Noninvasive Prenatal Testing Information for Healthcare Professionals

Noninvasive prenatal testing—Accurate information for your patients

Answers—simply, safely, sooner

The verifi Prenatal Test is a noninvasive prenatal screening that screens for multiple fetal chromosomal aneuploidies using a single maternal blood draw with high sensitivity and specificity. The basic test screens for T21 (Down syndrome), T18 (Edwards syndrome), and T13 (Patau syndrome). Testing for the most common sex aneuploidies and additional chromosomal disorders is also available.

  • Safe—Routine, noninvasive blood draw, just one tube (7–10 ml)
  • Accurate—Directly analyzes cell-free fetal and maternal DNA with our proprietary SAFeRTM algorithm; very low failure rate (0.1%)
  • Easy—Test as early as 10 weeks gestational age (8 weeks of fetal age as determined by date of conception).  No limitations regarding ethinicity, BMI, ART or egg donor cases.
  • Fast—Results reported to partner laboratory in 3 - 5 business days after sample receipt.  (Time to report may vary based on partner laboratory providing the test.)

Noninvasive prenatal testing (NIPT) helps reduce the need for invasive procedures View Webinar

Superior technology for informative noninvasive prenatal test results

Our noninvasive prenatal test takes advantage of deep massively parallel sequencing to provide clearer resolution for reliable answers.

  • Superior technology—Strong clinical evidence showing across-the-genome analysis in a real-world population
  • Comprehensive analysis—Provides option of comprehensive sex chromosome analysis
  • Informative results—Helpful classification that can indicate borderline results
  • Microdeletion and other aneuploidies option—Additional information on selected microdeletions and other aneuploidies (T9, T16) is also available

The SAFeR method calculates a Normalized Chromosome Value (NCV) for each chromosome, which significantly reduces data variation caused by GC content, sample-to-sample, and run-to-run variations. It is not a risk score, and it is not dependent on maternal age, maternal weight, or gestational age (after 10 weeks). Unlike SNP-based tests, the verifi Test is not affected by ethnicity.

verifi test with SAFeR Available Targeted Sequencing Tests
Definitive cut-off values provide clear screening results
Provides ambiguous risk scores similar to serum screens
Very low technical failure rate (0.1%) High failure rate (5-10% or greater)
Not constrained by BMI, ethnicity, or paternal sample
May rely on BMI, ethnicity, or paternal sample to improve accuracy
Accepts egg donors  

The basic verifi® Test screens for:

  • T21 (Down syndrome)
  • T18 (Edwards syndrome)
  • T13 (Patau syndrome)

Now a wider option is available for sex chromosomes at no extra charge:

  • Monosomy X (MX; Turner syndrome)
  • XXX (Triple X)
  • XXY (Klinefelter syndrome)
  • XYY (Jacobs syndrome)

Fetal sex (XX or XY)—aids in stratifying the risk for X-linked disorders such as hemophilia, Duchenne muscular dystrophy, or cases of ambiguous genitalia, such as congenital adrenal hyperplasia

Utilizing NIPT in a maternal-fetal medicine practice: Dr. Martin Chavez View VideoMartin Chavez, MD, a maternal-fetal medicine specialist, discusses noninvasive prenatal testing.

Test Performance Metrics

Test performance metrics are essential both before and after patients undergo prenatal aneuploidy screening.


Performance Metrics Considerations Before Screening

Sensitivity and Specificity

A test’s sensitivity and specificity can help you:

  • 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

Table 1. verifi Sensitivity and Specificity for Chromosomes 21, 18 and 131

Chromosome Samples Analyzed Sensitivity 95% CI Specificity 95% CI
21 500 >99.9%
(90/90)
96.0–100.0 99.8%
(409/410)
98.7–100.0
18 501 97.4%
(37/38)
86.2–99.9 99.6%
(461/463)
98.5–100.0
13 501 87.5%
(14/16)
61.7–98.5 >99.9%
(485/485)
99.2–100.0

