Genomic Sequencing in Maternal and Child Health

A special issue of Children (ISSN 2227-9067). This special issue belongs to the section "Pediatric Neonatology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 10996

Special Issue Editor


E-Mail Website
Guest Editor
Child Health Evaluative Sciences, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada
Interests: genome diagnostic and screening technologies; novel measures for assessing outcomes; understanding impacts of genomics on on patients; family members; health care providers; health care systems and socieety; health technology assessment

Special Issue Information

Dear Colleagues,

Exome and genome sequencing (ES/GS) exert profound influence on clinical care by ushering precision medicine into routine practice. Superior to conventional genetic tests in their ability to identify disease-causing variants in certain pediatric patient populations, these technologies are gaining traction as a gold standard diagnostic. However, further evidence of their value, value for money, and ethically appropriate use as diagnostic tools in the prenatal and early postnatal period is warranted. Beyond the diagnostic application of these technologies for prenatal, early postnatal, and pediatric care, attention is turning to their application to prenatal and newborn screening, where no a priori indication for testing exists. Arguably, the recommended reporting of secondary findings identified in the context of diagnostic applications of ES/GS suggests that the use of these technologies as screening tools is already taking place. While understanding the DNA code of an apparently healthy fetus, a newborn baby, or a young child may provide invaluable guidance and optimize individual and family health outcomes, harmful consequences are also plausible. Carefully deliberated principles and comprehensive evidence on the patient, provider, health system, and societal impacts of the use of these technologies in a screening context are urgently needed to enable the appropriate use of a range of applications of ES/GS in the maternal and child health context.

Dr. Robin Z. Hayeems
Guest Editor

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. Children is an international peer-reviewed open access monthly 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 2400 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

  • exome/genome sequencing
  • child health
  • prenatal screening and diagnosis
  • newborn screening and diagnosis
  • evidence-informed funding and policy decision making
  • ethical implications

Published Papers (7 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review, Other

11 pages, 440 KiB  
Article
Open-Source Artificial Intelligence System Supports Diagnosis of Mendelian Diseases in Acutely Ill Infants
by Joseph Reiley, Pablo Botas, Christine E. Miller, Jian Zhao, Sabrina Malone Jenkins, Hunter Best, Peter H. Grubb, Rong Mao, Julián Isla and Luca Brunelli
Children 2023, 10(6), 991; https://doi.org/10.3390/children10060991 - 1 Jun 2023
Cited by 1 | Viewed by 1449
Abstract
Mendelian disorders are prevalent in neonatal and pediatric intensive care units and are a leading cause of morbidity and mortality in these settings. Current diagnostic pipelines that integrate phenotypic and genotypic data are expert-dependent and time-intensive. Artificial intelligence (AI) tools may help address [...] Read more.
Mendelian disorders are prevalent in neonatal and pediatric intensive care units and are a leading cause of morbidity and mortality in these settings. Current diagnostic pipelines that integrate phenotypic and genotypic data are expert-dependent and time-intensive. Artificial intelligence (AI) tools may help address these challenges. Dx29 is an open-source AI tool designed for use by clinicians. It analyzes the patient’s phenotype and genotype to generate a ranked differential diagnosis. We used Dx29 to retrospectively analyze 25 acutely ill infants who had been diagnosed with a Mendelian disorder, using a targeted panel of ~5000 genes. For each case, a trio (proband and both parents) file containing gene variant information was analyzed, alongside patient phenotype, which was provided to Dx29 by three approaches: (1) AI extraction from medical records, (2) AI extraction with manual review/editing, and (3) manual entry. We then identified the rank of the correct diagnosis in Dx29’s differential diagnosis. With these three approaches, Dx29 ranked the correct diagnosis in the top 10 in 92–96% of cases. These results suggest that non-expert use of Dx29’s automated phenotyping and subsequent data analysis may compare favorably to standard workflows utilized by bioinformatics experts to analyze genomic data and diagnose Mendelian diseases. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
Show Figures

