AUSTIN, Texas--(BUSINESS WIRE)--Natera, Inc. (NASDAQ: NTRA), a leader in personalized genetic testing and diagnostics, today announced the publication of the landmark SMART study in the American Journal of Obstetrics and Gynecology (AJOG), one of the world's leading Obstetrics and Gynecology medical journals. The SMART study enrolled more than 20,000 patients at 21 medical centers globally and is the largest prospective non-invasive prenatal testing (NIPT) study ever performed. All results included in the analysis were validated with genetic confirmation. This publication focuses on the performance of SNP-based NIPT (Panorama) to screen for 22q11.2 deletion syndrome (22q11.2DS); a separate publication will report on test performance for the common aneuploidies.1 The authors state that, “this study shows that prenatal screening for 22q11.2DS with SNP-based cfDNA has high sensitivity and specificity in a diverse, real-world population. These findings demonstrate that routine noninvasive prenatal screening with cfDNA for genetic disorders beyond aneuploidy is possible with high accuracy.”
Key findings include:
- 22q11.2DS had a higher-than-expected prevalence of 1/1,524 pregnancies in this cohort. This is comparable to other conditions broadly recommended for routine screening, such as cystic fibrosis (~1 in 2,500).2-3
- Panorama was able to detect all cases of the most common (2.5-3Mb) 22q11.2DS, and 83% of all 22q11.2DS.
- Panorama’s false positive rate was low, 0.05%, resulting in a positive predictive value (PPV) of 53% or 1 in 2. For context, historical serum screening tests have PPVs of ~3% or 1 in 29 for trisomy 21.4
- None of the patients with a pregnancy affected by 22q11.2DS had an abnormal first trimester ultrasound, highlighting the unique potential of NIPT to add valuable information early in pregnancy.
When discussing the value of screening for 22q, the authors concluded that, “the PPV of cfDNA for 22q11.2DS is higher and the false positive rate is lower than that associated with other accepted screening tests such as traditional first trimester combined screening, and comparable to cfDNA screening for some of the aneuploidies.” They went on to add that, “positive screening tests should be followed by a diagnostic test.”
“Testing for 22q makes sense due to the high prevalence of the condition and because treatment at the time of birth may improve outcomes. Because 22q is relatively common, and the false positive rate is low, the PPV is higher than with the very rare microdeletions,” said Mary Norton, M.D., professor, UCSF, and one of the principal investigators of SMART. “It is critically important that testing be combined with appropriate counseling from a genetic counselor, or from a nurse or physician with adequate training in genetics so that patients understand the limitations of the test and the need for diagnostic follow-up.”
"The SMART study evaluated real-world performance of cell-free DNA-based non-invasive prenatal screening for the 22q11.2 deletion syndrome in a large, prospective trial with complete tracking of outcomes," said Pe’er Dar, M.D., Montefiore Medical Center, Bronx NY, and the other principal investigator in SMART. "The 22q11.2 deletion syndrome, also known as DiGeorge syndrome, is a leading cause for congenital heart defects and neurodevelopmental delay, and is actually more common than Down syndrome in young women.5-7 We found that about 1 in 1,500 pregnancies was affected with this syndrome, and the SNP-based NIPT accurately identified most of the cases, with a low false positive rate. The findings of this study support, for the first time, an expansion of routine prenatal screening to include screening for a chromosomal microdeletion such as the 22q11.2 deletion syndrome. Parents who screen positive will have to be counseled and offered a diagnostic test such as CVS or amniocentesis. A confirmed prenatal diagnosis of this syndrome will not only be informative to parents but may also improve the outcome of the affected infants."
The authors note that “the importance of 22q11.2 is evident given the significant clinical sequelae and prevalence that is higher than some of the currently screened aneuploidies.8 Moreover, the long-term sequelae associated with 22q11.2DS, such as autism spectrum disorder and schizophrenia, and the potential benefits of early neonatal therapy for hypocalcemia and immune deficiency, justify consideration of prenatal screening.”9-11
“Prompt diagnosis can play an important role in improving the quality of life for individuals affected by 22q11.2 deletion syndrome. The 22q11.2 community therefore supports early identification including via prenatal and neonatal screening,” said Professor Donna McDonald-McGinn, 22q11.2 society chair, Children's Hospital of Philadelphia, and University of Pennsylvania. “Importantly, prenatal suspicion of 22q11.2 deletion syndrome allows for evaluation, confirmatory testing, and delivery at high-level healthcare facilities where neonates have access to potentially life-saving interventions including cardiac surgery, as well as treatment for other key features such as low calcium, immune deficiency, feeding, swallowing and breathing issues, all with the goal of optimizing long-term outcome while obviating the protracted diagnostic odyssey frequently traversed by families.”12-14
To learn more about the impact of 22q deletion screening for affected patients and their families, click here for a patient story.
