Benzinga | Jan 20, 2022 08:38AM EST

Natera's Highlights SMART Study; Says Study Demonstrates High Accuracy Of Co's Panorama NIPT For 22q11.2 Deletion Screening

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.