Klinik ve Ülke Verilerimiz Işığında Rhesus D Genotiplemesi ile Desteklenmiş Rhesus D Negatif Gebe İzlem Programı Uygulamanın Prosedür Spesifik Maliyet-Etkinlik Analizi

Yıl 2018, Cilt: 2 Sayı: 1, 18 - 39, 11.02.2018

Şule Özel Serkan Bodur Yaprak Engin-üstün

Öz

Amaç: Ülkemiz şartlarında fetal RhD
genotiplemesi ile hedeflenmiş antenatal anti-D profilaksi programı uygulamanın
maliyet etkinlik ve uygulanabilirlik analizini yapmaktır.

Materyal -Metot: RhD genotiplemesi yolu ile
hedeflenmiş antenatal anti-D profilaksi programı ile evrensel anti-D
profilaksisi programlarını karşılaştırmak amacı ile ulusal perinatal
istatistikler, yayınlanmış literatür, hastanemiz hasta kayıtları ve ulusal
maliyet kaynakları gözden geçirilerek bir analiz modeli oluşturuldu.

Bulgular: RhD negatif gebelik oranı
%10.1 ve bu gebeliklerdeki RhD negatif fetüs oranı %21.4'idi. Antenatal ve
postnatal profilaksi programına katılım oranı sırası ile %26.3 ve %66.7'idi.
Hastalarımızın %7'sinde sensitizasyon riskli olaylar nedeni ile ikiden fazla
anti-D profilaksisi yapılmıştı. Anti-D Immunglobulin (300µgr) birim maliyeti
295.2TL'idi. Evrensel antenatal profilaksi programına ait 'Gebelik başına
ortalama maliyet' 564,8TL'idi. Bu maliyetin aşılmamasını sağlayacak RhD
geneotipleme birim maliyeti 52.4TL olarak belirlendi. Bu program yürütüldüğünde
her yıl 551 (%0.38) hastanın yanlış negatiflik nedeniyle sensitizasyon riski
yaratacak şekilde profilaksi programı dışında kalacağı ve 6328 (%4.37) hastanın
ise yanlış pozitiflik nedeni ile gereksiz antenatal anti-D profilaksisi
almaları gerekeceği belirlendi.

Sonuç: Antenatal RhD genotiplemesi,
postpartum profilaksi programı ile birlikte uygulandığı tüm klinik seneryolar
için ek maliyet oluşturmaktadır. Hem maliyeti azaltacak hasta sayısı ve
oranının ülkemizde Avrupa ülkelerinden daha az olması hem de mevcut hasta
populasyonun daha çok postpartum profilaksi programına uygun hastane
başvurularında bulunması nedeni ile ülkemizde profilaksi programına RhD
geneotiplemesinin eklenmesinin maliyet etkin bir yaklaşım olmayacağını
görüşündeyiz. Yine de bireysel hasta görüşmeleri esnasında RhD genotiplesi yolu
ile gereksiz anti-D profilaksisinden ve bu sayede işlemin getirebileceği çok
düşük ihtimalli olası yan etkilerden kaçınılabileceği hususunda bilgilendirmede
bulunmak da etik bir yaklaşım olabilir.

Anahtar Kelimeler

Anti-D, Maliyet etkinliği, Ekstraselüler serbest fetal DNA, Genotipleme, RhD immünoglobulin

Procedure Specific Cost-Effectiveness Analysis of Implementing a Rhesus D Genotyping Targeted Rhesus D Negative Pregnancy Monitoring Program in Turkey

Öz

Aim: To analyze the feasibility of fetal Rhesus D
(RhD) genotyping targeted antenatal anti-D prophylaxis program under the
specific conditions of Turkey.

Material and Method: An analyzing method was
built to compare the two prophylaxis programs by utilizing national perinatal
statistics, published literature, hospital patient records and national cost
resources.

Results: The incidence of RhD negative pregnancy and RhD
negative fetus in those pregnancies, were 10.1% and 21.4%, respectively. The
attendance rate of antenatal and postnatal prophylaxis programs were 26.3% and
66.7%, respectively and 7% of those patients required additional doses. The
average cost of anti-D immunoglobulin was 77.7 US$. The average per pregnancy
cost of universal antenatal prophylaxis program was 148.6 US$. The individual
cost of RhD gene genotyping shouldn’t be exceeding 13.7 US$ not to increase
expenditure. In the case of program implementation; 551 (0.38%) patients would
be falsely excluded and additional 6328 (4.37%) patients had to receive
unnecessary prophylaxis each year.

Conclusion: Antenatal RhD genotyping is bearing
additional cost in all clinical scenarios when followed by postpartum prophylaxis.
The implementation of RhD genotyping targeted anti-D prophylaxis program in
Turkey would not be a cost-effective approach, due to the facts that the number
and proportion of patients who cause cost reduction were found to be far more
lower than European countries and that the existing patient population is
mostly applying to hospitals appropriate for postpartum prophylaxis. However,
it would be an ethical approach to inform patients at the individual level
about the potential benefits of antenatal RhD genotyping.

