The clinical utility of DNA-based screening for fetal aneuploidy by primary obstetrical care providers in the general pregnancy population

Abstract

Objective:To assess the clinical utility of cell-free DNA (cfDNA)-based screening for aneuploidies offered through primary obstetrical care providers to a general pregnancy population.Methods:Patient educational materials were developed and validated and providers were trained. Serum was collected for reflexive testing of cfDNA failures. Providers and patients were surveyed concerning knowledge, decision making, and satisfaction. Pregnancy outcome was determined by active or passive ascertainment.Results:Between September 2014 and July 2015, 72 providers screened 2,691 women. The five largest participating practices increased uptake by 8 to 40%. Among 2,681 reports, 16 women (0.6%) were screen-positive for trisomy 21, 18, or 13; all saw genetic professionals. Twelve were confirmed (positive predictive value (PPV), 75%; 95% CI, 48–93%) and four were false-positives (0.15%). Of 150 failures (5.6%), 79% had a negative serum or subsequent cfDNA test; no aneuploidies were identified. Of 100 women surveyed, 99 understood that testing was optional, 96 had their questions answered, and 95 received sufficient information. Pretest information was provided by the physician/certified nurse midwife (55) or office nurse/educator (40); none was provided by genetic professionals.Conclusion:This first clinical utility study of cfDNA screening found higher uptake rates, patient understanding of basic concepts, and easy incorporation into routine obstetrical practices. There were no reported cases of aneuploidy among cfDNA test failures.Genet Med advance online publication 12 January 2017

Genetic Counselors’ Perspectives About Cell‐Free DNA: Experiences, Challenges, and Expectations for Obstetricians

“…There is both patient and public interest in learning about fetal sex (Harrington et al 1996;Newson 2008). At the same time, there are rising concerns about the use of cfDNA for this purpose (Chandrasekharen et al 2014;Chapman and Benn 2013;Farrell et al 2014;Palomaki et al 2017). While genetic counselors were familiar with these trends, they were surprised to frequently observe situations in which patients' motivation to learn about fetal sex took precedence over the interest in using cfDNA to identify chromosomal or subchromosomal abnormalities, an issue expected to become worse given the finding that low-risk obstetric patients are increasingly motivated to use cfDNA for this purpose.…”

“…Specifically, participants underscored the need for obstetricians to understand the concept of positive predictive value in order to individualize patients' risk of a fetal condition based on the screen results. This concept has been an important part of prenatal screening for decades but is of particular importance in cfDNA screening, which is not only increasingly being used among the low-risk obstetric population but also provides a risk assessment about numerous conditions not assessed by conventional screens with an associated detection rate for each (Suskin et al 2016;Palomaki et al 2017). As part of this, they recommended obstetricians become familiar with and use some of the novel and valuable tools emerging from professional societies and researchers to help understand and communicate individualized risk information to patients.…”

“…cfDNA was initially recommended for use in high-risk pregnancies (e.g., advanced maternal age, an abnormal screen or ultrasound, or a reproductive history indicating high risk) (ACOG Bulletin 163; Devers et al 2013). Since its introduction, data and clinical practice guidelines have emerged supporting the use of the screen in the low-risk general obstetric population, a trend that is gaining momentum (Benn et al 2015;Chitty and Bianchi 2013;Gregg et al 2017;Haymon et al 2014;Pergament et al 2014;Zhang et al 2015;Palomaki et al 2017). As a result, a greater number of women will be offered and consider the utility of cfDNA screening for their pregnancies, a process that is influenced by its positive predictive value for individual patients.…”

Current controversies in prenatal diagnosis 2: Cell‐free DNA prenatal screening should be used to identify all chromosome abnormalities

“…They are unfamiliar with microdeletions and expressed concern about using cfDNA to detect them in view of variable or unknown phenotypic expression . Furthermore, at least 12% of women do not want to know the baby's sex and report receiving information about cfDNA testing in only 5 minutes . Health professionals report spending an average of 6 minutes answering parents' questions before testing—so how are we going to be able to explain the implication of expanded cfDNA screening?…”

A Paradigm Shift: Considerations in Prenatal Cell-Free DNA Screening

“…Recent studies and updated guidelines illustrate that obstetric care providers are rapidly adopting cfDNA for not only high-risk patients but also pregnant women at standard risk of fetal chromosomal aneuploidy (22,34). The practice is sometimes termed DNA first, in which cfDNA is used as a primary screening method.…”