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

Glenn E Palomaki, Edward M Kloza, Barbara M O'Brien, Elizabeth E Eklund, Geralyn M Lambert-Messerlian, Glenn E Palomaki, Edward M Kloza, Barbara M O'Brien, Elizabeth E Eklund, Geralyn M Lambert-Messerlian

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.

Figures

Figure 1
Figure 1
Weekly DNAFirst test enrollment of the five largest participating practices, expressed as a percentage of historical serum screening.Week of study enrollment (horizontal axis) versus weekly test volume (expressed as a percentage of serum screening volume in the previous 6 months). Practices A through C began enrolling soon after study initiation and exceeded historical screening rates by 30, 13, and 14% (horizontal dashed lines) by weeks 6, 3, and 13, respectively (vertical dashed lines). Practices D and E began enrollment later but matched historical rates quickly (at 16 and 20 weeks) and exceeded those rates by 40 and 8%, respectively.
Figure 2
Figure 2
Flowchart showing DNAFirst testing for trisomies 21, 18, and 13, along with additional testing for initial test failures and selected outcomes. Overall, 2,691 women agreed to testing and 2,685 samples had DNA sequencing. Of the 2,681 cfDNA tests reported, 0.6% (16) were screen-positive, 5.6% (150) failed to report at least one chromosome, and the remaining 93.8% (2,515) were screen-negative. FP, false positive; TP, true positive.

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