Non-invasive prenatal chromosomal aneuploidy testing--clinical experience: 100,000 clinical samples

PLoS One. 2014 Oct 7;9(10):e109173. doi: 10.1371/journal.pone.0109173. eCollection 2014.


Objective: As 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 design: The 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.

Results: NIPT 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.

Conclusion: NIPT 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aneuploidy*
  • Chromosome Disorders / diagnosis
  • Female
  • Genetic Testing* / methods
  • Genetic Testing* / standards
  • Humans
  • Pregnancy
  • Prenatal Diagnosis* / methods
  • Prenatal Diagnosis* / standards
  • Reproducibility of Results
  • Sensitivity and Specificity

Grant support

The study was based on clinical samples submitted for testing. Sequenom Laboratories performed the testing, data collection, analysis and manuscript drafting. Test costs were paid for by the patient in the form of co-pay and/or their insurance company. As such the funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.