Table 2. verifi Sensitivity and Specificity for XX, XY and Monosomy X (MX)1

Sex Chromosome Classification Number Analyzed Sensitivity 95% CI Specificity 95% CI Accuracy 95% CI
XX 508 97.6%
(243/249)
94.8-99.1 99.2%
(257/259)
97.2-99.9 98.4% 96.9-99.3
XY 508 99.1%
(227/229)
96.9-99.9 98.9%
(276/279)
96.9-99.8 99.0% 97.7-99.7
MX 508 95.0%
(19/20)
75.1–99.9 99.0%
(483/488)
97.6–99.7 N/A N/A

Sensitivity and specificity are test specific, not patient specific. As such, they are not expected to change significantly based on an individual patient’s clinical picture (e.g. maternal age, ultrasound findings, etc)

Performance Metrics Considerations After Screening


Positive Predictive Value (PPV)

A test’s PPV can help you determine how likely a positive result is to be a true positive versus a false positive.


PPV is based on the sensitivity and specificity of the test AND the prevalence of the condition in the population being tested.


Why Prevalence Matters for PPVs

  • Since the prevalence of autosomal trisomies (e.g. trisomy 21) increases with maternal age, so do the PPVs.
  • Trisomy 21 is the most prevalent autosomal trisomy in livebirths. Thus, the PPVs are higher for trisomy 21 than for trisomies 18 and 13, which are less common.

PPVs calculated using verifi sensitivities and specificities1 and the published prevalence estimates of trisomy 21, trisomy 18, and trisomy 13 at 10 weeks gestation for different maternal ages2.


  • The PPVs above are calculated based solely on age-related prevalence; the presence of other aneuploidy risk factors (e.g. ultrasound abnormalities) would likely increase the PPV over those shown here.

Why Specificity Matters for PPVs

  • While the PPVs are lower for younger women, it is important to remember that regardless of maternal age, PPVs for NIPT will be higher than those of traditional serum screening because NIPT has significantly higher specificity (a lower false positive rate)3.

PPVs calculated using verifi and first trimester combined screening sensitivities and specificities1,4 and published prevalence estimates of trisomy 21, trisomy 18, and trisomy 13 at 10 weeks gestation for different maternal ages2.

For patients with a positive NIPT result:

  • To calculate a patient’s individual PPV, you may wish to use the PPV calculator endorsed by ACOG5
  • Counsel the patient about the NIPT results, the likelihood of a true positive (PPV), and the recommendation for confirmatory diagnostic testing6

References

1 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.
2 Gardner RJM, Sutherland GR, Shaffer LG. Parental age counseling and screening for fetal trisomy. Chromosome abnormalities and genetic counseling. 4 ed: Oxford University Press; 2012:403-416.
3 Bianchi DW, Parker RL, Wentworth J, et al. DNA sequencing versus standard prenatal aneuploidy screening. N Engl J Med. 2014;370(9):799-808.
4 Nicolaides KH. Screening for fetal aneuploidies at 11 to 13 weeks. Prenat Diagn. 2011;31(1):7-15.
5 The American Congress of Obstetricians and Gynecologists. NIPT Cell Free DNA Screening Predictive Value Calculator. National Society of Genetic Counselors (NSGC) and Perinatal Quality Foundation (PQF). Endorsed December 2015. 2015; http://www.acog.org/Resources-And-Publications/Endorsed-Documents. Accessed January 28, 2015.
6 Committee Opinion No. 640: Cell-free DNA Screening for Fetal Aneuploidy. Obstet Gynecol. 2015;126(3):e31-37.


Screening Twin Pregnancies

Screening for fetal aneuploidy in twin gestations poses unique challenges such as lower levels of DNA available for analysis from each fetus. By expanding the sensitivity and overall capability of the assay, the verifi Prenatal Test is available for use in twin pregnancies. For twin pregnancies, the verifi Test screens for T21, T18, T13 and the presence of Y chromosome (optional). The verifi Test can be used in both monozygotic and dyzygotic pregnancies.

