Newborn Screening in the United States: A Vision for Sustaining and Advancing Excellence (2025)
Chapter: 3 Grounding NBS Decision Making in Ethical Principles and Values
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Grounding NBS Decision Making in Ethical Principles and Values
“Nothing is perfect. It’s subjective to every parent. Some people want to have the peace of mind [by knowing all the likelihoods] and some people just want to have a clear answer. It just depends on the parent . . . do they want to live in the gray?” – Parent
Newborn screening (NBS) in the United States continues to evolve in response to discussions over inclusion of additional conditions, incorporation of new screening technologies, increased understanding of diseases and treatments, and ongoing efforts to connect screening with clinical follow-up and care. It also contends with overarching considerations around family choice and autonomy, and issues that raise technical, ethical, legal/policy, and implementation questions. As a result, a foundation to inform decision making for NBS programs, funding processes, insurance coverage, informed consent, and related research remains timely and necessary. This chapter explores principles, values, and considerations that help guide ethical decision making in the context of public health programs. It discusses this report’s application of such principles and values to newborn screening to inform the analyses presented in the remainder of the report.
EXAMINING NEWBORN SCREENING AS A PUBLIC HEALTH SERVICE
Newborn screening as a public health service and the role of government in its implementation emerged as an “accident of history” and a practical necessity as this service took shape in its early years
(Clayton, 2024; Levy, 2021) (see Chapter 1 for a brief history of public health newborn screening). When looking to the future of newborn screening in the United States, it is worth stepping back to reexamine whether this premise still holds true.
Newborn screening as a universally provided service can draw on philosophical concepts around the value of enabling a just or fair society, equality of opportunity, and investment of resources where they can create the greatest opportunity (Rawls, 2001). Equality of opportunity draws on the idea that every individual—regardless of their background or circumstances—should have a chance to succeed. Public health newborn screening contributes to this chance for the approximately 7,000 infants identified each year as at risk for conditions that affect their morbidity or mortality (Gaviglio et al., 2023a). Newborn screening as a public health intervention also represents an investment of resources toward ensuring that no child dies from a preventable or treatable condition. Two examples help illustrate the positive health impacts of newborn screening:
- Eleven NBS programs identified severe combined immunodeficiency (SCID) in 1 in 58,000 infants. Infants identified through screening had a high rate of survival (87 percent) for SCID, which is an otherwise fatal diagnosis (Kwan et al., 2014).
- Public health newborn screening in Utah identified spinal muscular atrophy (SMA) in 1 in 20,000 infants. All infants identified met important developmental milestones through up to 5 years of age—inconsistent with the natural history of SMA (Wong et al., 2024).
The field of public health is sometimes perceived as focusing on preventing infectious disease, with vaccination programs being one of the most visible examples. However, its role is much broader, encompassing many facets that impact the health of populations. The 10 Essential Public Health Services,1 originally released in 1994 and revised in 2020, has stood for three decades as a key framework outlining core public health functions. Newborn screening programs align with the public health services embedded in this framework, including monitoring and addressing the causes of health risks. Providing a universal means to identify infants born with serious, urgent, and treatable health conditions supports the underlying goal of promoting the health of all people in the United States. To be successful in this mission, newborn screening involves other public health functions and services, including effective communication, evaluation and quality improvement, workforce development, and organizational infrastructure.
It is also worth considering the potential implications were newborn screening provided in alternative ways, rather than as a service
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1 https://www.cdc.gov/public-health-gateway/php/about/index.html (accessed March 24, 2025).
implemented through public health programs. The primary alternative to the current public health approach to newborn screening would likely be to carry out all newborn screening through health care systems, as part of birth and clinical care services. Indeed, care providers and health care systems already fulfill important roles in implementing public health newborn screening and delivering care to babies identified through screening (see Chapter 2 and elsewhere in the report). However, variation in resources, priorities, and practices between and even within health care systems suggests that newborn screening communications, blood spot collection and screening, reporting of results, follow-up, and other performance aspects would likely vary not only state to state, as in the current system, but from hospital or birth setting to hospital. Health care settings are not designed to fulfill the same obligations to all babies or to operate with the same resources and authorities as state/territorial and federal governments. Leaving the implementation of newborn screening programs to private or nonprofit sectors (through health care systems or others) appears likely to reduce consistency, could limit or negatively affect the near-universal provision of newborn screening to all babies born in the United States, and could amplify existing differences around diseases and variants included on screening panels and other program features.
A role for newborn screening as a public health service in the United States remains relevant, and for public entities to be involved in overseeing and implementing it fairly, effectively, and sustainably. Subsequent sections of this chapter describe how the committee approached the mission and scope of newborn screening as a public health endeavor upholding public health principles, and the relationship of public health newborn screening to other parts of the ecosystem, such as clinical care and research. This analysis also informed the vision described throughout this report for the next chapter of public health newborn screening.
ESTABLISHING A FOUNDATION FOR ALIGNED AND CONSISTENT DECISION MAKING
As public health newborn screening moves into its next era, competing needs and tensions persist. Those who benefit from public health newborn screening through detection and connection to care are often a different group than experiences harms related to screening (e.g., false positives, unclear results, psychosocial stress)—each of these groups may have different priorities and concerns related to the future of newborn screening. Patient advocacy groups have expressed deep concerns with barriers to adding conditions to NBS panels. Ethicists and policy makers have raised concerns regarding the opportunity costs of expanding newborn screening, as well as continued differences among programs arising from variation in screening panels and follow-up within and across states. As technology has evolved, scientists, advocates, and others have suggested an expanded role
for genomic sequencing in NBS programs, raising technical, ethical, legal, and implementation questions. The introduction of new classes of therapies with high price tags raises concerns about access to treatment for diagnosed patients. Lawsuits brought by privacy advocates over storage and secondary uses of newborn dried blood spots have led to the destruction of millions of specimens in Minnesota, Texas, and Michigan (Hughes et al., 2022). Legal scholars and others have strongly criticized the use of blood spots by law enforcement (Grant, 2022; Ram, 2022). If unaddressed, these and other tensions, challenges, and pressures may imperil the effectiveness of this essential public health service (Currier, 2022; McCandless and Wright, 2020).
One approach to making choices when faced with tensions and competing priorities is to look to the process of ethical decision making. In addition to complying with legal obligations, a process of ethically informed analysis aims to ground decisions guiding newborn screening around shared commitments, principles, and values that can be explained and justified to those involved with and affected by these programs. Such a process can promote clarity of reasoning and support greater consistency and efficiency.
The process of ethical decision making provides philosophical and methodological tools to examine the goals and values of screening, help weigh trade-offs among options when making decisions, understand tensions that may arise between or among these alternatives, and, when appropriate, identify the path chosen based on principles and priorities. As highlighted by the American Public Health Association, “Resolving ethical tensions does not mean finding the right answer; rather, it means searching for a morally appropriate way forward, all things considered” (APHA, 2019, p. 7). As drawn from Mattison (2000) and APHA (2019), features of this process include attention to
- Determining the public health goals, gathering information, and understanding the circumstances affecting the decision.
- Identifying ethical principles and values, including where such principles and values are in tension, and look to guidance from relevant ethical and theoretical frameworks, codes of conduct, or other guidance.
- Considering possible courses of action, and assessing their implications for affected individuals and communities, including the consequences of different choices on anticipated benefits, harms, and outcomes.
