Non-Invasive Prenatal Testing for Fetal Aneuploidy (Powered by Constellation)

NIPT Overview

2007537 Non-Invasive Prenatal Testing for Fetal Aneuploidy

ARUP offers non-invasive prenatal testing (NIPT) as early as 9 weeks gestation to help manage your patient’s pregnancy. Maternal blood is used to screen for specific chromosomal aneuploidies in the fetus, and results are reported as either "low risk" or "high risk" based on internal risk scores. In addition, each patient report includes interpretive comments carefully drafted by ARUP medical directors and genetic counselors. In rare cases, a specimen may not pass quality metrics or fall outside the limitation of the algorithm, and a result may not be provided. Specific guidance will be provided in such cases. For a "high risk" result, the likelihood of the fetus actually being affected (based on published or internal data) will be provided to help you and your patient decide on next steps. As NIPT is a screening test and is not diagnostic for the conditions reported, any patient with a result indicating a potential abnormality should be offered confirmatory invasive testing via amniocentesis or CVS, or testing of the baby after delivery.1

What is reported in ARUP's NIPT?

The risks for:
  • Trisomy 21 (Down syndrome)
  • Trisomy 18
  • Trisomy 13
  • Triploidy/vanishing twin
  • Sex chromosome aneuploidies:
    • Monosomy X (Turner syndrome)
    • XXX (Triple X syndrome)
    • XXY (Klinefelter syndrome)
    • XYY
Also included are:
  • Fetal fraction (%)
  • Fetal sex (patient may opt out)

How does ARUP's NIPT perform?

In a cross-validation study, ARUP's NIPT was completely concordant with results generated by Natera's Panorama. Like Panorama, ARUP's NIPT has the ability to distinguish between fetal and maternal DNA in the mother’s blood, and to detect aneuploidies in fetal fractions as low as 3%. As for concordance with clinical outcome, ARUP's NIPT was found to be >99% accurate for aneuploidies and fetal sex determination.2 NIPT is performed at ARUP's genomics laboratory using multiplexed single-nucleotide polymorphism (SNP) analysis and massively parallel sequencing. Data are uploaded to Natera’s Constellation (a cloud-based general-purpose copy number analysis software) that facilitates interpretation by ARUP's medical directors and genetic counselors. By eliminating the extra transport to Natera, sample integrity and turn-around time are improved.

  ARUP Validation Data PPV*
Agreement with Panorama Concordance with Clinical Outcome
Low Risk (negative) 100% (146/146) 98.3% (58/59)** NA
Trisomy 21 100% (18/18) >99% (11/11) 91%3
Trisomy 18 100% (9/9) >99% (3/3) 93%3
Trisomy 13 100% (5/5) >99% (1/1) 38%3
Monosomy X 100% (8/8) >99% (1/1) 50%3
Sex chromosome trisomy (XXX, XXY, XYY) 100% (11/11) NA (0/0) 54% (XXX); 63% (XXY); 88% (XYY)4
Triploidy or twin 100% (4/4) >99% (9/9) No data
Fetal Sex 100% (99/99) >99% (73/73) 100% 3

* PPV (positive predictive value) indicates the percentage of pregnancies that were classified as high risk by NIPT and were found to actually have the aneuploidy based on published or internal data.
** One sample, which was 46,XY (normal male) by karyotype on amniocytes, exhibited a distinct pattern of XXY, suggesting a possible difference between placental DNA found in plasma and the actual fetal DNA. Independent review by Natera also called this case XXY.

1. Gregg A et al. Noninvasive prenatal screening for fetal aneuploidy, 2016 update: a position statement of the American College of Medical Genetics and Genomics. Genet Med. 2016; 1056-65. PMID: 27467454

2. ARUP Whitepaper: Noninvasive prenatal testing for fetal aneuploidy, Powered by Natera’s Constellation, results to date as of November 2016

3. Dar P et al. Clinical experience and follow-up with large scale single-nucleotide polymorphism-based non-invasive prenatal aneuploidy testing. Am J Obstet Gynecol 2014; 211(5):527e1-527 e17. PMID: 25111587

4. ARUP historical data