Large-Scale Pre-Diagnosis Study of Fetal RHD Genotyping by PCR on Plasma DNA from RhD-Negative Pregnant Women

Sciellour, C. Rouillac-Le; Puillandre, Philippe; Gillot, Rolande; Baulard, C??line; M??tral, Sylvain; Kim, Caroline Le Van; Cartron, Jean‐Pierre; Colin, Yves; Brossard, Y.

doi:10.2165/00066982-200408010-00004

Cited by 87 publications

(37 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, if an RhD positive fetus is misdiagnosed as RhD negative, due to sub-optimal RhD NIPD test performance [8,9,11-14], there will be an increased risk of sensitisation (0.9-1.5%) due to antenatal prophylaxis being withheld in these cases [32,33]. Table 3 shows the number of additional sensitisations predicted in England and Wales at different NIPD test sensitivity levels for a two-dose policy.…”

Section: Resultsmentioning

confidence: 99%

“…Fetal RHD genotyping of this material has the potential to enable antenatal prophylaxis targeted at the 60% of pregnancies with an RhD positive fetus, thereby saving anti-D costs. NIPD test accuracy figures in the range 94.8% - 100% have been reported [8,9,11-14], although studies exhibit certain shortcomings [15]. By 2007, many European countries had introduced NIPD testing for the small number of sensitised women in order to identify high risk pregnancies (fetus RhD positive) [10,14,16].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

Szczepura

Osipenko

Freeman

2011

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

BackgroundPostnatal and antenatal anti-D prophylaxis have dramatically reduced maternal sensitisations and cases of rhesus disease in babies born to women with RhD negative blood group. Recent scientific advances mean that non-invasive prenatal diagnosis (NIPD), based on the presence of cell-free fetal DNA in maternal plasma, could be used to target prophylaxis on "at risk" pregnancies where the fetus is RhD positive. This paper provides the first assessment of cost-effectiveness of NIPD-targeted prophylaxis compared to current policies.MethodsWe conducted an economic analysis of NIPD implementation in England and Wales. Two scenarios were considered. Scenario 1 assumed that NIPD will be only used to target antenatal prophylaxis with serology tests continuing to direct post-delivery prophylaxis. In Scenario 2, NIPD would also displace postnatal serology testing if an RhD negative fetus was identified. Costs were estimated from the provider's perspective for both scenarios together with a threshold royalty fee per test. Incremental costs were compared with clinical implications.ResultsThe basic cost of an NIPD in-house test is £16.25 per sample (excluding royalty fee). The two-dose antenatal prophylaxis policy recommended by NICE is estimated to cost the NHS £3.37 million each year. The estimated threshold royalty fee is £2.18 and £8.83 for Scenarios 1 and 2 respectively. At a £2.00 royalty fee, mass NIPD testing would produce no saving for Scenario 1 and £507,154 per annum for Scenario 2. Incremental cost-effectiveness analysis indicates that, at a test sensitivity of 99.7% and this royalty fee, NIPD testing in Scenario 2 will generate one additional sensitisation for every £9,190 saved. If a single-dose prophylaxis policy were implemented nationally, as recently recommended by NICE, Scenario 2 savings would fall.ConclusionsCurrently, NIPD testing to target anti-D prophylaxis is unlikely to be sufficiently cost-effective to warrant its large scale introduction in England and Wales. Only minor savings are calculated and, balanced against this, the predicted increase in maternal sensitisations may be unacceptably high. Reliability of NIPD assays still needs to be demonstrated rigorously in different ethnic minority populations. First trimester testing is unlikely to alter this picture significantly although other emerging technologies may.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

Szczepura

Osipenko

Freeman

2011

BMC Pregnancy Childbirth

View full text Add to dashboard Cite

show abstract

“…Non-invasive prenatal RHD analysis is currently most frequently performed using real-time PCR, either in conjunction with manual or automated procedures for the extraction of cell-free DNA from the maternal plasma/ serum samples [4,9,13,15,16,19]. In this study, we analysed the foetal RHD status by mass spectrometry, in combination with automated system for the extraction of cell-free DNA from maternal plasma.…”

Section: Discussionmentioning

confidence: 99%

High throughput non-invasive determination of foetal Rhesus D status using automated extraction of cell-free foetal DNA in maternal plasma and mass spectrometry

Grill

Banzola

et al. 2008

Arch Gynecol Obstet

View full text Add to dashboard Cite

Purpose To examine the potential high throughput capability and eYciency of an automated DNA extraction system in combination with mass spectrometry for the noninvasive determination of the foetal Rhesus D status. Methods A total of 178 maternal plasma samples from RHD-negative pregnant women were examined, from which DNA was extracted using the automated Roche MagNA Pure™ system. Presence of the foetal RHD gene was detected by PCR for RHD exon 7 and subsequent analysis using the Sequenom MassArray™ mass spectrometric system. Results We determined that as little as 15 pg of RHD-positive genomic DNA could be detected in a background of 585 pg of RHD-negative genomic DNA. The analysis of the clinical samples yielded a sensitivity and speciWcity of 96.1 and 96.1%, respectively. Conclusion Our study indicated that automated DNA extraction in combination with mass spectrometry permits the determination of foetal Rhesus D genotype with an accuracy comparable to the current approaches using realtime PCR.

show abstract

“…Prenatal determination of fetal rhesus blood group in pregnancies at risk of haemolytic disease of the fetus and newborn is important 2. The previous approach for the prediction of fetal blood group was to use fetal material from amniotic fluid.…”

Section: Discussionmentioning

confidence: 99%

“…The disadvantage of the technique is ease of contamination at sample collection or within the laboratory and great care must be taken to exclude this by adequate controls. The Bristol collaborative group has demonstrated 100% accuracy with this technique in 137 pregnancies 2. Recent developments of this technique have significantly reduced the number of invasive procedures carried out for fetal rhesus D typing.…”

Section: Discussionmentioning

confidence: 99%

Non-invasive antenatal diagnosis of fetal rhesus status in an alloimmunised patient

Gowri

2009

Case Reports

View full text Add to dashboard Cite

Alloimmunisation against the RhD red cell surface antigen was the most common cause of haemolytic disease of the fetus and newborn until recently. Maternal plasma has now almost replaced fetal cells obtained by amniocentesis or chorionic villous sampling, as the source of fetal DNA, hence eliminating the need for invasive sampling procedures. The fetal rhesus typing was done from maternal plasma in a woman in her fourth pregnancy, though she was isoimmunised in her previous pregnancies and needed invasive tests like cordocentesis in the past. The fetus was diagnosed to be rhesus negative from maternal plasma and that avoided the need for amniocentesis or cordocentesis.

show abstract

Large-Scale Pre-Diagnosis Study of Fetal RHD Genotyping by PCR on Plasma DNA from RhD-Negative Pregnant Women

Abstract: Fetal RHD genotyping from maternal plasma DNA in different clinical situations may be used with confidence.

Cited by 87 publications

References 32 publications

A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

A new fetal RHD genotyping test: Costs and benefits of mass testing to target antenatal anti-D prophylaxis in England and Wales

High throughput non-invasive determination of foetal Rhesus D status using automated extraction of cell-free foetal DNA in maternal plasma and mass spectrometry

Non-invasive antenatal diagnosis of fetal rhesus status in an alloimmunised patient

Contact Info

Product

Resources

About