- Analyzing how a course of action aligns with core values, and making a choice that can be explained and justified.
Attention to these concepts helps to ensure more intentional, transparent decisions to preserve and improve newborn screening.
UNDERSTANDING COMMUNITY VIEWS TO INFORM ETHICALLY GROUNDED DECISION MAKING
Grounding decisions in an ethical manner involves assessing the best available factual evidence, understanding the lived experience of those involved, providing opportunities for direct or indirect participation of those communities and stakeholders toward finding solutions and informing the decision-making process, and explicitly thinking through how the proposed public health action or program can be publicly justified and explained. As stated in the American Public Health Association (APHA) Code of Ethics, “Empirical studies and anecdotal evidence show that when done well, public deliberation can yield more informed, considered, civic-minded, egalitarian discussions and mutually supported decisions” (APHA, 2019, p. 10).
Eliciting information on views, concerns, and priorities of a wide array from individuals and groups who compose the NBS community is key. A number of prior publications have assessed such views, particularly from parents and providers, in areas that include the focus of newborn screening, role of new genomic technologies, preferences around decision making and consent, and experiences in the context of specific diseases (see, for example, Andrews et al., 2022 Bailey et al., 2006; Crossnohere et al., 2022; Goldenberg et al., 2014; Hiraki et al., 2006; Lisi and McCandless, 2016; Miller et al., 2015; Tarini et al., 2018). As additional input to this study and to better understand the wide-ranging perspectives of individuals or groups interested in or affected by newborn screening—including laboratory and follow-up professionals, patients, families, advocacy organizations, care providers, administrators, and technology and therapeutics developers—input was sought through virtual listening sessions and an online questionnaire.2 Selected issues and quotes below reflect the challenges and opportunities facing the NBS system and participants’ views on charting an ethical and equitable course forward.
Scaling Condition-by-Condition Review in an Era of Rapid Discovery
Each state determines which conditions to include on its routine, public health NBS panel. As described in Chapter 2, states draw on federal guidance provided through the Recommended Uniform Screening Panel (RUSP). Adding a condition to the RUSP is a lengthy and multistep process that typically takes several years (HRSA, 2022). The slow nature of this process is inherent in the comprehensiveness of the required nomination package, the rigor of the evidence review, and the need to provide national guidance (Bailey et al., 2021; Kemper et al., 2014). As of 2024,
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2 See Appendix A for details on this component of information gathering; input received is summarized in Susanna Haas Lyons Engagement Consulting, 2024.
only nine conditions have been added to the RUSP since its creation in 2010 (HRSA, 2024a). The sustainability of this process has come under scrutiny for its limited capacity to keep pace with the development of new disease therapies and for the burden it places on the rare disease advocacy community and others to support the development of the evidence base needed for RUSP nomination (Andrews et al., 2022; Armstrong, 2024; Kennedy, 2024).
A valid NBS test and valid treatment may exist for a disease, [but] it takes the better part of a decade to get it [added to the RUSP], and taxes the advocacy organizations who can least afford to spend their valuable time and resources on this.
—Parent of a child with a rare disease
New conditions are added to the RUSP regularly and are expected to be added to each NBS program in a timely manner. Tremendous resources and expertise including laboratory technology, clinical care, informatics, data analytics, and project management are required to add new conditions to programs that have limited resources and daily responsibilities of screening and following thousands of newborns.
—NBS lab professional
The process of adding conditions to NBS programs is way too slow and reliant on old criteria that are no longer valid [in] our era of increasingly precise and cost-effective genomic screening tools. That’s why federal guidance through the RUSP is, in my view, excessively conservative. This conservatism trickles down to state labs, which often follow the guidance and don’t have the resources to add much else through pilot programs.
—Parent of a child with a rare disease
Embedding Equity Within the NBS System
Universal access to newborn screening is a deeply valued feature of current NBS programs that can reduce health disparities (Brosco et al., 2015). Although every baby has access to newborn screening, an infant will receive screening for different conditions depending on the state or territory in which they are born, meaning a baby born in one state may receive screening for a condition while a baby born in another state may not (NewSTEPs, 2023a). The quality and timeliness of screening vary from state to state as well, furthering geographic inequities (GAO, 2016; McGarry et al., 2023; NewSTEPs, 2023b). Molecular screening tests may not be designed inclusively for babies of different ancestral origins, leading to false positives and negatives for children of non-European descent (Bosfield et al., 2021; McGarry et al., 2023).
Babies identified via newborn screening will have different access to the provision of evidence-based care based on where they live as well as their socioeconomic status and race (McColley et al., 2022; Sohn and Timmermans, 2019). There are noteworthy gaps in care for certain conditions, including sickle cell disease; fewer than half of Medicaid-enrolled children with sickle cell anemia receive annual transcranial doppler screening—a standard of care—and only half receive disease-modifying treatment (Schieve et al., 2022). Different conditions attract different levels of financial research investment from industry and advocacy groups, which may ultimately lead to gaps in evidence generation (Bailey, 2022). The NBS system wrestles with how to embed equity throughout the system, beyond initial screening access, and across geographic, socioeconomic, ancestral, and racial/ethnic dimensions.
There isn’t uniformity from state to state, meaning sometimes families find out about their child’s condition based on luck of residence alone. Even federally recommended disease[s] don’t have to be added in every state. Luck or happenstance shouldn’t be a factor in determining if a child has a rare disease not immediately apparent at birth.
—Parent of a child with a rare disease
While infants are generally screened universally, the system for followup and treatment for screen-positive infants mirrors our health care system. [Some] Infants are lost to follow-up or don’t receive treatment in a timely manner.
—Health care provider
Although I appreciate the desire to press forward and help more children, we absolutely need to make sure that the current system is equitably working for everyone. Otherwise, we will continue to leave children behind. Progress rarely appreciates thoughtful reassessments, so we need to prioritize ensuring that public health interventions work for the entire population before moving forward and continuing to drive health disparities.
—Health researcher
Considering New Screening Technologies in an Underresourced System
Echoing debates around incorporating tandem mass spectrometry into newborn screening in the 1990s, the NBS system currently wrestles with whether and, if so, how to apply emerging screening technologies, such as next-generation DNA sequencing. DNA sequencing as a platform technology for newborn screening could exponentially expand the
number of conditions screened (Brunelli et al., 2023; Tarini, 2007). It could also create a deluge of complex and/or uncertain results for families and providers who may not have the expertise to interpret such information (Ross and Clayton, 2019; Tarini and Goldenberg, 2012). Furthermore, the collection and reuse of personal genetic information raises evolving social, ethical, and legal implications (Grant, 2022; Ram, 2022; Ross and Clayton, 2019). What factors should guide decision making on the role of this technology for newborn screening, while maintaining turnaround deadlines and the quality of service delivery required for the programs, remain open questions.
Expanding a system that is underresourced and therefore inefficient and underperforming, fails more people while continuing to fall short of current goals. Improvements to the current system, achieving better efficiency would free up resources for new efforts.
—Public health professional
As technology advances, it’s easy to want to advance newborn screening as well. However, it requires thoughtful consideration about whether these advances truly advance newborn screening. Are we doing things for research purposes or to actually help babies and their families?
