Proceedings of a Workshop—in Brief

The Promise and Perils of Next-Generation DNA Sequencing at Birth

Proceedings of a Workshop—in Brief

Since the 1960s, when many states in the United States piloted newborn testing for phenylketonuria (PKU) and subsequently enacted screening laws, public health newborn screening (NBS) programs have successfully reduced morbidity and mortality among children with inborn errors of metabolism (Friedman et al., 2017). The widespread adoption in the 1990s of tandem mass spectrometry (MS/MS) as the primary screening methodology greatly expanded the number of metabolic disorders that could be detected. Today, newborn genome sequencing, if added to public health NBS, is poised to further increase the number of detectable disorders (Bick et al., 2022). However, sequencing newborns raises a host of ethical, legal, and social questions as well as practical and logistical hurdles for adoption and implementation, as either a part of public health programs or a complement.

Given the rise in programs employing whole genome sequencing (WGS) and whole exome sequencing (WES) during the newborn phase around the country and internationally, the National Academies of Sciences, Engineering, and Medicine’s Roundtable on Genomics and Precision Health brought together experts from health care, industry, academia, the federal and state governments, and patient and consumer advocacy groups to discuss these issues during a public workshop on June 7, 2023. The main goal of the workshop, noted Natasha Bonhomme, founder of Expecting Health, a program of Genetic Alliance, was to examine the use of DNA sequencing to supplement traditional NBS for conditions that are treatable but not clinically evident in the newborn phase. Additionally, the workshop aimed to (1) examine known and expected benefits, and potential harms, of widespread utilization of newborn genome sequencing; (2) explore ethical, data security, and ownership issues associated with DNA sequencing of newborns at birth; and (3) address issues of next-generation NBS (e.g., sequencing) equity in the United States.

Research is underway to understand people’s reactions to, desires for, and concerns about newborn genome sequencing. It is important to have conversations about what it means to ensure that families receive the best of newborn genome sequencing while recognizing the fundamental questions of whether such testing should be done, Bonhomme said. In the workshop, discussions focused on sequencing in healthy newborns, not those who are critically ill, and on how it can be implemented responsibly and equitably, rather than if it should be implemented at all (Box 1).

KEYNOTE ADDRESS

The workshop was framed with key questions related to how newborn genome sequencing may be integrated into clinical and public health settings. Aaron Goldenberg, professor and vice-chair in the Department of Bioethics at Case Western Reserve University School of Medicine, began by discussing important distinctions between sequencing in clinical and research program settings versus within current public health NBS programs and how these distinctions have important implications for informed consent, return of results, and follow-up care. NBS practices and policies and families’ experiences may also inform the implementation strategies for newborn genome sequencing programs. Goldenberg raised key questions that are crucial for addressing the practice and policy challenges associated with genomic newborn sequencing.

Questions related to screening healthy versus sick newborns and the use of genomics as a preventative measure versus identifying the cause of an undiagnosed illness were discussed, followed by issues of assessing utility and how genomic information may be used to inform clinical and personal health decisions. Questions were also posed about the data that would be generated and how results may be returned to families. For example, should the full genome be sequenced at birth or targeted sequencing be used throughout the lifespan to screen for particular conditions at specific ages? Who should be responsible for analyzing raw data, what should parents receive, when should results be returned, who should deliver that information to families, and how? When a child may have a condition, parents cope with myriad issues—from screening to diagnosis to confirmation to treatment. How can support services be provided throughout this ongoing process? Because newborn genome sequencing will reveal information about gene variants that may never lead to disease in an individual, could it create “patients in waiting”? What, Goldenberg asked, would be the psychosocial impacts?

Pressing issues exist around the privacy and security of newborn genome sequencing data, including how they will be shared and used and what should happen to samples, raw data, and analyzed data after screening is completed. How can the system encourage ethical stewardship of NBS and genome sequencing data, and how can trust be promoted? “We need to establish a culture where equity and ethics are foundational and fully integrated into research, translational, and care pathways,” Goldenberg said. Those who work in these fields could promote regulatory structures and health care systems that support these changes, build robust educational engagement strategies where the viewpoints of parents are heard, and integrate parent and community views into changes throughout the process, he suggested.

