Aaron J. Goldenberg

The Ethical Hazards and Programmatic Challenges of Genomic Newborn Screening

DVANCES IN NEXT-GENERATION SEQUENCING TECHnologies have the potential to spur better integration of genetic testing into patient care. Appropriateutilizationofthesetechnologieswillrequire the capacity to manage, interpret, and communicate large amountsofpersonalgeneticinformation. 1 Becausetheclinicalinfrastructurenecessarytosupporttheseactivitiesiscurrently limited, 2 it is likely that the earliest applications of whole-genome sequencing will be restricted to settings in which genetic testing is already a routine part of clinical or publichealthpractice,suchasstatenewbornscreening(NBS) programs. Theuseofnext-generationsequencingwillenablethedetection of a larger number of deleterious genetic variants, thereby expanding the number of pediatric disorders evaluatedwithoutsubstantiallyincreasingthecostsofNBS. 3 These important public health goals may encourage early adoptionofwhole-exomeandwhole-genomesequencingbystate NBS programs. However, if implemented by state programs, new sequencing technologies may have a number of undesirable effects that threaten the moral foundation and coremissionofonethenation’smostsuccessfulpublichealth initiatives. For nearly half a century, state NBS programs have tested millions of children annually to identify medical conditions that, if untreated, result in severe physical, mental, or developmentalharms.Thechildwelfareconsiderationsthat support these public health initiatives are compelling and have prompted most states to require NBS for all children, often with significant limitations on parents’ ability to request an exemption. The moral justification for compulsory NBS screening derives from the state’s interest in protecting its most vulnerable citizens from preventable harm. Although the diseases evaluated by these programs are exceptionally rare, the opportunity to intervene and dramatically alter a child’s life course and expectancy has been regarded as sufficient to preempt any claims of parental autonomy.

State Laws Regarding the Retention and Use of Residual Newborn Screening Blood Samples

BACKGROUND: After newborn screening has been completed, many states retain residual newborn screening dried blood samples for various purposes, including program evaluation, quality assurance, and biomedical research. The extent to which states possess legal authority to retain residual dried blood samples (DBS) and use them for purposes unrelated to newborn screening is unclear. OBJECTIVE: The purpose of this study was to evaluate state laws regarding the retention and use of DBS. METHODS: State statutes and regulations related to newborn screening of all 50 states plus the District of Columbia were accessed online between November 2008 and December 2009 and reviewed by 2 independent reviewers to determine the extent to which the retention and use of DBS were addressed. RESULTS: The retention or use of DBS has not been addressed in 18 states. In 4 states, DBS becomes state property. Eight states require that parents be provided information regarding the retention of DBS. Parents in 5 states may request the destruction of their childs residual sample. Parental consent is required under certain circumstances to release DBS for research in 6 states. One state prohibits DBS from being used for research purposes. CONCLUSIONS: States have wide variability in their policies regarding the retention and use of DBS. Many states have not addressed key issues, and some states that retain DBS may be acting outside the scope of their legal authority. The lack of transparency on the part of states in retaining DBS may undermine public trust in state newborn screening programs and the research enterprise.

Not without my permission: Parents' willingness to permit use of newborn screening samples for research

Background: State newborn screening (NBS) programs are considering the storage and use of NBS blood samples for research. However, no systematic assessment of parents’ attitudes exists. Methods: We conducted an Internet-based survey of a nationally representative parent sample. We examined parents’ willingness (1) to permit use of their children’s NBS samples for research with/without their permission and (2) to allow NBS sample storage. Using bivariate and multinomial logistic regression, we examined the association of parent and child characteristics with parents’ willingness to permit NBS sample storage and use for research, respectively. Results: The response rate was 49.5%. If permission is obtained, 76.2% of parents were ‘very or somewhat willing’ to permit use of the NBS sample for research. If permission is not obtained, only 28.2% of parents were ‘very or somewhat willing’. Of parents surveyed, 78% would permit storage of their children’s NBS sample. Parents who refused NBS sample storage were also less willing to permit use of the NBS sample for research. Conclusions: Three-quarters of parents would permit use of their children’s NBS samples for research – if their permission is obtained. Parents not in favor of storing NBS samples often opposed the use of NBS samples for research.

Ethical issues with newborn screening in the genomics era

Continued technological advances have made the prospect of routine whole-genome sequencing (WGS) imminent. To date, much of the discussion about WGS has focused on its application and use in clinical medicine. Relatively little attention has been paid to the potential integration of WGS into newborn screening programs. Given the structure and scope of these programs, it is possible that the early applications of WGS will occur in state-run newborn screening programs. Assessment of the pressing ethical issues currently facing the newborn screening community will provide insight into the challenges that lie ahead in the genomics era.

Parents' interest in whole-genome sequencing of newborns.

Purpose:The aim of this study was to assess parents’ interest in whole-genome sequencing for newborns.Methods:We conducted a survey of a nationally representative sample of 1,539 parents about their interest in whole-genome sequencing of newborns. Participants were randomly presented with one of two scenarios that differed in the venue of testing: one offered whole-genome sequencing through a state newborn screening program, whereas the other offered whole-genome sequencing in a pediatrician’s office.Results:Overall interest in having future newborns undergo whole-genome sequencing was generally high among parents. If whole-genome sequencing were offered through a state’s newborn-screening program, 74% of parents were either definitely or somewhat interested in utilizing this technology. If offered in a pediatrician’s office, 70% of parents were either definitely or somewhat interested. Parents in both groups most frequently identified test accuracy and the ability to prevent a child from developing a disease as “very important” in making a decision to have a newborn’s whole genome sequenced.Conclusion:These data may help health departments and children’s health-care providers anticipate parents’ level of interest in genomic screening for newborns. As whole-genome sequencing is integrated into clinical and public health services, these findings may inform the development of educational strategies and outreach messages for parents.Genet Med 16 1, 78–84.

