Non-Invasive Prenatal Testing

Next-generation sequencing has enabled a new era of prenatal testing, that of non-invasive prenatal testing (NIPT), by sequencing cell-free DNA from maternal blood. While there has been a push to expand the range of genetic conditions reported from NIPT as well as to use it beyond high-risk pregnancies, there are still a number of challenges this type of testing faces. Cell-based diagnostic methods are being developed in this area to provide a more concrete non-invasive diagnostic in addition to a non-invasive screening. The Inaugural Non-Invasive Prenatal Testing symposium will discuss non-invasive testing technologies and cell-retrieval methods, current progress in developing accurate and affordable tests in both cell-free and cell-based areas, and updates on and comparisons to current invasive diagnostic methods and outcomes. Special attention will be paid to carrier screening and how this type of testing provides a basis for prenatal diagnostics.


SC15: Preimplantation Genetic Screening and Diagnostics: A Technology Overview

*Separate registration required


8:00 am Registration & Morning Coffee


8:25 Chairperson’s Opening Remarks

W. Andrew Faucett, Professor, Genomic Medicine, Geisinger Health System

8:30 FEATURED PRESENTATION: The Future of NIPT: Cell-Free DNA vs. Intact Fetal Cells vs. Invasive Diagnostic Testing

Ron_WapnerRonald J. Wapner, M.D., Professor, Obstetrics and Gynecology, Vice Chair, Research, Director, Reproductive Genetics, Columbia University Medical Center

Noninvasive prenatal testing is constantly evolving. The use and application of currently available technology will be explained and compared with what is on the horizon. Next-generation sequencing and new technologies along with their indications will be explored.

9:00 Noninvasive Prenatal Diagnosis: Using Fetal Cells Is a Reality

Amy_BremanAmy Breman, Ph.D., FACMG, Assistant Professor, Molecular and Human Genetics, Baylor College of Medicine; Director, Chromosomal Microarray Lab , Baylor Genetics

We are focused on developing a fetal cell-based method of NIPT during the first trimester as a routine clinical test. We are now able to molecularly confirm recovery of fetal cells on a regular basis. Using whole genome amplification of 1-5 cells, it is possible to perform array CGH and NGS-based copy number analysis with these fetal cells. This method has the potential to detect CNVs at a resolution of 1 megabase.

9:30 TRIC: A New Window into the Developing Placenta and Fetal Genome

Randy_ArmantD. Randall Armant, Professor, Obstetrics & Gynecology, Wayne State University School of Medicine

Safe access to fetal tissue is the “Holy Grail” of noninvasive prenatal testing. Trophoblast Retrieval and Isolation from the Cervix (TRIC) captures placental cells as early as 3 weeks after conception, and holds promise for fetal genetic and obstetrical complication testing. TRIC provides an intact human genome for molecular analysis. Additionally, biomarker analysis after TRIC can assess perinatal risk in the first trimester for preeclampsia, fetal growth restriction and miscarriage.

10:00 Genome-Wide Prenatal Cell Free DNA Testing: Validation and Clinical Experience

Daniel_GrosuDaniel S. Grosu, MD, MBA, CMO, Clinical and Medical Affairs, Sequenom, Inc.

A significant proportion of chromosomal and subchromosomal abnormalities in the prenatal setting are not detectable by conventional cfDNA testing. Most of this informational gap can be bridged through a genome-wide approach that reports on copy number variation at a karyotype level of resolution (≥7 Mb in size) across the entire genome, in addition to select microdeletions less than 7 Mb in size.

10:30 Coffee Break


11:00 False Negative cell free DNA Screening Result in a Newborn with Trisomy 13

Yang_CaoYang Cao, PhD, Fellow, Clinical Cytogenetics/Molecular Genetics, Laboratory Medicine and Pathology, Mayo Clinic

We report a case of false negative cell free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal cytogenetic studies suggested that extra-embryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cell free fetal DNA is derived from the placenta and therefore may not accurately represent the fetal genetic information

11:30 Maternal Cell-Free DNA-Based Screening for Fetal Microdeletions: Clinical Experience and Diagnostic Follow-Up

Svetlana_TatsenkiSvetlana Yatsenki, Associate Director, Clinical Genomics Labs, Obstetrics, Gynecology, & Reproductive Sciences, University of Pittsburgh, School of Medicine

Commercial companies are now offering expanded NIPS panels including screening for common microdeletion syndromes, as well as for genome-wide abnormalities. We present our clinical experience with a phenotypically normal mother and fetus who tested positive for 22q deletion via maternal plasma cfDNA testing, and discuss pitfalls of NIPS, clinical and diagnostic approach to a patient with a positive NIPS result.

