Cambridge Healthtech Institute’s 6th Annual

Advances in Prenatal Molecular Diagnostics Symposium

Trends, Advances and Prospects

6 May 2019

Cell-free DNA testing in prenatal diagnostics has steadily moved beyond aneuploidy, but we are still facing challenges in validation and clinical implementation. The number of invasive tests has been steadily declining, and the complexity, cost, and ethical concerns surrounding cfDNA screening continues to rise – meanwhile, cell-based testing edges ever closer to commercialization, which would usher in another era of validation, implementation, and patient education. Beyond these types of prenatal tests, the field must also grapple with advancements in whole genome and whole exome sequencing, expanded carrier screening, mosaicism, and genetic counseling, and the role each of these may play in making decisions to continue a pregnancy or perform fetal therapy. Cambridge Healthtech Institute’s 6th Annual Advances in Prenatal Molecular Diagnostics symposium will bring together experts and thought leaders to discuss these topics and more.

Final Agenda

8:00 Registration Open and Morning Coffee



8:55 Chairperson’s Remarks

Patrizia Paterlini-Brechot, PhD, MD, Cellular & Molecular Biology, University Paris Descartes, France

9:00 Termination of Pregnancy Following a Prenatal Diagnosis of Down Syndrome: A Qualitative Study of the Decision-Making Process of Pregnant Couples

Lou_StinaStina Lou, PhD, Senior Researcher, Center for Fetal Diagnostics, Aarhus University Hospital, Denmark

In Denmark, when Down syndrome (DS) is prenatally diagnosed, termination rates are high (>95%). Based on semi-structured interviews with 21 couples, who had recently terminated due to DS, we found that the decision to terminate in case of DS was often made before pregnancy. The couples felt grief following the diagnosis, and the termination was considered right but burdensome. None had felt pressure to terminate from doctors or social network.

9:30 Shifting from Genome Wide SNP-Based Array Analysis to Whole Exome Sequencing in Prenatal Diagnosis

de_Leeuw_NicoleNicole de Leeuw, PhD, Clinical Laboratory Geneticist, Theme Leader Intellectual Disability & Congenital Anomalies, Human Genetics, Radboud University Medical Center, The Netherlands

Genome wide high-resolution SNP-based array analysis is routinely used in our laboratory for the detection of copy number variations (CNVs) in foetal DNA in case of structural ultrasound anomalies, but since January 2017 a growing number of prenatal whole exome sequencing trio analyses are being performed, because of the higher diagnostic yield. Our experiences and strategies will be presented, including some of the challenges encountered in daily laboratory practice.

10:00 Clinical Implementation of Prenatal Exome Sequencing for Fetal Structural Abnormalities: Benefits, Challenges, and Guidance Needed

Mellis_RhiannonRhiannon Mellis, MBBS, MSc, MRCPCH, Clinical Research Fellow, Genetics, NE Thames Regional Genetics Service, Great Ormond Street Hospital, United Kingdom

Since 2016 our regional genetics laboratory has offered rapid fetal exome sequencing on a research basis, and it will soon be introduced into NHS standard care . I will present our experience, discussing clinical utility, outcomes and the clinical challenges of case selection, fetal phenotyping, variant interpretation and counselling as we move towards clinical implementation.

10:30 Coffee Break


11:00 Technical Insights into Next-Generation Sequencing Analysis of DNA from Circulating Trophoblastic Cells

Paterlini-Brechot_PatriziaPatrizia Paterlini-Brechot, PhD, MD, Cellular & Molecular Biology, University Paris Descartes, France

Isolation of rare trophoblastic cells from blood is a technical challenge with impact on the number of collected fetal cells and on the quality of their DNA. By using the ISET (Isolation by Size of Tumor/Trophoblastic cells) system, we have developed protocols for isolation of fixed and live circulating trophoblastic cells, cell-free DNA collection allowing scalable NGS analysis of circulating fetal cells and cfDNA. We show the results and technical challenges and discuss the potential clinical impact or non-invasive prenatal diagnosis.

