Routine Fetal RhD Genotyping for RhD- Pregnant Women

NCT ID: NCT00832962

Last Updated: 2015-03-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

2532 participants

Study Classification

OBSERVATIONAL

Study Start Date

2009-01-31

Study Completion Date

2013-10-31

Brief Summary

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The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second will be a conventional management, i.e. without RHD fetal typing (GENIFERH 1 control group). The two groups will consist of 13 maternity wards spread over French territory. The second study (GENIFERH 2) is an evaluation of RhD fetal typing diagnostic performance and biological feasibility in routine antenatal practice with development of knew technical support; it will be based on more than 3500 fetal genotypings performed during one year by the five laboratories participating at the two studies.

Detailed Description

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Alloimmunisation against the RhD (RH) red cell surface antigen is the commonest cause of haemolytic disease of the fetus and newborn. It can be avoided by anti D immunoglobulin administration (RhIg). At the end of year 2005, new recommendations about anti-D prophylaxis in France proposed that all RhD negative pregnant women should be given anti-D immunoglobulin at 28 weeks' gestation. However, about one third of these women would be carrying an RhD negative fetus and would receive the treatment unnecessarily. A non-invasive fetal RHD typing kit, CE labelled since June 2007, is available and could be proposed to all RhD negative pregnant women. Applicable from the end of the first trimester of pregnancy on fetal DNA isolated from maternal plasma, this assay allows RhIg to be specifically injected to unsensitized pregnancies with RhD positive fetus only, and to promote the use of antenatal RhIg prophylaxis in a rational approach with economical and ethical impact.The study is divided in two sub-studies. The first one is an economical and performance comparison between two antenatal management strategies of RhD negative pregnant women: the first one will comprise non invasive RhD fetal typing during the second trimester of pregnancy (GENIFERH 1 RhD typing group), and the second will be a conventional management, i.e. without RHD fetal typing (GENIFERH 1 control group). The two groups will consist of 13 maternity wards spread over French territory. The second study (GENIFERH 2) is an evaluation of RhD fetal typing diagnostic performance and biological feasibility in routine antenatal practice with development of knew technical support; it will be based on more than 3500 fetal genotypings performed during one year by the five laboratories participating at the two studies.

Conditions

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Rhesus Negative Pregnant Women

Study Design

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Study Time Perspective

PROSPECTIVE

Study Groups

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1

Adult Rh negative pregnant patients from 7 selected centers (SAINT ANTOINE hospital, CHU Marseille, CHU Nantes, CHU Lille, LOUIS MOURIER Hospital, SAINT VINCENT-PAUL Hospital, CH POISSY)

Genotyping

Intervention Type GENETIC

Whole blood sample

2

Adult Rh negative pregnant patients from 6 selected centers (Tenon hospital, Jean VERDIER Hospital, La Pitie-Salpetriere Hospital, Cochin Hospital, Robert Debre Hospital, BICHAT Hospital)

Usual prophylaxis

Intervention Type OTHER

Prophylactic anti-RhD

Interventions

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Genotyping

Whole blood sample

Intervention Type GENETIC

Usual prophylaxis

Prophylactic anti-RhD

Intervention Type OTHER

Other Intervention Names

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Prophylactic anti-RhD

Eligibility Criteria

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Inclusion Criteria

* Adult Rh negative pregnant patients ( ≥ 18 years)
* Valid and confirmed result of Rh D negative status.(one copy saved into the obstetrical records)
* Absence of actively produced anti-D antibody as shown on laboratory examination of a blood sample taken within the first trimester of pregnancy.
* Evolving pregnancy at the time of inclusion in the study ( between 8 and 26 gestation weeks as confirmed by early sonography).
* Absence of a previous invasive fetal RHD genotyping ( chorionic villous sampling, amniocentesis).
* Patient having signed an informed consent for the study.
* Inclusion and delivery expected in the same maternity ward
* Patient affiliated to a social security regimen.

Exclusion Criteria

* Evolving pregnancy seen for the first time after 26 gestation weeks.
* Poor understanding of the objectives of the study ( language barrier, ...)
* Delivery expected in a maternity ward not participating at the study.
* Fetal RHD invasive genotyping performed during early pregnancy on amniotic fluid or chorionic villus.
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yves BROSSARD, MD

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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Hopital Saint Antoine

Paris, , France

Site Status

Countries

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France

References

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Branger B, Winer N. [Epidemiology of anti-D allo-immunization during pregnancy]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S87-1S92. French.

Reference Type BACKGROUND
PMID: 16495833 (View on PubMed)

Parant O. [Comparison of the efficacy of different methods for the prevention of anti-D allo-immunization during pregnancy: targeted strategy limited to risk situations or associated with systematic prevention in the 3rd trimester]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S93-1S103. French.

Reference Type BACKGROUND
PMID: 16495834 (View on PubMed)

Bennett PR, Le Van Kim C, Colin Y, Warwick RM, Cherif-Zahar B, Fisk NM, Cartron JP. Prenatal determination of fetal RhD type by DNA amplification. N Engl J Med. 1993 Aug 26;329(9):607-10. doi: 10.1056/NEJM199308263290903.

