Hücre-dışı Fetal DNA‘dan Gerçek-zamanlı PZR ile Fetal Rhesus D tespitinin Maliyet Değerlendirmesi

Year 2020, Volume: 10 Issue: 3, 124 - 127, 24.12.2020

Büşra Yasa , Orhan Sahın , Selcuk Sozer Tokdemir

https://doi.org/10.26650/experimed.2020.823916

Abstract

Maternal plazmadan hücre-dışı fetal DNA'nın (hdfDNA) tespitinde son yıllarda elde edilen başarılar, hamilelik süresince uygulanabilir, invazif olmayan tarama ve tanı testlerini destekleyen temel teknik-lerin gelişmesine olanak sağlamıştır. Yakın zamanda yaptığımız bir çalışmada, invazif işlem gerektirmeden gebelerden alınan periferik kandan hücre-dışı DNA izole edilerek, gerçek zamanlı polimeraz zincir reaksiyonu (PZR) yöntemiyle fetal Rhesus D (RhD) ve cinsi-yet belirlenmesi gerçekleştirilmiştir. Bu ve benzeri çalışmalar neti-cesinde, kullanılan tekniğin fetal RhD tayininde yüksek doğruluk oranlarına sahip olduğu ve tanı amaçlı kullanıma uygun olduğu gösterilmiştir. Tanıda elde edilen bu başarı, özellikle RhD negatif (-) gebelere uygulanan işlemleri en aza indirilerek tedavide yol gös-tericidir. Bu bağlamda, sunduğumuz bu çalışmada Türkiye Cum-huriyeti, Sosyal Güvenlik Kurumu, Sağlık Uygulama Tebliği (SUT) verileri referans alınarak, günümüzde RhD (-) gebelere uygulanan ek izlem testlerin ve tedavinin oluşturduğu maliyet ile fetal RHD ge-notiplemesi sonucu ortaya çıkan maliyetin kıyaslaması gerçekleşti-rilmiştir. Ayrıca, böyle bir yaklaşımın hastalık tanı sürecine yapmış olduğu destek değerlendirilmiştir.Sonuç olarak, her RhD (-) gebe için, gerçek zamanlı PZR uygula-narak fetal RHD genotiplesi ile hali hazırda kullanılan ek tetkik ve tedaviler kıyaslandığında, 523,19 TL (3,5 kat) daha az maliyetli ol-duğu gösterilmiştir. Bu testin, iş yoğunluğu, hastane maliyetleri ve hastaya uygulanan gereksiz tedavilerin azalması yönünde yenilikçi bir yöntem olduğu görülmektedir. Ayrıca, bu ve benzeri yaklaşım-lar, erken tedavinin başlatılması ve gereksiz müdahale ve maliyet-ten kaçınılmasına olanak sağlayacaktır.

Keywords

Hücre dışı fetal DNA, genotipleme, maliyet analizi

Supporting Institution

İstanbul Üniversitesi Bilimsel Araştırma Projeleri Birimi

Project Number

29083

Cost Evaluation of Fetal Rhesus D Genotyping by Real-time PCR from cell-free Fetal DNA

Abstract

The detection of cell-free fetal DNA (cffDNA) from maternal plas-ma has enabled the development of essential prenatal diagnostic techniques supporting the non-invasive screening and diagnostic tests in recent years.We performed a non-invasive real-time polymerase chain reac-tion (PCR) using cell-free DNA isolated from the peripheral blood of pregnant women to determine fetal Rhesus D (RhD) and sex. Consistent with the findings of similar studies, our results revealed high accuracy rates of PCR in determining fetal RhD, making it suitable for diagnostic use, thereby indicating its effectiveness as a guide in treating and especially in minimizing the procedures ap-plied to pregnant women who are RhD negative.This study compared the cost incurred between follow-up testing and treatment of RhD (-) pregnant women and the fetal RHD geno-typing based on Health Implementation Notification (SUT) data of the Social Security Administration of the Republic of Turkey. Addi-tionally, the role of PCR to the diagnostic process was evaluated.Our results showed that fetal RHD genotyping costs 523.19 TL (3.5 times) less for each RhD (-) pregnant women compared with the current additional tests and treatments. PCR with cffDNA is an innovative method that minimizes workload, hospital costs, and unnecessary tests and treatment. In addition, this method allows an early initiation of treatment and avoidance of unnecessary in-tervention and cost.

