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| ID | Type | Description | Link |
|---|---|---|---|
| IC 0606 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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) |
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| 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) |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Genotyping | Genetic | Whole blood sample |
| |
| Usual prophylaxis |
| Measure | Description | Time Frame |
|---|---|---|
| cost-effectiveness of the two strategies of antenatal management by comparing the rate of RhD negative women eligible for receiving RHIG that would have not receive prophylactic anti-RhD in the two populations, the one with fetal RHD typing and the other | At the end of the study |
| Measure | Description | Time Frame |
|---|---|---|
| Assessment of the applicability of non invasive fetal RHD typing in the antenatal management of unimmunized Rh-negative pregnant patients in different settings. | At the end of the study | |
| performance assessment of high throughput fetal RHD genotyping in hospital laboratories. |
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Inclusion Criteria:
Exclusion Criteria:
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Adult Rh negative pregnant women followed in the participating centers
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| Name | Affiliation | Role |
|---|---|---|
| Yves BROSSARD, MD | Assistance Publique - Hôpitaux de Paris | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hopital Saint Antoine | Paris | 75012 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16495833 | Background | 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. | |
| 16495834 | Background | 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. |
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| ID | Term |
|---|---|
| D005838 | Genotype |
| ID | Term |
|---|---|
| D055614 | Genetic Phenomena |
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Whole blood sample (0.5 ml)
| Other |
Prophylactic anti-RhD |
|
|
| At the end of the study |
| Evaluation of the technical support needed to realize high throughput fetal RHD genotyping by authorized laboratories. | At the end of the study |
| Development and diffusion of external quality controls for non invasive fetal RHD genotyping. | At the end of the study |
| 8341334 | Background | 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. |
| 9266934 | Background | 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. |
| 9274585 | Background | 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. |
| 9529358 | Background | 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. |
| 11474588 | Background | 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. |
| 9777844 | Background | 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. |
| 15230639 | Background | 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. |
| 1824267 | Background | 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. |
| 10607679 | Background | 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. |
| 17000250 | Background | 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. |
| 9845707 | Background | 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. |
| 15251949 | Background | 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. |
| 15209914 | Background | 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. |
| 16495837 | Background | 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. |
| 16020496 | Background | 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. |
| 17068167 | Background | 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. |
| 17547570 | Background | 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. |
| 10342698 | Background | 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. |
| 30547830 | Derived | 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. |