—NBS follow-up professional
The next evolution in newborn screening is going to be sequencing . . . using sequencing technology. We’ve been bound or limited by tandem mass spectrometry, which is limited [to] inborn errors of metabolism . . . Most conditions are not inborn errors of metabolism that affect infants and children. . . . There are therapies for these conditions now. And there’s a way to identify [infants] before they become symptomatic . . . I can give you numerous examples of children, where their lives were saved by newborn screening, the new newborn screening of sequencing.
—Health industry representative
Balancing the Universality of Screening and Parental Choice
The near universality of newborn screening in the United States is seen as one of the program’s greatest strengths, and many argue that this would not last if screening involved a parental informed consent process (APHL, 2016). The current nonconsented (opt-out) screening approach is generally based on the benefits to the child and society of screening for conditions that are serious, urgent, and treatable, and the potential for harm if a parent refuses such screening (APHL, 2016; Faden et al., 1982). As conditions that stray from the criteria of urgent, severe, and treatable
are considered for inclusion, there are calls to (1) reassess the consented or nonconsented approach to screening, (2) consider risks—both known and unknown, and (3) explore other potential models (Bailey and Gehtland, 2015; Currier, 2022; Ross, 2010; Tarini, 2007).
As we move forward, maybe the question that needs to be asked is, “Is identification and treatment of this condition urgent enough that parental consent should be waived?” And if that answer is “No,” then the condition may not belong with NBS but could [be] offered to parents at a later date outside of the NBS program.
—NBS laboratory professional
The current system provides not enough information and agency to parents. Informed consent should be required, and it should not be an opt-out system.
—Parent
Addressing the Unmet Needs of the Rare Disease Community
Rare disease patients and their families contend with gaps in research, treatment options, and access to care, along with significant obstacles to obtain diagnoses (EveryLife Foundation, 2023; Halley et al., 2022; Stoller, 2018; Von Der Lippe et al., 2022). Many within the rare disease community see the NBS system as a critical tool to avert a protracted diagnostic odyssey and jumpstart research into treatments (EveryLife Foundation, 2023). What information should guide evidence review and decision making for inclusion of conditions in newborn screening and whether conditions without current medical treatments or interventions should be included on screening panels are of interest to many involved with or affected by rare diseases. Whether public health newborn screening should be the mechanism to meet many unmet needs affecting the rare disease community and how to address strains on the current NBS system remain unanswered questions.
The most important need of the rare disease community is more effective treatments for more diseases. . . . Development of new treatment or more effective treatment of any rare disease depends on identifying patients early enough, ideally presymptomatic, so the treatment benefits can be better demonstrated. Newborn screening can be the spark of treatment development that in turn fuels the further expansion of newborn screening. . . . It’s a chicken-and-egg dilemma that constrains both newborn screening and treatment development. We can only break out of it if we find a way to tackle both at the same time.
—Parent of a child with a rare disease
Every day that a test is not made available is a day that a child entering this world can be missed and forced to endure unnecessary hardship. Knowledge doesn’t take away the condition, it is always there. Knowledge allows informed decision making. Knowledge helps to avoid unnecessary burdens on exploratory pipelines. Knowledge allows for quality-of-life improvements. Knowledge allows for future family planning decision making. Knowledge allows for memories to me made, for the precious lives of our children to not be wasted searching for answers. Knowledge is everything.
—Parent of a child with a rare disease
Colliding Interests over Storage and Secondary Use of Blood Spots
Potential conflicts between public health and privacy concerns over storage and secondary use of blood spots pose a threat to public health newborn screening and have erupted into several court cases in recent years. Although the landscape of policies regulating this issue vary, states typically retain the dried blood spots collected from babies for quality assurance and control, and often for secondary research that can advance public health or other goals. Legal challenges have disputed various retention and consent policies and specific uses of these dried blood spots, including access to specimens by law enforcement in New Jersey and storage and secondary research use in Michigan (Hughes et al., 2022). Concerns around retention and reuse of blood spots without informed consent have also contributed, at least in part, to reauthorization failures for the NBS Saves Lives Act (Sterman and Molina, 2023). Privacy and civil rights concerns about storage and secondary use of blood spots must be considered to preserve trust and build trustworthiness in the NBS system.
Although these bloodspots have amazing potential for equitable public health research, the failure to protect bloodspots from misuse in criminal investigations and the lack of transparency in storing and using these bloodspots severely damages public trust.
—Health researcher
A nonconsented/mandated public health program has a big responsibility to promote trust and to not inadvertently cause harm by being distracted by special interests outside of the scope of newborn screening.
—Health care provider
Wavering Public Trust amid Limited Awareness
The effectiveness of public health actions and policies is rooted in public trust gained through basing decisions on ethical, scientific, and
professional standards. Trust is a key component for acceptance of public health guidance, and the COVID-19 pandemic brought to light the consequence of weak or absent trust and the importance of building institutional accountability and trustworthiness (Best et al., 2021; Taylor et al., 2023 Warren et al., 2020). Trust in public health broadly has eroded among several constituencies, and the growing number of lawsuits concerning residual dried blood spots threaten to undermine trust in the NBS system specifically (Hughes et al., 2022; RWJF, 2021). For many parents whose child does not receive an at-risk screening result, newborn screening is a barely recalled experience, contributing to lack of awareness of the program and its goals (DeLuca, 2018; Hasegawa et al., 2011). Ensuring that newborn screening is a trustworthy system will be important to the ability of programs to meet their mandate to screen all infants born in the United States.
In a post-COVID America, it appears that the more parents hear about newborn screening, the more they may distrust and seek to opt out of it, despite its demonstrated benefits for newborns as a whole. Better, more nuanced, and earlier parent education may help to enhance parental and community trust—as would more robust privacy protections for NBS samples/data on the back end.
—Privacy advocate
I think I do remember them taking blood from my second baby, but that was it. They never came back and never reported the results.
—Parent
The general public has poor understanding of [newborn screening]. There’s a lack of trust by many about any government programs—add to this the apprehension about genetic information being shared. Lack of education about newborn screening leaves state and federal programs vulnerable to funding loss or worse. At a minimum, there should be more education for expectant parents (grandparents) to prepare them for potentially receiv[ing] out-of-range results.
—Health care provider
Improving NBS Delivery Without Systems for Data Collection and Integration
“Evidence is also an ethical issue” in policy and programmatic decisions on the future of newborn screening (Baily, 2023). Which information on potential benefits, harms, and suitability of screening for a condition through public health newborn screening should guide assessment, and the extent and types of evidence required remain areas of debate.
Data collection through state and territorial NBS programs is also currently siloed and typically ends when a tested infant transitions to the health care system. Recently, there has been a push to collect and connect screening, short-term, and longitudinal data to improve NBS delivery, assess and address disparities, and better understand how newborn screening affects longer-term health outcomes. The current system is limited by information technology and data capacity and lack of interoperability, hindering achievement of these aims (Watson et al., 2022).
We focus a lot on screening, but there’s no data or national system to count the number of kids who are screened positive.