Innovative developments in workflow and bioinformatics have led to improved accuracy of classifying aneuoploidy-affected samples. Using our improved alogorithm to analyze 115 maternal plasma samples from twin pregnancies, the twins option correctly screened:7

  • 3/3 cases with T21 present in one twin
  • 1/1 case with T18 present in both twins (monochorionic)
  • 91/91 cases with at least one male twin
  • No false positives reported in this data set

7 Verinata Health, Inc. (2012) Accurate Aneuploidy Detection in Twin Pregnancies with an Optimized Algorithm for the verifi Prenatal Test. Redwood City, CA

Test results

Reports will contain results for chromosomes 21, 18, and 13. Test reports will include one of three possible results for chromosomes 21, 18, and 13: “No Aneuploidy Detected”, “Aneuploidy Detected”, or “Aneuploidy Suspected (Borderline Value)”.

  • "No Aneuploidy Detected" - this result is reassuring but does not ensure an unaffected pregnancy
  • "Aneuploidy Detected" - this result suggest an increased likelihood of the fetus to be affected. However, there is a small chance that the result may not reflect the chromosomes of the fetus
  • "Aneuploidy Suspected (Borderline Value)" - this result gives an indication that although there is a higher risk for fetal aneuploidy than a “No Aneuploidy Detected” result, the chances of a false positive are slightly greater than the results in the “Aneuploidy Detected” zone.  Both “ANEUPLOIDY SUSPECTED (Borderline Value)” and “ANEUPLOIDY DETECTED” results should be confirmed by an invasive procedure if a more definitive diagnosis is desired. Illumina recommends that no irreversible clinical decisions should be made based on these screening results alone.  If a definitive diagnosis is desired, chorionic villus sampling or anmiocentesis would be necessary.

For singleton pregnancies sex chromosome results are reported in cases where requested.  If there are no sex chromosome aneuploidies, then the report will indicate XX or XY status.   It is for the provider and patient to decide if the fetal sex information is to be revealed to the patient.

How it works

Physician recommends and orders test for patient

Requisition and Informed Consent forms are completed, patient proceeds to blood draw

Blood sample and test request form are sent back to lab

Lab processes and analyzes the sample

Test results are sent to healthcare provider


Illumina genetic counselors are available to provide guidance on laboratory results.

How to order

The Illumina verifi NIPT service is offered through regional and reference laboratories as well as select national laboratory partners. These partners send their samples to an Illumina CLIA lab in Redwood City for processing. Reports are then sent back to the partner labs.

This model is helping us build a network of reliable laboratory partners who can access and analyze the verifi Prenatal Test in addition to offering value-added services to further enhance the patient and physician experience.

As the leader in next-generation sequencing (NGS) technology, we will continue to supply virtually all major NIPT providers with the instruments and reagents they need. We will also continue to focus our scientific and clinical expertise on ongoing research and clinical studies to validate future NIPT applications, and expand NIPT access and knowledge.

For questions or assistance, contact verifi Prenatal Test customer service at 855.266.6563 or verifisupport@illumina.com.

 

View Laboratory Partner List »

 

Illumina support

Our singular focus on maternal and fetal health affects everything we do to help you provide the best care for your patient.

Genetic counselors An in-house group of genetic counselors is available to provide guidance on laboratory results.

Lab directors Experienced directors manage our state-of-the-art, CAP-accredited, CLIA-certified laboratory.

Client services The Client Services group is on-site and readily available to provide helpful, timely support.

Educational support Illumina is proud to support CME and other educational programs for healthcare professionals.

Does insurance cover the verifi Prenatal Test?

More insurers see the value of this test. As a result, more patients will be able to obtain the test at a low cost through their insurance plans. The best way to confirm if the test is covered by a particular insurance plan is to have patients ask their insurance providers.

FAQ
General
  • What conditions does the verifi Prenatal Test screen for?

    Trisomy 21 - Trisomy 21 (also called Down syndrome) occurs when three copies of Chromosome 21 are present instead of two. Down syndrome is the single most common cause of mental retardation. It can be associated with intellectual disabilities and multiple physical problems such as congenital heart defects, hearing impairment, eye disorders, among others. The life expectancy for an individual with Down syndrome is into adulthood.

