequencing of maternal plasma cell–free DNA for first-trimester detection of trisomy 21 and trisomy 18. Am J Obstet Gynecol 2012;206:322.e1-322.e5. https://doi.org/10.1016/j.ajog.2012.01.029.
10. Chitty LS, Hill M, White H, Wright D, Morris S. Noninvasive prenatal testing for aneuploidy–ready for prime time? Am J Obstet Gynecol 2012;206:269–75. https://doi.org/10.1016/j.ajog.2012.02.021.
11. Nicolaides KH. Nuchal translucency and other first-trimester sonographic markers of chromosomal abnormalities. Am J Obstet Gynecol 2004;191:45–67. https://doi.org/10.1016/j.ajog.2004.03.090.
12. Mazloom AR, Džakula Ž, Oeth P, Wang H, Jensen T, Tynan J, et al. Noninvasive prenatal detection of sex chromosomal aneuploidies by sequencing circulating cell‐free DNA from maternal plasma. Prenat Diagn 2013;33:591–7. https://doi.org/10.1002/pd.4127.
13. [Chiu RWK, Akolekar R, Zheng YWL, Leung TY, Sun H, Chan KCA, et al. Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study. BMJ 2011;342:c7401–c7401. https://doi.org/10.1136/bmj.c7401.
14. Palomaki GE, Kloza EM, Lambert-Messerlian GM, Haddow JE, Neveux LM, Ehrich M, et al. DNA sequencing of maternal plasma to detect Down syndrome: An international clinical validation study. Genetics in Medicine 2011;13:913–20. https://doi.org/10.1097/GIM.0b013e3182368a0e.
15. Verweij EJ, van den Oever JME, de Boer MA, Boon EMJ, Oepkes D. Diagnostic Accuracy of Noninvasive Detection of Fetal Trisomy 21 in Maternal Blood: A Systematic Review. Fetal Diagn Ther 2012;31:81–6. https://doi.org/10.1159/000333060.
16. Dan S, Wang W, Ren J, Li Y, Hu H, Xu Z, et al. Clinical application of massively parallel sequencing‐based prenatal noninvasive fetal trisomy test for trisomies 21 and 18 in 11 105 pregnancies with mixed risk factors. Prenat Diagn 2012;32:1225–32. https://doi.org/10.1002/pd.4002.
17. Lo YMD, Tsui NBY, Chiu RWK, Lau TK, Leung TN, Heung MMS, et al. Plasma placental RNA allelic ratio permits noninvasive prenatal chromosomal aneuploidy detection. Nat Med 2007;13:218–23. https://doi.org/10.1038/nm1530.
18. Fan HC, Blumenfeld YJ, El-Sayed YY, Chueh J, Quake SR. Microfluidic digital PCR enables rapid prenatal diagnosis of fetal aneuploidy. Am J Obstet Gynecol 2009;200:543.e1-543.e7. https://doi.org/10.1016/j.ajog.2009.03.002.
19. Evans MI, Wright DA, Pergament E, Cuckle HS, Nicolaides KH. Digital PCR for Noninvasive Detection of Aneuploidy: Power Analysis Equations for Feasibility. Fetal Diagn Ther 2012;31:244–7. https://doi.org/10.1159/000337544.
20. Lo YMD, Lun FMF, Chan KCA, Tsui NBY, Chong KC, Lau TK, et al. Digital PCR for the molecular detection of fetal chromosomal aneuploidy. Proceedings of the National Academy of Sciences 2007;104:13116–21. https://doi.org/10.1073/pnas.0705765104.
21. Chitty LS, Kistler J, Akolekar R, Liddle S, Nicolaides K, Levett L. Multiplex ligation-dependent probe amplification (MLPA): a reliable alternative for fetal chromosome analysis? The Journal of Maternal-Fetal & Neonatal Medicine 2012;25:1383–6.https://doi.o rg/10.3109/1 4767058.2011.636093.
22. Cuckle H, Benn P, Pergament E. Maternal cfDNA screening for Down syndrome – a cost sensitivity analysis. Prenat Diagn 2013;33:636–42. https://doi.org/10.1002/pd.4157.
23. Nicolaides KH, Syngelaki A, Gil M, Atanasova V, Markova D. Validation of targeted sequencing of single‐nucleotide polymorphisms for non‐invasive prenatal detection of aneuploidy of chromosomes 13, 18, 21, X, and Y. Prenat Diagn 2013;33:575–9. https://doi.org/10 .1002/pd.4103.