—Medical geneticist
A PATH FORWARD FOR PUBLIC HEALTH NEWBORN SCREENING GROUNDED IN BIOETHICAL FOUNDATIONS
These and other areas identified raise questions about the path forward for public health newborn screening. One of the reasons decision making for newborn screening is complex is because it involves an interplay not only of multiple viewpoints, but also of multiple bioethical contexts. Dried blood spot screening, in which every baby’s blood is collected and tested at birth, is designed as a public health program. As such, its fundamental purpose is rooted in improving the collective health of the U.S. population (Currier, 2022; Kass, 2001). However, the implementation of newborn screening is experienced by individual families as part of clinical care, with samples typically collected in the hospital, birth center, or at home after birth, results follow-up communicated by their primary care provider, and the health effects ultimately experienced by individual patients (HRSA, 2023). Public health infrastructure involved in newborn screening can also be used as part of research efforts, such as to conduct consented pilot studies that evaluate the risks and benefits of screening for new conditions, advances that can be difficult (or arguably impossible) to gather through other means (see Chapter 6).
Public health ethics, clinical ethics, and research ethics address ethical issues in these different health and research contexts. While these three areas draw on shared principles such as autonomy, beneficence, nonmaleficence, and justice (Beauchamp and Childress, 1979, 2019), they can approach or weigh such principles differently depending on the populations and fundamental goals being served, with implications for decision making in these domains. The following sections briefly explore how ethical principles are applied in these three contexts.
Public Health Ethics
Public health as a discipline focuses on health challenges at the population level and particularly on programs designed to prevent disease or to promote or sustain health (Kass, 2001).3 The Centers for Disease Control and Prevention defines public health ethics as the following:
Because public health actions are often undertaken by governments and are directed at the population level, the principles and values which guide public health can differ from those which guide actions in biology and clinical medicine (bioethics and medical ethics) which are more patient or individual-centered.4
The ethics of public health interventions are generally judged based on the balance of harms and benefits across the population as a whole. In prioritizing the health of a population, most or all individuals in that population take on some degree of burden for a clear health benefit that can only be achieved through population-level interventions, although individuals may or may not directly benefit from the intervention. Population-level public health interventions are justified based on a shared understanding of benefit and minimal risk. As wide participation in screening is necessary for the desired benefits, and as risks are minimal, NBS programs may involve minimal procedures for obtaining individual consent. State and territorial public health newborn screening, for example, is generally opt-out, meaning the baby’s blood is automatically collected and screened unless the parent or caregiver refuses (King and Smith, 2016).
Because of the focus of public health programs on population health, the types of interventions employed align with criteria that include the following:
- The risks are low, and there is clear and convincing evidence of significant benefit.
- The risks and benefits are such that the majority of the community would reasonably be expected to agree that the balance of risks and benefits is appropriate (with some important considerations for equity, discussed below).
- No subset of the population systematically receives a greater share of the benefits and burdens.
- There is no alternative approach that can achieve the same goal as well as the proposed public health program (Kass, 2001).
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3 See https://www.cdc.gov/public-health-gateway/php/about/index.html (accessed March 20, 2024).
4 See https://www.cdc.gov/scientific-integrity/php/public-health-ethics/index.html (accessed December 12, 2024).
Contemporary public health ethics frameworks also emphasize values such as transparent and trustworthy governance and decision making and equity as critical elements (APHA, 2019; Lee et al., 2020; Parasidis and Fairchild, 2022).
Clinical Ethics
The study of clinical ethics is generally focused on guiding the care of individual patients by their clinicians. Clinical ethics centers the best interests of the individual person, prioritizing the capacitated patient’s right to autonomous decision making and evaluating risks and benefits of alternatives in terms of the individual patient’s or family’s goals, values, and preferences (Varkey, 2021). The range of potential interventions that can be offered in the context of clinical care are broader than those that can be ethically justified in the context of public health because they are specifically targeted for the betterment of an individual and can incorporate a wider range of benefits and risks that reflect patients’ diverse preferences (Kass, 2001; Swain et al., 2008; Thomas et al., 2002). In clinical care, an individual is in a position to weigh these risks and benefits and make decisions according to their own values and preferences (Varkey, 2021).
Being able to respect a patient’s autonomy via informed consent requires three elements: the capacity to make a decision that reflects one’s own values; adequate information about the risks, benefits, and alternatives of a choice to inform that decision; and freedom from coercion that could otherwise limit that choice (Faden and Beauchamp, 1986). If an otherwise fully capacitated adult lacks capacity temporarily (e.g., due to unconsciousness) or has become incapacitated indefinitely (e.g., a patient affected by Alzheimer’s disease), a surrogate decision maker who is often the next of kin is generally asked to make a substituted judgment on the patient’s behalf. This allows a trusted associate of the patient to apply known values to a clinical decision (Varkey, 2021).
As a further specification of clinical ethics, pediatric ethics helps assess how to respect autonomy, ensure beneficence, and protect against nonmaleficence in the context of a primary patient who does not have practical (i.e., a younger child or infant) or at least legal (i.e., an older adolescent) capacity to make medical decisions on behalf of themselves. The American Academy of Pediatrics recognizes multiple standards that may be employed when surrogates (usually parents) make decisions on behalf of children and conversations around the issues involved in pediatric clinical decision making continue (Katz et al., 2016; Salter et al., 2023). Historically, medical decision making in children has centered on a “best-interest” standard, meaning adhering to a decision that would be in the best interests of an average patient in the same situation (Kopelman, 1997; Varkey, 2021). However, parental decisions about their child’s medical
care are generally respected, understanding that parents must balance the needs of the minor patient with those of the entire family and are rarely overridden unless such decisions cross a threshold of abuse or neglect (Diekema, 2004; Ross, 2019). Newborn screening and subsequent care, by definition, involve infants without capacity to consent and are thus informed by the frameworks employed for surrogate decision making in pediatric contexts.
Research Ethics
Research ethics generally guides the study and generation of new medical and scientific knowledge. A primary goal of such research is often not to benefit the individual participant, but rather future patients like them. The ethical protection of human research participants (human subjects) has been the focus of landmark reports such as the Belmont Report (National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research, 1979) and is subject to regularity requirements that include attention to whether risks to the individual participant are likely to outweigh potential benefits to the participant, or to the patient community of which they are a part (see 45 CFR Part 46). An adult patient may reasonably decide to enroll in a clinical trial for a novel treatment with a higher risk profile if they assess that the risk is outweighed by the potential benefit to their own health, for example if they have terminal cancer that has been resistant to all authorized and widely used treatments.
Additional research protections exist for certain groups of people, including fetuses, neonates, and children. As described in a Presidential Commission report, a “key impetus for a separate regulatory subpart addressing additional protections for child participants in research was the recognition that, while adults can consent to assume research risks, children cannot” (Presidential Commission for the Study of Bioethical Issues, 2013, p. 37). Under 45 CFR 46, along with conducting the research in accordance with sound ethical principles and making adequate provision for soliciting assent of the children and permission of their parents or guardians, children are allowed to be enrolled in clinical trials that are of minimal risk to themselves; greater than minimal risk if there is the prospect of direct benefit to the child or “the research is likely to yield generalizable knowledge about the [child]’s disorder or condition” (§46.406), or with authorization from the secretary of the Department of Health and Human Services when “the research presents an opportunity to understand, prevent, or alleviate a serious problem affecting the health or welfare of children” (§46.407). Contemporary and responsive research ethics models also emphasize engaging individuals and communities to inform ethically grounded approaches to conducting research and
mitigating potential research-related harms. Such models emphasize public engagement by funding agencies, research institutions, institutional review boards, and investigators to understand the needs, values, and preferences across the research continuum. As part of this process, it is important to include the voices of persons traditionally underrepresented in research and those who face vulnerabilities in the research process (Dawson et al., 2020; Fisher 2014; Schott et al., 2023; Solomon, 2013).