Reference Type BACKGROUND
PMID: 8341334 (View on PubMed)

Aubin JT, Le Van Kim C, Mouro I, Colin Y, Bignozzi C, Brossard Y, Cartron JP. Specificity and sensitivity of RHD genotyping methods by PCR-based DNA amplification. Br J Haematol. 1997 Aug;98(2):356-64. doi: 10.1046/j.1365-2141.1997.2193040.x.

Reference Type BACKGROUND
PMID: 9266934 (View on PubMed)

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 Aug 16;350(9076):485-7. doi: 10.1016/S0140-6736(97)02174-0.

Reference Type BACKGROUND
PMID: 9274585 (View on PubMed)

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 Apr;62(4):768-75. doi: 10.1086/301800.

Reference Type BACKGROUND
PMID: 9529358 (View on PubMed)

Brossard Y, Sender A, Cartron JP, Huchet J, Pinon F, Blot P, David G. [Value of RHD fetal genotyping in the prevention of anti-D immunization]. Bull Acad Natl Med. 2001;185(2):329-36. French.

Reference Type BACKGROUND
PMID: 11474588 (View on PubMed)

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 Oct 10;352(9135):1196. doi: 10.1016/s0140-6736(05)60534-x. No abstract available.

Reference Type BACKGROUND
PMID: 9777844 (View on PubMed)

Rouillac-Le Sciellour C, Puillandre P, Gillot R, Baulard C, Metral S, Le Van Kim C, Cartron JP, Colin Y, Brossard Y. Large-scale pre-diagnosis study of fetal RHD genotyping by PCR on plasma DNA from RhD-negative pregnant women. Mol Diagn. 2004;8(1):23-31. doi: 10.1007/BF03260044.

Reference Type BACKGROUND
PMID: 15230639 (View on PubMed)

Colin Y, Cherif-Zahar B, Le Van Kim C, Raynal V, Van Huffel V, Cartron JP. Genetic basis of the RhD-positive and RhD-negative blood group polymorphism as determined by Southern analysis. Blood. 1991 Nov 15;78(10):2747-52.

Reference Type BACKGROUND
PMID: 1824267 (View on PubMed)

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 Jan 1;95(1):12-8.

Reference Type BACKGROUND
PMID: 10607679 (View on PubMed)

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 Oct;195(4):1163-73. doi: 10.1016/j.ajog.2006.07.033.

Reference Type BACKGROUND
PMID: 17000250 (View on PubMed)

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 Dec 10;339(24):1734-8. doi: 10.1056/NEJM199812103392402.

Reference Type BACKGROUND
PMID: 9845707 (View on PubMed)

Finning K, Martin P, Daniels G. A clinical service in the UK to predict fetal Rh (Rhesus) D blood group using free fetal DNA in maternal plasma. Ann N Y Acad Sci. 2004 Jun;1022:119-23. doi: 10.1196/annals.1318.019.

Reference Type BACKGROUND
PMID: 15251949 (View on PubMed)

van der Schoot CE. Molecular diagnostics in immunohaematology. Vox Sang. 2004 Jul;87 Suppl 2:189-92. doi: 10.1111/j.1741-6892.2004.00481.x. No abstract available.

Reference Type BACKGROUND
PMID: 15209914 (View on PubMed)

Cortey A, Brossard Y, Beliard R, Bourel D. [Prevention of fetomaternal rhesus-D allo-immunization. Perspectives]. J Gynecol Obstet Biol Reprod (Paris). 2006 Feb;35(1 Suppl):1S119-1S122. French.

Reference Type BACKGROUND
PMID: 16495837 (View on PubMed)

Zimmermann B, El-Sheikhah A, Nicolaides K, Holzgreve W, Hahn S. Optimized real-time quantitative PCR measurement of male fetal DNA in maternal plasma. Clin Chem. 2005 Sep;51(9):1598-604. doi: 10.1373/clinchem.2005.051235. Epub 2005 Jul 14.

Reference Type BACKGROUND
PMID: 16020496 (View on PubMed)

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 Dec;52(12):2211-8. doi: 10.1373/clinchem.2006.074997. Epub 2006 Oct 26.

Reference Type BACKGROUND
PMID: 17068167 (View on PubMed)

Daniels G, van der Schoot CE, Olsson ML. Report of the Second International Workshop on molecular blood group genotyping. Vox Sang. 2007 Jul;93(1):83-8. doi: 10.1111/j.1423-0410.2007.00926.x.

Reference Type BACKGROUND
PMID: 17547570 (View on PubMed)

Hayes RJ, Bennett S. Simple sample size calculation for cluster-randomized trials. Int J Epidemiol. 1999 Apr;28(2):319-26. doi: 10.1093/ije/28.2.319.

Reference Type BACKGROUND
PMID: 10342698 (View on PubMed)

Darlington M, Carbonne B, Mailloux A, Brossard Y, Levy-Mozziconacci A, Cortey A, Maoulida H, Simon T, Rousseau A, Durand-Zaleski I; GENIFERH1 Study Group. 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 Childbirth. 2018 Dec 14;18(1):496. doi: 10.1186/s12884-018-2114-5.

Reference Type DERIVED
PMID: 30547830 (View on PubMed)

Other Identifiers

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IC 0606

Identifier Type: -

Identifier Source: secondary_id

P 060410

Identifier Type: -

Identifier Source: org_study_id

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