12:00 pm Non-Invasive Prenatal Testing for Fetal Aneuploidy: Clinical Service Issues

Peter_BennPeter Benn, Professor, Genetics and Genome Sciences, University of Connecticut Health Center

Noninvasive testing for fetal aneuploidies through the analysis of cell-free DNA in maternal plasma has become a well-established component of prenatal care. Performance of the testing and reasons why there are false-positive and false-negative results are becoming understood. Testing is increasingly being used by low-risk women and the scope of testing now includes additional abnormalities, notably microdeletion syndromes. Recent studies that document performance of the testing will be reviewed.

12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:30 Session Break


2:00 Chairperson’s Remarks

Ronald J. Wapner, M.D., Professor, Obstetrics and Gynecology, Vice Chair, Research, Director, Reproductive Genetics, Columbia University Medical Center

2:05 Points to Consider When Validating an NIPT for FDA

Donna Roscoe, Ph. D., Branch Chief, Molecular Genetics Branch, Division of Molecular Genetics and Pathology, Office of In Vitro Diagnostics, CDRH, FDA

Non-invasive prenatal testing (NIPT) is an innovative diagnostic method for prenatal screening to identify chromosomal abnormalities. To help promote the availability of safe and effective NIPTs, companies interested in seeking FDA approval for their test can work interactively with FDA using the pre-submission process to develop analytical and clinical validation strategies. This talk will discuss the points to consider when planning validation protocols for the unique aspects of NIPTs.


2:25 Implementation of a Non-Invasive Prenatal Diagnostic Test for Multiple Single Gene Disorders into a Clinical Setting: Experience from the UK

Michael_ParksMichael Parks, Ph.D., Developmental Scientist, Regional Genetics, Birmingham Women’s NHS Foundation Trust

Through the NIPSIGEN project, we have recently proven that non-invasive prenatal diagnosis of single gene disorders can also be implemented into clinical service at a feasible cost for the UK National Health Service. The molecular diagnostic method that we have developed at Birmingham Women’s Hospital for NIPD of a panel of single gene disorders has proven to be both accurate and affordable. After having successfully tested patients at risk of bearing a child affected by Duchenne/Becker muscular dystrophies, spinal muscular atrophy, congenital adrenal hyperplasia and cystic fibrosis, we have now implemented such testing into clinical practice. This talk will include clinical data from the newly developed genetic test and will elaborate on the implementation process of NIPD for SGDs into clinical practice.

2:45 Helping Patients Decide if NIPT is the Best Test

Andy_FaucettW. Andrew Faucett, Professor, Genomic Medicine, Geisinger Health System

NIPT is a screening test with unique communication and informed consent issues, not a diagnostic test. Patients want to know their future child will be healthy and often do not understand the types of chromosomal changes that can be detected prenatally today. With our growing knowledge about the risk for pathogenic copy number variations, how do we insure patients are receiving test results that will help them make informed decisions?

3:05 Refreshment Break


3:35 Introducing Expanded Carrier Screening in the Reproductive and Prenatal Genetic Clinic

Ignatia_Van_den_VeyerIgnatia B. Van den Veyver, Professor, OB-GYN and Molecular Human Genetics, Baylor College of Medicine

Pan-ethnic expanded carrier screening (ECS) is now offered by various providers and includes more conditions than recommended by professional societies. Different ECS test employ different methods for mutation detection and include variable numbers of diseases. I will review current professional guidelines for carrier screening, differences between standard carrier screening and ECS, different ECS platforms, benefits and pitfalls of ECS, as well as practical and ethical aspects will be discussed.

4:05 PANEL DISCUSSION: Expanded Carrier Screening – A Changing Paradigm

Ignatia_Van_den_VeyerIgnatia B. Van den Veyver, Professor, OB-GYN and Molecular Human Genetics, Baylor College of Medicine

Anthony_GreggAnthony R. Gregg, MD, FACOG, FACMG, B.L. Stalnaker Professor, Director, Division of Maternal Fetal Medicine, Director, Obstetrics - UF Health Shands, University of Florida College of Medicine

Jim_GoldbergJames Goldberg, MD, Chief Medical Officer, Counsyl

Kim_MartinKim Martin, MD, Senior Global Medical Director, Women's Health, Natera

Expanded carrier screening has become an oft-debated topic in the prenatal clinic as the number of disorders it can detect increases and the applications become more widespread. Questions for discussion include:

  • Should all couples undergo expanded carrier screening either preconception or prenatally?
  • Is it time to modify professional guidelines on carrier screening?
  • Can expanded carrier screening account for a diverse modern population?

4:35 Close of Symposium