EXAMPLES OF PRIOR APPROACHES TO ETHICAL DECISION MAKING IN NEWBORN SCREENING
The current approach to newborn screening in the United States draws on a history of literature and analyses that have guided program choices, including on diseases that are appropriate to include in screening. The current criteria for conditions included on NBS panels, which focus on conditions that significantly affect health, are detectable in newborns, and for which effective treatment is available, hearken back to an influential set of criteria proposed by Wilson and Jungner in 1968 to guide public health screening programs (see Box 3-1). Wilson and Jungner’s criteria were developed largely to inform a different public health context—screening adults for chronic diseases. However, two inborn errors
BOX 3-1
Criteria Proposed by Wilson and Jungner for Public Health Disease Screening Programs
- The condition sought should be an important health problem.
- There should be an accepted treatment for patients with recognized disease.
- Facilities for diagnosis and treatment should be available.
- There should be a recognizable latent or early symptomatic stage.
- There should be a suitable test or examination.
- The test should be acceptable to the population.
- The natural history of the condition, including development from latent to declared disease, should be adequately understood.
- There should be an agreed policy on whom to treat as patients.
- The cost of case-finding (including diagnosis and treatment of patients diagnosed) should be economically balanced in relation to possible expenditure on medical care as a whole.
- Case-finding should be a continuing process and not a “once and for all” project.
SOURCE: Wilson and Junger, 1968.
of metabolism—phenylketonuria and galactosemia—were mentioned in the paper, suggesting this guidance was not solely meant for application toward adult public health (Wilson and Jungner, 1968). As such, these criteria have both utility and limitations when applied to the context of screening newborns. Nevertheless, they have provided an important foundation for subsequent analyses and critiques.
In the 2000s, in response to the highly variable landscape of conditions screened across state-run NBS programs since their inception in the 1960s, developments in screening technologies, and advancing understanding of medical genetics, the Health Resources and Services Administration’s Maternal and Child Health Bureau commissioned the American College of Medical Genetics and Genomics (ACMG) to develop recommendations to inform newborn screening (ACMG Newborn Screening Expert Group, 2006). Guiding principles identified in the 2006 ACMG report included newborn screening as a public health responsibility; benefit to affected newborns as the primary driver of policy decisions with secondary consideration to the interests of unaffected newborns, families, health professionals, and the public; the importance of evidence in making decisions about newborn screening; and public and professional education and awareness as essential to NBS success. The ACMG report identified 29 primary conditions it recommended be part of public health newborn screening.
Others expressed reservations with aspects of the evaluation process used to generate the ACMG report and its recommendations (Botkin et al., 2006; Moyer et al., 2008; Natowicz, 2005). Concerns were raised about the report’s emphasis on professional opinion, which is considered the weakest form of evidence for policy decisions by the U.S. Preventative Services Task Force and others. The rigor with which these opinions were ascertained was also questioned, both in terms of the survey design as well as in the composition and balance of expertise surveyed. Literature reviews supporting the ACMG recommendations were criticized for potential lack of independence and lack of appropriate methodology. Nevertheless, the ACMG’s recommendations and ensuing critiques, along with subsequent refinements to the process for evaluating and considering diseases for inclusion, have elevated the importance of rigorous evidence review as a foundation for the program (ACMG Newborn Screening Expert Group, 2006; Botkin et al., 2006; Kemper et al., 2014; Moyer et al., 2008; Natowicz, 2005). A 2008 ethical analysis undertaken by the President’s Council on Bioethics reflected on how benefits and harms from newborn screening are conceived, including the potential social or research benefits beyond those to an identified child’s well-being. The resulting report sought a framework to balance benefits and harms of screening, respect for parental decision making, concerns about the implications of unclear results, the role of research in
understanding currently untreatable conditions, the promise of further technical advances, the scale of resources required by population-level health programs, ultimately distinguishing between conditions ethically appropriate to include in mandatory screening (having an effective treatment and direct benefit to child welfare), and conditions that could be part of voluntary screening panels and would require parental consent (President’s Council on Bioethics, 2008).
The approaches articulated in these reports and others have informed NBS decision making. These developments collectively focused on creating a more equitable screening system for all Americans and ultimately led to the creation of the RUSP, greater uniformity across state and territorial NBS programs, and incorporation of a framework for reviewing conditions considered for addition to the RUSP (CDC, 2012). Since these analyses, decision making and criteria for inclusion on the RUSP have continued to evolve (HRSA, 2024b; Kemper et al., 2014). Notably, the original conditions named in the ACMG report—which formed the basis for the RUSP—have never been reassessed.
The past two decades have seen additional calls to expand newborn screening beyond conditions that meet criteria articulated in these reports, such as including conditions with less severe effects, that emerge later in childhood, or that lack available treatments (Currier, 2022). There have been calls to expand research associated with state and territorial NBS public health programs to facilitate addition of new conditions to NBS panels, better understand and treat heritable disease, or study other health issues.5 There have been ongoing debates about the appropriate roles for newer, genomic-based screening technologies (see Chapter 5). Ethical decision-making frameworks for the next era of newborn screening remain necessary and timely in light of these ongoing debates on the scope and aims of newborn screening and the range of needs and tensions described earlier in this chapter.
PRINCIPLES AND VALUES CENTRAL TO EXCELLENCE IN PUBLIC HEALTH NEWBORN SCREENING
Contemporary public health codes of ethics elevate additional principles and values as part of identifying appropriate paths forward around public health actions, particularly when faced with multiple goals and competing viewpoints (APHA, 2019). These considerations include not only the ethical permissibility of a course of action, but also its inter-
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5 See Chapter 5 for a discussion of research needs relevant to newborn screening and an explanation of the legal landscape guiding storage and reuse of newborn screening blood spots for research.
sections with respect for individuals and communities, reciprocity and proportionality around anticipated benefits and harms, effectiveness and responsible use of scare resources, accountability and transparency, and consultation with affected parties through public participation (APHA, 2019). While additional values and broader system-level considerations can be incorporated in multiple ways, this report highlights the role of three closely intertwined concepts that are critical for maintaining and strengthening an excellent NBS system now and into the future: effectiveness, trustworthiness, and equity.
Achieving and Maintaining the Effectiveness of NBS Programs
Effectiveness is central to achieving the value proposition of public health newborn screening (Berberich, 2024; Holtzman and Watson, 1998). Ensuring that public health newborn screening is effectively meeting its goals is supported by the provision of validated, timely, and accurate newborn screening, coupled with timely linkage from screening to confirmatory or follow-up testing, and to genetic counseling and care when necessary. NBS effectiveness enables infants and their families to benefit from treatments for screened conditions in time to make a difference in reducing morbidity and mortality.
Maintaining NBS effectiveness is a necessary part of preserving broad support for the mission and implementation of newborn screening as a public health endeavor, not only among the millions of parents and caregivers whose babies are screened each year, but also among the range of federal, state, and local policy makers who put in place the policies, programs, and resources guiding and sustaining this effort; the networks of public health and clinical professionals essential to carrying out screening, diagnosis, and care; and the U.S. public willing to support the role and purpose of newborn screening.
