Journal Mobile Options
Table of Contents
Vol. 29, No. 4, 2011
Issue release date: June 2011

Fetal RHD Genotyping in Maternal Plasma at 11–13 Weeks of Gestation

Akolekar R. · Finning K. · Kuppusamy R. · Daniels G. · Nicolaides K.H.
To view the fulltext, log in and/or choose pay-per-view option

Individual Users: Register with Karger Login Information

Please create your User ID & Password





Contact Information











I have read the Karger Terms and Conditions and agree.

To view the fulltext, please log in

To view the pdf, please log in

Abstract

Objective: To examine the feasibility of fetal RHD genotyping at 11–13 weeks’ gestation from analysis of circulating cell-free fetal DNA (ccffDNA) in the plasma of RhD negative pregnant women using a high-throughput robotic technique. Methods: Stored plasma (0.5 ml) from 591 RhD negative women was used for extraction of ccffDNA by a robotic technique. Real-time quantitative polymerase chain reaction (PCR) with probes for exons 5 and 7 of the RHD gene was then used to determine the fetal RHD genotype, which was compared to the neonatal RhD phenotype. Results: In total there were 502 (85.7%) cases with a conclusive result and 84 (14.3%) with an inconclusive result. The prenatal test predicted that the fetus was RhD positive in 332 cases and in all of these the prediction was correct, giving a positive predictive value of 100% (95% CI 96.8–100). The test predicted that the fetus was RhD negative in 170 cases and in 164 of these the prediction was correct, giving a negative predictive value for RhD positive fetuses of 96.5% (95% CI 93.7–99.2). Conclusion: The findings demonstrate the feasibility and accuracy of non-invasive fetal RHD genotyping at 11–13 weeks with a high-throughput technique.



Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Lo YM, Corbetta N, Chamberlain PF, Rai V, Sargent IL, Redman CW, Wainscoat JS: Presence of fetal DNA in maternal plasma and serum. Lancet 1997;350:485–487.
  2. Lo YM, Hjelm NM, Fidler C, Sargent IL, Murphy MF, Chamberlain PF, Poon PM, Redman CW, Wainscoat JS: Prenatal diagnosis of fetal RhD status by molecular analysis of maternal plasma. N Engl J Med 1998;339:1734–1738.
  3. Faas BH, Beuling EA, Christiaens GC, von dem Borne AE, van der Schoot CE: Detection of fetal RhD-specific sequences in maternal plasma. Lancet 1998;352:1196.
  4. Finning KM, Martin PG, Soothill PW, Avent ND: Prediction of fetal D status from maternal plasma: introduction of a new noninvasive fetal RHD genotyping service. Transfusion 2002 42:1079–1085.
  5. Tabor A, Bang J, Nørgaard-Pedersen B: Feto-maternal haemorrhage associated with genetic amniocentesis: results of a randomized trial. Br J Obstet Gynaecol 1987;94:528–534.
  6. Brambati B, Guercilena S, Bonacchi I, Oldrini A, Lanzani A, Piceni L: Feto-maternal transfusion after chorionic villus sampling: clinical implications. Hum Reprod 1986;1:37–40.
  7. Geifman-Holtzman O, Grotegut CA, Gaughan JP: Diagnostic accuracy of noninvasive fetal Rh genotyping from maternal blood – a meta-analysis. Am J Obstet Gynecol 2006;195:1163–1173.
  8. Legler TJ, Muller SP, Haverkamp A, Grill S, Hahn S: Prenatal RhD testing: A review of studies published from 2006 to 2008. Transfus Med Hemother 2009;36:189–198.
  9. Daniels G, Finning K, Martin P, Massey E: Noninvasive prenatal diagnosis of fetal blood group phenotypes: current practice and future prospects. Prenat Diagn 2009;29:101–107.
  10. Van der Schoot CE, Soussan AA, Koelewijn J, Bonsel G, Paget-Christiaens LG, de Haas M: Non-invasive antenatal RHD typing. Transfus Clin Biol 2006;13:53–57.
  11. 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;336:816–818.
  12. Snijders RJ, Noble P, Sebire N, Souka A, Nicolaides KH: UK multicentre project on assessment of risk of trisomy 21 by maternal age and fetal nuchal-translucency thickness at 10–14 weeks of gestation. Lancet 1998;352:343–346.
  13. Kagan KO, Wright D, Baker A, Sahota D, Nicolaides KH: Screening for trisomy 21 by maternal age, fetal nuchal translucency thickness, free β-human chorionic gonadotropin, and pregnancy-associated plasma protein-A. Ultrasound Obstet Gynecol 2008;31:618–624.
  14. Raport CJ, Gosling J, Schweickart VL, Gray PW, Charo IF: Molecular cloning and functional characterization of a novel human CC chemokine receptor (CCR5) for RANTES, MIP-1β, and MIP-1α. J Biol Chem 1996;271:17161–17166.
  15. Zhang J, Fidler C, Murphy MF, Chamberlain PF, Sargent IL, Redman CW, Hjelm NM, Wainscoat JS, Lo YM: Determination of fetal RhD status by maternal plasma DNA analysis. Ann NY Acad Sci 2000;906:153–155.
  16. Costa JM, Giovangrandi Y, Ernault P, Lohmann L, Nataf V, El Halali N, Gautier E: Fetal RHD genotyping in maternal serum during the first trimester of pregnancy. Br J Haematol 2002;119:255–260.
  17. Randen I, Hauge R, Kjeldsen-Kragh J, Fagerhol MK: Prenatal genotyping of RHD and SRY using maternal blood. Vox Sang 2003;85:300–306.
  18. Brojer E, Zupanska B, Guz K, Orziñska A, Kaliñska A: Noninvasive determination of fetal RHD status by examination of cell-free DNA in maternal plasma. Transfusion 2005:45:1473–1480.
  19. Al-Yatama MK, Mustafa AS, Al-Kandari FM, Khaja N, Zohra K, Monem RA, Abraham S: Polymerase-chain-reaction-based detection of fetal rhesus D and Y-chromosome-specific DNA in the whole blood of pregnant women during different trimesters of pregnancy. Med Princ Pract 2007;16:327–332.
  20. Machado IN, Castilho L, Pellegrino J Jr, Barini R: Fetal RHD genotyping from maternal plasma in a population with a highly diverse ethnic background. Rev Assoc Med Bras 2006;52:232–235.
  21. Minon JM, Gerard C, Senterre JM, Schaaps JP, Foidart JM: Routine fetal RHD genotyping with maternal plasma: a four-year experience in Belgium. Transfusion 2008;48:373–381.
  22. Singleton BK, Green CA, Avent ND, Martin PG, Smart E, Daka A, Narter-Olaga EG, Hawthorne LM, Daniels G: The presence of an RHD pseudogene containing a 37 base pair duplication and a nonsense mutation in Africans with the Rh D-negative blood group phenotype. Blood 2000;95:12–18.
  23. Freeman K, Szczepura A, Osipenko L: Non-invasive fetal RHD genotyping tests: a systematic review of the quality of reporting of diagnostic accuracy in published studies. Eur J Obstet Gynecol Reprod Biol 2009;142:91–98.
  24. Wright CF, Burton H: The use of cell-free fetal nucleic acids in maternal blood for non-invasive prenatal diagnosis. Hum Reprod Update 2009;15:139–151.
  25. Page-Christiaens GC, Bossers B, van der Schoot CE, DE Haas M: Use of bi-allelic insertion/deletion polymorphisms as a positive control for fetal genotyping in maternal blood: first clinical experience. Ann NY Acad Sci. 2006;1075:123–129.
  26. Chan KC, Ding C, Gerovassili A, Yeung SW, Chiu RW, Leung TN, Lau TK, Chim SS, Chung GT, Nicolaides KH, Lo YM: Hypermethylated RASSF1A in maternal plasma: a universal fetal DNA marker that improves the reliability of noninvasive prenatal diagnosis. Clin Chem 2006;52:2211–2218.
  27. Lo YM, Tein MS, Lau TK, Haines CJ, Leung TN, Poon PM, Wainscoat JS, Johnson PJ, Chang AM, Hjelm NM: Quantitative analysis of fetal DNA in maternal plasma and serum: implications for noninvasive prenatal diagnosis. Am J Hum Genet 1998;62:768–775.
  28. Daniels G: Human Blood Groups, ed 2. Oxford, Blackwell Science, 2002.


Pay-per-View Options
Direct payment This item at the regular price: USD 38.00
Payment from account With a Karger Pay-per-View account (down payment USD 150) you profit from a special rate for this and other single items.
This item at the discounted price: USD 26.50