    Trisomy 18 - Trisomy 18 (also called Edwards syndrome) occurs when three copies of Chromosome 18 are present instead of two. Edwards syndrome is the second most common autosomal trisomy - and it is associated with multiple malformations. It can cause severe physical, , and organ defects, such as cleft palate, club foot, kidney defects, and congenital heart defects and is associated with severe intellectual disability.. The life expectancy for an infant born with Edwards syndrome is usually less than one year.

    Trisomy 13 - Trisomy 13 (also called Patau syndrome) occurs when three copies of Chromosome 13 are present instead of two. Patau syndrome is the one of the common autosomal trisomy seen at birth. It can cause severe physical, mental, and organ defects, such as cleft palate, club foot, facial defects, and congenital heart defects. The life expectancy for an infant born with Patau syndrome is usually less than one year.

    Monosomy X - Monosomy X (also called Turner syndrome) occurs when only one sex chromosome (the X chromosome) is present, and the second sex chromosome is missing. Turner syndrome affects approximately one out of every 2000 live born females. It can cause severe organ defects, such as congenital heart defects, renal anomalies, lymphodema, short stature, hypothyroidism, gonadal dysgenesis, and possible learning disabilities. Turner syndrome is a common aneuploidy that can result in a miscarriage.

    XXX - Triple X syndrome may not cause any signs or symptoms. If symptoms do appear, they may include: tall stature, delayed development of speech and language skills, weak muscle tone (hypotonia), and learning difficulties.

    XXY - Signs and symptoms of Klinefelter syndrome are variable and can include physical and cognitive issues. Learning disabilities, delayed speech and language development can be present. Males with Klinefelter syndrome often have tall statue and small testes (hypogonadism) that do not produce normal amounts of testosterone. This can lead to delayed or incomplete puberty, breast enlargement (gynecomastia), and infertility.

    XYY - Signs and symptoms of 47,XYY syndrome are variable. There is an increased risk of learning disabilities and delayed development of speech and language skills. Delayed development of motor skills, weak muscle tone, and behavioral and emotional difficulties are also possible. A small percentage of males with 47,XYY syndrome are diagnosed with autistic spectrum disorders, which are developmental conditions that affect communication and social interaction.

    Trisomy 9 - A rare chromosomal condition with the vast majority of instances resulting in miscarriage in the 1st trimester. While the majority of live births will not survive the early postnatal period, those that do will have serious health concerns, which often include intellectual disability and cardiac defects. Most of the cases that survive, are likely to be mosaic trisomy 9.

    Trisomy 16 - The most commonly occurring autosomal trisomy seen in first trimester miscarriages. Rare survivors with mosaic trisomy 16 or trisomy 16 CPM are at increased risk for health concerns including intra-uterine growth restriction, intellectual disability, and cardiac defects.

    Microdeletions - Microdeletions are chromosomal disorders caused by small missing pieces of chromosome material. They are usually not visible by standard methods of chromosome analysis. Microdeletions can occur on any of the 23 pairs of chromosomes. Some occur more commonly in a specific area of a particular chromosome and have been linked to known genetic syndromes. Most occur by chance, rather than being inherited from a parent, and can occur with no prior family history and without other risk factors, such as advanced parental age. Results from routine pregnancy screening are usually normal.

    22q11.2 syndrome – 22q11.2 syndrome (also called DiGeorge syndrome,Velocardiofacial syndrome) affects approximately one out of every 4,000 live births. Signs and symptoms are variable but it can be associated with learning problems, congenital heart defects, palatal abnormalities. Life expectancy is usually normal.

    1p36 deletion syndrome – 1p36 deletion syndrome affects approximately one out of every 4,000 to 10,000 live births and is associated with characteristic craniofacial features, seizures, brain and heart defects. Intellectual disability is variable. Life expectancy depends on the severity of features but can be normal.
    Angelman syndrome* – Angelman syndrome (also called 15q11.2 deletion syndrome) affects approximately one out of every 12,000 live births. Signs and symptoms of Angelman syndrome include intellectual disability, speech impairment, and seizures. Life expectancy is usually normal. *The microdeletion region is the same region for Angelman and Prader-Willi syndromes (15q11.2). NIPT will not distinguish between these two syndromes. Further testing is necessary.