Sustaining Trustworthiness in the Mission and Implementation of Public Health Newborn Screening
“The most important asset that public health can have is the public’s trust that work is being done on its own behalf” (Kass, 2001, p. 1782). An ethical and high-quality NBS system must be one that is trustworthy; it must deserve to be trusted by the many constituencies participating in and using this system. Strengthening the NBS system to address ethical complexities, mitigate harms, and maximize benefits requires trustworthiness, which in turn entails features such as transparency and engagement (Beans, 2024; Clayton, 2024; Goldenberg, 2024; Hassan, 2024; Ram, 2024; Tanksley, 2024; Wallis, 2024).
As the committee heard during the study, building trust takes time. Legal and ethical thinking has moved toward the position that people are entitled to know their health information and be part of the process (NASEM, 2018).6 Public health newborn screening often operates in the background as an essentially mandated program, but ongoing and expanding calls seek to bring greater systematic awareness and understanding of newborn screening to families and providers (ACOG Committee on Genetics, 2019; Botkin et al., 2016; Davis et al., 2006; Therrell et al., 2011). Greater family awareness and education about public health newborn screening are particularly important given the tension between building trustworthiness and the nonconsented nature of screening in many jurisdictions. Educating about public health newborn screening—particularly its purpose and benefits, when and how it will happen, and parental options concerning both screening and the retention and reuse of the residual dried blood spots—provides families the agency to act as partners in the NBS system, and in turn build trust. Understanding who is best equipped to deliver this information to families and communities in a way that builds trustworthiness is important, and newborn screening decision makers may be able to learn from other health interventions that engage pregnant patients in the community, where they live. See Chapter 4 for the importance of viewing families as partners in the NBS system.
Building trust will also require engaging with community views to continue to ground decision making about the future of newborn screening in an ethical manner. Many ethical and social concerns about the practice of public health newborn screening can be better understood through research on community views. Such research could be designed to understand views on consent for public health newborn screening, storage and reuse of dried blood spots, or a broader range of screening-related benefits (see Chapter 6). Building public trust without losing communities that have little earned trust in public health and health care programs and understanding and mitigating issues that may lead people to opt out of public health newborn screening will all be important.
Understanding and operationalizing the concept of trustworthiness involves multiple dimensions and has been the subject of a body of prior research (Nong, 2023; Taylor et al., 2023). For example, features that feed into and support trustworthiness include acting in accordance with ethical principles, prioritizing the public’s best interests and needs, and maintaining excellence in the performance of major program functions. These include ensuring the timeliness, validity, and accuracy of screening test results; safely, securely, and ethically managing storage and use of dried blood spots and any derived data; and demonstrating high performance
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6 21st Century Cures Act, Pub. L. No. 114-255.
through quality assurance and improvement measures. Operating with transparency and proactively addressing sources of mistrust, engaging stakeholders to understand values and needs and participate as partners, and creating and using clear and effective communication materials also build trustworthiness. Examples of areas highlighted during the study’s information gathering that affect public perceptions of trustworthiness include earlier, more effective, and more nuanced education about newborn screening and the importance of data privacy protections (see Chapter 4).
Paying Attention to Equity Dimensions that Affect How Well Public Health Newborn Screening Serves All Babies
As a population-level investment in the well-being of infants born in U.S. states and territories, equity is a foundational aspect of newborn screening. NBS programs, subsequent diagnosis and care for identified babies, and the surrounding research enterprise need to serve the needs of all infants born in the United States and their families.
The nature of newborn screening, designed to reach every baby born in the United States, has the potential to serve as a powerful tool to reduce disparities in time to diagnosis for communities underserved by the health care system (Brosco et al., 2015). Just because babies may be screened equally, in the sense that their blood is collected and sent to a laboratory for testing, does not necessarily mean that all aspects of NBS programs, or the larger system, are equitable. Paying careful attention to equity in newborn screening involves multiple dimensions (see Table 3-1). When screening tests are not designed inclusively, infants of non-European descent tend to have higher rates of false positives and negatives (Bosfield et al., 2021; Gaviglio, 2021; McGarry et al., 2023; Peng et al., 2020). Studies suggest that infants from underserved communities experience longer times to confirmatory diagnosis and treatment initiation after identification through newborn screening (Gaviglio, 2021; McColley et al., 2023; Singh, 2022). In addition, care for diagnosed babies can depend on family circumstances, which may be affected by geographic and socioeconomic factors such as uneven distribution of specialists, ability to travel to appointments or specialized facilities, and the nature of the family’s health insurance coverage.
Expanding public health screening without recognizing or addressing major inequities in other parts of the NBS system will never be more than partially successful and could even exacerbate disparities, particularly in the context of limited resources and new high-priced therapies such as gene therapies (Gaviglio et al., 2023b; Sobotka and Ross, 2023). Although not every dimension of equity described in Table 3-1 is in the purview
TABLE 3-1 Several Dimensions of Equity and Their Relevance to Newborn Screening
| Conceptual Dimension | Illustrative Example in the Context of Newborn Screening |
|---|---|
| Policy and Input (Nature and inclusiveness of decision making) Prioritization, investment, and other decision-making processes need to elevate a range of voices. Attention needs to be paid to how newborn screening can avoid perpetuating past injustices and/or correct past injustices when possible. |
Current focus and composition of voting members of the federal Advisory Committee on Heritable Disorders in Newborns and Children (ACHDNC) is not representative of the breadth of issues and full range of interested and affected parties involved in public health newborn screening. |
| Geography Not all states screen for the same diseases, the screening assays used by different states vary in their performance, and not all states have the same access to specialists for identified conditions. |
Genetic counselors and clinical geneticists are geographically concentrated in metropolitan areas, and some states have few to no practitioners (Jenkins et al., 2021; NSGC, 2020). |
| Screening Deployment All babies need fair and equal opportunities to receive newborn screening. |
Newborn screening generally reaches all babies and families; it is carried out on an estimated 98% of babies born in U.S. states and territories (Sohn and Timmermans, 2019). |
| Assay Performance and Evaluation Screening assays and confirmatory diagnostic tests need to perform accurately for all members of the population; performance should be evaluated in representative populations to ensure accuracy and reduce the likelihood of disparate effectiveness. |
Infants of African descent are at a higher risk of receiving false positives from commonly used molecular NBS assays for mucopolysaccharidosis type I (Bosfield et al., 2021). |
| Diagnosis All babies identified through screening need an equitable opportunity to receive timely confirmatory diagnostic testing and be handed off to the clinical care system where needed. |
Infants from minoritized racial/ethnic groups who screen positive for cystic fibrosis receive diagnostic follow-up later than recommended and later than their White peers (McColley et al., 2023). |
| Care/Treatment All identified babies need longer-term connection and access to care, but disparities reflect features of the U.S. health care system. |
Fewer Medicaid-enrolled children with congenital hypothyroidism receive recommended, evidence-based care (i.e., follow-up thyroid stimulating hormone testing) than their privately insured peers (Kemper et al., 2020). |
| Conceptual Dimension | Illustrative Example in the Context of Newborn Screening |
|---|---|
| Research/Attention The research portfolio informing newborn screening (and heritable disorders more broadly) needs to include topics relevant to diverse communities, including those that have been historically underserved. |
Different conditions attract different levels of financial research investment from industry and advocacy groups, which may ultimately lead to gaps in evidence generation (Bailey, 2022). |
NOTE: NBS = newborn screening.
of public health newborn screening to address, the ramifications of each must be considered when making decisions about the policy and practice of newborn screening.
