Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85 000 cases

Abstract

ObjectiveThe primary goal of this study was to provide clinically relevant information for appropriate patient counseling.MethodDemographics and test metrics were reviewed for 86 658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes.ResultsOf 86 658 cases, 85 298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value (PPV) was 83.5% (608/728); observed PPVs for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual PPVs are determined by a patient's prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age.ConclusionThis large‐scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization. © 2015 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Fetal aneuploidy screening with cell-free DNA in late gestation

“…This has opened the door for serious discussion about offering NIPT as a primary pregnancy screen to all women. Our recent clinical experience publication showed that most women choosing NIPT were at less than 23 weeks gestation [24]. The lategestation samples described here performed similarly with regards to screen positive result, turnaround time, and cancelation rate to the recent all-gestational age cohort study [24].…”

“…Our recent clinical experience publication showed that most women choosing NIPT were at less than 23 weeks gestation [24]. The lategestation samples described here performed similarly with regards to screen positive result, turnaround time, and cancelation rate to the recent all-gestational age cohort study [24]. All patients with high-risk indications should receive appropriate counseling and be offered confirmatory diagnostic testing, regardless of gestational age.…”

The implications of non-invasive prenatal testing failures: a review of an under-discussed phenomenon

“…Of these, 43 cases (0.7%) did not receive a result because of laboratory technical issues: 33 (0.5%) because of interfering substance and 10 cases (0.2%) because of insufficient DNA. In a recent update from the same laboratory on 86 658 cases, only 101 patients (0.1%) did not obtain a result because of laboratory technical issues . It is of note that among the failed cases there were no aneuploidies detected.…”

A National Referral Laboratory’s Experience with the Implementation of SNP-Based Non-invasive Prenatal Screening for Fetal Aneuploidy and Select Microdeletion Syndromes

“…Reports from reference laboratories have been broadly consistent with the estimates of detection rates (DRs) and false-positive rates (FPRs) established in these trials [2][3][4][5][6]. Additionally, both proof of principle [7][8][9] and data from reference laboratories [10,11] have indicated that screening is possible for select sets of microdeletion syndromes.…”