Non-Invasive Prenatal Chromosomal Aneuploidy Testing - Clinical Experience: 100,000 Clinical Samples

Abstract

ObjectiveAs the first laboratory to offer massively parallel sequencing-based noninvasive prenatal testing (NIPT) for fetal aneuploidies, Sequenom Laboratories has been able to collect the largest clinical population experience data to date, including >100,000 clinical samples from all 50 U.S. states and 13 other countries. The objective of this study is to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT.Study DesignThe study includes plasma samples collected from patients with high-risk pregnancies in our CLIA–licensed, CAP-accredited laboratory between August 2012 to June 2013. Samples were assessed for trisomies 13, 18, 21 and for the presence of chromosome Y-specific DNA. Sample data and ad hoc outcome information provided by the clinician was compiled and reviewed to determine the characteristics of this patient population, as well as estimate the assay performance in a clinical setting.ResultsNIPT patients most commonly undergo testing at an average of 15 weeks, 3 days gestation; and average 35.1 years of age. The average turnaround time is 4.54 business days and an overall 1.3% not reportable rate. The positivity rate for Trisomy 21 was 1.51%, followed by 0.45% and 0.21% rate for Trisomies 18 and 13, respectively. NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age ≥35 undergoing amniocentesis. In this population 3519 patients had multifetal gestations (3.5%) with 2.61% yielding a positive NIPT result.ConclusionNIPT has been commercially offered for just over 2 years and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients. The accuracy and NIPT assay positivity rate are as predicted by clinical validations and the test demonstrates improvement in the current standard of care.

Has Noninvasive Prenatal Testing (NIPT) Come of Age?

“…The objective of a recent study was to give a robust clinical picture of the current laboratory performance of the MaterniT21 PLUS LDT [6]. Samples were assessed for trisomies 13,18,21, and for the presence of chromosome Y-specific DNA.…”

“…NIPT positivity rates are similar to previous large clinical studies of aneuploidy in women of maternal age C35 undergoing amniocentesis. In this population, 3519 patients had multifetal gestations (3.5 %) with 2.61 % yielding a positive NIPT result [6]. NIPT has been commercially offered for just over 3 years, and the clinical use by patients and clinicians has increased significantly.…”

“…NIPT has been commercially offered for just over 3 years, and the clinical use by patients and clinicians has increased significantly. The risks associated with invasive testing have been substantially reduced by providing another assessment of aneuploidy status in high-risk patients [6].…”

Review of Clinical Next-Generation Sequencing

“…19 In addition, NGS technologies are used in analyzing cell-free DNA in the prenatal setting. 20,21 Targeted panels for cancer testing also vary between laboratories. 6 Targeted panels may be broad, including genes for both solid and hematologic malignancies, or may be more focused for a particular type of malignancy (such as myeloid neoplasms).…”

“…20,26,27 This testing is often referred to as a liquid biopsy. The potential applications of sequencing ctDNA include screening or diagnosis of cancer, monitoring for progression or relapse, and guiding therapy for a patient with a known cancer diagnosis.…”