PUBLIC HEALTH NEWBORN SCREENING FOR THE ERA AHEAD: THIS REPORT’S APPROACH
Drawing on these frameworks and values, the approach taken by this report emphasizes how public health newborn screening aligns with ethical foundations informing public health and focuses on supporting and strengthening the excellence of the NBS through effectiveness, trustworthiness, and equity where opportunities exist. It is essential to emphasize that some elements intertwined with newborn screening or that help fully address needs of the many parties who participate in this system remain critically important, but they are not well suited to public health programs or do not fall within the ability of public health to address in isolation. Intersecting needs in clinical care and research settings require taking a system-level approach, with active and ongoing engagement among the diversity of stakeholders and rightsholders involved. This is necessary to align values as issues continue to emerge and evolve, and to support effective decision making for both NBS programs and for the broader NBS and disease treatment system.
The report emphasizes the following features in guiding decision making about newborn screening as a public health endeavor.
Align Decisions for Newborn Screening Conducted as a Universal, Public Health Service with Public Health Ethics
Universal newborn screening, implemented through state and territorial public health departments to screen all babies at birth, falls within the purview of public health ethics. Newborn screening as a public health program uses a population-level screening paradigm that considers balancing
risks, benefits, and decision making through a population-level lens rather than an individual, person-level lens. Such a mandated public health program is generally only justifiable if risks are minimal, benefits are viewed as significant and important by a majority of the population, and alternative approaches (such as relying on detection and diagnosis of a condition later as part of clinical care) are unlikely to achieve the same benefit.
Focus Public Health Newborn Screening on Reducing Morbidity and Mortality
To align with public health values and principles, universal, at-birth newborn screening conducted as a population-level screening program needs to focus on conditions that are serious, urgent, and have a therapeutic intervention rigorously shown to reduce babies’ morbidity and mortality. These criteria align with the public health mission of newborn screening to reduce morbidity and mortality and advance child welfare.
Focus Public Health Newborn Screening on Certain Types of Conditions
Deploying universal, population-level screening requires there to be widely shared views that anticipated benefits are significant, that these outweigh anticipated harms, and that alternative approaches (such as diagnosis later through the care system) are unlikely to achieve these benefits. The public health aim that justifies universal newborn screening focuses on child welfare through the identification of conditions that affect screened infants’ morbidity and mortality because they are serious, urgent, and treatable. Practically and ethically, it is also important to ensure that the current foundation of public health newborn screening works effectively and equitably for everyone before pressing forward with large expansions.
Rare diseases, though individually rare, collectively affect an estimated 10 percent of the U.S. population.7 Screening for a greater number of rare diseases that meet the criteria for public health newborn screening would mean that a greater number of infants with disease will be identified as at risk, diagnosed, and treated. As such, expanding the number of conditions included in public health newborn screening could be one potential way to increase the net population benefit of the NBS program; however, expanding the scope of newborn screening to include conditions that are, for example, later onset or have no available treatment, would not align with the public health paradigm of the program. Other
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7 See https://rarediseases.info.nih.gov (accessed March 24, 2025).
approaches, including through clinical care or research, may need to be explored to screen for conditions that do not meet the high bar necessary for inclusion in public health newborn screening.
Subsections below describe how the terms serious, urgent, and treatable can be conceptualized in the context of public health newborn screening and how the committee considered them for the purposes of this report.
Screening for Conditions Having Serious Health Effects
In alignment with public health criteria and prior reports from ACMG and others, the approach to public health at-birth newborn screening primarily focuses on identifying serious genetic conditions prior to the onset of symptoms (Andermann et al., 2008). It is difficult to define terms such as serious. Many definitions have been used, often focusing on morbidity and mortality. Such concepts are always viewed through the lens of an individual’s or their family’s subjective experience and priorities regarding their quality of life; what is serious for one individual may be deemed relatively unimportant for another (Boardman and Clark, 2022; FDA, 2022; Kleiderman et al., 2024; Roy et al., 2021; Wertz and Knoppers, 2002). In addition, context matters, as living with certain diseases or disabilities can be facilitated or greatly impeded by a person’s surrounding environment. Lack of agreement on the meaning of serious is particularly relevant when considering whether or not to expand newborn screening to include conditions that less clearly meet current inclusion criteria, those with a less clear knowledge base on the range of disease variants and their manifestations, or where there is less agreement on the nature, severity, and timing of the effects. Although the term serious cannot be easily defined, the committee generally considered it to mean diseases that have significant negative health effects on an affected baby’s morbidity and/or mortality.
Screening for Conditions That Are Urgent to Address
Although the term urgent can be interpreted in variable ways, the committee generally viewed it as indicating a need to act presymptomatically early in a baby’s life—or to be primed to act quickly during early life—to prevent negative effects on morbidity and mortality (e.g., dietary management for medium-chain acyl-coenzyme A dehydrogenase deficiency to prevent death) (Marsden et al., 2021).
Perspectives differ on whether to expand public health NBS panels to conditions that have later onset of symptoms during childhood or conditions that can be effectively treated later, after symptoms arise. Some have argued for the value of reducing the diagnostic odyssey and ensuring timely treatment, while others have argued that to screen for these in
the newborn period introduces potential burdens or harms of providing information that creates undue stress associated with being “patients in waiting” (Kelly et al., 2016; Moyer et al., 2008).
Including such conditions in public health newborn screening is one mechanism to meet diagnostic and treatment aims, but it is not the only one. Later onset conditions and/or those that can be effectively treated when symptoms arise could arguably be addressed through clinical screening or diagnostic testing later in childhood, rather than through public health screening at birth (Sobotka and Ross, 2023). While there are significant barriers associated with clinical diagnosis and care, these barriers can be better addressed by interventions to improve clinical care systems for such patients and families, as opposed to using population-level newborn screening.
Similarly, perspectives differ on reporting information for the purposes of understanding a baby’s carrier status for a disease (rather than being affected by the disease itself), informing parental health or lifestyle choices, informing family reproductive choices, or realizing other potential benefits as part of public health newborn screening. In these cases, the balance of potential benefits and harms is less certain in the context of a large-scale public program and individual parents have widely variable preferences in desire for this information (Joseph et al., 2016; Moultrie et al., 2020; Tluczek et al., 2022). A patient’s own preferences (i.e., the child’s) would guide this decision but their preferences are unknowable as newborns. Although clinical care and research settings have substantial challenges and limitations of their own, it is again difficult to make a clear case for these types of conditions as part of routine, population-wide public health newborn screening.
Screening for Conditions That Are Treatable
Similar logic applies when considering whether universal, at-birth newborn screening as a public health program should expand to include conditions that lack demonstrably efficacious interventions. Arguments for expansion point to the potential benefits to families with rare conditions of avoiding the diagnostic odyssey, accessing clinical trials while the child is still presymptomatic, informing reproductive choices for the family, and others (Alexander and van Dyck, 2006; EveryLife Foundation, 2023; Susanna Haas Lyons Engagement Consulting, 2024). While some families will undoubtedly derive value from this knowledge, surveys suggest that perspectives on having screening for these types of conditions vary widely (Ersig et al., 2023; Timmins et al., 2022). Parents are free to request screening for additional conditions as part of their child’s clinical care, if they are able to do so. This is, of course, with the acknowledgment
that the cost of clinical testing can be a high, and sometimes insurmountable, burden for some families. But as discussed above, public health decisions are generally targeted toward improving the health of a community, necessarily balancing scarce resource allocation at state and federal levels, rather than on the personalized needs of any given individual child or family to tailor clinical interventions.
