How Community-Based ObGyns Implement Noninvasive Prenatal Testing into an Effective Process
Genevieve Fairbrother, MD, MPH
Chief Medical Officer
Atlanta Women’s Health Group
“Prenatal testing for chromosomal abnormalities is designed to provide an accurate assessment of a patient’s risk of carrying a fetus with a chromosomal disorder.”1
So begins the latest American College of Obstetricians and Gynecologists (ACOG) Practice Bulletin on screening for fetal aneuploidy. Most women opt for prenatal aneuploidy screening, indicating just how valuable this information is to them.
Community ObGyns have the dual obligations of offering their patients a timely aneuploidy screening test that maximizes the chance of detecting an affected fetus and offering a test that minimizes false-positive results. False-positive results lead to emotionally exhausting and expensive medical odysseys that may conclude with a needless invasive test that interrupts a pregnancy.
In 2017, there were 3.86 million births in the United States, and 82.4% of these births were to women younger than 35.2 Because of the higher birth rate in younger women, 80% of babies with trisomy 21 were born to women under age 35.3 Standard screening modalities place this low-risk cohort at increased risk for unnecessary invasive diagnostic testing.
The challenge for practitioners is to determine how best to identify affected pregnancies while minimizing risk and emotional discomfort to most pregnant women. Understanding the benefits and limitations of the testing modalities and recognizing the importance of positive predictive value (PPV) allows providers to select the ideal screening test.
Prior to the advent of cell-free DNA (cfDNA), standard aneuploidy screening tests possessed an intrinsic 5% false-positive rate. The 1-in-20 false-positive rate meant that an average 26-year-old pregnant woman, with a risk of 1:1,290 for a trisomy 21-affected pregnancy,1 would find that a positive test result was 65 times more likely to be a false positive than a true positive. Paradoxically, offering pregnant women under age 35 a standard screening test with a 5% intrinsic falsepositive rate means that they are more likely to receive a positive screen than a woman older than 35 who is offered a cfDNA-based test.
In making the case for using cfDNA aneuploidy testing in the general risk population, both the benefits and limitations of the test should be explored. The efficacy of a test is reflected in the sensitivity. cfDNA screens detect true positives at a rate of >99%. The accuracy of a test is reflected statistically with specificity. The rise in specificity reflects the decrease in the false-positive rate. Falsepositive rates are additive, so it is critical for the general ObGyn to judiciously avoid testing for rare conditions that needlessly increase the false-positive rate without materially adding benefit to the low-risk patient. Workflow in a community setting rests on several factors: testing parameters, test limitations, timeliness, accuracy, technical resources, and cost.
To receive CME credit, please read the articles and go to www.omniaeducation.com/NIPT to access the post-test and evaluation.
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.
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.
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.
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.
This activity is supported by an independent educational grant from Roche Diagnostics.
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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- Rose NC, Kaimal AJ, Dugoff L, Norton ME; American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Obstetrics; Committee on Genetics; Society for Maternal-Fetal Medicine. Screening for fetal chromosomal abnormalities: ACOG Practice Bulletin, number 226. Obstet Gynecol. 2020;136(4):e48-e69.
- Martin JA, Hamilton BE, Osterman MJK, Driscoll AK, Drake P. Births: final data for 2017. Natl Vital Stat Rep. 2018;67(8):1-50.
- National Down Syndrome Society. Down syndrome facts. https://www.ndss.org/about-down-syndrome/down-syndrome-facts/. Accessed October 4, 2020.
- The Fetal Medicine Foundation. https://fetalmedicine.org.
- Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015;372(17):1589-1597.
- Fairbrother G, Burigo J, Sharon T, Song, K. Prenatal screening for fetal aneuploidies with cell-free DNA in the general pregnancy population: a cost-effectiveness analysis. J Matern Fetal Neonatal Med. 2016;29(7):1160-1164.