CONSIDERING THE BENEFITS AND RISKS OF NEWBORN GENOME SEQUENCING

State NBS programs face tradeoffs due to the limited money spent on public health programs, said Ellen Wright Clayton, the Craig-Weaver Professor of Pediatrics and professor of health policy at Vanderbilt University Medical Center and professor of law at Vanderbilt Law School. If resources are diverted to newborn genome sequencing, less money would remain for other programs. Although state NBS programs do a remarkable job of follow-up, access to interventions can be spotty and sometimes costly, she said. Some considerations for newborn genome sequencing include knowing what to look for and whether the newborn period is the only possible stage; Clayton noted that screening for different conditions during multiple life stages may be more beneficial.

Participants were cautioned against over indexing on the potential negatives, risks, and challenges of implementing WGS in healthy newborns by Robert Green, professor of medicine at Harvard Medical School. The utility and cost-effectiveness of sequencing will be challenging to define due to the thousands of genes in a genome, multitude of variants for each gene, and variety of ways that clinicians and families interpret and use genomic information they receive. Surveys have shown that 70 percent of parents want genomic information (Goldenberg et al., 2014), but its benefit over the lifetime of a child and within that child’s family is not yet valued.

Parents perceive the benefits and harms of NBS differently, said Mike Hu, cofounder of Project GUARDIAN and adjunct associate research scientist

at Columbia University. Harms are “widely defined,” such that parents may consider negative feelings from a false positive result to be a harm. However, benefits are identified more narrowly and focus mostly on the therapeutic benefits screening provides by increasing early diagnosis and treatments. Many benefits of NBS, as seen by parents, are not routinely counted as such; for example, the positive psychosocial impacts of avoiding a lengthy diagnostic odyssey. When screening yields a diagnosis, often nonpharmaceutical interventions can begin, which carries significant benefits. As a parent and advocate of a child with a rare disease, Hu noted that NBS is about what the results mean to not just the child but also the child’s family, who bear the brunt of the psychosocial impacts and provide the bulk of their care. Families need to be involved in decision making around

NBS from beginning to end; maintaining the status quo is failing affected families, he said.

Models of Newborn Genome Sequencing

Acknowledging that the successful and equitable deployment of newborn genome sequencing is complex, Amy Gaviglio, founder, genetic counselor, and public health genetics and rare disease consultant at Connetics Consulting, LLC, described four possible use models for newborn sequencing in the future:

• “As-indicated”: it is used to identify a genotype associated with a present phenotype, such as in the neonatal and pediatric intensive care units;
• Replacement: it would, when applicable, replace what is being used for standard NBS;
• Adjacent: it would be used as a supplement to traditional NBS; and
• Lifespan: data produced are applied across the lifespan.

Gaviglio emphasized the importance of clearly defining key terms (e.g., “education” and “trust”) because they may mean different things to different people. “Newborn screening,” for example, could mean the current mandated public health screening or consented genome sequencing. She asked participants to consider what can be learned from the experiences of people working in the current NBS system, pilot programs investigating the logistics of establishing small-scale newborn sequencing programs, and feedback from the many relevant groups, such as parents, clinicians, state public health workers, regulators, patient advocates, and industry.

IMPLEMENTING NEWBORN GENOME SEQUENCING PROGRAMS: LESSONS LEARNED FROM PILOT PROJECTS

BeginNGS¹

To make progress toward eliminating the diagnostic odyssey for families, work at Rady Children’s Hospital has resulted in BeginNGS, said Nathaly Sweeney, assistant professor of pediatrics at the University of California, San Diego and an investigator with the Rady Children’s Institute for Genomic Medicine. BeginNGS is an AI-analyzed genome sequencing system that uses training and adaptive learning to deliver precision medicine information to families affected by rare disease. The intent is to automate many of the processes in the genomics screening pipeline, which should facilitate scaling up newborn genome sequencing and its followup. However, there are currently barriers to using BeginNGS equitably and at scale. For example, the incidence of rare disorders and the variant spectrum within genomes vary among races, ethnicities, and ancestries, but the current reference data skew toward people of Northern European origins, Sweeney said. Additionally, the incidence, natural history, and clinical utility of interventions for ultra-rare disorders are poorly understood.

