Evolving noninvasive screening options, such as noninvasive prenatal tests (NIPT), offer early genetic screening for chromosomal conditions using just one tube of blood—as early as 10 weeks into a patient’s pregnancy.
Other types of prenatal screening and diagnostic tests may require more than one office visit, multiple blood draws, or carry a higher risk of false positive results. Diagnostic tests, such as chorionic villus sampling (CVS) or amniocentesis, provide definite results for most chromosome conditions but have an associated risk of miscarriage.
NIPT is noninvasive to the mother or baby with high detection rates and low false positives. The American Congress of Obstetricians and Gynecologists (ACOG) and International Society of Prenatal Diagnosis (ISPD), along with other professional societies, have stated that NIPT is an available screening option for all pregnant women.1,2
The Verifi Prenatal Test is one such noninvasive test that screens for aneuploidy of chromosomes 21, 18, and 13. Additional screening is available for sex chromosome aneuploidies and select microdeletions 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. The results are reported in approximately 3–5 days after the sample is received. Depending on demand, the time to report may vary.
Click on the below to view the sensitivity and specificity data table.
|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
Decide which prenatal screening option(s) to offer your patients
Determine which laboratory to use
Counsel patients about benefits and limitations of the aneuploidy screening options (detection rates and false positive rates)
Click on the below to view the sensitivity and specificity data table.
|Condition||Sensitivity||95% CI||Specificity||95% CI|
NIPT performance for trisomies 21, 18, and 13 in singleton pregnancies as reported in a large, independent meta-analysis3
Data from a meta-analysis of 37 published NIPT studies between January 2011 and January 2015.
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 (e.g. trisomy 21) increases with maternal age, so do the PPVs.
The American College of Medical Genetics (ACMG) recommends that laboratories provide patient-specific PPV when reporting positive results.4 Our test reports provide this information.
For Verifi and Verifi Plus, 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.
Click on the below to view a sample test report
|Chromosome 21||POSITIVE: Aneuploidy detected
Results consistent with pregnancy at increased risk for trisomy 21.
|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.
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. The PPVs below are calculated based on age-related prevalence; the presence of other aneuploidy risk factors (e.g. ultrasound abnormalities) would likely increase the PPVs over those shown here.
Counsel the patient about the NIPT results, the likelihood of a true positive (PPV), and the recommendation for confirmatory diagnostic testing.10,11
The Verifi Prenatal Test has the lowest failure rate in the industry of 0.1%, excluding administered failed samples—that means that 99.9% of the time a result is provided13. 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. Test failure rates are substantially lower with whole-genome sequencing versus other methodologies.13-16
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.13Access PDF
We’re committed to providing laboratories and health care partners with comprehensive solutions and 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.
With over 99.7% of NIPT samples in these studies run on Illumina NGS technology, we’re helping advance breakthrough in prenatal screening. It’s what makes the verifi Prenatal Test, with the lowest failure rate of any noninvasive prenatal test on the market, the best choice for patients.
Click on the below to view the samples run data table.
|Test (Company)||Current technology platform||Platform provider||Number of published samples|
|Illumina NGS||Ion Proton NGS||Affymetrix array|
|Bambni Test (Berry Genomics)||NGS||Illumina||3,268||0||0|
|MaterniT21 PLUS Test (Sequenom)||NGS||Illumina||293,243||0||0|
|NIFTY Test (BGI)||NGS||Illumina||168,655||0||0|
|Panorama Prenatal Screen (Natera)||NGS||Illumina||55,077||0||0|
|PrenaTest (LifeCodexx AG)||NGS||Illumina||504||0||0|
|Verifi Prenatal Test (Illumina)||NGS||Illumina||113,561||0||0|
|IONA Test (Premaltha)||NGS||Ion Proton||0||684||0|
|Harmony Prenatal Test (Arlosa)*||Array||Affymetrix||44,313||0||1,677|
A PubMed search for "cell-free, DNA, prenatal," "noninvasive prenatal testing," and "noninvasive prenatal screening" was performed on November 30, 2015. All validation and clinical studies using unique samples were included, where a current clinical NIPT provider performed sample analysis. Case studies and studies published in a language other than English were excluded. A total of 59 published studies were surveyed. Data calculations on file. Illumina, Inc. 2015. NGS = next-generation sequencing; either whole-genome or targeted.
*In 2014, Ariosa switched from sequencing to arrays for clinical samples despite limited published data on this platform.
Theoretical example of the number of invasive procedures requested due to NIPT failure and false positive rates of the assays. Failure rates include assay failures and samples rejected due to low fetal fraction. Assay failure rate for the Harmony test is based on NGS studies and may not be consistent with actual test results achieved using the array-based Harmony Test currently in use.13-19
†Affected pregnancies with a screening test failure were excluded from the number of detected T21.
The Verifi Prenatal Test was developed by, and its performance characteristics were determined by Verinata Health, Inc. 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. It has not been cleared or approved by the U.S. Food and Drug Administration.