Quantitative-fluorescent-PCR versus full karyotyping in prenatal diagnosis of common chromosome aneuploidies in southern Spain

Mᵃ José de la Paz-Gallardo; Francisca S. Molina García; Tomas de Haro-Muñoz; Mᵃ Carmen Padilla-Vinuesa; Mercedes Zafra-Ceres; José A. Gomez-Capilla; Carolina Gomez-Llorente

doi:10.1515/cclm-2014-0781

Article

Quantitative-fluorescent-PCR versus full karyotyping in prenatal diagnosis of common chromosome aneuploidies in southern Spain

Mᵃ José de la Paz-Gallardo , Francisca S. Molina García , Tomas de Haro-Muñoz , Mᵃ Carmen Padilla-Vinuesa , Mercedes Zafra-Ceres , José A. Gomez-Capilla and Carolina Gomez-Llorente

Published/Copyright: December 2, 2014

Published by

Become an author with De Gruyter Brill

Submit Manuscript Author Information

From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 53 Issue 9

Abstract

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.

Keywords: abnormal ultrasound findings; karyotyping; nuchal translucency; quantitative fluorescent polymerase chain reaction (QF-PCR)

Corresponding author: M^a José de la Paz-Gallardo, Facultad de Medicina, Departamento de Bioquímica y Biología Molecular III e Inmunología, Universidad de Granada, Avd/Madrid s/n 18071, Granada, Spain, Phone: +34 958243524, Fax: +34958249015, E-mail: mjdelapaz@ugr.es

Acknowledgments

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.

References

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;17:115–8.10.1046/j.1469-0705.2001.00340.xSearch in Google Scholar PubMed

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: 828–34.10.2353/jmoldx.2010.090224Search in Google Scholar PubMed PubMed Central

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;13:140–7.10.1097/GIM.0b013e3182036763Search in Google Scholar PubMed

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;19:3–9.10.1038/ejhg.2010.138Search in Google Scholar PubMed PubMed Central

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;32:1197–204.10.1002/pd.3986Search in Google Scholar PubMed

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;25:452–5.10.1136/bmj.38730.655197.AESearch in Google Scholar PubMed PubMed Central

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;1075:288–98.10.1196/annals.1368.039Search in Google Scholar PubMed

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;23:949–55.10.3109/14767050903334893Search in Google Scholar PubMed

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;30:509–17.10.1002/pd.2503Search in Google Scholar PubMed

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;31:454–8.10.1002/pd.2716Search in Google Scholar PubMed

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;32:680–5.10.1002/pd.3888Search 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;126:279–97.10.1530/rep.0.1260279Search 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;366:123–8.10.1016/S0140-6736(05)66790-6Search 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;25:65–72.10.1002/pd.1086Search in Google Scholar PubMed

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;27:34–9.10.1002/pd.1615Search in Google Scholar PubMed

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;51:209–18.10.1016/j.ejmg.2008.02.003Search in Google Scholar PubMed

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;29:40–9.10.1002/pd.2192Search in Google Scholar PubMed

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;29:11–4.10.1002/pd.2107Search in Google Scholar PubMed

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;10:541–8.10.1093/humupd/dmh046Search in Google Scholar PubMed

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;112:1369–75.10.1111/j.1471-0528.2005.00695.xSearch in Google Scholar PubMed

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;52:669–74.10.1089/gtmb.2013.0082Search in Google Scholar PubMed

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;10:839–46.10.1093/molehr/gah108Search in Google Scholar PubMed

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;52:454–6.10.1016/j.tjog.2013.06.008Search in Google Scholar PubMed

Received: 2014-7-30

Accepted: 2014-10-29

Published Online: 2014-12-2

Published in Print: 2015-8-1

You are currently not able to access this content.

Articles in the same Issue

https://doi.org/10.1515/cclm-2014-0781

Keywords for this article

abnormal ultrasound findings; karyotyping; nuchal translucency; quantitative fluorescent polymerase chain reaction (QF-PCR)