Special Issue "Ethical and Psychosocial Aspects of Genomics in the Neonatal Period"

A special issue of International Journal of Neonatal Screening (ISSN 2409-515X).

Deadline for manuscript submissions: 30 June 2022 | Viewed by 8244

Special Issue Editors

Dr. Lynn Wein Bush
E-Mail Website1 Website2
Guest Editor
PhD MS MA, Department of Pediatrics, Division of Genetics and Genomics, Boston Children’s Hospital and Center for Bioethics, Harvard Medical School, Boston, MA 02115, USA
Interests: bioethics; rare diseases; ethical and psychosocial aspects of genomics; newborn screening; newborn sequencing; prenatal diagnosis and screening; pediatric innovative therapies; fetal therapies; inborn errors of metabolism; neurodevelopmental disorders; pediatric clinical genomics; clinical ethics; research ethics
Dr. Olaf Bodamer
E-Mail Website
Guest Editor
Park Gerald Chair of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA
Interests: Kabuki syndrome; lysosomal storage disorders; personalized medicine; newborn screening
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Special Issue Information

Dear Colleagues,

As the application of genomics in the neonatal period accelerates, it is important for the global community to critically examine the ethical and psychosocial implications —potential benefits and potential harms — shaped in large part by the current scientific and resource allocation landscape. Genome-based technologies, ranging from large targeted panel screens to comprehensive whole genome sequencing to innovative therapies, pose contextually nuanced opportunities and challenges, with differing calculus when utilized in a neonatal intensive care unit as compared with a mandated public health screening program. Consideration for the complexities of the decision-making process and counseling are essential whether for ill or healthy neonates, and especially if faced with a high level of variability, uncertainty, or access limitations.

We welcome scholarly submissions with diverse perspectives related to these and other ethical and psychosocial aspects of integrating genomics in the neonatal period. The scope of inquiry for this Special Issue is broad, with substantive empirical research (quantitative, qualitative, or mixed methodologies), reports of developing novel approaches to better evaluate or minimize psychological distress, updated reviews of the literature, and brief commentaries with an ethical analysis amongst those being encouraged.

While not an exhaustive list of topics, suggested themes of interest involving genomics in the NBS and/or NICU setting include the following:

  • International, regional, cultural, and comparative perspectives
  • Newborn population-based for neurological, auditory, or visual conditions not currently screened for, with some not manifesting until later in childhood
  • Implications of secondary and incidental findings
  • Impact of variable phenotypes and uncertain prognosis, including age of onset
  • Uncertain or unknown genotype-phenotype correlation
  • Disclosure of adult-onset conditions
  • Balancing the best interests of the child with the interests and perspectives of the family and society
  • Identifying and disclosing carrier status, including distinctions between true carriers and individuals with variant risk alleles (1 or 2)
  • Financial/reimbursement issues with universal health care systems versus non-government run programs
  • Informed consent issues for public health initiative
  • Identification of risk when the diversity of the population is not yet adequately reflected in the variant databases, including ascertainment bias
  • Criteria decision-point to expand conditions using newborn genome panels
  • Blurring the distinction between health, illness, disability, normalcy, and rarity
  • Diagnostic odyssey
  • Genomic information to eventually shift diagnosis or therapy to the prenatal period
  • Sequencing to inform management, including new genetic therapies

Dr. Lynn Wein Bush
Dr. Olaf Bodamer
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Neonatal Screening is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • neonatal sequencing
  • neonatal genomics
  • newborn sequencing
  • newborn genomics
  • newborn screening
  • incidental findings
  • secondary findings
  • carrier status
  • best interest of the child
  • adult onset
  • uncertainty
  • variable phenotype

Published Papers (7 papers)