    Prader-Willi syndrome* – Prader-Willi syndrome (also called 15q11.2 deletion syndrome) affects approximately one out of every 10,000-25,000 live births and is associated with hypotonia, morbid obesity, delayed motor and language skills, intellectual disability, and hypogonadism. Life expectancy is usually normal, but may be reduced depending on the severity of symptoms
    *The microdeletion region is the same region for Angelman and Prader-Willi syndromes (15q11.2). NIPT will not distinguish between these two syndromes. Further testing is necessary.

    Wolf-Hirschhorn syndrome (4p- syndrome) - Wolf-Hirschhorn syndrome (also called 4p- syndrome) affects approximately one out of every 50,000 live births. Signs and symptoms include growth deficiency, hypotonia, craniofacial features, intellectual disability, heart and brain abnormalities. Life expectancy depends on the severity of features.

    Cri du Chat syndrome (5p- syndrome) – Cri du Chat syndrome (also called 5p-syndrome) affects approximately one out of every 20,000-50,000 live births. Signs and symptoms include intellectual disability, speech delay, and a cat-like cry. Mortality rate is 10% in the first year; otherwise life expectancy is usually normal, but will depend on the severity of features.

  • Does the verifi Prenatal Test report fetal sex?

    Fetal sex will only be reported if the sex chromosomes option is ordered. If the sex chromosomes option is ordered, and no sex chromosome aneuploidies are detected, the result is reported as either XX or XY. It is for the provider and patient to decide if the fetal sex information is to be revealed to the patient.

  • Can you report the fetal sex without reporting sex chromosome aneuploidies?

    No. Fetal sex is only analyzed when the sex chromosomes option is ordered. This option includes six analysis categories (XX, XY, XXY, XXX, XYY, and Monosomy X). There is no option to request testing for only fetal sex analysis with the verifi Prenatal Test.

  • How can I indicate that I want the sex chromosomes option for my patient?

    The original verifi Test will remain for chromosomes 21, 18, and 13. The sex chromosome option is an optional second check on the test request form.

  • Does it take longer to get the report on sex chromosomes and is there any extra cost?

    No. There is no additional cost for the sex chromosome option. Time to report remains the same—results are usually reported to the ordering provider within 3 – 5 business days after sample receipt. (Time to report may vary based on the partner laboratory providing the test. Please refer to the partner’s website for accurate estimate of turnaround time.)

  • If a sex chromosome aneuploidy is detected, does a patient still need an invasive follow-up procedure?

    Illumina recommends that no irreversible clinical decisions should be made based on these screening results alone. If definitive diagnosis is desired, chorionic villus sampling or amniocentesis would be necessary.

  • How can I indicate I want the microdeletion option for my patient?

    The microdeletion option tests for a number of disorders and T9 and T16 (see above). Check the box to order this option.

Resources

Continuing Medical Education (CME)Learn MoreIllumina is committed to supporting independent medical education for women's healthcare providers. Click above to participate in a free CME activity about "The Role of Noninvasive Prenatal Screening in Optimizing Fetal Outcomes".

Clinical laboratory experience with noninvasive prenatal testing in twin gestations Download Poster A poster presentation from the 2015 Annual Meeting of the Society for Maternal- Fetal Medicine.

DNA Sequencing versus Standard Prenatal Aneuploidy Screening Read Article Prenatal testing with the use of cfDNA has significantly lower false positive rates and higher positive predictive values for detection of trisomies 21 and 18 than standard screening.


verifi Test Brochure
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An MFM's Perspective on NIPTDownload PDF Dr. Chavez discusses the benefits of NIPT for prenatal screening of fetal chromosomal aneuploidies.


Options in Prenatal Testing.
A genetic counseling video to help educate your patients*
Download Video

 

*Estimated file size is 300 MB


The Value of Noninvasive Prenatal Testing (NIPT) Download PDF

 
 
Guidelines and policy statements

The field of noninvasive prenatal diagnosis is developing rapidly. For reference we are including a short list of guidelines from leading institutions in the field of women’s healthcare.

The verifi 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.

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