Noninvasive Prenatal Screening

Learn why more pregnant women can benefit from NIPS

NIPS is a breakthrough solution for prenatal screening. Rethink old paradigms and see why NIPS has proven superiority to traditional screening in women of every age or risk category.

Prelude Value

Prelude Value

How does Prelude maximize chromosomal abnormality detection and minimize test failures?

Society Guidelines

Do professional societies recognize the utility of NIPS in the general population?

Analytic Validity

Can NIPS accurately detect whether a common chromosomal abnormality is present or absent in a sample?

Clinical Validity

Does NIPS accurately identify pregnancies at risk for chromosomal abnormalities?

Clinical Utility

Does NIPS provide information that will improve outcomes in the general population?

Counsyl PreludeTM Prenatal Screen Value

Prelude is ideal for expectant mothers, their healthcare providers, and health plans because it performs better than traditional maternal serum screens and results in fewer unnecessary invasive procedures.

Focused conditions

Primarily focused on common chromosomal abnormalities as recommended by guidelines,1,2 including Down syndrome, trisomy 18, and trisomy 13 with an option for sex chromosomal abnormalities*

Superior Technology

Whole genome sequencing (WGS) leverages data from the entire genome so results are reliable even at low fetal fractions. Industry-leading test failure rate of 0.1% reduces need for unnecessary invasive procedures3,4

Clear Risk Assessment

Individualized positive predictive values and
residual risks are reported so each patient has clarity of her personal risk based on maternal age and gestational age

* By physician request, Prelude can also assess the risk for certain microdeletion syndromes associated with deletions in five chromosomal regions; 1p36, 22q11.2, 4p16.3, and 5p15.2. Microdeletion testing is considered an “add-on” test and is billed separately.

Methodology matters: All cell-free DNA technologies are not the same

Even small changes in test failure rates can significantly impact test performance, specifically a lab’s effective detection rate and positive predictive value.2 Our industry-leading test failure rate of 0.1% helps reduce anxiety, leads to fewer unnecessary procedures, and yields more reliable test results.

Individualized risk assessments enable patients to more easily weigh the advantages and disadvantages of follow-up diagnostic testing2

“Doctor, if my results are positive, what’s the chance my baby is affected?”

25 y/o patient at 16 weeks with a positive NIPS result for Down syndrome has a PPV of 70.1%. This patient would have a 70.1% chance of having an affected pregnancy.*

 42 y/o patient at 12 weeks with the same positive NIPS result for Down syndrome has a PPV of 98.5%. This patient would have a 98.5% chance of having an affected pregnancy.

* Using NIPS, the PPV is 20x higher than with traditional screening in the general OB population

Society Guidelines

The following professional societies recommend that all women, regardless of risk, should be offered prenatal assessment for aneuploidy and recognize that with appropriate counseling, NIPS is a primary option for all women with singleton pregnancies:

The American College of Obstetricians and Gynecologists1
The Society for Maternal-Fetal Medicine2
The American College of Medical Genetics and Genomics5
International Society for Prenatal Diagnosis6
The National Society of Genetic Counselor7

“ACMG recommends informing all pregnant women that NIPS is the most sensitive screening option for traditionally screened aneuploidies.” 5

Analytic Validity

Can NIPS accurately detect whether a common aneuploidy is present or absent in a sample?

Test performance for Prelude has been validated against reference lab data and clinical outcomes data.8

Call Analytic Sensitivity (95% CI) Analytic Specificity (95% CI) Analytic Accuracy (95% CI)

T21 Determination

100% (75.3-100)

100% (66.4-100)

100% (84.6-100)

T18 Determination

100% (29.2-100)

100% (82.4-100)
100% (84.6-100)

T13 Determination

100% (15.8-100)

100% (83.2-100)

100% (84.6-100)

Even in challenging cases, Prelude shows high analytical specificity and sensitivity due to unique assay features and bioinformatics, such as:8

  • Plasma and DNA extraction placed together on the same platform to reduce sample mix-up
  • A custom consolidation algorithm to decrease turnaround time
  • A contamination metric to increase quality control
  • Fetal fraction is measured and reported in all samples
  • A call review intervention when fetal fraction is inconsistent with a weak aneuploidy signal
  • Mathematical models to account for sequencing depth
  • Large maternal copy number variants (mCNVs) are censored to reduce false positives
  • Batch specific normalization to improve X and Y measurements

Clinical Validity

Does NIPS accurately identify pregnancies at risk for aneuploidy?

Dozens of studies performed in the clinical setting have shown NIPS to outperform traditional multiple marker screening, in both the the high-risk and general obstetric population.

Test performance comparison for NIPS and traditional screening in the general obstetric population10

Positive Predictive Value for Trisomy 21

Traditional Screening
<5%
NIPS
>60%
15x improvement

False Positive Rate for Trisomy 21

Traditional Screening
5%
NIPS
0.05%
100x improvement

Regardless of the population, NIPS is more sensitive, has higher positive predictive values and a lower false positive rate.9,10,11

Clinical Utility

Does NIPS provide actionable information that will improve outcomes?

More than 10 clinical studies show that adoption of NIPS in the high risk population leads to substantially fewer unnecessary invasive tests performed.12,13,14

Unnecessary invasive procedures

Traditional Screening
140K
NIPS
8K
94% reduction

Procedure-related loss

Traditional Screening
698
NIPS
42
94% reduction

Broadening the use of the NIPS to general population would lead to a similar reduction in unnecessary procedures and related fetal loss.15

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FAQ

What conditions are included in the Counsyl PreludeTM Prenatal Screen?

