Clinical experience with single‐nucleotide polymorphism‐based non‐invasive prenatal screening for 22q11.2 deletion syndrome

Abstract

ObjectivesTo evaluate the performance of a single‐nucleotide polymorphism (SNP)‐based non‐invasive prenatal test (NIPT) for the detection of fetal 22q11.2 deletion syndrome in clinical practice, assess clinical follow‐up and review patient choices for women with high‐risk results.MethodsIn this study, 21 948 samples were submitted for screening for 22q11.2 deletion syndrome using a SNP‐based NIPT and subsequently evaluated. Follow‐up was conducted for all cases with a high‐risk result.ResultsNinety‐five cases were reported as high risk for fetal 22q11.2 deletion. Diagnostic testing results were available for 61 (64.2%) cases, which confirmed 11 (18.0%) true positives and identified 50 (82.0%) false positives, resulting in a positive predictive value (PPV) of 18.0%. Information regarding invasive testing was available for 84 (88.4%) high‐risk cases: 57.1% (48/84) had invasive testing and 42.9% (36/84) did not. Ultrasound anomalies were present in 81.8% of true‐positive and 18.0% of false‐positive cases. Two additional cases were high risk for a maternal 22q11.2 deletion; one was confirmed by diagnostic testing and one had a positive family history. There were three pregnancy terminations related to screening results of 22q11.2 deletion, two of which were confirmed as true positive by invasive testing.ConclusionsClinical experience with this SNP‐based non‐invasive screening test for 22q11.2 deletion syndrome indicates that these deletions have a frequency of approximately 1 in 1000 in the referral population with most identifiable through this test. Use of this screening method requires the availability of counseling and other management resources for high‐risk pregnancies. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd. on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

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.…”

“…A major difficulty in clinical experience studies has been that confirmation studies have been substantially incomplete [2][3][4]11] and this study also has incomplete followup data. Low follow-up rates can be attributable to multiple factors including referral of confirmatory testing to different laboratories and incomplete documentation.…”

“…Peripheral blood specimens were collected and sent by 2-day air transportation to the Natera laboratory without plasma separation prior to shipment. Laboratory procedures were as described elsewhere [7,11,[15][16][17][18][19][20]. Following the NIPS analyses, all patient reports were communicated electronically to Echevarne and to the individual referring physicians and clinics.…”

“…The cases included in this study did not include any that have been previously reported in an evaluation of the SNP-based NIPT for fetal aneuploidy [3]. However, a minority of the cases receiving microdeletion NIPT have been included in prior reports (from February 2014 to February 2015) [11,20,21].…”

“…Following the reporting of cases with a high risk for a microdeletion syndrome, a test modification was introduced that was expected to significantly reduce the FPR [11,20,21]. This modification involved a change in the confidence level needed to call a high risk result and reflex resequencing of those microdeletion tests that were positive at the standard, low, depth of read (LDOR) with the resequencing carried out at a higher depth of read (HDOR) [20].…”