Background: Quantitative-fluorescent polymerase chain reaction (QF-PCR) is a reliable, rapid, and economic technique for prenatal diagnosis of the most common abnormalities. However, conventional karyotyping is expensive and requires a much longer time to yield results. It is currently under debate whether the replacement or restriction of karyotyping reduces the quality of prenatal test results. This study was undertaken to determine the percentage of clinically significant chromosomal abnormalities that would not be detected if QF-PCR was the main analysis method and karyotyping reserved for cases with increased nuchal translucency (NT) and/or abnormal ultrasound findings and to estimate the difference in cost between QF-PCR and full karyotyping.
Methods: Nine hundred twenty-eight pregnant women underwent an invasive procedure at our center between May 2009 and December 2012, yielding 580 (62.5%) chorionic villous samples and 348 (37.5%) amniotic fluid samples. Samples were studied by both QF-PCR and full karyotyping. Karyotyping and detailed ultrasound findings were retrospectively analyzed.
Results: If QF-PCR was the main analytic method and full karyotyping reserved for cases with elevated NT (≥4.5) and/or abnormal ultrasound findings, 12.7% of the patients would have required full karyotyping, 99% of the clinically significant chromosomal abnormalities would have been detected, and the cost would have been 54% lower than a policy of full karyotyping for all.
Conclusions: Detailed prenatal ultrasound scan can reduce the need for conventional karyotyping as a complement to QF-PCR in most prenatal samples, offering rapid results and reducing parental anxiety and healthcare costs.
The authors are grateful to Richard Davies for assistance with the English version.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Financial support: CGLL has a postdoctoral fellowship from the Plan Propio of the University of Granada.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
1. Levett LJ, Liddle S, Meredith R. A large-scale evaluation of amnio-PCR for the rapid prenatal diagnosis of fetal trisomy. Ultrasound Obstet Gynecol 2001;17:115–8. Search in Google Scholar
2. Badenas C, Rodríguez-Revenga L, Morales C, Mediano C, Plaja A, Pérez-Iribarne MM, et al. Assessment of QF-PCR as the first approach in prenatal diagnosis. J Mol Diagn 2010;12: 828–34. Search in Google Scholar
3. Allingham-Hawkins DJ, Chitayat D, Cirigliano V, Summers A, Tokunaga J, Winsor E, et al. Prospective validation of quantitative fluorescent polymerase chain reaction for rapid detection of common aneuploidies. Genet Med 2011;13:140–7. Search in Google Scholar
4. Gekas J, van den Berg DG, Durand A, Vallée M, Wildschut HI, Bujold E, et al. Rapid testing versus karyotyping in Down’s syndrome screening: cost-effectiveness and detection of clinically significant chromosome abnormalities. Eur J Hum Genet 2011;19:3–9. Search in Google Scholar
5. Mann K, Hills A, Donaghue C, Thomas H, Ogilvie CM. Quantitative fluorescence PCR analysis of >40,000 prenatal samples for the rapid diagnosis of trisomies 13, 18 and 21 and monosomy X. Prenat Diagn 2012;32:1197–204. Search in Google Scholar
6. Chitty LS, Kagan KO, Molina FS, Waters JJ, Nicolaides KH. Fetal nuchal translucency scan and early prenatal diagnosis of chromosomal abnormalities by rapid aneuploidy screening: observational study. Br Med J 2006;25:452–5. Search in Google Scholar
7. Shaffer LG, Bui TH. Molecular cytogenetic and rapid aneuploidy detection methods in prenatal diagnosis. Am J Med Genet C Semin Med Genet 2007;145:87–98. Search in Google Scholar
8. Leung WC, Lau ET, Lau WL, Tang R, Wong SF, Lau TK, et al. Rapid aneuploidy testing (knowing less) versus traditional karyotyping (knowing more) for advanced maternal age: what would be missed, who should decide? Hong Kong Med J 2008;14:6–13. Search in Google Scholar
9. Cirigliano V, Voglino G, Marongiu A, Cañadas P, Ordoñez E, Lloveras E, et al. Rapid prenatal diagnosis by QF-PCR: evaluation of 30,000 consecutive clinical samples and future applications. Ann NY Acad Sci 2006;1075:288–98. Search in Google Scholar
