A Genomic Solution for Noninvasive Prenatal Screening
NIPT (noninvasive prenatal testing) sensitivity and specificity are important considerations in choosing a test. The Verifi Prenatal Test is a highly accurate, noninvasive test that screens for aneuploidy of chromosomes 21, 18, and 13. Additional screening is available for sex chromosome aneuploidies, select microdeletions, and all autosomal trisomies in singleton pregnancies.
In twin pregnancies, screening for aneuploidy in chromosomes 21, 18, and 13 and the option to screen for the absence of the Y chromosome is available. Results are reported approximately 3–5 days after the sample is received. Depending on demand, the time to report may vary. Test performance metrics, including NIPT sensitivity, positive predictive values (PPV), and specificity data, are detailed below.
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Publication: 85,000 NIPT Cases
Noninvasive prenatal testing in the general obstetric population: Clinical performance and counseling considerations in over 85,000 cases.
Test Performance Metrics for the Verifi Prenatal Test
Sensitivity and specificity for aneuploidy detected samples compared with published validation metrics
| CLIA Laboratory | Validation Study* | |||
|---|---|---|---|---|
| Condition | Observed Sensitivity† (Range)‡ | Observed Specificity† (Range)‡ | Sensitivity | Specificity |
| Trisomy 21 | 99.49% (98.66–99.53%) | 99.77% (98.92–99.91%) | 100% | 99.76% |
| Trisomy 18 | 97.23% (94.20–98.15%) | 99.69% (99.51–99.85%) | 97.37% | 99.57% |
| Trisomy 13 | 97.98% (95.56–98.87%) | 99.84% (99.77-99.93%) | 87.50% | 100% |
* Illumina. Analytical Validation of the Verifi prenatal test: Enhanced Test Performance for Detecting Trisomies 21, 18, and 13 and the Option for Classification of Sex Chromosome Status. Illumina White Paper. 2012.
† Observed sensitivity and specificities were calculated using available outcome data with the cohort size adjusted for the proportion of positive cases with confirmed outcomes.
‡ The low end of the range was based on the assumption that all unreported outcomes are discordant, and high end of the range was based on the assumption that all unreported outcomes are concordant.
Performance Metrics Considerations After Screening
PPV based on performance metrics
Positive predictive value (PPV) refers to the proportion of positive test results that are truly positive. PPV is based on the sensitivity and specificity of the test and the prevalence of the condition in the population being tested. Because the prevalence of autosomal trisomies (eg trisomy 21) increases with maternal age, so do the PPVs.
For Verifi and Verifi Plus Prenatal Tests, if a woman receives an aneuploidy detected result for trisomy 21, trisomy 18, or trisomy 13 in a singleton pregnancy, the report will include a PPV based on the test’s sensitivity and specificity for the condition, maternal age, and gestational age.
Sample Test Report
| Chromosome | Results | PPV (%) |
|---|---|---|
| Chromosome 21 | POSITIVE: Aneuploidy detected Results consistent with pregnancy at increased risk for trisomy 21. |
95% |
| Chromosome 18 | NEGATIVE: No aneuploidy detected Results consistent with two copies of chromosome 18. |
|
| Chromosome 13 | NEGATIVE: No aneuploidy detected Results consistent with two copies of chromosome 13. |
Why Specificity Matters for PPVs
While PPVs are lower in younger women, PPVs for NIPT will be higher than those of traditional serum screening at all maternal ages because NIPT has significantly higher specificity (a lower false positive rate).1
Why Prevalence Matters for PPVs
Because the prevalence of autosomal trisomies (eg, trisomy 21) increases with maternal age, so do the PPVs. Trisomy 21 is the most prevalent autosomal trisomy in live births. Thus, the PPVs are higher for trisomy 21 than for trisomies 18 and 13, which are less common, as seen in the graphs below.
The PPVs below are calculated based on age-related prevalence; the presence of other aneuploidy risk factors (eg, ultrasound abnormalities) would likely increase the PPVs over those shown here.
NIPT PPVs by maternal age
PPVs calculated using sensitivity and specificity data from a meta-analysis of 35 NIPT studies and published estimates of aneuploidy prevalence at 10 weeks gestation for different maternal age groups.2-3 The potential PPV range, illustrated by the error bars, was calculated using 95% confidence intervals (CI) for sensitivity and specificity.
Assessing Test Failure Rate
The Verifi Prenatal test has a low failure rate of 0.6%.4 It uses next-generation sequencing to analyze cfDNA fragments across the whole genome, which has proven advantages over other NIPT methodologies such as targeted sequencing and array-based methods.
That’s important, and clinically relevant, because not only do test failures negatively impact patient care, they also adversely affect test metric parameters such as sensitivity, specificity, and PPV. By choosing the Verifi Prenatal Test, the clinical impact of failures can be reduced.5
The Illumina Difference
We’re committed to providing laboratories with test options to improve human health. Published data shows that NGS with whole-genome sequencing (WGS) is the NIPT technology of choice when compared to targeted approaches.
Offering the Verifi Prenatal Test in Your Lab
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Additional Resources
Learn more about the Verifi Prenatal Test
Get details about the Verifi Prenatal Test in one easy-to-read handout, which includes information about test options and performance data, as well as a sample report.
Learn more about the Verifi Plus Prenatal Test
Get the essential information about the broad range of the Verifi Plus Prenatal Test, including specifics on chromosomal aneuploidies identified, and read a sample report.
Choosing the Verifi Plus Prenatal Test
Gain deeper insight into the Verifi Plus Prenatal Test in this brochure, which discusses microdeletions, specific conditions and incidence rates, and offers clinical evidence.
References
- Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;370(9):799-808.
- Gil MM, Accurti V, Santacruz B, Plana MN, Nicolaides KH. Analysis of cell-free DNA in maternal blood screening for fetal aneuploidies: updated meta-analysis. Ultrasound Obstet Gynecol. 2017 Apr 11. doi: 10.1002/uog.17484.
- Taneja PA, Snyder HL, de Feo E, Kruglyak KM, Halks-Miller M, Curnow KJ, Bhatt S. Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85 000 cases. Prenat Diagn. 2016 Mar;36(3):237-43. doi: 10.1002/pd.4766. Epub 2016 Jan 27. PMID: 26715197; PMCID: PMC4819889.
- Data on file. Illumina, Inc 2022.
- Norton ME, Jacobsson B, Swamy GK, et al. Cell-free DNA analysis for noninvasive examination of trisomy. N Engl J Med. 2015: 372(17): 1589-97.
Verifi™ and Verifi™ Plus were developed by, and their performance characteristics were determined by Verinata Health, Inc. (VHI) a wholly owned subsidiary of Illumina, Inc. The VHI laboratory is CAP-accredited and certified under the Clinical Laboratory Improvement Amendments (CLIA) as qualified to perform high complexity clinical laboratory testing. They have not been cleared or approved by the U.S. Food and Drug Administration.