Newborn Screening in the United States: A Vision for Sustaining and Advancing Excellence (2025)
Chapter: Front Matter
Consensus Study Report
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This activity was supported by contract no. HHSP233201400020B; task order no. 75P00123F37117 between the National Academy of Sciences and the Office on Women’s Health of the Department of Health and Human Services and by grant 2023-332496 from the Chan Zuckerberg Initiative DAF, an advised fund of the Silicon Valley Community Foundation. Any opinions, findings, conclusions, or recommendations expressed in this publication do not necessarily reflect the views of any organization or agency that provided support for the project.
International Standard Book Number-13: 978-0-309-99216-9
International Standard Book Number-10: 0-309-99216-8
Digital Object Identifier: https://doi.org/10.17226/29102
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Suggested citation: National Academies of Sciences, Engineering, and Medicine. 2025. Newborn screening in the United States: A vision for sustaining and advancing excellence. Washington, DC: National Academies Press. https://doi.org/10.17226/29102.
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COMMITTEE ON NEWBORN SCREENING: CURRENT LANDSCAPE AND FUTURE DIRECTIONS
JEWEL MULLEN (Chair), University of Texas at Austin Dell Medical School
DON BAILEY, Genomics and Translational Research Center, RTI International
MEI BAKER, University of Wisconsin School of Medicine and Public Health
WENDY K. CHUNG, Boston Children’s Hospital and Harvard Medical School
TITILOPE A. FASIPE, Texas Children’s Hospital and Baylor College of Medicine
FAITH FLETCHER, Baylor College of Medicine
MEGHAN HALLEY, Stanford University
AMANDA INGRAM, Tennessee Department of Health
JOSÉ A. PAGÁN, New York University
JOCHEN PROFIT, Stanford University; California Perinatal Quality Care Collaborative; and California Maternal Quality Care Collaborative
SCOTT M. SHONE, North Carolina State Laboratory of Public Health
KAYTE SPECTOR-BAGDADY, University of Michigan Medical School
BETH A. TARINI, Children’s National Hospital
KRYSTAL TSOSIE, Arizona State University and Native BioData Consortium
Study Staff
KATHERINE BOWMAN, Study Codirector, Senior Program Officer
EMILY PACKARD DAWSON, Study Codirector, Program Officer
SARAH BEACHY, Senior Program Officer
GAYATRI SOMAIYA, Senior Program Assistant
MICHAEL BERRIOS, Research Associate
EMILY McDOWELL, Research Associate (March–June 2024)
EMILY BACKES, Deputy Board Director, Board on Children, Youth, and Families
CLARE STROUD, Senior Board Director, Board on Health Sciences Policy
Consultants
ANNE JOHNSON, Founder and Lead Science Writer, Creative Science Writing, LLC
SUSANNA HAAS LYONS, Civic Engagement Specialist, Susanna Haas Lyons Consulting
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Reviewers
This Consensus Study Report was reviewed in draft form by individuals chosen for their diverse perspectives and technical expertise. The purpose of this independent review is to provide candid and critical comments that will assist the National Academies of Sciences, Engineering, and Medicine in making each published report as sound as possible and to ensure that it meets the institutional standards for quality, objectivity, evidence, and responsiveness to the study charge. The review comments and draft manuscript remain confidential to protect the integrity of the deliberative process.
We thank the following individuals for their review of this report:
STANTON L. BERBERICH, The University of Iowa
JOAN M. DUWVE, Indiana University, Indianapolis
ALEX KEMPER, Nationwide Children’s Hospital
ANNIE KENNEDY, EveryLife Foundation for Rare Diseases
SYLVIA MANN, Hawaii Department of Health
JELILI OJODU, Association of Public Health Laboratories
NATALIE RAM, University of Maryland
CHARLENE SON RIGBY, Global Genes
LAINIE FRIEDMAN ROSS, University of Rochester
WILLIAM M. SAGE, Texas A&M University
SARAH VIALL, Oregon Health & Science University
AMBROISE WONKAM, Johns Hopkins University
Although the reviewers listed above provided many constructive comments and suggestions, they were not asked to endorse the conclusions or recommendations of this report nor did they see the final draft before its release. The review of this report was overseen by ELI Y. ADASHI, Brown University, and ZULFIQAR A. BHUTTA, The Hospital for Sick Children, University of Toronto. They were responsible for making certain that an independent examination of this report was carried out in accordance with the standards of the National Academies and that all review comments were carefully considered. Responsibility for the final content rests entirely with the authoring committee and the National Academies.
Acknowledgments
The committee would like to express its sincere gratitude to the speakers and panelists who shared their insights with the committee and those who responded to an online questionnaire and participated in virtual listening sessions as part of the study’s call for input, and the many organizations that shared information about the study and opportunities for engagement through their networks.