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Research

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Article
A Public Dialogue to Inform the Use of Wider Genomic Testing When Used as Part of Newborn Screening to Identify Cystic Fibrosis
Int. J. Neonatal Screen. 2022, 8(2), 32; https://doi.org/10.3390/ijns8020032 - 09 May 2022
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Abstract
Cystic fibrosis (CF) has been included within the UK national newborn screening programme since 2007. The approach uses measures of immunoreactive trypsin (IRT) in dried blood spot samples obtained at day 5 of life. Samples which reveal IRT results >99.5th centile go on [...] Read more.
Cystic fibrosis (CF) has been included within the UK national newborn screening programme since 2007. The approach uses measures of immunoreactive trypsin (IRT) in dried blood spot samples obtained at day 5 of life. Samples which reveal IRT results >99.5th centile go on to be tested for a limited panel of CF mutations. While the programme works well and achieves a high level of sensitivity and specificity, it relies upon repeat testing in some cases and identifies probable carriers, both potentially provoking parental anxiety. In addition, the limited CF mutation panel may not fully reflect the ethnic diversity within the UK population. The use of wider genomic screening, made possible by next-generation sequencing to replace more limited panels, can be used to avoid these shortcomings. However, the way in which this approach is employed can either be designed to maximise specificity by limiting reporting to combinations of known pathogenic mutations or can maximise sensitivity by also reporting combinations of pathogenic mutations together with variants of uncertain significance. The latter approach also increases the number of Cystic Fibrosis Screen-Positive Inconclusive Diagnosis (CFSPID) designations reported, resulting in uncertainty for parents. To help consider the design of the programme, a dialogue was commissioned by the UK National Screening Committee (UKNSC) to elicit the views of members of the public without direct experience of CF, to determine if there was a preference for maximising the sensitivity or the specificity of CF screening. The participants initially expressed a clear preference to maximise sensitivity and avoid missing CF cases, but after time to reflect and consider the implications of their choice, a number changed their views so as to tolerate some missed cases if this resulted in greater certainty of outcome; this became the majority view. It is proposed that it may be a generalisable finding that the public, when facing whole-population screening programmes, may require significant time and information to inform and make their choices and may attach great importance to clarity and certainty of outcome in the screening process. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)
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Article
Genomics and Newborn Screening: Perspectives of Public Health Programs
Int. J. Neonatal Screen. 2022, 8(1), 11; https://doi.org/10.3390/ijns8010011 - 28 Jan 2022
Cited by 1 | Viewed by 1104
Abstract
This study assesses the benefits and challenges of using genomics in Newborn Screening Programs (NBS) from the perspectives of State program officials. This project aims to help programs develop policies that will aid in the integration of genomic technology. Discussion groups were conducted [...] Read more.
This study assesses the benefits and challenges of using genomics in Newborn Screening Programs (NBS) from the perspectives of State program officials. This project aims to help programs develop policies that will aid in the integration of genomic technology. Discussion groups were conducted with the NBS Program and Laboratory Directors in the seven HRSA Regional Genomics Collaboratives (August 2014–March 2016). The discussion groups addressed expected uses of genomics, potential benefits, and challenges of integrating genomic technology, and educational needs for parents and other NBS stakeholders: Twelve focus groups were conducted, which included participants from over 40 state programs. Benefits of incorporating genomics included improving screening modalities, supporting diagnostic procedures, and screening for a wider spectrum of disorders. Challenges included the costs of genomics, the ability to educate parents and health care providers about results, and the potential negative psychosocial impact of genomic information. Attempts to address the challenges of integrating genomics must focus on preserving the child welfare goals of NBS programs. Health departments will need to explore how genomics could be used to enhance programs while maintaining universal access to screening. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)