Keywords

Fetal cell-free DNA, RHD, genotyping, cost analysis

Project Number

29083

References

• 1. Fasano RM. Hemolytic disease of the fetus and newborn in the molecular era. Seminars in Fetal and Neonatal Medicine 2016; 21(1): 28-34. [CrossRef ]
• 2. Kumar S, Regan F. Management of pregnancies with RhD allo-immunisation. British Medical Journal 2005; 330(7502): 1255-8. [CrossRef ]
• 3. de Haas M, Thurik FF, Koelewijn JM, van der Schoot CE. Haemolytic disease of the fetus and newborn. Vox Sanguinis 2015; 109(2): 99-113. [CrossRef ]
• 4. Boggione CT, Luján Brajovich ME, Mattaloni SM, Di Mónaco RA, García Borrás SE, Biondi CS, et al. Genotyping approach for non-in-vasive foetal RHD detection in an admixed population. Blood Transfus 2017; 15(1): 66-73.
• 5. Smits-Wintjens VEHJ, Walther FJ, Lopriore E. Rhesus haemolytic disease of the newborn: Postnatal management, associated mor-bidity and long-term outcome. Semin Fetal Neonatal Med 2008; 13(4): 265-71. [CrossRef ]
• 6. Lo YMD, Bowell PJ, Selinger M, Mackenzie IZ, Chamberlain P, Gil-lmer MDG, et al. Prenatal determination of fetal RhD status by analysis of peripheral blood of rhesus negative mothers. The Lan-cet 1993; 341(8853): 1147-8. [CrossRef ]
• 7. Dovč-Drnovšek T, Klemenc P, Toplak N, Blejec T, Bricl I, Rožman P. Reliable determination of fetal RhD status by RHD genotyping from maternal plasma. Transfus Med Hemotherapy 2013; 40(1): 37-43. [CrossRef ]
• 8. Benachi A, Delahaye S, Leticee N, Jouannic JM, Ville Y, Costa JM. Impact of non-invasive fetal RhD genotyping on management costs of rhesus-D negative patients: Results of a French pilot study. Eur J Obstet Gynecol Reprod Biol 2012; 162(1): 28-32. [CrossRef ]
• 9. González-González C, Garcia-Hoyos M, Trujillo-Tiebas MJ, Lor-da-Sanchez I, Rodríguez De Alba M, Infantes F, et al. Application of fetal DNA detection in maternal plasma: A prenatal diagnosis unit experience. In: Journal of Histochemistry and Cytochemistry 2005; 53(3): 307-14. [CrossRef ]
• 10. Yang H, Llewellyn A, Walker R, Harden M, Saramago P, Griffin S, et al. High-throughput, non-invasive prenatal testing for fetal rhesus D status in RhD-negative women: A systematic review and me-ta-analysis. BMC Medicine 2019; 22(13): 1-172. [CrossRef ]
• 11. Yaşa B, Şahin O, Öcüt E, Seven M, Sözer S. Assessment of Fetal Rhesus D and Gender with Cell-Free DNA and Exosomes from Ma-ternal Blood. Reprod Sci 2020; doi: 10.1007/s43032-020-00321-4 [CrossRef ]
• 12. Lambertino JRM, Villegas SMG. Rh Alloimmunization in pregnan-cy womens, A look to diagnosis and therapeutic approach. Gine-col Obstet Mex 2014; 82(11): 744-54.
• 13. Clausen FB, Barrett AN, Akkök CA, Armstrong-Fisher S, Bergström KD, Boggione CT, et al. Noninvasive fetal RHD genotyping to gu-ide targeted anti-D prophylaxis-an external quality assessment workshop. Vox Sang 2019; 114(4): 386-393. [CrossRef ]
• 14. Schmidt LC, Cabral ACV, Faria MA, Monken F, Tarazona-Santos E, Martins ML. Noninvasive fetal RHD genotyping from maternal plasma in an admixed Brazilian population. Genet Mol Res 2014; 13(1): 799-805. [CrossRef ]
• 15. Macher HC, Noguerol P, Medrano-Campillo P, Garrido-Mírquez MR, Rubio-Calvo A, Carmona-González M, et al. Standardization non-invasive fetal RHD and SRY determination into clinical rou-tine using a new multiplex RT-PCR assay for fetal cell-free DNA in pregnant women plasma: Results in clinical benefits and cost sa-ving. Clin Chim Acta 2012; 413(3-4): 490-4. [CrossRef ]
• 16. Sparks TN, Caughey AB. How should costs and cost-effectiveness be considered in prenatal genetic testing? Seminars in Perinato-logy 2018; 42(5): 275-282. [CrossRef ]
• 17. Darlington M, Carbonne B, Mailloux A, Brossard Y, Levy-Mozzico-nacci A, Cortey A, et al. Effectiveness and costs of non-invasive foetal RHD genotyping in rhesus-D negative mothers: A French multicentric two-arm study of 850 women. BMC Pregnancy Child-birth 2018; 18(1): 496. [CrossRef ]
• 18. Sherwood K, Weimer ET. Characteristics, properties, and potential applications of circulating cell-free dna in clinical diagnostics: a fo-cus on transplantation. Journal of Immunological Methods 2018; 463: 27-38. [CrossRef ]
• 19. Kostenko E, Chantraine F, Vandeweyer K, Schmid M, Lefevre A, Hertz D, et al. Clinical and Economic Impact of Adopting Nonin-vasive Prenatal Testing as a Primary Screening Method for Fetal Aneuploidies in the General Pregnancy Population. Fetal Diagn Ther 2019; 45(6): 413-423. [CrossRef ]