It is important to note that the definition of treatment can be interpreted narrowly, focusing primarily on interventions such as drugs or dietary changes. However, other kinds of health interventions, including physical, occupational, and speech therapy, may significantly improve functional status and quality of life for affected children. The linchpin of the definition of treatment is evidence of significant benefit, such that most people would agree that its potential benefits outweigh the burdens of screening. If a treatment is demonstrated to reduce morbidities and mortality, then the actual mechanism of treatment (e.g., drug versus physical therapy) should not be a barrier to inclusion in public health newborn screening. The concept of medical interventions needs to account for multiple types of evidence-based interventions that reduce morbidity for individuals identified through screening and prioritize research and investment into these varied forms of interventions and services.
Questions about Carrier Status
Questions have been raised about testing for or reporting carrier status as part of public health newborn screening. If carrier status manifests in infancy as a serious, urgent, and treatable condition, then that would align with the mission of public health newborn screening, which focuses on detecting serious, urgent conditions that are treatable if identified in infancy. For example, in rare instances, female carriers of X-linked conditions can be symptomatic (Migeon, 2020), which has been a point of consideration for X-linked conditions previously considered for NBS panels (Condition Review Workgroup, 2017). For autosomal recessive conditions, being a carrier can have health risks or implications that may impact an infant later in life (NASEM, 2020; Shi et al., 2021). However, this information has no immediate clinical usefulness for the newborn (Clayton, 2010). Ultimately, health implications related to carrier status that arise in adulthood and/or cannot be intervened on in infancy do not align with the public health mission of newborn screening to detect infants with serious conditions and connect them to care and intervention.
However, the reality is that carrier status may be detected when screening for a primary condition (e.g., detection of sickle cell trait
when screening for sickle cell disease) (APHL, 2015). This issue raises practical, ethical, and legal questions concerning whether to report such information. A core tension lies between the desire for transparency on the one hand and the protection of individual and public health goals on the other (Miller et al., 2009). The rationale for an opt-out (rather than opt-in) consent model for public health newborn screening rests on the premise that the anticipated benefits of identifying babies with serious, treatable conditions outweigh the potential harms of sharing that information, and there is a different set of benefits and harms when it comes to carrier status. For example, disclosing carrier status could result in psychological harms to the family, who may not wish to receive information about their baby’s genetic status that is not actionable, and could elicit concerns about the possibility of insurance or reproductive discrimination later in life (Tluczek et al., 2022). However, generating a finding and withholding that information from families could undermine public trust in the newborn screening (Goldenberg et al., 2019). Further conversations and empirical research are needed to understand the balance of benefits and harms, and spectrum of parental perspectives, for reporting such information.
In light of these issues, wherever a newborn screening program is aware that incidental or secondary findings may be generated, it is important to plan for those situations in program policies and practices. If programs elect to notify families or clinicians of such findings, it is vital that this notification be given thoughtfully, making it clear that there is no immediate health concern and providing appropriate information about what the results mean and what additional steps might be considered (NASEM, 1994).
The Role of Consent in Newborn Screening
Routine public health newborn screening is currently undertaken as a universal screening program at birth, generally through an opt-out (rather than opt-in) approach (King and Smith, 2016). Some have proposed that one solution to needs and tensions around newborn screening is to integrate a wider range of conditions into newborn screening in tandem with a more robust consent process that would allow parents to choose the conditions for which they wish to have their child screened. Theoretically, there are two ways this could be approached: by implementing explicit consent for all at-birth screened conditions, or by moving to a two-panel system in which a subset of urgent, severe and treatable conditions is universally screened and other conditions are included on an optional, consented panel (Currier, 2022; Gaviglio, 2024; President’s Council on Bioethics, 2008).
In practice, however, the nature and complexity of the many hundreds of diseases that could be included, the burden of making these complex decisions without the support of their personal physician (e.g., the child’s pediatrician), and the complex logistics of its implementation at the population level present major challenges. Some have expressed worries that adding a second, optional panel to at-birth screening might result in a greater number of parents opting out of the recommended universal panel. Further, one would need to consider the public resources that would be required to set up, track, and maintain a system to allow individual consent for a range of diseases, given the widely variable public opinion as to its value.
These costs would also need to be weighed against alternative methods of improving public health, which may be particularly difficult to justify if many of the new conditions lack effective treatments. States already vary in how they implement newborn screening or perform consented pilot studies,8 and several research initiatives present parents with optional panels of screened diseases (e.g., Early Check, BabySeq); lessons may be able to be drawn from these (Peay et al., 2022). However, all such implications for program excellence, trustworthiness, and equity would need to be better understood before recommending changes to universal public health screening at large scale across the full population.
Addressing System Needs Beyond Routine Public Health Newborn Screening
Newborn screening is often charged as the mechanism to serve disparate needs and stakeholders—all of which are important but not all of which are well suited under the model of a public health program. The parameters guiding ethical decision making for routine, universal, at-birth newborn screening as a public health program are necessarily narrow owing to the population-based nature of the screening program itself. Public health newborn screening cannot and should not be the sole, or even the primary, solution to the broader problem of delays in rare disease diagnosis, to longstanding challenges around access and capacity in the clinical care system for patients and families with genetic diseases, and to the need to identify and develop new treatments for diseases. Taking a more strategic view at the system level will be important to addressing these other priorities.
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8 For example, the Massachusetts Department of Public Health may authorize pilot studies for conditions. Participation is voluntary and written consent is collected. See https://nensp.umassmed.edu/sites/nensp.umassmed.edu/files/English.pdf (accessed December 18, 2024).
CONCLUSIONS
A decision-making approach grounded in ethical principles and values can help envision a path forward to navigate the mounting tensions, challenges, and pressures facing newborn screening in the United States while preserving and strengthening what is already considered a public health achievement. This leads to the following conclusions:
Conclusion 3-1: As a program guided by public health ethics, focusing public health newborn screening on conditions that are serious, urgent, and have a therapeutic intervention rigorously shown to reduce morbidity and mortality in affected infants aligns with this mission to advance child welfare. Deploying universal, population-level screening requires there to be widely shared views that anticipated benefits outweigh anticipated harms and that alternative approaches are unlikely to achieve the same net benefits.
Conclusion 3-2: Expanding the scope of universal, at-birth newborn screening would no longer align with the public health mission of the program and would require expanded consent procedures (for example, to include conditions with later onset or no available treatment, or potential benefits beyond babies’ morbidity and mortality). However, the ramifications that changing the consent paradigm for performing routine public health newborn screening would have on equity and program performance would need to be better understood before implementing at large scale.
Conclusion 3-3: When considering the concept of an available treatment or intervention in assessing whether to add a condition to public health newborn screening, evidence for the magnitude of benefit (improvement in child morbidity and mortality) is most important rather than the specific type of intervention.
Conclusion 3-4: The rare disease community has unmet needs that are valid, important, and in need of public attention and investment, but not all of them can be well addressed by state-run public health NBS programs. Doing so risks compromising the integrity and sustainability of public health NBS programs; investment in other dimensions of research and care remain essential to address these additional needs.
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