NC NEXUS²

Cynthia Powell, professor of pediatrics and genetics at the University of North Carolina at Chapel Hill School of Medicine, discussed the decision aids that were developed for recruiting families into the North Carolina Newborn Exome Sequencing for Universal Screening (NC NEXUS) program. Parents used these tools to learn how newborn genome sequencing provides information distinct from other NBS methods and found them easy to use, trustworthy, and helpful (Paquin, 2019). Although the decision aids were useful, to be successful at a public health scale, she noted, more information will be required to share with families before birth. Powell highlighted additional benefits and challenges to sequencing. Some benefits are the ability to expand the range of detectable conditions, decrease false positives, and identify the molecular basis of certain conditions, which allows for specific diagnoses and effective treatments. One challenge is the inability to know the clinical validity of these results in a population of healthy newborns, because of uncertainty about the penetrance for each pathogenic molecular variant detected.

The NBSeq Project

Steven E. Brenner, professor of plant and microbial biology, bioengineering, and molecular and cell biology at University of California, Berkeley and adjunct professor of bioengineering and therapeutic sciences at University of California, San Francisco, described findings from the

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UCSF NBSeq Project. It evaluated the effectiveness of WES to screen for inborn errors of metabolism compared with the specificity and sensitivity of current NBS by tandem MS/MS. Researchers found that in 88 percent of cases, automated WES analysis successfully identified gene variants that could be the underlying cause of a disorder, when assessed against clinical diagnosis. However, tandem MS/MS offered an order of magnitude higher sensitivity and specificity than WES (Adhikari et al., 2020). Some sensitivity issues were attributable to using WES rather than WGS, for example, since large deletions went undetected. Another challenge was interpreting the significance of point variants, especially in noncoding regions. The number of missed cases makes exome sequencing unsuitable to replace current NBS technology. However, exome data can provide essential additional information to a clinician when NBS identifies a disorder. As NBS results may drive treatment development, adding genomic technology to newborn screening is an opportunity to advance that cycle, said Brenner. In many pilot projects, participant diversity is limited. However, in NBSeq, researchers sampled nearly all affected newborns in California from 2005–2013 (Adhikari et al., 2020), and revealed that NBSeq appeared less effective at identifying variants from populations underrepresented in previous studies.

The BabySeq Project³

Comprehensive genome sequencing will likely yield a world of useful medical information, Green said, so universal newborn sequencing may have great advantages. The BabySeq Project is a randomized trial examining the utility of newborn genome sequencing. In the first phase, researchers found that 11 percent of sequenced infants had unanticipated monogenic disease risks (Ceyhan-Birsoy et al., 2019), and these findings were all actionable (Green et al., 2023). After genomic results were returned, parents who consented to have their newborn sequenced had no measurable increases in distress or significant increases in health care costs (Pereira et al., 2021). Furthermore, genomic information from the newborn informed the health of the entire family. For example, three newborns in BabySeq were discovered with adult cancer predispositions, and all three mothers also carried these predispositions. After a 5-year follow-up, each woman had undergone risk-reducing surgeries (Green et al., 2023).

Early Check⁴

Early Check is a North Carolina–based research program that expands the state’s public health NBS program to screen for additional rare but serious early childhood–onset health conditions, said Holly Peay, senior research scientist at RTI International and director of the Early Check Program. Genome sequencing will be added to the study later in 2023 but deciding which results to return has been one of the most significant challenges. Surveying found that even if a condition was not currently treatable, parents wanted to know because they would advocate for treatment development to benefit their child, said Sylvia Mann, supervisor of the Genomics Section at the State of Hawaii Department of Health. Many relevant parties in this process could collaboratively develop a consensus framework and decision-making process to identify the gene/disease pairs that are appropriate to return using genome sequencing, Peay noted.

The numerous sources of uncertainty associated with newborn genome sequencing will make it more difficult to achieve the best clinical and psychosocial outcomes. This is a long-term challenge that will require thoughtfully developing educational tools to understand benefits and limitations and cooperative engagement among parties such as geneticists, clinical specialists, ethicists, families, and primary care providers, Peay said. Educational materials will also be needed for nongeneticist clinicians so they can better interpret the results, effectively communicate with families about the results’ meaning, and understand the options for results that require near-term action. As evidence is collected to address these complex issues, longer-term precision health outcomes could be envisioned, she suggested. Newborn sequencing could identify hundreds to thousands of rare genetic disorders using a single test and advance drug development while supporting the broadest access to treatment and research options. She mentioned both opportunities to improve public health by incorporating risks for common health

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conditions into sequencing-based NBS and challenges and concerns to be studied and addressed.