The committee is grateful to the Susanna Haas Lyons Consulting team, including Susanna Haas Lyons, civic engagement specialist; Anson Ching, civic engagement specialist; and Kiana Alaei, data analyst, for their design, thoughtful facilitation, and careful analysis of the results of the engagement activities, and to the additional National Academies staff members and Mirzayan Science and Technology Policy fellows who served as facilitators and note-takers for the listening sessions: Kathryn Asalone, Constanza Vidal Bustamente, Eva Childers, Rayane Silva Curran, Lotte de Jong, Michelle Drewry, Clara Herrera, Alexis Myers, Wesley Schnapp, Maya Thirkill, and Justin Wang. The committee is also grateful for the many contributions of Anne Johnson, science writer, Eva Childers, assistance with figures, along with the National Academies Research Center for assistance with fact checking.
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Contents
Concepts Underpinning Public Health Newborn Screening
Emerging Tensions in Public Health Newborn Screening
2 CURRENT LANDSCAPE OF NEWBORN SCREENING IN THE UNITED STATES
Overview of Public Health Newborn Screening in the United States
Disorders Included in Public Health Newborn Screening
Implementation of NBS Programs
3 GROUNDING NBS DECISION MAKING IN ETHICAL PRINCIPLES AND VALUES
Examining Newborn Screening as a Public Health Service
Establishing a Foundation for Aligned and Consistent Decision Making
Understanding Community Views to Inform Ethically Grounded Decision Making
A Path Forward for Public Health Newborn Screening Grounded in Bioethical Foundations
Examples of Prior Approaches to Ethical Decision Making in Newborn Screening
Principles and Values Central to Excellence in Public Health Newborn Screening
Public Health Newborn Screening for the Era Ahead: This Report’s Approach
4 SUPPORTING AND SUSTAINING HIGH-PERFORMING NBS PROGRAMS
NBS Programs at the Core of the Public Health NBS Effort
NBS Program Data Collection and Performance Management
Ensuring NBS Program Excellence in a Performance Framework
5 THE RESPONSIBLE APPLICATION OF EMERGING TECHNOLOGIES IN PUBLIC HEALTH NEWBORN SCREENING
Current Landscape of DNA-Based Tests in the NBS Ecosystem
Considerations for Incorporating Genomic Sequencing into Public Health Newborn Screening
6 THE RESEARCH ENTERPRISE RELEVANT TO NEWBORN SCREENING
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Boxes, Figures, and Tables
BOXES
S-1 Summary of Recommendations: A Road Map Forward
1-1 Newborn Screening in the United States
2-1 Terms Relevant to the Screening and Diagnosis of Conditions
2-2 Key Players Across the Broader NBS Ecoystem
2-3 Federal Partners Involved in Newborn Screening
2-5 Variability Across State and Territorial NBS Programs
3-1 Criteria Proposed by Wilson and Jungner for Public Health Disease Screening Programs
4-2 Timeliness in Public Health Newborn Screening of Dried Blood Spots
4-3 Two Examples of Models to Support Excellence in Public Health Newborn Screening
5-1 Genomic Sequencing Defined
5-2 Ongoing Newborn Sequencing Studies
5-3 Frameworks for Ethical Genomics Data Use and Sharing
6-1 Areas of Research for Artificial Intelligence and Machine Learning in Newborn Screening
6-2 Selected Questions to Address as Part of NBS Research
6-3 Examples of NBS-Related Studies Enabled by a Coordinated Research Network
7-1 Goals to Be Addressed with Increased National Vision and Coordination
7-3 Selected Examples of Starting Points and Near-Term Actions
FIGURES
S-1 A summary of recommendations: A road map forward
1-1 Timeline of federal action related to newborn screening
2-1 Basic steps in the NBS process
2-2 Players in the NBS ecosystem
2-4 Recommended Uniform Screening Panel decision matrix
5-1 Staged approach to molecular analysis in public health newborn screening
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Preface
As a former state and federal public health leader, I always considered participating in National Academies studies a continuation of my public service. When asked to chair the Committee on the Current Landscape and Future Directions of Newborn Screening, I recognized my additional privilege and responsibility to promote the individual contributions of fellow committee members—experts in research, ethics, law, economics, laboratory science, and public health—that also volunteered their time. Equally important to me was to discern and respect the excellence of National Academies staff who are the backbone of our work. Our committee had accepted the charge to accelerate through 12 months of collective learning and deliberation to recommend ways to strengthen newborn screening, one of the nation’s greatest twentieth century public health achievements. Great public health achievements, such as early detection of heritable conditions in newborns to reduce their associated morbidity and mortality, should not just be historic. Their beneficial effects must extend to future generations.
That goal informed the congressional directive to the U.S. Department of Health and Human Services Office on Women’s Health to commission a National Academies study to make newborn screening programs stronger and more resilient to the challenges the future holds. The Chan Zuckerberg Initiative further supported our work, affording a community engagement component that elucidated viewpoints from people and groups professionally and personally affected by newborn screening and rare diseases. As chair, I especially appreciated that since there is
no singular or one-size-fits-all approach to engaging communities, our committee members also amplified perspectives of members of the rare disease community with whom they worked closely. Those perspectives fostered our consistent recognition that to uphold equity, our recommendations must extend to groups with the most common rare conditions and to those with the rarest and still undiagnosed disorders.