Panorama reveals a baby’s risk for severe genetic disorders as early as nine weeks into pregnancy. The test uses a unique single-nucleotide polymorphism (SNP)-based technology to analyze fetal/placental DNA obtained through a blood draw from the mother. It is the only commercially available test that differentiates between maternal and fetal DNA to assess the risk of aneuploidies. The test also screens twin pregnancies for zygosity and fetal sex of each baby, and identifies risk for more genetic conditions in twin pregnancies than any other NIPT. Panorama is one of several genetic screening tests from Natera designed to help families on the path to parenthood. Natera has published 24 papers, studying over 1.3 million patients, since the launch of Panorama – the largest body of evidence in the space today. Panorama has been developed and its performance characteristics determined by Natera, the CLIA-certified laboratory performing the test. The test has not been cleared or approved by the US Food and Drug Administration (FDA). CAP accredited, ISO 13485 certified, and CLIA certified.
Natera™ is a global leader in cell-free DNA testing, dedicated to oncology, women’s health, and organ health. Our aim is to make personalized genetic testing and diagnostics part of the standard of care to protect health and enable earlier and more targeted interventions that help lead to longer, healthier lives. Natera’s tests are validated by more than 100 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas and San Carlos, California. For more information, visit www.natera.com.
All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera’s recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov.
- Dar P, Jacobsson B, Clifton R, et al. Cell-free DNA screening for prenatal detection of 22q11.2 deletion syndrome. AJOG, 2022 in press.
- Hamosh A, FitzSimmons SC, Macek Jr M, Knowles MR, Rosenstein BJ, Cutting Gr. Comparison of the clinical manifestations of cystic fibrosis in black and white patients. J Pediatr. 1998;132(2):255-259.
- O’Sullivan BP, Freedman SD. Cystic fibrosis. Lancet. 2009;373(9678):1891-1904.
- 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.
- Botto LD, May K, Fernhoff PM, et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics. 2003;112(1 Pt 1):101-7.
- Olsen L, Sparsø T, Weinsheimer SM, et al. Prevalence of 453 rearrangements in the 22q11.2 region and population-based risk of neuropsychiatric and developmental disorders in a Danish population: a case-cohort study. Lancet Psychiatry. 2018;5(7):573-580.
- McDonald-McGinn DM, Sullivan KE, Marino B, et al. 22q11.2 deletion syndrome. Nat Rev Dis Primers. 2015;19:1:15071.
- Gregg AR, Skotko BG, Benkendorf JL, 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;18:1056–1065.
- Morrow BE, McDonald-McGinn DM, Emanuel BS, Vermeesch JR, Scambler PJ. Molecular genetics of 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(10):2070-2081.
- Dugoff, L, Mennuti, MT, McDonald‐McGinn, DM. The benefits and limitations of cell‐free DNA screening for 22q11.2 deletion syndrome. Prenat Diagn. 2017;37(1):53–60.
- Quartermain MD, Hill KD, Goldberg DJ, et al. Prenatal Diagnosis Influences Preoperative Status in Neonates with Congenital Heart Disease: An Analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Pediatr Cardiol. 2019;40(3):489-496.
- Bassett AS, McDonald‐McGinn, DM, Devriendt K, al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011;159(2): 332–339.
- Cheung ENM, George SR, Andrade DM, et al. Neonatal hypocalcemia, neonatal seizures, and intellectual disability in 22q11.2 deletion syndrome. Genet Med. 2014;16(1):40-44.
- Grand K, Katz LEL, Crowley TB, et al. The impact of hypocalcemia on full scale IQ in patients with 22q11.2 deletion syndrome. Am J Med Genet A. 2018;176(10):2167-2171.