IMPLEMENTING NEWBORN SEQUENCING AT SCALE

While speakers discussed the benefits of newborn genome sequencing based on experiences in pilot studies, challenges to large-scale implementation were focused on health care systems. Speakers highlighted challenges including expanding and diversifying the workforce (Box 2); alleviating the pressure on existing NBS programs; navigating the complexities of paying for and ensuring value from newborn genome sequencing; and managing data privacy and security.

Preserving the Existing NBS System

A research study of 42 experts, representing multiple relevant groups within the NBS system, identified challenges to modernizing the NBS public health system, Peay noted. Respondent concerns included the need for new infrastructure and expertise, coordination across multiple governmental agencies, and funding to revise the system to integrate technologies such as WGS (Andrews et al., 2022). Adding genome sequencing to NBS will strain an already overtaxed system, she said. Expanding pilot studies to test implementation models could provide evidence to help decision makers see what works well and what challenges remain. Another possible solution is public–private partnerships or regional public health laboratories where resources and expertise can be shared and the burden on NBS systems can be reduced, Peay said. Despite equity in state NBS programs, a challenge raised by multiple speakers throughout the workshop was the inequities in the health care system,

particularly in follow-up care. If genome sequencing creates additional demands on the system, existing inequities are likely to be exacerbated, especially for families with low health literacy or whose first language is not English, said Mann.

Exploring Cost

A major consideration in health care is how much tests and treatments cost in relation to their benefits, said David Veenstra, professor in the Department of Pharmacy and the Comparative Health Outcomes, Policy & Economics Institute at the University of Washington. Payors are pushing for value and cost-effectiveness. A study examining the cost-effectiveness of universal genomic screening for several adult-onset conditions found that it was better to test closer to 20 years of age (Guzauskas et al., 2023), implying less relative value in screening newborns for adult-onset conditions. When considering economic value of genomic sequencing of newborns, prevalence is the most important factor, he said; sequencing for the most prevalent and actionable conditions and combining conditions can help achieve the most economic value.

Managing Genetic Privacy

Crystal Grant, former Technology Fellow at ACLU Speech, Privacy, and Technology Project, raised concerns about the loss of genetic privacy that genome sequencing has created. Due to that and the potential for unethical data misuse and abuse, in particular the ease with which law enforcement can access and use genomic data without the person’s consent or knowledge, universal newborn genome sequencing carries too great a risk, said Grant. Genomic data will be used by law enforcement to disproportionately target Black and Brown Americans, she cautioned, citing a current lawsuit on the topic.⁵ Without laws in place that control access to personal genomic data, abuses by law enforcement will continue, Grant added. There are also concerns that personal genomic information could be used to discriminate against people, Powell noted. Additionally, work from the Brenner lab has shown that even when functional genomics data are anonymized to current standards and made publicly available, it is sometimes possible to reidentify the source of the data, putting research participants’ privacy at risk.

WORKING WITH FAMILIES: RESPONSIBLE AND EQUITABLE DEPLOYMENT

How can groups that have been and continue to be mistreated, underrepresented, and underserved in both research and health care be respectfully engaged, asked Faith Fletcher, assistant professor in the Center for Medical Ethics and Health Policy at Baylor College of Medicine and a Greenwall Foundation Faculty Scholar in Bioethics. “If we’re interested in engaging and including Black infants and newborns in screening, we have to engage Black mothers and Black women in the conversation,” she said. Asking questions, such as about how Black women want to receive genomic information, is a step toward righting the health care system’s history of untrustworthy behavior toward Black people and other marginalized people, she added. To facilitate a shift toward trustworthiness, Fletcher noted, the responsibility lies with researchers and health care professionals to engage communities in ways that elicit suggestions and begin to build trust.

Fletcher proposed steps for advancing genomics health equity:

• Modeling meaningful partnerships and engagement efforts to “move us forward”;
• Prioritizing and respecting the perspectives, moral agency, expertise, and local knowledge of socially marginalized groups through authentic engagement;
• Engaging in cross-disciplinary collaboration, critical reflection, and courageous conversations;
• Using empirical data to generate more scholarship on the many aspects of newborn genome sequencing, including its ethical, legal, and social issues, and informing evidence-based guidance;
• Advocating for specific funding opportunities that strengthen community-driven agendas for genomics and precision medicine in underserved communities; and

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• Creating opportunities to train the next generation of culturally competent health equity scholars, researchers, and practitioners.

