The Story Behind GUARDIAN, a Groundbreaking Newborn Screening Study

We are proud to participate in the recently launched GUARDIAN (Genomic Uniform-screening Against Rare Diseases In All Newborns) study. The largest genomic newborn screening study to-date in North America, we are using whole genome sequencing to test 100,000 newborns in New York.

This method, not currently utilized routinely for primary newborn screening, will analyze for over 250 treatable conditions in newborns to equitably support and improve the health of the next generation of children.

In this Q&A, Dr. Paul Kruszka, Chief Medical Officer of GeneDx at Sema4, elaborates on the significance of the GUARDIAN study, its expanded menu of genes to screen for, and the main goal of the study. You can also read our press release to learn more.

What is the driving force behind the launch of the GUARDIAN study?

We are entering a new era of genomics and rare diseases, specifically focusing on treatment. Currently, “the diagnostic odyssey,” a timeline from when a disease starts until it is diagnosed, has caused irreparable damage to many children due to late diagnosis. GUARDIAN is a landmark study, providing us with the potential to shorten the diagnostic odyssey down to nothing for diseases that can be screened.

Newborn screening, especially with technologies like whole genome sequencing, along with the therapeutic options available for rare diseases, have driven us to join forces with four other entities to launch GUARDIAN. The study will enable the identification of diseases in infants before symptoms develop, providing us with a chance to treat them and prevent irreversible damage.

GUARDIAN is expanding the menu of diseases that you can screen for, and one of its premises is to screen for diseases that a treatment is available for. With whole genome sequencing, this allows for scaling because we’re sequencing the whole genome so we can pick whatever gene we want from this test. Going forward, this will allow us to continue to add new genes and new rare diseases to the screening for the next decade as tests become available.

GUARDIAN will radically change healthcare for children in the United States. Anyone working at Sema4|GeneDx should be proud of this study because we’re at the forefront of genomics, making a big difference in newborns and in population health.

What is the contributing role of Sema4|GeneDx in the study?

GeneDx has played an active role as a partner in the design of the study since the very beginning. Our initial contributions included a gene testing list, determining the process of extracting DNA from the patients and the exact samples to use, the sequencing of the samples, and data analysis. We participated in the study planning and test validation to ensure that everything will run smoothly.

Now that the study is designed and the tests are validated, we sequence all the samples, analyze the data, and generate reports to send back to the ordering providers in New York. We’re proud to play a big part in this process.

Where and how soon can parents enroll their newborns in the GUARDIAN study?

The study officially kicked off in New York City shortly after Labor Day. The first newborns have already been enrolled, with collected samples in the hundreds. Our goal is to test 100,000 newborns in New York.

This study is currently focused on New York City offering us the opportunity to screen a diverse population. A parent, regardless of income or health insurance, will have the option to enroll in the GUARDIAN study if their newborn baby is delivered in certain hospitals in New York City.  If the study is successful, then we believe whole genome sequencing will be adopted as the standard of care for newborn screening. It could result in similar programs in the rest of the state of New York, other parts of the U.S., and around the world.

When do you expect to have initial data points on the impact of the GUARDIAN study?

I think we will have preliminary data in 2023 covering the diagnostic yield, how the process goes, the consent rate, the participation rate, and more. Longitudinal data will come a little later.

The potential of the GUARDIAN study is profound. It’s almost mind boggling knowing that I’ve spent most of my career in the diagnostic odyssey, seeing children in clinics that could have been diagnosed a lot earlier in their lives with the proper diagnostic tools.

The key for me and our team is to eliminate the diagnostic odyssey. It is the ultimate goal of this study.


Sema4|GeneDx is a leader in genomic testing and analysis for rare disorders and helps to identify genetic variants responsible for genetic disorders and health risks. Our rapid genome and exome testing provides verbal results within 5-7 days and delivers clinically actionable test reports with fewer reported variants of uncertain significance due to our extensive database and deep clinical expertise. For more information on our whole genome and exome sequencing, please visit

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