ACCURACY OF NON-INVASIVE PRENATAL TESTING USING MASSIVELY PARALLEL SEQUENCING FOR DETECTING TRISOMY 21: A META-ANALYSIS
DOI:
https://doi.org/10.53625/jirk.v5i8.12110Keywords:
Noninvasive Prenatal Testing, Massively Parallel Sequencing, Trisomy 21, Down Syndrome, PregnancyAbstract
Background:Non-Invasive Prenatal Testing (NIPT) for fetal trisomy 21 aneuploidy has been widely adopted in clinical practice due to its superior accuracy. NIPT has also been developed and validated as an option for early detection of genetic abnormalities prior to invasive diagnostic procedures. The aim of this study was to evaluate the accuracy of NIPT using Massively Parallel Sequencing (MPS) technology for screening Down syndrome in singleton pregnancies across all trimesters.
Methods:This systematic review and meta-analysis analyzed literature on the accuracy of NIPT with MPS technology for Down syndrome screening in singleton pregnancies across all trimesters, following PRISMA guidelines. Eight studies were included, and data extraction was performed independently by three reviewers. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool.
Results:Among 485,365 pregnant women screened for major autosomal trisomies confirmed by fetal karyotype or newborn phenotype, 2,092 cases were verified from the total population. The sensitivity of NIPT for detecting trisomy 21 ranged from 0.80 (95% CI: 0.73–0.87) to 1.00 (95% CI: 0.48–1.00) based on the eight identified studies. NIPT showed very high specificity, with most studies reporting a specificity of 1.00 (95% CI: 1.00–1.00).
Conclusion: NIPT using MPS technology demonstrated very high sensitivity and specificity in detecting trisomy 21 (Down syndrome) in singleton pregnancies across all trimesters. It is a reliable and effective screening tool due to its high accuracy in detecting true-positive cases and minimizing false-positive results.
References
American College of Obstetricians and Gynecologists. Screening for fetal chromosomal abnormalities. ACOG Practice Bulletin No. 226. Obstet Gynecol. 2020;136(4):e48–69. Available from: https://journals.lww.com/greenjournal/fulltext/2020/10000/screening_for_fetal_chromosomal_abnormalities_.44.aspx
Laššáková S, Šenkyřík P, Pazourková E, Hořínek A, Calda P, Břešťák M, et al. Rapid non-invasive prenatal screening test for trisomy 21 based on digital droplet PCR. Sci Rep. 2023;13(1):21233. Available from: https://www.nature.com/articles/s41598-023-50330-x
Bull MJ. Down syndrome. N Engl J Med. 2020;382(24):2344–52. Available from: https://www.nejm.org/doi/full/10.1056/NEJMra1706537
Antonarakis SE, Skotko BG, Rafii MS, Strydom A, Pape SE, Bianchi DW, et al. Down syndrome. Nat Rev Dis Primers. 2020;6(1):9. Available from: https://www.nature.com/articles/s41572-019-0143-7
Srebniak MI, Joosten M, Knapen MFCM, Arends LR, Polak M, van Veen S, et al. Frequency of submicroscopic chromosomal aberrations in pregnancies without increased risk for structural chromosomal aberrations: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2018;51(4):445–52.
Dai P, Yang Y, Zhao G, Gu Z, Ren H, Hu S, et al. A dPCR-NIPT assay for detection of trisomies 21, 18 and 13 in a single-tube reaction: could it replace serum biochemical tests as a primary maternal plasma screening tool? J Transl Med. 2022;20(1):576.
Steinfort K, Van Houtven E, Jacquemyn Y, Blaumeiser B, Loquet P. Difference in procedure-related risk of miscarriage between early and mid-trimester amniocentesis: a retrospective cohort study. Diagnostics. 2021;11(6):1041.
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.
Lo TK, Chan KYK, Kan ASY, So PL, Kong CW, Mak SL, et al. Decision outcomes in women offered noninvasive prenatal test (NIPT) for positive Down screening results. J Matern Fetal Neonatal Med. 2019;32(2):348–50.
Bianchi DW, Parker RL, Wentworth J, Madankumar R, Saffer C, Das AF, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;370(9):799–808.
Chitty LS, Wright D, Hill M, Verhoef TI, Daley R, Lewis C, et al. Uptake, outcomes, and costs of implementing non-invasive prenatal testing for Down’s syndrome into NHS maternity care: prospective cohort study in eight diverse maternity units. BMJ. 2016;354:i3426.
Zhu H, Jin X, Xu Y, Zhang W, Liu X, Jin J, et al. Efficiency of non-invasive prenatal screening in pregnant women at advanced maternal age. BMC Pregnancy Childbirth. 2021;21(1):675.
Ge Y, Li J, Zhuang J, Zhang J, Huang Y, Tan M, et al. Expanded noninvasive prenatal testing for fetal aneuploidy and copy number variations and parental willingness for invasive diagnosis in a cohort of 18,516 cases. BMC Med Genomics. 2021;14(1):216.
Chen Y, Yu Q, Mao X, Lei W, He M, Lu W. Noninvasive prenatal testing for chromosome aneuploidies and subchromosomal microdeletions/microduplications in a cohort of 42,910 single pregnancies. Hum Genomics. 2019;13(1):60.
Jeon YJ, Zhou Y, Li Y, Guo Q, Chen J, Quan S, et al. Feasibility study of non-invasive fetal trisomy 18 and 21 detection with semiconductor sequencing platform. PLoS One. 2014;9(10):e110240.
Porreco RP, Garite TJ, Maurel K, Marusiak B, Ehrich M, Van Den Boom D, et al. Noninvasive prenatal screening for fetal trisomies 21, 18, 13 and common sex chromosome aneuploidies using massively parallel genomic sequencing of DNA. Am J Obstet Gynecol. 2014;211(4):365.e1–12.
Lu YS, Chen YY, Ding SY, Zeng LL, Shi LC, Li YJ, et al. Performance analysis of non-invasive prenatal testing for trisomy 13, 18, and 21: a large-scale retrospective study (2018–2021). Heliyon. 2024;10(13):e25911.
McCullough RM, Almasri EA, Guan X, Geis JA, Hicks SC, Mazloom AR, et al. Non-invasive prenatal chromosomal aneuploidy testing: clinical experience with 100,000 samples. PLoS One. 2014;9(10):e109173.
Kypri E, Ioannides M, Achilleos A, Koumbaris G, Patsalis P, Stumm M. Non-invasive prenatal screening tests – update 2022. J Lab Med. 2022;46(5):311–20.
Akolekar R, Beta J, Picciarelli G, Ogilvie C, D’Antonio F. Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2015;45(1):16–26.
Hui L, Bianchi DW. Fetal fraction and noninvasive prenatal testing: what clinicians need to know. Prenat Diagn. 2020;40(2):155–63.
Hartwig TS, Ambye L, Sørensen S, Jørgensen FS. Discordant non-invasive prenatal testing (NIPT): a systematic review. Prenat Diagn. 2017;37(6):527–39.
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(1):1. doi:10.3390/genes12010001
Sarno L, Revello R, Hanson E, Akolekar R, Nicolaides KH. Prospective first-trimester screening for trisomies by cell-free DNA testing in twin pregnancy. Ultrasound Obstet Gynecol. 2016;47(6):705–11.
Curnow KJ, Wilkins-Haug L, Ryan A, Kirkizlar E, Stosic M, Hall MP, et al. Detection of triploid, molar, and vanishing twin pregnancies by a SNP-based noninvasive prenatal test. Am J Obstet Gynecol. 2015;212(1):79. e1–79. e9.
