NIPT: Overview of Technology
Morry Fiddler, PhD
Insight Medical Genetics
Professor Emeritus, DePaul University
Chicago, IL
Haichuan Zhang, PhD
Celula (China) Medical Technology, Ltd.
Shanghai, PRC
Since its introduction and support by the American College of Obstetricians and Gynecologists in 2011, noninvasive prenatal testing (NIPT) has undergone rapid adoption and evolution.1 NIPT rests on a history of prenatal diagnostics to detect chromosomal disorders that began in the 1960s.2 Since that time, the addition of chorionic villus sampling (CVS) to the list of invasive procedure options fueled the desire to obtain prenatal assessments at earlier stages of pregnancy. This advance was followed by the development of noninvasive approaches to avoid the procedural risks and, for many women, the discomforts of both amniocentesis and CVS. The desire for improved sensitivities and specificities of screening converged with a nascent body of work regarding the presence and nature of circulating cell-free DNA (cfDNA),3-5 the development of massively parallel sequencing (MPS),6,7 and techniques to count DNA fragments. This convergence and continued advancement of technologies, coupled with a deepening understanding of cfDNA, has given women’s health care providers a powerful and expanding screening tool to assess the genomic status of a developing fetus. With new technology advancements, NIPT using cfDNA and fetal cells will further evolve to replace amniocentesis and CVS in the future.
Biologic Basis of NIPT
The presence of cfDNA has been known for about 70 years.8 Approximately 10% of the DNA in maternal circulation is of fetal origin, although that proportion ranges from <3% to >20% in any individual9; the remaining ~90% of circulating DNA is maternal. Most of this cfDNA is derived from the placenta,5 with a considerably lesser contribution from the fetus itself. The DNA in circulation is typically found as small fragments of 150 to 200 base pairs,10 which is thought to be derived mostly from DNA generated by apoptosis (programmed cell death) of placental cells, but may also be from live cells in a much smaller quantity.
In addition to the size of the DNA fragments in circulation, 2 features of cfDNA are of particular importance to the design and implementation of technologies for the noninvasive assessment of fetal status: the proportion of fetal DNA relative to the maternal contribution in circulation during pregnancy, known as the fetal fraction, and the timing of a detectable level of fetal DNA in circulation, which is usually by 7 weeks.11,12 Additionally, fetal DNA is continually being refreshed with a half-life of <20 minutes and disappears from maternal circulation within a few hours postpartum, which eliminates concerns of a “carryover” effect from one pregnancy to the next.12
The presence of fetal cells in maternal circulation is much rarer compared to cfDNA. The number of fetal cells that can be successfully identified and isolated from 10 mL of maternal blood is often reported as well below 100. The presence of fetal cells in maternal circulation has been reported as nucleated red blood cells, trophoblasts, lymphocytes, and granulocytes.13 The process of fetal cell isolation is generally much more tedious than cfDNA, and the efficiency of isolation can be inconsistent from sample to sample.
Despite these challenges, fetal cells, once isolated, likely contain the complete genetic information of the fetus without maternal background and limitations from the short DNA fragmentation in cfDNA. Fetal cells in maternal circulation provide a path for an accurate noninvasive analysis of all genetic diseases beyond aneuploidy.
Applying Guidelines in Practice: Noninvasive Prenatal Testing
This activity is designed to meet the educational needs of the obstetrician and gynecologist, family physician, internal medicine physician, physician assistant, nurse practitioner, and certified nurse midwife.
Supported by an educational grant from:
Roche Diagnostics
Activity Information
Expired
Credits: 1.0 AMA PRA Category 1 Credits™
Released: 11/25/2020
Valid until: 11/25/2021
Expired
To receive CME credit, please read the articles and go to www.omniaeducation.com/NIPT to access the post-test and evaluation.
OVERVIEW:
This supplement is designed to provide ObGyn clinicians with current information on the cell-free DNA screening test options available for fetal chromosomal abnormalities. These screening tests are commonly referred to as Noninvasive Prenatal Screening (NIPS). In August 2020, the American College of Obstetricians and Gynecologists (ACOG) issued a Practice Bulletin entitled “Screening for Fetal Chromosomal Abnormalities” (PB #226). This Practice Bulletin included expanded information regarding the use of NIPS in all patients regardless of maternal age or baseline risk. It also identified NIPS as the most sensitive and specific test for screening for the most common aneuploidies. The authors of this supplement provide additional information on the technology, performance, and clinical utilization of NIPS testing.
REVIEWERS/CONTENT PLANNERS/AUTHORS:
Ann Early has nothing to disclose.
Genevieve L. Fairbrother MD, MPH, FACOG has nothing to disclose.
Morry Fiddler, PhD receives a salary from Insight Medical Genetics.
Barry A. Fiedel, PhD has nothing to disclose.
Amanda Hilferty has nothing to disclose.
Robert Schneider, MSW has nothing to disclose.
Lee P. Shulman, MD, FACMG, FACOG receives consulting fees from Biogix, Celula, Cooper Surgical, Natera, and Vermillion/Aspira and is a speaker for Bayer, Lupin Pharmaceuticals, Inc., and Myriad.
Andrew F. Wagner, MD, FACMG, FACOG has nothing to disclose.
Haichuan Zhang, PhD has ownership interest in Celula China Medical Technology Co.
LEARNING OBJECTIVES:
After participating in this educational activity, participants should be better able to:
- Overcome barriers and demonstrate competency in integrating ACOG/Society for Maternal-Fetal Medicine Noninvasive Prenatal Testing Committee Opinions/Practice Bulletins recommendations into clinical decisionmaking surrounding prenatal visits for all pregnant patients.
- Explain the benefits and disadvantages of traditional fetal chromosomal aneuploidy screening tests compared with noninvasive screening tests.
- Define the technology that is the basis of the various noninvasive screening tests, including the role that fetal fraction plays in influencing results.
- Explain the expanding role of NIPS in the general obstetrical population.
ACCREDITATION AND CREDIT DESIGNATION STATEMENTS:
Global Learning Collaborative (GLC) is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to provide continuing medical education for physicians.
Global Learning Collaborative designates this enduring material for a maximum of 1 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.
TARGET AUDIENCE:
This activity is designed to meet the educational needs of the obstetrician and gynecologist, family physician, internal medicine physician, physician assistant, nurse practitioner, and certified nurse midwife.
COMMERCIAL SUPPORT:
This activity is supported by an independent educational grant from Roche Diagnostics.
Disclaimer
The views and opinions expressed in this educational activity are those of the faculty and do not necessarily represent the views of GLC and Omnia Education. This presentation is not intended to define an exclusive course of patient management; the participant should use his/her clinical judgment, knowledge, experience, and diagnostic skills in applying or adopting for professional use any of the information provided herein. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patients’ conditions and possible contraindications or dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities. Links to other sites may be provided as additional sources of information. Once you elect to link to a site outside of Omnia Education you are subject to the terms and conditions of use, including copyright and licensing restriction, of that site.
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Reproduction of this material is not permitted without written permission from the copyright owner.
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