10. Comas C, Echevarria M, Carrera M, Serra B. Rapid aneuploidy testing versus traditional karyotyping in amniocentesis for certain referral indications. J Matern Fetal Neonatal Med 2010;23:949–55. Search in Google Scholar
11. Hills A, Donaghue C, Waters J, Waters K, Sullivan C, Kulkarni A, et al. QF-PCR as a stand-alone test for prenatal samples: the first 2 years’ experience in the London region. Prenat Diagn 2010;30:509–17. Search in Google Scholar
12. Speevak MD, McGowan-Jordan J, Chun K. The detection of chromosome anomalies by QF-PCR and residual risks as compared to G-banded analysis. Prenat Diagn 2011;31:454–8. Search in Google Scholar
13. Papoulidis I, Siomou E, Sotiriadis A, Efstathiou G, Psara A, Sevastopoulpu E, et al. Dual testing with QF-PCR and karyotype analysis for prenatal diagnosis of chromosomal abnormalities. Evaluation of 13,500 cases with consideration of using QF-PCR as a stand-alone test according to referral indications. Prenat Diagn 2012;32:680–5. Search in Google Scholar
14. Hulten MA, Dhanjal S, Pertl B. Rapid and simple prenatal diagnosis of common chromosome disorders: advantages and disadvantages of the molecular methods FISH and QF-PCR. Reproduction 2003;126:279–97. Search in Google Scholar
15. Caine A, Maltby AE, Parkin CA, Waters JJ, Crolla JA. Prenatal detection of Down’s syndrome by rapid aneuploidy testing for chromosomes 13, 18, and 21 by FISH or PCR without a full karyotype: a cytogenetic risk assessment. Lancet 2005;366:123–8. Search in Google Scholar
16. Donaghue C, Mann K, Docherty Z, Ogilvie CM. Detection of mosaicism for primary trisomies in prenatal samples by QF-PCR and karyotype analysis. Prenat Diagn 2005;25:65–72. Search in Google Scholar
17. Kagan KO, Chitty LS, Cicero S, Eleftheriades M, Nicolaides KH. Ultrasound findings before amniocentesis in selecting the method of analysing the sample. Prenat Diagn 2007;27:34–9. Search in Google Scholar
18. Putzova M, Soldatova I, Pecnova L, Dvorakova L, Jencikova N, Goetz P, et al. QF-PCR-based prenatal detection of common aneuploidies in the Czech population: five years of experience. Eur J Med Genet 2008;51:209–18. Search in Google Scholar
19. Cirigliano V, Voglino G, Ordoñez E, Marongiu A, Paz Cañadas M, Ejarque M, et al. Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR, results of 9 years of clinical experience. Prenat Diagn 2009;29:40–9. Search in Google Scholar
20. Ogilvie CM, Yaron Y, Beaudet AL. Current controversies in prenatal diagnosis 3: For prenatal diagnosis, should we offer less or more than metaphase karyotyping? Prenat Diagn 2009;29:11–4. Search in Google Scholar
21. Nicolini U, Lalatta F, Natacci F, Curcio C, Bui TH. The introduction of QF-PCR in prenatal diagnosis of fetal aneuploidies: time for reconsideration. Hum Reprod Update 2004;10:541–8. Search in Google Scholar
22. Ogilvie CM, Lashwood A, Chitty L, Waters JJ, Scriven PN, Flinter R. The future of prenatal diagnosis: rapid testing or full karyotype? An audit of chromosome abnormalities and pregnancy outcomes for women referred for Down’s Syndrome testing. Br J Obstet Gynaecol 2005;112:1369–75. Search in Google Scholar
23. Škerget AE, Herodež SS, Zagorac A, Zagradišnik B, Mujezinović F, Vokač NK. Slovenian five-year experiences with rapid prenatal diagnosis of common chromosome aneuploidies using quantitative-fluorescence polymerase chain reaction. Genet Test Mol Biomarkers 2013;52:669–74. Search in Google Scholar
24. Cirigliano V, Voglino G, Cañadas MP, Marongiu A, Ejarque M, Ordoñez E, et al. Rapid prenatal diagnosis of common chromosome aneuploidies by QF-PCR. Assessment on 18000 consecutive clinical samples. Mol Hum Reprod 2004;10:839–46. Search in Google Scholar
25. Chen CP, Chang SD, Su JW, Chen YT, Wang W. Prenatal diagnosis of mosaic trisomy 12 associated with congenital overgrowth. Taiwan J Obstet Gynecol 2013;52:454–6. Search in Google Scholar
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