Clinical trial NCT00832962: Routine Fetal RhD Genotyping for RhD- Pregnant Women
Official title: Effectiveness of Routine Fetal RhD Genotyping for RhD- Pregnant Women
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Rhesus Negative Pregnant Women
Keywords: Rhesus D
Anti-D allo-immunization
Fetal RHD genotyping
anti-D immunoglobulins
anti-D prophylaxis
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2009-01-30
Enrollment: 2532
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult Rh negative pregnant women followed in the participating centers

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: At the end of the study
Secondary outcomes:
measure: Assessment of the applicability of non invasive fetal RHD typing in the antenatal management of unimmunized Rh-negative pregnant patients in different settings.
timeFrame: At the end of the study
measure: performance assessment of high throughput fetal RHD genotyping in hospital laboratories.
timeFrame: At the end of the study
measure: Evaluation of the technical support needed to realize high throughput fetal RHD genotyping by authorized laboratories.
timeFrame: At the end of the study
measure: Development and diffusion of external quality controls for non invasive fetal RHD genotyping.
timeFrame: At the end of the study
Other outcomes:
Locations:
city: Paris
country: France
facility: Hopital Saint Antoine
Study officials:
affiliation: Assistance Publique - Hôpitaux de Paris
name: Yves BROSSARD, MD
role: PRINCIPAL_INVESTIGATOR
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