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

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

Ron M McCullough  1 , Eyad A Almasri  1 , Xiaojun Guan  1 , Jennifer A Geis  1 , Susan C Hicks  1 , Amin R Mazloom  1 , Cosmin Deciu  1 , Paul Oeth  1 , Allan T Bombard  1 , Bill Paxton  1 , Nilesh Dharajiya  1 , Juan-Sebastian Saldivar  1
Affiliations

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

Ron M McCullough et al. PLoS One. .

Abstract

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.

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Conflict of interest statement

Competing Interests: 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. The authors have read the journal's policy and have the following conflicts: ownership of stocks or shares and a paid employee of Sequenom Laboratories. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Gestational Age Distribution at Time of Non-invasive Prenatal Testing.
This figure shows the frequency distribution by week of the gestational age of the fetus at the time testing. Percent of patients in each trimester is displayed in the inset table.
Figure 2
Figure 2. Clinical Reasons for Non-invasive Prenatal Testing.
This figure shows the clinical indication for testing. Advanced maternal age is defined as maternal age at birth of 35 or greater for singletons, 32 or greater for twins and 27 or greater for triplets or more. Subtotals for multiple indications include any time the indication is selected.
Figure 3
Figure 3. Impact of BMI on Final Results.
This figure shows a breakdown of final results when binned by maternal BMI. The number of patients in each bin is displayed above their respective bin.
Figure 4
Figure 4. NIPT T21 Modeled Performance at Low Fetal Fractions.
In figure, 27,824 samples that passed all laboratory quality criteria with fetal fractions between 4 and 8% were fitted into two normal distributions, one for euploids and one for T21 positives. The fitted distribution was used to estimate specificity and sensitivity.
Figure 5
Figure 5. Clinical Impact of Non-invasive Prenatal Testing.
All positive NIPT samples are recommended for invasive testing. Invasive procedure related miscarriages numbers based on a 0.5–1.0% frequency range.
See this image and copyright information in PMC

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