There are opportunities to advance equity in NBS and health care, said Cheedy Jaja, assistant dean for Global Engagement and associate professor at the University of South Florida College of Nursing. Specifically, state NBS programs have a communication gap, partially because they are mandated by law. Families need to understand the benefits of NBS and the harms of not participating, such as a missed diagnosis which could have led to life-altering treatments. Nurses are well positioned to assist in communicating and guiding parents through the challenges of NBS and newborn genome sequencing. The legal mandate, where screening occurs without informed consent from parents, also referred to as an opt-out system, will likely come under stress when genome sequencing of newborns becomes commonplace. Sequencing will require more explicit informed consent from parents, likely best received before birth. To combat this stress, he suggested that a new model be created for how relevant parties are engaged and which voices are heard. It should focus on empowering and engaging parents and community leaders so that they have an active stake in NBS programs.

Participants heard from one such community leader, Teonna Woolford, CEO of Sickle Cell Reproductive Health Education Directive. Woolford is a patient advocate who was diagnosed with sickle cell disease (SCD) through traditional NBS. Woolford had her genome sequenced as an adult to determine her risk for developing leukemia. She and her family waited 4–6 weeks for the results, during which time she mused about whether knowing her risk would empower her or cause her to live in fear. She discussed the emotional toll the wait took on her and her family and suggested that access to mental health counseling would have been valuable.

Woolford expressed concerns about the social and economic world not keeping pace with scientific advancements. More than 60 percent of people with SCD are on public insurance, which means they do not have access to the same resources as those with more means. How can the system ensure genome sequencing is accessible and care is equitable for those who are traditionally underserved? The medical and research community has lost the trust of the SCD community, she said, highlighting her experience of how health care professionals weaponized her knowledge against her, labeling her as drug seeking when she communicated which narcotics work for her. This lack of trust has also arisen from having only one FDA-approved therapy for SCD for 30 years. People in the SCD community need to be educated on the full scope of what sequencing is and is not. Empowering SCD patients with knowledge enables them to make informed decisions. Finally, she noted, there are benefits to speaking directly with affected communities, ask them what their needs are and how they want to receive genomic and educational information.

Patient advocacy organizations can have large impacts for their communities. The work of the National MPS Society was discussed by Terri Klein, president and CEO of the organization. Its Pathways program provides comprehensive support, including medical, clinical, financial, and mental health support, to families whose child has been diagnosed with mucopolysaccharidosis (MPS). Through efforts by the society, MPS I and MPS II are now both on the recommended uniform screening panel and screened for in many states. The society’s patient advocacy work improves outcomes by educating families about the benefits of NBS and newborn sequencing. However, the society recently investigated the reach of its program and discovered that it was only serving 40 percent of families affected by MPS. It examined demographics of those families, revealing a significant gap within underrepresented groups. This led to reorganizing how and where the society performs outreach. It also enacted internal changes to increase the diversity of its leadership and staff, Klein said. For the society to fulfill its mission, it aims to address disparities in outreach, education, and follow-up care in all populations affected by MPS.

NEWBORN SEQUENCING AND THE FUTURE OF PRECISION HEALTH

Speakers explored the question; can newborn sequencing change the trajectory of precision health? Work from

the Mount Sinai BioMe biobank, which reflects the population diversity in New York City, was presented by Noura Abul-Husn, vice president of genomic health at 23andMe and associate professor of medicine at the Icahn School of Medicine at Mount Sinai. Disparities exist in who is aware of their genetic risks, due to patient-, provider-, and system-level barriers to accessing clinical genetic testing and other factors, including medical and family histories and whom the biomedical and clinical communities perceive as high-risk populations, said Abul-Husn. She argued that universal newborn sequencing could address certain disparities.

A study focusing on how genomic data could be used across the lifespan compared WGS to targeted gene panels. It found that WGS was twice as likely to identify positives and likely positives (Abul-Husn et al., 2023). However, all racial and ethnic groups did not benefit equally from this improved detection. People who identified as Black or African American had no significant improvement in the diagnostic yield and there were high rates of inconclusive results (Abul-Husn et al., 2023). The lag in the ability to interpret genetic data from certain racial and ethnic populations is preventing screening’s benefits from being equally accessible for everyone, she said.