24. Pandya PP, Kondylios A, Hilbert L, Snijders RJM, Nicolaides KH. Chromosomal defects and outcome in 1015 fetuses with increased nuchal translucency. Ultrasound in Obstetrics & Gynecology 1995;5:15–9. https://doi.org/10.1046/j.1469-0705.1995.05010015.x.
25. Souka AP, Snijders RJM, Novakov A, Soares W, Nicolaides KH. Defects and syndromes in chromosomally normal fetuses with increased nuchal translucency thickness at 10–14 weeks of gestation. Ultrasound in Obstetrics & Gynecology 1998;11:391–400. https://doi.org/10.1046/j.1469-0705.1998.11060391.x.
26. Kagan KO, Avgidou K, Molina FS, Gajewska K, Nicolaides KH. Relation Between Increased Fetal Nuchal Translucency Thickness and Chromosomal Defects. Obstetrics & Gynecology 2006;107:6–10. https://doi.org/10.1097/01.AOG.0000191301.63871.c6.
27. Alamillo CML, Krantz D, Evans M, Fiddler M, Pergament E. Nearly a third of abnormalities found after first‐trimester screening are different than expected:10‐year experience from a single center. Prenat Diagn 2013;33:251–6. https://doi.org/10.1002/pd.4054.
28. Gruchy N, Decamp M, Richard N, Jeanne‐Pasquier C, Benoist G, Mittre H, et al. Array CGH analysis in high‐risk pregnancies: comparing DNA from cultured cells and cell‐free fetal DNA. Prenat Diagn 2012;32:383–8. https://doi.org/10.1002/pd.2861.
29. Hillman SC, Mcmullan DJ, Williams D, Maher ER, Kilby MD. Microarray comparative genomic hybridization in prenatal diagnosis: a review. Ultrasound in Obstetrics & Gynecology 2012;40:385–91. https://doi.org/10.1002/uog.11180.
30. Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, et al. Chromosomal Microarray versus Karyotyping for Prenatal Diagnosis. New England Journal of Medicine 2012;367:2175–84. https://doi.org/10.1056/NEJMoa1203382.
31. Jayashankar SS, Nasaruddin ML, Hassan MF, Dasrilsyah RA, Shafiee MN, Ismail NAS, et al. Non-Invasive Prenatal Testing (NIPT): Reliability, Challenges, and Future Directions. Diagnostics 2023;13:2570. https://doi.org/10.3390/diagnostics13152570.
32. Zhang H, Gao Y, Jiang F, Fu M, Yuan Y, Guo Y, et al. Non‐invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146 958 pregnancies. Ultrasound in Obstetrics & Gynecology 2015;45:530–8. https://doi.org/10.1002/uog.14792.
33. Mokhtar R, Hans P, Sinha A. Comparing Non-invasive Prenatal Testing With Invasive Testing for the Detection of Trisomy 21. Cureus 2022. https://doi.org/10.7759/cureus.31252.
34. Krummenauer F, Kalden P, Kreitner KF. [Cohen’s kappa or McNemar’s test? A comparison of binary repeated measurements]. Rofo 1999;171:226–31.
35. Wei L, Zhang J, Shi N, Luo C, Bo L, Lu X, et al. Association of maternal risk factors with fetal aneuploidy and the accuracy of prenatal aneuploidy screening: a correlation analysis based on 12,186 karyotype reports. BMC Pregnancy Childbirth 2023;23:136. https://doi.org/10.1186 /s12 884-023-05461-4.
36. Wu X, Li Y, Xie X, Su L, Cai M, Lin N, et al. Clinical Review of Noninvasive Prenatal Testing. The Journal of Molecular Diagnostics 2020;22:1469–75. https://doi.org/10.1016/j.jmoldx .2020.09.008.
37. Carbone L, Cariati F, Sarno L, Conforti A, Bagnulo F, Strina I, et al. Non-Invasive Prenatal Testing: Current Perspectives and Future Challenges. Genes (Basel) 2020;12:15. https://doi.org/10.3390/genes12010015.
38. Cai M, Lin N, Chen X, Li Y, Lin M, Fu X, et al. Non-invasive prenatal testing for the diagnosis of congenital abnormalities: Insights from a large multicenter study in southern China. Brazilian Journal of Medical and Biological Research 2023;56. https://doi.org/10.1590/1414-431x2023e12506.

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