Anahtar Kelimeler

Anti-D, Cost-effectiveness, Extracellular free fetal DNA, Genotyping, RhD immunoglobulin

Kaynakça

• Referans3. Lee D, Contreras M, Robson SC, et al. Recommendations for the use of anti-D immunoglobulin for Rh prophylaxis. British Blood Transfusion Society and the Royal College of Obstetricians and Gynaecologists. Transfus Med 1999;9:93e7.
• Referans10. 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. European Journal of Obstetrics, Gynecology, & Reproductive Biology. 2012;162(1):28-32.
• Referans4. Crowther CA, Keirse MJ. Anti-D administration in pregnancy for preventing rhesus alloimmunisation. Cochrane Database Syst Rev 2000;CD000020.
• Referans5. Chilcott J, Lloyd Jones M, Wight J, et al. A review of the clinical effectiveness and cost-effectiveness of routine anti-D prophylaxis for pregnant women who are rhesus-negative. Health Technol Assess 2003;7.iiie62.
• Referans6. Clausen FB, Christiansen M, Steffensen R, Jorgensen S, Nielsen C, Jakobsen MA, et al. Report of the first nationally implemented clinical routine screening for fetal RHD in D- pregnant women to ascertain the requirement for antenatal RhD prophylaxis. Transfusion. 2012;52(4):752-8. doi: 10.1111/j.537-2995.011.03362.x. Epub 2011 Oct 13.
• Referans7. de Haas M, van der Ploeg CPB, Scheffer PG, Verlinden DA, Hirschberg H, Abbink F, et al. A nation-wide fetal RHD screening programme for targeted antenatal and postnatal anti-D. ISBT Science Series. 2012;7:164-7.
• Referans8. Hyland CA, Gardener GJ, Davies H, Ahvenainen M, Flower RL, Irwin D, et al. Evaluation of non-invasive prenatal RHD genotyping of the fetus. The Medical journal of Australia. 2009;191(1):21-5.
• Referans9. Mackie FL, Hemming K, Allen S, Morris RK, Kilby MD. The accuracy of cell-free fetal DNA-based non-invasive prenatal testing in singleton pregnancies: a systematic review and bivariate meta-analysis. BJOG : an international journal of obstetrics and gynaecology. 2016;31(10):1471-0528.
• Referans11. Hawk AF, Chang EY, Shields SM, Simpson KN. Costs and clinical outcomes of noninvasive fetal RhD typing for targeted prophylaxis. Obstetrics & Gynecology. 2013;122(3):579-85.
• Referans12. Szczepura A, Osipenko L, Freeman K. A new fetal RHD genotyping test: costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales. BMC Pregnancy & Childbirth. 2011;11:5.
• Referans19. García-Enguídanos A, Calle ME, Valero J, Luna S, Domínguez-Rojas V. Risk factors in miscarriage: a review. Eur J Obstet Gynecol Reprod Biol. 2002 May 10;102(2):111-9.
• Referans13. Teitelbaum L, Metcalfe A, Clarke G, Parboosingh JS, Wilson RD, Johnson JM. Costs and benefits of non-invasive fetal RhD determination. Ultrasound in Obstetrics & Gynecology. 2015;45(1):84-8.
• Referans14. Neovius M, Tiblad E, Westgren M, Kublickas M, Neovius K, Wikman A. Cost-effectiveness of first trimester non-invasive fetal RHD screening for targeted antenatal anti-D prophylaxis in RhD-negative pregnant women: a model-based analysis. BJOG. 2016;123(8):1337-46. doi: 10.111/471-0528.13801. Epub 2015 Dec 10.
• Referans15. Gordon LG, Hyland C, Hyett J, O’Brien H, Millard G, Flower R, Gardener G. Non-invasive fetal RHD genotyping of RhD negative pregnant women for targeted anti-D therapy in Australia: a cost-effectiveness analysis. Under press.
• Referans16. Chitty LS, Finning K, Wade A, Soothill P, Martin B, Oxenford K, Daniels G, Massey E. Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study. BMJ 2014;349:g5243.
• Referans17. NICE Guideline. Diagnostics guidance [DG25].High-throughput non-invasive prenatal testing for fetal RHD genotype. November 2016. https://www.nice.org.uk/guidance/dg25/resources
• Referans18. Haimila K, Sulin K, Kuosmanen M, Sareneva I, Korhonen A, Natunen S, Tuimala J, Sainio S. Targeted antenatal anti-D prophylaxis program for RhD-negative pregnant women – outcome of the first two years of a national program in Finland.
• Referans1. Bowman JM. The prevention of Rh immunization. Transfus Med Rev 1988;2:129e50.
• Referans20. Hyland CA, Gardener GJ, Davies H, Ahvenainen M, Flower RL, Irwin D, et al. Evaluation of non-invasive prenatal RHD genotyping of the fetus. The Medical journal of Australia. 2009;191(1):21-5.
• Referans21. Akın G, Dostbil N. Türkiye’de kan grubu araştırmaları. Ankara Üni. Dil ve Tarih-Coğrafya Fakültesi Dergisi. 2005;45(2):1-15.
• Referans22. Daniels G. Variants of RhDecurrent testing and clinical consequences. Br J Haematol 2013;161:461e70.
• Referans23. Daniels G, Finning K, Martin P, et al. Noninvasive prenatal diagnosis of fetal blood group phenotypes: current practice and future prospects. Prenat Diagn 2009;29:101e7.
• Referans24. van der Schoot CE, Tax GH, Rijnders RJ, et al. Prenatal typing of Rh and Kell blood group system antigens: the edge of a watershed. Transfus Med Rev 2003;17:31e44.
• Referans25. Finning K, Martin P, Summers J, Massey E, Poole G, Daniels G. Effect of high throughput RHD typing of fetal DNA in maternal plasma on use of anti-RhD immunoglobulin in RhD negative pregnant women: prospective feasibility study. BMJ.2008;336:816-8.
• Referans2. Urbaniak SJ. The scientific basis of antenatal prophylaxis. Br J Obstet Gynaecol 1998;105(Suppl 18):11e8.