11:30 Fetal Cells in Maternal Blood for Prenatal Diagnosis – From R&D to Clinic

Singh_RipudamanRipudaman Singh, PhD, MBA, CTO, ARCEDI Biotech Aps, Denmark

Technological advances in enrichment, manipulation and analyses of rare fetal cells from maternal blood have been made in the last 5 years. For the last 11 years, we have tried to answer some critical questions pertaining to fetal cells and their use in prenatal diagnosis. After developing a robust technology which is both scalable and cost effective, ARCEDI Biotech, in collaboration with Aarhus University Hospital, has launched the first ever cell-based NIPD in Denmark, covering approximately 17,000 pregnancies per year. Results from that clinical launch will be presented and discussed.

12:00 Enjoy Lunch on Your Own

13:00 Session Break


13:25 Chairperson’s Remarks

Hamutal Meiri, PhD, MBA, Chairman, ASPRE Consortium; CEO, TeleMarpe, Israel

13:30 Noninvasive Detection of Aneuploidy by Cell-Free DNA in Early and Recurrent Pregnancy Loss

Yuval_YaroYuval Yaron, MD, Director, Prenatal Genetic Diagnostic Unit, Tel Aviv Sourasky Medical Center, Israel

Early pregnancy loss is caused by numerical chromosomal aberrations in >50% of cases. Chromosomal analysis of the products of conception has been shown to be cost-saving if used to guide further workup. In our study, we demonstrate that maternal serum cell-free DNA-based testing can achieve a high degree of accuracy (78%-85%) which is higher than that of routine cytogenetic analysis. We suggest that cfDNA-based testing for early pregnancy loss serve as the first-tier test for assessment of early pregnancy loss.

14:00 Confined Placental and Fetal Mosaicism: Prevalence, Outcome and Impact on Non-Invasive Prenatal Testing Results

Bay Lund_Ida CharlotteIda Charlotte Bay Lund, MD, Clinical Genetics, Center for Fetal Diagnostics, Aarhus University Hospital, Denmark

Mosaicism in CVS can be divided into: 1) whole chromosome mosaicism, and 2) copy number variants (CNV) mosaicism. The risk of true fetal mosaicism is equally high for whole chromosome and CNV mosaicism. The detection of mosaicism using Non-Invasive Prenatal Testing (NIPT) depends on level of mosaicism and pregnancies which need follow-up can be missed by NIPT.

14:30 Clinical Implementation of Non-Invasive Prenatal Diagnosis (NIPD) for Single Gene Disorders

Chandler, NatalieNatalie Chandler, FRCPath, PhD, Senior Clinical Scientist, NE Thames Regional Genetics Laboratory, Great Ormond Street Hospital, United Kingdom

I will present our experience with a variety of technologies that our accredited laboratory utilises for non-invasive prenatal diagnosis of single gene disorders. I will discuss the limitations of each method and the challenges faced in developing these services in a clinical laboratory.

15:00 Refreshment Break


15:30 Molecular Approach for a Personalized Diagnosis of Preeclampsia with an Attempt for an in vitro Prevention Model by DNA Editing with CRISPR/Cas 9

Meiri_HamutalHamutal Meiri, PhD, MBA, Chairman, ASPRE Consortium; CEO, TeleMarpe, Israel

ASPRE is a multicenter study to predict the risk and prevent it by aspirin. PP13 is a placental protein that supports blood supply to the pregnancy and turns mothers immune tolerant to the fetus. Low PP13 expression by mutations are associated with high risk to preeclampsia. Polypeptide replenishment or gene editing may cure preeclampsia. Could future PGD and implantation be a path to cure preeclampsia?

16:30 The Challenge of Identifying Very Early Biomarkers of Preeclampsia

Vaiman_DanielDaniel Vaiman, PhD, Research Director; Development, Reproduction, Cancer; INSERM, France

Preeclampsia is one of the most frequent disease of pregnancy, characterized classically by hypertension and proteinuria. Preeclampsia can be relatively efficiently taken care of, using low doses of aspirin, when the drug is administered before the 16th week of pregnancy when the disease is asymptomatic. Amongst the accessible biomarkers are plasmatic molecules, as well as ultrasound parameter potentially able to detect by Doppler analysis placental vascularization defects.

17:00 Close of Symposium