The SAFE project: towards non-invasive prenatal diagnosis

2009 ◽  
Vol 37 (2) ◽  
pp. 460-465 ◽  
Author(s):  
Deborah G. Maddocks ◽  
Medhat S. Alberry ◽  
George Attilakos ◽  
Tracey E. Madgett ◽  
Kin Choi ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Large Scale ◽  
Single Gene ◽  
Cost Effective ◽  
Maternal Plasma ◽  
Molecular Techniques ◽  
Maternal Circulation ◽  
Haemolytic Disease ◽  
Non Invasive ◽  
New Biomarkers

After the revolutionary detection of ffDNA (free fetal DNA) in maternal circulation by real-time PCR in 1997 and advances in molecular techniques, NIPD (non-invasive prenatal diagnosis) is now a clinical reality. Non-invasive diagnosis using ffDNA has been implemented, allowing the detection of paternally inherited alleles, sex-linked conditions and some single-gene disorders and is a viable indicator of predisposition to certain obstetric complications [e.g. PET (pre-eclampsia)]. To date, the major use of ffDNA genotyping in the clinic has been for the non-invasive detection of the pregnancies that are at risk of HDFN (haemolytic disease of the fetus and newborn). This has seen numerous clinical services arising across Europe and many large-scale NIPD genotyping studies taking place using maternal plasma. Because of the interest in performing NIPD and the speed at which the research in this area was developing, the SAFE (Special Non-Invasive Advances in Fetal and Neonatal Evaluation) NoE (Network of Excellence) was founded. The SAFE project was set up to implement routine, cost-effective NIPD and neonatal screening through the creation of long-term partnerships within and beyond the European Community and has played a major role in the standardization of non-invasive RHD genotyping. Other research using ffDNA has focused on the amount of ffDNA present in the maternal circulation, with a view to pre-empting various complications of pregnancy. One of the key areas of interest in the non-invasive arena is the prenatal detection of aneuploid pregnancies, particularly Down's syndrome. Owing to the high maternal DNA background, detection of ffDNA from maternal plasma is very difficult; consequently, research in this area is now more focused on ffRNA to produce new biomarkers.

Non Invasive Screening for Fetal RHD-Genotype in All D-Negative Women Is Reliable and Cost-Effective.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 556-556
Author(s):  
C. Ellen Van der Schoot ◽  
Aicha Ait Soussan ◽  
Gouke J. Bonsel ◽  
Masja de Haas
Keyword(s):  
Cord Blood ◽  
Pregnant Women ◽  
Large Scale ◽  
Serological Test ◽  
Cost Effective ◽  
Maternal Plasma ◽  
Serological Tests ◽  
Non Invasive ◽  
Automated Assay ◽  
Cell Free Fetal Dna