Our committee’s tasks included recommending an approach to improving current state-run screening programs, adding new conditions to screening panels, modernizing laboratory infrastructure, incorporating and scaling new technologies, and ensuring equitable longitudinal followup and quality of life. We also aimed to provide an analysis of potential screening-associated harms and benefits to individuals, families, and society. Informed by longstanding guidance, such as Wilson and Junger’s principles for screening, we adhered to principles of public health and research ethics as well as legal policy as we undertook each task. Because of this approach, the committee’s considerations on trust, transparency, consent, use of dried blood spots, equity, education, and program quality weave throughout many chapters, rather than residing as single topics.
As we listened to presenters at our three public workshops, our committee quickly determined our imperatives to delineate the functions and future for effective and coordinated governmental public health newborn screening and to differentiate them from newborn screening research, including the application of emerging technologies. We also heard and agreed with the observations and advice of public health, legal, and ethical scholars that it is critical to uphold the current opt-out approach to public health newborn screening so it can remain accessible to every infant born in the United States. The message to uphold trust and transparency to preserve newborn screening as a core public health program also resounded, as did the need to establish additional ways to educate a diverse public about its benefits. We acknowledged the call to support high-quality programs and expertise across all states and to measure their performance and impact. Our committee’s recommendation to establish stronger national coordination, leadership, and guidance may help accomplish those goals.
As we valued the current—and anticipated the future—use of new and advanced technologies, the committee was also clear that they are not a replacement for public health newborn screening. Our recommendations for strengthening newborn screening programs are not an effort to maintain the status quo. Increasing the resilience of the system against future challenges, including the application of innovative technologies, entails protecting program integrity by upholding transparency, trust, equity, ethics, and quality across public health programs, research, and technological advancement.
In closing, I am grateful for the collegiality and excellent contributions of my fellow committee members. Each one exemplified a commitment to public service, intellectual humility, and collaboration that made my undertaking this work a joy. I also recognize the unflagging support, expertise, and equanimity of our leaders, Katherine Bowman, senior program officer, and Emily Packard Dawson, program officer; the partnering coordination of Gayatri Somaiya, senior program assistant; and the contributions of additional project staff Emily Backes, Sarah Beachy, and Michael Berrios. Lastly, I commend the work of every person and organization that partners to ensure every child can benefit from the promise of newborn screening.
Jewel Mullen, Chair
Committee on Newborn Screening: Current Landscape and Future Directions
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Acronyms and Abbreviations
| ACHDNC | Advisory Committee on Heritable Disorders in Newborns and Children |
| ACMG | American College of Medical Genetics and Genomics |
| AHRQ | Agency for Healthcare Research and Quality |
| APHA | American Public Health Association |
| APHL | Association of Public Health Laboratories |
| CDC | Centers for Disease Control and Prevention |
| CDE | common data element |
| CF | cystic fibrosis |
| CFTR | cystic fibrosis transmembrane conductance regulator (protein involved in CF) |
| DBS | dried blood spot |
| DCC | data coordination center |
| eCR | electronic case reporting |
| ED3N | Enhancing Data-driven Disease Detection in Newborns |
| EHR | electronic health record |
| ELC | Epidemiology and Laboratory Capacity |
| ELSI | ethical, legal, and social issues |
| ERG | Evidence Review Group |
| FDA | Food and Drug Administration |
| GAO | Government Accountability Office |
| gnomAD | Genome Aggregation Database |
| HHS | U.S. Department of Health and Human Services |
| HRSA | Health Resources and Services Administration |
| ICoNS | International Consortium of Newborn Sequencing |
| LIMS | laboratory information management system |
| LPDR | Longitudinal Pediatric Data Resource |
| NBS | newborn screening |
| NBS Co-Propel | Cooperative Newborn Screening System Priorities Program |
| NBS Excel | National Center for Newborn Screening System Excellence |
| NBS Propel | State Newborn Screening System Priorities Program |
| NBSTRN | Newborn Screening Translational Research Network |
| NBSxWGS | Newborn Screening by Whole-Genome Sequencing |
| NCATS | National Center for Advancing Translational Sciences |
| NewSTEPs | Newborn Screening Technical assistance and Evaluation Program |
| NGS | next-generation sequencing |
| NHGRI | National Human Genetics Research Institute |
| NICHD | Eunice Kennedy Shriver National Institute on Child Health and Human Development |
| NIH | National Institutes of Health |
| NSIGHT | Newborn Sequencing in Genomic Medicine and Public Health |
| NSQAP | Newborn Screening Quality Assurance Program |
| PAG | patient advocacy group |
| PCR | polymerase chain reaction |
| PKU | phenylketonuria |
| RCDC | Research, Condition, and Disease Categorization |
| RUSP | Recommended Uniform Screening Panel |
| SCID | severe combined immunodeficiency |
| SMA | spinal muscular atrophy |
| VRDBS | virtual repository of dried blood spots |
| VUS | variant of uncertain significance (genetic) |
| WHO | World Health Organization |
