Fetal Screening in RH1 Negative Pregnant Women: Experience in Switzerland

Overview

Journal Biomedicines

Specialty Biomedical Engineering

Date 2023 Oct 28

PMID 37893020

Authors

Bernd Schimanski

Rahel Krauchi

Jolanda Stettler

Sofia Lejon Crottet

Christoph Niederhauser

Frederik Banch Clausen

Stefano Fontana

Markus Hodel

Sofia Amylidi-Mohr

Luigi Raio

Claire Abbal

Christine Henny

Affiliations

Soon will be listed here.

Abstract

RH1 incompatibility between mother and fetus can cause hemolytic disease of the fetus and newborn. In Switzerland, fetal genotyping from maternal blood has been recommended from gestational age 18 onwards since the year 2020. This facilitates tailored administration of RH immunoglobulin (RHIG) only to RH1 negative women carrying a RH1 positive fetus. Data from 30 months of noninvasive fetal screening is presented. Cell-free DNA was extracted from 7192 plasma samples using a commercial kit, followed by an in-house qPCR to detect exons 5 and 7, in addition to an amplification control. Valid results were obtained from 7072 samples, with 4515 (64%) fetuses typed positive and 2556 (36%) fetuses being negative. A total of 120 samples led to inconclusive results due to the presence of maternal or fetal variants (46%), followed by women being serologically RH1 positive (37%), and technical issues (17%). One sample was typed false positive, possibly due to contamination. No false negative results were observed. We show that unnecessary administration of RHIG can be avoided for more than one third of RH1 negative pregnant women in Switzerland. This reduces the risks of exposure to a blood-derived product and conserves this limited resource to women in actual need.

References

McBain R, Crowther C, Middleton P . Anti-D administration in pregnancy for preventing Rhesus alloimmunisation. Cochrane Database Syst Rev. 2015; (9):CD000020. PMC: 7061251. DOI: 10.1002/14651858.CD000020.pub3. View

Daniels G, Finning K, Martin P . Noninvasive fetal blood grouping: present and future. Clin Lab Med. 2010; 30(2):431-42. DOI: 10.1016/j.cll.2010.02.006. View

Chitty L, Finning K, Wade A, Soothill P, Martin B, Oxenford K . Diagnostic accuracy of routine antenatal determination of fetal RHD status across gestation: population based cohort study. BMJ. 2014; 349:g5243. PMC: 4154470. DOI: 10.1136/bmj.g5243. View

Legler T, Luhrig S, Korschineck I, Schwartz D . Diagnostic performance of the noninvasive prenatal FetoGnost RhD assay for the prediction of the fetal RhD blood group status. Arch Gynecol Obstet. 2021; 304(5):1191-1196. PMC: 8490250. DOI: 10.1007/s00404-021-06055-1. View

Zipursky A, ISRAELS L . The pathogenesis and prevention of Rh immunization. Can Med Assoc J. 1967; 97(21):1245-57. PMC: 1923510. View

Kenny-Walsh E . Clinical outcomes after hepatitis C infection from contaminated anti-D immune globulin. Irish Hepatology Research Group. N Engl J Med. 1999; 340(16):1228-33. DOI: 10.1056/NEJM199904223401602. View

Rijnders R, Christiaens G, Bossers B, van der Smagt J, van der Schoot C, de Haas M . Clinical applications of cell-free fetal DNA from maternal plasma. Obstet Gynecol. 2004; 103(1):157-64. DOI: 10.1097/01.AOG.0000103996.44503.F1. View

Clausen F, Barrett A, Krog G, Finning K, Dziegiel M . Non-invasive foetal RhD genotyping to guide anti-D prophylaxis: an external quality assurance workshop. Blood Transfus. 2017; 16(4):359-362. PMC: 6034781. DOI: 10.2450/2017.0329-16. View

Noizat-Pirenne F, Verdier M, Lejealle A, Mercadier A, Bonin P, Peltier-Pujol F . Weak D phenotypes and transfusion safety: where do we stand in daily practice?. Transfusion. 2007; 47(9):1616-20. DOI: 10.1111/j.1537-2995.2007.01332.x. View

10.

Lo Y, Hjelm N, Fidler C, Sargent I, Murphy M, Chamberlain P . Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med. 1998; 339(24):1734-8. DOI: 10.1056/NEJM199812103392402. View

11.

Pilgrim H, Lloyd-Jones M, Rees A . Routine antenatal anti-D prophylaxis for RhD-negative women: a systematic review and economic evaluation. Health Technol Assess. 2009; 13(10):iii, ix-xi, 1-103. DOI: 10.3310/hta13100. View

12.

Finning K, Martin P, Soothill P, Avent N . Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service. Transfusion. 2002; 42(8):1079-85. DOI: 10.1046/j.1537-2995.2002.00165.x. View

13.

de Haas M, Thurik F, Koelewijn J, van der Schoot C . Haemolytic disease of the fetus and newborn. Vox Sang. 2015; 109(2):99-113. DOI: 10.1111/vox.12265. View

14.

Uzunel M, Tiblad E, Mortberg A, Wikman A . Single-exon approach to non-invasive fetal RHD screening in early pregnancy: An update after 10 years' experience. Vox Sang. 2022; 117(11):1296-1301. PMC: 9826394. DOI: 10.1111/vox.13348. View

15.

Ogasawara K, Sasaki K, Isa K, Tsuneyama H, Uchikawa M, Satake M . Weak D alleles in Japanese: a c.960G>A silent mutation in exon 7 of the RHD gene that affects D expression. Vox Sang. 2015; 110(2):179-84. DOI: 10.1111/vox.12322. View

16.

Flegel W . How I manage donors and patients with a weak D phenotype. Curr Opin Hematol. 2006; 13(6):476-83. DOI: 10.1097/01.moh.0000245694.70135.c3. View

17.

Scheffer P, de Haas M, van der Schoot C . The controversy about controls for fetal blood group genotyping by cell-free fetal DNA in maternal plasma. Curr Opin Hematol. 2011; 18(6):467-73. DOI: 10.1097/MOH.0b013e32834bab2d. View

18.

de Haas M, Finning K, Massey E, Roberts D . Anti-D prophylaxis: past, present and future. Transfus Med. 2014; 24(1):1-7. DOI: 10.1111/tme.12099. View

19.

Londero D, Merluzzi S, Dreossi C, Barillari G . Prenatal screening service for fetal RHD genotyping to guide prophylaxis: the two-year experience of the Friuli Venezia Giulia region in Italy. Blood Transfus. 2022; 21(2):93-99. PMC: 10072987. DOI: 10.2450/2022.0004-22. View

20.

Clausen F, Hellberg A, Bein G, Bugert P, Schwartz D, Dovc Drnovsek T . Recommendation for validation and quality assurance of non-invasive prenatal testing for foetal blood groups and implications for IVD risk classification according to EU regulations. Vox Sang. 2021; 117(2):157-165. PMC: 10686716. DOI: 10.1111/vox.13172. View