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January 03, 2022
Recent New York Times Coverage

Jan. 3, 2022

We are aware of a New York Times story published recently, which is focused on non-invasive prenatal screening for microdeletion syndromes. We want to share some additional context in order to provide the full picture.

  • Incorrect test accuracy claim removed: A summary of the article stated “screenings made by one large test maker, Natera, were incorrect about 85% of the time”. This is not true. In reality, our test is accurate in > 99% of cases. For example, in the SMART study, the largest prospective NIPT study ever conducted, we reported clinical results for 22q11.2 (22q) deletion syndrome to 18,014 patients, and we delivered a correct result to 17,982 of those patients (99.8%). Our results are even stronger with our new Panorama AI algorithm. In addition, we were able to successfully detect 75% of 22q deletions in the study, and 83% of cases with our improved algorithm. Importantly, the news outlet has now revised the summary article, removing this incorrect claim.
  • Performance claims lack context: The article describes the positive predictive value (PPV) of microdeletion testing as roughly 15% (1/8). While a false positive result can be difficult information for expectant families to receive, these PPVs compare favorably to historically accepted maternal serum based prenatal screening methods, which were used routinely on ~80% of all pregnancies for the past 40 years and are still recommended by ACOG today. In fact, historically accepted prenatal screening tests have a PPV around 3-5% (1/33-1/20) for chromosomal conditions. In contrast, Natera’s microdeletion test has PPVs ranging from ~5% to 50%, depending on the specific microdeletion syndrome being screened. The most common microdeletion syndrome, 22q, accounts for greater than 90% of our microdeletion orders and has a demonstrated PPV of 50% (1/2) using the latest version of Panorama tested in the SMART study. Using a weighted average PPV of all microdeletions (taking into considering how often they are ordered, and incidence) we screen is far higher than the 15%, quoted by the article.
  • Ignores the important role of screening tests: The purpose of screening tests like NIPT is to identify the subset of high risk individuals. In the general population of pregnancies the risk of 22q11.2 deletion syndrome is 1 in 2,000. Less than 1% of patients will have a high risk result for 22q on Panorama and if they do, the PPV is 1 in 2 (50%) with the current Panorama algorithm. The risk adjustment, from 1 in 2000 to 1 in 2 helps identify those who may need a diagnostic procedure to confirm the health of their pregnancy. The PPVs are lower for the other microdeletion tests, which account for a smaller portion of the test orders, but the concept remains the same. For example, cri du chat syndrome has an incidence of 1/20,000 in the general population and a PPV of ~5% (1/19). For this disorder, significantly less than 1% of patients will screen positive, identifying a small high risk cohort of patients who have a risk of 1 in 19 for the disorder and may benefit from a diagnostic procedure. Patients who screen positive should be referred to a specialist to consider confirmatory diagnostic testing such as amniocentesis, a procedure which ACOG recommends should be offered to all women, independent of their prior risk.
  • Ignores clinical utility and prevalence of the most common microdeletion: The story is focused on one aspect of the test performance (PPV) without context of the clinical impact on detecting affected pregnancies. For example, for 22q, the most common microdeletion syndrome, families spend an average of 4.7 years searching for a diagnosis, which is a very stressful experience. There are proactive measures that can be taken after birth that can improve the lives of individuals with the diagnosis of 22q11.2 deletion syndrome. These measures include delivery at a hospital with appropriate specialists where babies can have life-saving interventions such as heart surgery, as well as treatment for hypocalcemia to improve cognitive outcomes. It’s also important to point out that not all microdeletions are rare: the incidence of 22q11.2 deletion syndrome, at ~1 in 2000 pregnancies is more common than some other conditions for which ACOG currently recommends broad screening for such as cystic fibrosis, spinal muscular atrophy – which have an incidence between ~1/3500 to ~1/10,000.
  • Natera takes a responsible approach to managing positive results: We require a licensed physician to order tests, and we don’t perform testing unless a physician signs the requisition indicating that the patient has consented to testing. In addition, we put the PPV for each condition directly onto the patient report with a recommendation for confirmatory diagnostic testing, so physicians can discuss the results with their patients. We also believe all patients should have access to genetic counseling resources during their pregnancies – and Natera provides complimentary genetic information sessions so patients can speak directly to board-certified genetic counselors before or after their testing. While we’ve made significant effort to ensure we provide appropriate educational material and we believe we are transparent with our performance, we are committed to doing more to help educate patients about the performance of NIPT.

Natera has worked tirelessly to innovate and improve NIPT on behalf of patients and has invested significant R&D resources into improving the historically accepted PPVs of 3-5% for chromosomal conditions; today Natera can demonstrate PPVs > 90% across all age cohorts for the most common chromosomal condition. Natera is committed to providing robust evidence of the real-world performance of our tests. We conducted the largest multi-site prospective trial ever performed in the field of NIPT and microdeletions, and have published more than 100 peer-reviewed publications to demonstrate the performance of our portfolio of tests. We are incredibly proud of the impact our testing has on families during critical health moments.