Review

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Review
Select Ethical Aspects of Next-Generation Sequencing Tests for Newborn Screening and Diagnostic Evaluation of Critically Ill Newborns
Int. J. Neonatal Screen. 2021, 7(4), 76; https://doi.org/10.3390/ijns7040076 - 08 Nov 2021
Cited by 1 | Viewed by 1067
Abstract
In this review, we analyze medical and select ethical aspects of the increasing use of next-generation sequencing (NGS) based tests in newborn medicine. In the last five years, there have been several studies exploring the role of rapid exome sequencing (ES) and genome [...] Read more.
In this review, we analyze medical and select ethical aspects of the increasing use of next-generation sequencing (NGS) based tests in newborn medicine. In the last five years, there have been several studies exploring the role of rapid exome sequencing (ES) and genome sequencing (GS) in critically ill newborns. While the advantages include a high diagnostic yield with potential changes in interventions, there have been ethical dilemmas surrounding consent, information about adult-onset diseases and resolution of variants of uncertain significance. Another active area of research includes a cohort of studies funded under Newborn Sequencing in Genomic Medicine and Public Health pertaining to the use of ES and GS in newborn screening (NBS). While these techniques may allow for screening for several genetic disorders that do not have a detectable biochemical marker, the high costs and long turnaround times of these tests are barriers in their utilization as public health screening tests. Discordant results between conventional NBS and ES-based NBS, as well as challenges with consent, are other potential pitfalls of this approach. Please see the Bush, Al-Hertani and Bodamer article in this Special Issue for the broader scope and further discussion. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)