Genomic data obtained at birth may be used to make early diagnoses, predict and prevent disease, and aid in personalizing treatment across the lifespan. However, equity and access to genomics-driven personalized medicine for everyone could be ensured, Abul-Husn suggested, by the biomedical and clinical communities

• improving knowledge of genomic variation in diverse populations,
• piloting genomic screening programs that promote health equity,
• educating health care professionals in genomic medicine, and
• implementing genome-informed care in routine clinical practice.

David Bick, principal clinician for the Newborn Genomes Programme at Genomics England (a company owned by the UK Department of Health & Social Care), discussed the Generation Study,⁶ its newborn genome sequencing pilot study. The program offers an example of how sequencing might be implemented at a large scale in the United States. Working groups are charged with the logistics for study components, such as deciding what conditions should be evaluated, recruiting participants, addressing ethical issues, and ensuring that the conditions have treatment options that can be accessed equitably by all participants. In deciding what conditions to screen for, the study adheres to four “core principles”:

1. Strong evidence shows that the genetic variant(s), both pathogenic and likely pathogenic, causes the condition and can be reliably detected.
2. A high proportion of individuals who have the genetic variant(s) would be expected to have symptoms that would have a debilitating impact on quality of life if left undiagnosed.
3. Early or presymptomatic intervention for the condition leads to substantially improved outcomes in children, compared to intervention after the onset of symptoms.
4. Conditions screened for are only those for which the interventions are equitably accessible for all.

Several aspects to successful implementation of newborn genome sequencing were reviewed by Bick. First, analytic and clinical validity: labs and clinicians want to ensure that the interpreted results can be validated by an independent test. Second, proper data storage and use: communities want to trust that data are properly protected and is used “sensibly” to care for children. Finally, improving health outcomes: if states administer the programs, they will likely want evidence that genome sequencing will improve health for children and save money, Bick said.

Is enough known about newborn genome sequencing to say with confidence that a universal state newborn

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screening program will provide more benefit than harm, and that it will substantially improve public health given limited resources, asked Jeffrey Brosco, director for the Division of Services for Children with Special Health Needs at the Health Resources and Services Administration’s Maternal and Child Health Bureau, U.S. Department of Health and Human Services.⁷

In the 1960s, when state NBS programs began screening every newborn for PKU, many of the same ethics and policy questions that are being asked now about genome sequencing were raised about NBS. In the 1990s, tandem MS/MS was a significant technological disruption that expanded the number of conditions that could be screened for but did not significantly alter the public health model of state NBS, Brosco said. Similarly, genome sequencing will likely cause a technological disruption but may not shift the public health approach, he speculated, because state NBS programs could continue to focus on their historical role to identify conditions that require intervention, sometimes urgently. However, genome sequencing also has the potential to transform the state NBS system by providing genetic information that some families will find valuable, even if the benefits are indirect, Brosco continued.

No matter which genome sequencing is applied by state NBS programs, attention should be given to the care navigation pathway, Brosco noted. Every child who screens positive for a NBS condition should receive appropriate short- and long-term follow-up, he said, highlighting the goals of MCHB’s Blueprint for Change for CYSHCN.⁸ The Blueprint has four components: quality of life, access to services, financing of services, and health equity. As applied to state NBS programs, the goal is an equitable, interconnected system involving multiple partners, including federal and state agencies, to ensure that children identified with NBS conditions receive the services they need so they can play, go to school, and become healthy adults—and their families can also thrive, Brosco explained.

FINAL REFLECTIONS AND CLOSING REMARKS

The final session offered panelists an opportunity to reflect on the day’s discussions, their comments, and how this community of professionals and colleagues can work toward ethics, equity, and ensuring that support services are accessible for all families who need them (Box 3).

In considering the rollout of newborn genome sequencing, Bonhomme emphasized the critical role of engaging affected families and those who have been historically underserved, to understand what they perceive as the most valuable gains. Despite the valuable results obtained from the numerous pilot projects, no “set of best practices” exists for implementation at scale. State NBS programs are largely equitable (within state borders) and effective, so sequencing should not replace them. However, access to follow-up care, treatment options, and education and outreach to affected families are not equitable. Several speakers discussed the need for and benefits of increasing the diversity of the workforce. At the same time, speakers cautioned that as the workforce is diversified, those from historically underrepresented groups are not solely responsible for amending the health care system’s inequities.

