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Advancements in Newborn Sequencing: Potential Impacts on Public Health

Since the early days of clinical genetics—when we had far over-estimated the number of human genes and long before the human genome had been sequenced—geneticists have been predicting a day when newborns could have all their DNA sequenced at birth to screen for medical conditions. While this is not reality for most newborns, the good news is we now have the technology available to achieve this vision. Groundbreaking newborn sequencing research programs are poised to collect data that will ultimately bring this advancement forward and positively impact public health.

In North Carolina, Early Check is a statewide newborn screening research study led by RTI International, in partnership with the University of North Carolina at Chapel Hill. To date, the Early Check program has screened over 25,000 newborns in North Carolina for spinal muscular atrophy, Fragile X syndrome, and/or Duchenne muscular dystrophy. Participation in Early Check has given parents the knowledge and power to know if their baby has any of these health conditions and allow for early clinical intervention if any of these conditions are identified in the screening.

As early as summer 2023, the Early Check research study will be expanding to offer genome sequencing to parents to screen for hundreds of genetic conditions, as well as genetic risk for type 1 diabetes. Babies born in North Carolina will be eligible to receive this screening at no cost. Preparation for the expansion has been underway for over two years, and many valuable insights have been gained along the way. There have also been many lessons learned that helped shape the newborn sequencing study.

Five Lessons Learned from Planning a Newborn Sequencing Study

1. Experts need to develop a consensus framework and/or a consensus list of genes that are appropriate for sequencing-based newborn screening.

In the next few years, over a dozen research programs across the globe will be examining the genomes of newborns. Each program has independently developed methods to determine which genes to analyze and return to parents. The result: different research programs are screening for somewhat overlapping, yet inconsistent, groups of genetic conditions. Despite this, researchers can take advantage of these variations to explore the pros and cons of including different types of genes—along with associated health conditions—in newborn screening. Before newborn sequencing enters public health, it will be vital to use the experience gained from Early Check and other pilot studies to develop a standardized framework and a consensus gene list to ensure consistency in what is screened.

2. Community engagement and preliminary research suggests that genome sequencing does not scare away (most) parents.

So far, community engagement with parents in North Carolina indicates that they are excited about having newborn sequencing as an option. Enrollment numbers coming from similar studies demonstrate that a large portion of eligible parents choose to enroll. However, there has been much consideration regarding the potential risks of genome sequencing, including possible challenges such as genetic discrimination, increased parent anxiety, loss of an open future, and the creation of a generation of patients-in-waiting. In addition to demonstrating the feasibility and clinical utility of genome sequencing, newborn sequencing research studies will collect critical data to assess the reality of these risks. It is important that research studies figure out how to reduce the risks before moving sequencing to public health.

3. For now, the cost of genome sequencing remains a limiting factor.

While the cost of genome sequencing has dropped considerably, it remains much too expensive to use for every newborn. Current project budgets include millions of dollars just for the sequencing needed for each baby. Public-private partnerships are vital in making these projects feasible and to sustain the research. The price of sequencing is expected to drop to about $200 per baby soon—this number should continue to decrease over time. The Early Check team plans to have critical data ready by the time sequencing becomes affordable for public health newborn screening.

4. Rapid genome sequencing will ultimately be crucial.

Public health newborn screening programs conduct screening and return results to parents and providers within days. That is important because for some conditions—such as Menkes disease—the window for optimal intervention is small and a delay in diagnosis by even a few weeks can have a significant impact on the newborn’s outcomes. The turnaround time for standard genome sequencing— while now faster than we could have imagined 20 years ago—is not yet fast enough for public health newborn screening. Rapid genome sequencing will allow newborn sequencing to achieve turnaround times that are consistent with current newborn screening programs. In turn, babies can benefit from the earliest possible intervention.

5. Newborn sequencing opens the door to incorporate risk for common health conditions.

Thanks to decades of studies to understand the genetic basis of common health conditions—such as type 1 diabetes and celiac disease—researchers can generate polygenic risk scores (PRS) that can be used to estimate the likelihood that a newborn will develop specific conditions in their lifetime. Currently, there are limitations in the application of these scores for a variety of reasons. First, there are other factors besides genetic predisposition that influence the likelihood that a person will develop a common health condition. PRS results are also much more uncertain than sequencing results for single gene conditions. In addition, there is limited validation of PRS in historically underserved racial and ethnic groups, but the scores will continue to get better over time. Because sequencing a baby’s genome automatically generates the data needed to calculate PRS scores, it is important to conduct research to understand the possible benefits and limitations of providing information about newborns’ risks for later onset of common health conditions.

Nominations Open for Early Check’s Genome Sequencing Panels

These insights and lessons learned will be invaluable when Early Check expands to make genome sequencing available to parents, which will open the door for hundreds of genetic conditions to be identified and for clinicians to provide appropriate early interventions. As the team moves forward into the summer launch, we are accepting nominations for conditions to include in Early Check’s sequencing panels. If there is a genetic condition you want to nominate for inclusion in Early Check, you can access and complete a short nomination form. If you're interested in speaking with one of our experts, contact us using the form below.

Disclaimer: This piece was written by Heidi Cope (Senior Research Genetic Counselor), Holly Landrum Peay (Senior Research Scientist), and Cindy Powell to share perspectives on a topic of interest. Expression of opinions within are those of the author or authors.