Decision-making process for conditions nominated to the Recommended Uniform Screening Panel: statement of the US Department of Health and Human Services Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children

Purpose:The US Secretary of Health and Human Services provides guidance to state newborn screening programs about which conditions should be included in screening (i.e., the “Recommended Uniform Screening Panel”). This guidance is informed by evidence-based recommendations from the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children. This report describes the Advisory Committee’s revised decision-making process for considering conditions nominated to the panel.Methods:An expert panel meeting was held in April 2012 to revise the decision matrix, which helps to guide the recommendation process. In January 2013, the Advisory Committee voted to adopt the revised decision matrix.Results:The revised decision matrix clarifies the approach to rating magnitude and certainty of the net benefit of screening to the population of screened newborns for nominated conditions, and now includes the consideration of the capability of state newborn screening programs for population-wide implementation by evaluating the feasibility and readiness of states to adopt screening for nominated conditions.Conclusion:The revised decision matrix will bring increased quality, transparency, and consistency to the process of modifying the recommended uniform screening panel and will now allow formal evaluation of the challenges that state newborn screening programs face in adopting screening for new conditions.Genet Med 16 2, 183–187.

Public Attitudes Regarding the Use of Residual Newborn Screening Specimens for Research

BACKGROUND AND OBJECTIVES: Many state newborn screening (NBS) programs retain residual NBS bloodspots after the completion of screening. Potential uses for residual specimens include laboratory quality assurance, biomedical research, and, rarely, forensic applications. Our objective was to evaluate public opinion about the policies and practices relevant to the retention and use of residual bloodspots for biomedical research. METHODS: A total of 3855 respondents were recruited using 3 methods: focus groups (n = 157), paper or telephone surveys (n = 1418), and a Knowledge Networks panel (n = 2280). Some participants (n = 1769) viewed a 22-minute movie about the retention and use of residual specimens while other participants were provided only written information about this practice. All participants were surveyed using a 38-item questionnaire. RESULTS: A diverse set of participants was recruited. Respondents were very supportive of NBS in general and accepting of the use of residual bloodspots for important research activities. Respondents were evenly divided on the acceptability of NBS without parental permission, but the majority of respondents supported the use of an “opt-in” process for parental permission for residual bloodspot retention and use. Viewing the educational movie was associated with greater support for bloodspot retention and use. CONCLUSIONS: Our results show that the general public surveyed here was supportive of NBS and residual sample retention and research use. However, there was a clear preference for an informed permission process for parents regarding these activities. Education about NBS was associated with a higher level of support and may be important to maintain public trust in these important programs.

Retention and Research Use of Residual Newborn Screening Bloodspots

The storage and use of residual newborn screening dried blood specimens has generated significant controversy in the past 5 years, primarily because of public concerns over the lack of parental knowledge and consent for these activities. State policies addressing the management of these specimens vary widely, and there is currently little guidance to aid new state policy development to address the concerns of program professionals, investigators, and the general public. This article offers guidance for state policy based on multiple sources of data, including public attitudes, professional statements, state experience, and an analysis of the ethical, social, legal, and biomedical issues from a multidisciplinary group of scholars. This guidance will be useful for state programs that seek to develop policies that are informed by a contemporary analysis of the key ethical, legal, and social aspects of this practice. This article represents the work of the authors and does not represent American Academy of Pediatrics policy.

Assessing public attitudes on the retention and use of residual newborn screening blood samples: a focus group study.

This paper discusses attitudes and opinions of a diverse group of participants toward the retention and use of residual newborn blood samples for research. Data were drawn from focus groups based in six states in the USA, and results provide support for the retention and use of residual newborn blood samples for research when parental permission is asked beforehand. However, there were a number of concerns that also warrant attention for the development of policy and maintaining trust with the public, such as timing of permission, use of samples already stored, level of personal control of sample use and education. The results demonstrate the complexity of the topic and the ethical ambiguities associated with the retention and use of residual newborn blood samples.

Concerns of Newborn Blood Screening Advisory Committee Members Regarding Storage and Use of Residual Newborn Screening Blood Spots

OBJECTIVES We assessed attitudes and opinions of members of newborn blood screening (NBS) advisory committees regarding the storage and secondary research use of residual specimens from NBS. METHODS We conducted focus groups in 2008 and 2009 with NBS advisory committees (4 focus groups; n = 39 participants) in the Mountain States region (i.e., AZ, CO, MT, NM, NV, TX, UT, and WY). RESULTS Participants identified several challenges to implementing policies for storage of and research on residual newborn blood specimens. Themes that emerged from the data were public health relevancy; improvement of parental knowledge; impact of enhanced parental involvement; concerns over ownership, privacy, and confidentiality; identification of secondary research uses; and role of advisory committees. CONCLUSIONS Participants indicated that secondary uses of residual specimens entailed opportunities for improvements in NBS programs but also carried significant risks for their programs. Addressing concerns from stakeholders will be necessary for state-level adoption of national recommendations.