Bonhomme shared some of the themes explored during the workshop: (1) expanding who is involved in decision making about NBS and genome sequencing so that families and communities are key partners in the process; (2) building a trustworthy health care system; (3) managing and securing genome sequencing data are critical to protect genetic privacy; and (4) deciding which results to return to families, who decides what is returned, when and how to do that, and who should do so are complex decisions to resolve. The data and information shared “pushed us to challenge our own assumptions” about how to think about NBS and sequencing in newborns and “to establish a culture where equity and ethics are foundational,” Bonhomme said.

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DISCLAIMER This Proceedings of a Workshop—in Brief has been prepared by Kathryn Asalone, Michael Zierler, and Sarah H. Beachy as a factual summary of what occurred at the meeting. The statements made are those of the rapporteurs or individual workshop participants and do not necessarily represent the views of all workshop participants; the planning committee; or the National Academies of Sciences, Engineering, and Medicine.

*The National Academies of Sciences, Engineering, and Medicine’s planning committees are solely responsible for organizing the workshop, identifying topics, and choosing speakers. The responsibility for the published Proceedings of a Workshop—in Brief rests with the institution. The planning committee comprises Natasha Bonhomme, Expecting Health, a program of Genetic Alliance; Catherine Wicklund, Northwestern University, representing National Society of Genetic Counselors; April Adams, Baylor College of Medicine; Amy Gaviglio, Connetics Consulting, LLC; Aaron Goldenberg, Case Western Reserve University; Alex Kemper, The Ohio State University College of Medicine; Molly McGinnis, Genome Medical, Inc.; Ryan Taft, Illumina, Inc.; Joyce Tung, 23andMe, Inc.; and Karen Weck, University of North Carolina at Chapel Hill, representing College of American Pathologists.

REVIEWERS To ensure that it meets institutional standards for quality and objectivity, this Proceedings of a Workshop—in Brief was reviewed by April D. Adams, Baylor College of Medicine, and Emily Edelman, The Jackson Laboratory. Leslie Sim, National Academies of Sciences, Engineering, and Medicine, served as the review coordinator.

STAFF Sarah H. Beachy, Senior Program Officer; Kathryn Asalone, Associate Program Officer; Meredith Hackmann, Associate Program Officer; Samantha Schumm, Program Officer; Lydia Teferra, Research Associate; Aparna Cheran, Senior Program Assistant; and Gina Strohbach, Program Coordinator.

SPONSORS This workshop was partially supported by contracts between the National Academies of Sciences and 23andMe, Inc; American Academy of Nursing; American College of Medical Genetics and Genomics; American Medical Association; American Society of Clinical Oncology; American Society of Human Genetics; Association for Molecular Pathology; Biogen; Blue Cross Blue Shield Association; College of American Pathologists; Eisai, Inc; Geisinger Health; Genome Medical, Inc.; Health Resources and Services Administration (Contract No. HHSH250201500001I, Task Order No. 75R60220F34021); Illumina, Inc; The Jackson Laboratory (JAX); Kaiser Foundation Health Plan, Inc.; Myriad Genetics; National Institutes of Health (Contract No. HHSN263201800029I, Task Order No. HHSN26300010), including All of Us Research Program, National Cancer Institute, National Human Genome Research Institute, National Institute of Mental Health, and National Institute on Aging; National Society of Genetic Counselors; Regeneron Pharmaceuticals; the University of California, San Francisco; the University of Vermont Health Network Medical Group; U.S. Air Force Medical Service (Contract No. FA8052-17-P-0007); and Vibrent Health.

For additional information regarding the workshop, visit https://www.nationalacademies.org/event/06-07-2023/next-generation-screening-the-promise-and-perils-of-dna-sequencing-of-newborns-at-birth-a-workshop

SUGGESTED CITATION National Academies of Sciences, Engineering, and Medicine. 2023. The promise and perils of next-generation DNA sequencing at birth: Proceedings of a workshop—in brief. Washington, DC: The National Academies Press. https://doi.org/10.17226/27243.

Health and Medicine Division Copyright 2023 by the National Academy of Sciences. All rights reserved.