Abstract About 40% of D-negative pregnant women receive antenatal anti-D despite a D-negative fetus. We have developed an automated assay for fetal genotyping using cell-free fetal DNA from maternal plasma to restrict antenatal prophylaxis to women carrying a D-positive fetus. This will save anti-D of which is worldwide shortage, and will prevent the unnecessary administration of a blood product. 1 ml of plasma is automatically presented (Tecan) to a DNA isolation-robot (Roche). The DNA-eluate is tested (after automatically pipetting) in triplicate in a real-time RHD exon7-PCR (ApplBios). Results Plasma from 2415 D-negative pregnant women, whose blood was sent in for 28–30th week antibody screening, has been tested. In 35 cases (1.44%) the women (10 weak D and 25 normal D-positive) were typed as D-positive by repeated serological tests, and excluded from the study. 1465 of the plasma’s (61.59%) were typed RhD positive and 915 RhD negative. Because the RHD exon7-PCR will give positive results in D-negative women carrying D-negative variant RHD genes such as RHDΨ, we determined the incidence of these genes in our studygroup. In all cases (n=39) with Ct values below 33.2 DNA was isolated from maternal leukocytes. Of the 19 cases with extremely low Ct values (<32), 6 women carried an RHDΨ gene, 5 an RHD variant type VI, 3 weak D (type 1, 11 and 17) and 1 RHDdel. The 24 other women did not carry RHD genes. To compare the plasma PCR results with cord blood serology, all women and obstetric caregivers were sent questionnaires on cord blood serology. 55% responded (n=1257). For cases with discrepant results(n=21) or incompleted questionnaires(n=31) the laboratory which performed the cord blood typing was contacted. Finally, concordant results were obtained in 1249 of the cases. In 3 cases the genotype suggests D-positivity while serology is D-negative. In 5 cases no RHD-sequences were detected in plasma but cord blood was typed D-positive. For the discrepant cases it cannot be concluded yet, which assay gave the correct phenotype. Conclusion This is the first large scale automated study demonstrating the feasibility of screening D-negative women to restrict antenatal anti-D to women carrying D-positive fetuses. For the recognition of women at risk for immunization, the plasma-PCR test seems to be at least as reliable as the serological test. Furthermore, postnatal prophylaxis could have been given directly after delivery in all women with a positive PCR-result, saving cord blood serology tests and possibly increasing the effectiveness of postnatal prophylaxis. An economic evaluation demonstrated that this screening policy is cost effective in the Netherlands.

IS A LARGE-SCALE SCREENING FOR ALZHEIMER’S DISEASE POSSIBLE? YES, IN A FEW YEARS

2019 ◽  
pp. 1-2
Author(s):  
F. Ribaldi ◽  
D. Altomare ◽  
G.B. Frisoni
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Large Scale ◽  
Task Force ◽  
Cost Effective ◽  
The European Union ◽  
New Era ◽  
Non Invasive ◽  
Recent Meeting ◽  
Large Scale Screening

Recent evidence on blood-based biomarkers is pointing the way towards a new era of large-scale, feasible, cost-effective and non-invasive screening for Alzheimer’s disease (AD). This was one of the main focuses of the recent meeting of the European Union-North American Clinical Trials in AD (EU/US CTAD) Task Force, which took place in Barcelona in October 24-27, 2018, and convened drug and diagnostics developers from industry and academia in order to define a roadmap for the development and marketing of blood-based biomarkers (1).

Non-invasive prenatal diagnosis using cell-free fetal DNA in maternal plasma from PGD pregnancies

2009 ◽  
Vol 19 (5) ◽  
pp. 714-720 ◽  
Author(s):  
Ying Li ◽  
Gheona Altarescu ◽  
Paul Renbaum ◽  
Talia Eldar-Geva ◽  
Ephrat Levy-Lahad ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Maternal Plasma ◽  
Non Invasive ◽  
Fetal Dna ◽  
Cell Free Fetal Dna

Prenatal diagnosis using fetal cells in the maternal circulation

1995 ◽  
Vol 7 (2) ◽  
pp. 77-86 ◽  
Author(s):  
D Gänshirt ◽  
HSP Garritsen ◽  
W Holzgreve
Keyword(s):  
Prenatal Diagnosis ◽  
Single Gene ◽  
Chorionic Villus ◽  
Fetal Tissue ◽  
Chorionic Villus Sampling ◽  
Chromosomal Anomalies ◽  
Maternal Circulation ◽  
Fetal Cells ◽  
Fetal Blood Sampling ◽  
Sampling Procedures

Since the introduction of ultrasound into obstetrics during the 1960s, there has been rapid progress in the detection of genetic and nongenetic defects in utero. With the development of sampling procedures like amniocentesis, chorionic villus sampling (CVS) and fetal blood sampling, the obstetrician has been able to obtain fetal tissue and the parallel improvement in laboratory techniques has allowed the diagnosis of chromosomal anomalies and single gene defects from fetal cells. Amniocentesis and CVS have become well established techniques for routine prenatal diagnosis of chromosomal and metabolic disorders and fetal tissue is now accessible throughout all three trimesters.

Sign in / Sign up

Export Citation Format

Share Document