Other

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Commentary
Ethical Considerations for Equitable Access to Genomic Sequencing for Critically Ill Neonates in the United States
Int. J. Neonatal Screen. 2022, 8(1), 22; https://doi.org/10.3390/ijns8010022 - 21 Mar 2022
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Abstract
Rare diseases impact all socio-economic, geographic, and racial groups indiscriminately. Newborn screening (NBS) is an exemplary international public health initiative that identifies infants with rare conditions early in life to reduce morbidity and mortality. NBS theoretically promotes equity through universal access, regardless of [...] Read more.
Rare diseases impact all socio-economic, geographic, and racial groups indiscriminately. Newborn screening (NBS) is an exemplary international public health initiative that identifies infants with rare conditions early in life to reduce morbidity and mortality. NBS theoretically promotes equity through universal access, regardless of financial ability. There is however heterogeneity in access to newborn screening and conditions that are screened throughout the world. In the United States and some other developed countries, NBS is provided to all babies, subsidized by the local or federal government. Although NBS is an equitable test, infants admitted to neonatal intensive care units (NICUs) may not receive similar benefits to healthier infants. Newborns in the NICU may receive delayed and/or multiple newborn screens due to known limitations in interpreting the results with prematurity, total parenteral nutrition, blood transfusions, infection, and life support. Thus, genomic technologies might be needed in addition to NBS for equitable care of this vulnerable population. Whole exome (WES) and genome sequencing (WGS) have been recently studied in critically ill newborns across the world and have shown promising results in shortening diagnostic odysseys and providing clinical utility. However, in certain circumstances several barriers might limit access to these tests. Here, we discuss some of the existing barriers to genomic sequencing in NICUs in the United States, explore the ethical implications related to low access, consider ways to increase access to genomic testing, and offer some suggestions for future research in these areas. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)
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Commentary
Expanded Newborn Screening and Genomic Sequencing in Latin America and the Resulting Social Justice and Ethical Considerations
Int. J. Neonatal Screen. 2021, 7(1), 6; https://doi.org/10.3390/ijns7010006 - 21 Jan 2021
Cited by 2 | Viewed by 996
Abstract
Newborn screening (NBS) has widely been utilized in developed countries as a cost-effective public health strategy that reduces morbidity and mortality. Developing countries, however, are new to the NBS scene and have their own unique challenges, both in instituting the program as well [...] Read more.
Newborn screening (NBS) has widely been utilized in developed countries as a cost-effective public health strategy that reduces morbidity and mortality. Developing countries, however, are new to the NBS scene and have their own unique challenges, both in instituting the program as well as effectively acting on the results. NBS offers numerous ethical issues on a global scale, however, here we argue that there are unique ethical issues surrounding the development and expansion of newborn screening in Latin America given its highly heterogenous population. Once a NBS program is effectively instated, ethical considerations continue when pursuing expansion of screening to include further conditions. While Latin America grapples with the ethics of expanded newborn screening (ENBS), some developed countries discuss utility of genomic sequencing technologies in the newborn population. When the ability to detect further pathology is expanded, one must know what to do with this information. As rare diseases are identified either on ENBS or via genome sequencing, access to treatments for these rare diseases can be a real challenge. If we consider newborn screening as a global initiative, then we need more than a deontology approach to analyze these challenges; we need an approach that considers the unique characteristics of each territory and tremendous heterogeneity that exists prior to the implementation of these programs. As genomic technology advances further in the developed world, while some developing countries still lack even basic newborn screening, there is a further widening of the gap in global health disparities. The question is posed as to who has responsibility for these newborns’ lives on an international level. Without an approach towards newborn screening that accounts for the diverse global population, we believe optimal outcomes for newborns and families across the world will not be achieved. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)
Commentary
Ethical Issues Surrounding Newborn Screening
Int. J. Neonatal Screen. 2021, 7(1), 3; https://doi.org/10.3390/ijns7010003 - 09 Jan 2021
Cited by 1 | Viewed by 1348
Abstract
It would be difficult to overestimate the importance of persistent, thoughtful parents and their importance in the development of treatments for their children’s rare disorders. Almost a century ago in Norway, observant parents led a brilliant young physician-scientist to his discovery of the [...] Read more.
It would be difficult to overestimate the importance of persistent, thoughtful parents and their importance in the development of treatments for their children’s rare disorders. Almost a century ago in Norway, observant parents led a brilliant young physician-scientist to his discovery of the underlying cause of their children’s profound developmental delay—i.e., phenylketonuria, or PKU. Decades later, in a recovering war-ravaged Britain, an equally persistent mother pressed the scientists at Birmingham Children’s Hospital to find a way to treat her seriously damaged daughter, Sheila, who suffered from PKU. Living on the financial edge, this mother insisted that Bickel and colleagues develop such a diet, and she volunteered Sheila to be the patient in the trial. The scientists concluded that the low phenylalanine diet helped but needed to be started very early—so, newborn screening was born to permit the implementation of this. Many steps brought us to where we are today, but these courageous parents made it all begin. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)
Commentary
Ethical and Psychosocial Implications of Genomic Newborn Screening
Int. J. Neonatal Screen. 2021, 7(1), 2; https://doi.org/10.3390/ijns7010002 - 09 Jan 2021
Cited by 3 | Viewed by 1424
Abstract
The potential for genomic screening of the newborn, specifically adding genomic screening to current newborn screening (NBS), raises very significant ethical issues. Regardless of whether NBS of this type would include entire genomes or only the coding region of the genome (exome screening) [...] Read more.
The potential for genomic screening of the newborn, specifically adding genomic screening to current newborn screening (NBS), raises very significant ethical issues. Regardless of whether NBS of this type would include entire genomes or only the coding region of the genome (exome screening) or even sequencing specific genes, the ethical issues raised would be enormous. These issues include the limitations of bioinformatic interpretation of identified variants in terms of pathogenicity and accurate prognosis, the potential for substantial uncertainty about appropriate diagnosis, therapy, and follow-up, the possibility of much anxiety among providers and parents, the potential for unnecessary treatment and “medicalizing” normal children, the possibility of adding large medical costs for otherwise unnecessary follow-up and testing, the potential for negatively impacting medical and life insurance, and the almost impossible task of obtaining truly-informed consent. Moreover, the potentially-negative consequences of adding genomic sequencing to NBS might jeopardize all of NBS which has been and continues to be so beneficial for thousands of children and their families throughout the world. Full article
(This article belongs to the Special Issue Ethical and Psychosocial Aspects of Genomics in the Neonatal Period)
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