In accordance with professional society guidelines,¹ Prelude screens for the common autosomal aneuploidies; trisomy 21 (Down syndrome), trisomy 18, and trisomy 13. By physician request, Prelude can also screen for sex chromosomal abnormalities and/0r five microdeletion syndromes; 1p36,  4p16.3, 5p15.2, 15q11.2, and 22q11.2. Microdeletion testing is considered an “add-on” test and is billed separately.

Aren’t all noninvasive screening tests the same?

No. There are several different approaches for NIPS. The Prelude Prenatal Screen leverages whole genome sequencing (WGS) methodology with custom bioinformatics and assay improvements that maximize accuracy and minimize test failures.8 A key differentiator is that at low fetal fractions, Prelude detects more aneuploidy the first time the test is run and has an industry-leading test failure rate of 0.1% (compared to other methods with a 1%-4% failure rate).3 This leads to fewer redraws and fewer unnecessary invasive procedures.4

Who is the intended population?

The Prelude Prenatal Screen is intended for any woman with a singleton or twin pregnancy electing prenatal screening for fetal aneuploidy. This is consistent with professional guidelines from the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), the National Society of Genetic Counselors (NSGC), the American College of Genetics and Genomics (ACMG) and others. Testing can be performed from 10 weeks gestation.

How does the positive predictive value (PPV) for NIPS in the general obstetric population compare to the PPV for traditional screening?

In the general obstetric population, NIPS has a 100-fold higher PPV compared to traditional multiple marker screening.10

Has NIPS been shown to improve health outcomes?

Yes, NIPS more accurately identifies pregnancies at high-risk for aneuploidy in the general obstetric population when compared to traditional screening modalities.9-11 Clinical data demonstrates that NIPS leads to fewer unnecessary invasive procedures in the high-risk population12-14 and modeled data demonstrates similar results in the general obstetric population.15

Do medical societies recommend NIPS as a first-line test for the general obstetric population?

Yes. ACOG, SMFM, ACMG, International Society for Prenatal Diagnosis (ISPD), and NSGC recommend that all women, regardless of risk, should be offered prenatal assessment for aneuploidy and recognize that with appropriate counseling, NIPS is a primary option for all women with singleton pregnancies.1-7

What is the test failure rate for the Prelude Prenatal Screen?

Based on custom bioinformatics and WGS methodology, the Prelude Prenatal Screen has an industry-leading test failure rate of 0.1%.⁸

References

  1. Practice Bulletin No. 163 Summary: Screening for Fetal Aneuploidy. 2016. Obstet Gynecol 127(5): 979–81.
  2. Society for Maternal-Fetal Medicine (SMFM) Publications Committee. #36 Prenatal aneuploidy screening using cell-free DNA. 2015. Am J Obstet Gynecol 212(6):711-716.
  3. Yaron Y. 2016. The Implications of Non-Invasive Prenatal Testing Failures: A Review of an under-Discussed Phenomenon. Prenatal Diagnosis 36 (5). Wiley Online Library: 391–96.
  4. Artieri CG, et al. 2017. Noninvasive Prenatal Screening at Low Fetal Fraction: Comparing Whole-Genome Sequencing and Single-Nucleotide Polymorphism Methods.” Prenat Diagn 37 (5): 482–90.
  5. Gregg AR, et al. 2016 Noninvasive prenatal screening for fetal aneuploidy, 2016 update: A position statement of the American College of Medical Genetics and Genomics. Genet Med, 18(10):1056-65.
  6. Benn P, et al. 2015. Position statement from the Chromosome Abnormality Screening Committee on behalf of the Board of the International Society for Prenatal Diagnosis. Prenat Diagn 35(8):725-734.
  7. National Society of Genetic Counselors (NSGC) Position Statement on Prenatal Cell-Free DNA Screening. October 2016. https://www.nsgc.org/p/bl/et/blogaid=805 (Accessed 6/8/2018)
  8. Data on file, Counsyl
  9. Bianchi, DW, et al. 2014. DNA Sequencing versus Standard Prenatal Aneuploidy Screening. N Engl J Med 370(9): 799–808.
  10. Norton ME, et al. 2015. Cell-Free DNA Analysis for Noninvasive Examination of Trisomy. N Engl J Med, 372(17): 1589–97.
  11. Gil, MM, et al. 2017. Analysis of Cell-Free DNA in Maternal Blood in Screening for Aneuploidies: Updated Meta-Analysis. Ultrasound Obstet Gynecol 50 (3): 302–14.
  12. Warsof SL, et al. 2015. Overview of the Impact of Noninvasive Prenatal Testing on Diagnostic Procedures. Prenat Diagn 35 (10): 972–79.
  13. Khalifeh A, et al. 2016. Trends in Invasive Prenatal Diagnosis: Effect of Sequential Screening and Noninvasive Prenatal Testing. Fetal Diagnosis and Therapy 39 (4): 292–96.
  14. Hui L, et al. 2017. Population-Based Impact of Noninvasive Prenatal Screening on Screening and Diagnostic Testing for Fetal Aneuploidy. Genetics in Medicine: Official Journal of the American College of Medical Genetics 19 (12): 1338–45.
  15. Fairbrother G, et al. 2016. Prenatal Screening for Fetal Aneuploidies with Cell-Free DNA in the General Pregnancy Population: A Cost-Effectiveness Analysis. J Matern Fetal Neonatal Med 29 (7): 1160–64.