Figure 1

15 pages, 434 KiB  
Article
Intensive Care Clinicians’ Perspectives on Ethical Challenges Raised by Rapid Genomic Testing in Critically Ill Infants
by Sachini Poogoda, Fiona Lynch, Zornitza Stark, Dominic Wilkinson, Julian Savulescu, Danya Vears and Christopher Gyngell
Children 2023, 10(6), 970; https://doi.org/10.3390/children10060970 - 30 May 2023
Viewed by 1288
Abstract
Rapid genomic testing (rGT) enables genomic information to be available in a matter of hours, allowing it to be used in time-critical settings, such as intensive care units. Although rGT has been shown to improve diagnostic rates in a cost-effective manner, it raises [...] Read more.
Rapid genomic testing (rGT) enables genomic information to be available in a matter of hours, allowing it to be used in time-critical settings, such as intensive care units. Although rGT has been shown to improve diagnostic rates in a cost-effective manner, it raises ethical questions around a range of different areas, including obtaining consent and clinical decision-making. While some research has examined the perspectives of parents and genetics health professionals, the attitudes of intensive care clinicians remain under-explored. To address this gap, we administered an online survey to English-speaking neonatal/paediatric intensivists in Europe, Australasia and North America. We posed two ethical scenarios: one relating to obtaining consent from the parents and the second assessing decision-making regarding the provision of life-sustaining treatments. Descriptive statistics were used to analyse the data. We received 40 responses from 12 countries. About 50–75% of intensivists felt that explicit parental consent was necessary for rGT. About 68–95% felt that a diagnosis from rGT should affect the provision of life-sustaining care. Results were mediated by intensivists’ level of experience. Our findings show divergent attitudes toward ethical issues generated by rGT among intensivists and suggest the need for guidance regarding ethical decision-making for rGT. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
Show Figures

Figure 1

11 pages, 252 KiB  
Article
Rapid Genomic Testing in Intensive Care: Health Professionals’ Perspectives on Ethical Challenges
by Katie Arkell, Christopher Gyngell, Zornitza Stark and Danya F. Vears
Children 2023, 10(5), 824; https://doi.org/10.3390/children10050824 - 1 May 2023
Cited by 1 | Viewed by 1986
Abstract
Ultra-rapid genomic sequencing (urGS) is increasingly used in neonatal and pediatric intensive care settings (NICU/PICU), demonstrating high diagnostic and clinical utility. This study aimed to explore the perspectives of healthcare professionals (HPs) and the challenges raised by urGS, particularly when making treatment decisions. [...] Read more.
Ultra-rapid genomic sequencing (urGS) is increasingly used in neonatal and pediatric intensive care settings (NICU/PICU), demonstrating high diagnostic and clinical utility. This study aimed to explore the perspectives of healthcare professionals (HPs) and the challenges raised by urGS, particularly when making treatment decisions. Four focus groups and two interviews were conducted with HPs who had experience using urGS in NICU/PICU. Inductive content analysis was used to analyze the data. Nineteen HPs participated overall (eight clinical geneticists, nine genetic counselors, and two intensivists). One challenging area of practice identified by HPs was setting realistic expectations for outcomes of urGS among HPs and families. HPs reported modifying pre-test counseling to include life-limiting diagnoses as a possible test outcome and felt concerned about the timing of the test and its impact on parent–child bonding. UrGS results of uncertain prognostic significance posed considerable challenges. Moral distress arose when families and HPs were misaligned regarding treatment goals following the urGS diagnosis. We identified areas of practice that remain ethically challenging for HPs using urGS in the NICU/PICU. HPs experiences of using urGS in the NICU/PICU could inform specialized training in withdrawal of treatment decision making for the genomics workforce. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
18 pages, 647 KiB  
Article
Framing the Family: A Qualitative Exploration of Factors That Shape Family-Level Experience of Pediatric Genomic Sequencing
by Hadley Stevens Smith, Emily S. Bonkowski, Madison R. Hickingbotham, Raymond Belanger Deloge and Stacey Pereira
Children 2023, 10(5), 774; https://doi.org/10.3390/children10050774 - 25 Apr 2023
Viewed by 1465
Abstract
Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level [...] Read more.
Families of children with rare and undiagnosed conditions face many psychosocial and logistical challenges that may affect their approach to decisions about their child’s care and their family’s well-being. As genomic sequencing (GS) is increasingly incorporated into pediatric diagnostic workups, assessing the family-level characteristics that shape the experience of pediatric GS is crucial to understanding how families approach decision-making about the test and how they incorporate the results into their family life. We conducted semi-structured interviews with parents and other primary caregivers of pediatric patients who were evaluated for a suspected genetic condition and who were recommended to have GS (n = 20) or who had recently completed GS (n = 21). We analyzed qualitative data using multiple rounds of thematic analysis. We organized our thematic findings into three domains of factors that influence the family-level experience of GS: (1) family structure and dynamics; (2) parental identity, relationships, and philosophies; and (3) social and cultural differences. Participants conceptualized their child’s family in various ways, ranging from nuclear biological family to support networks made up of friends and communities. Our findings can inform the design and interpretation of preference research to advance family-level value assessment of GS as well as genetic counseling for families. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
Show Figures

Figure 1

Review

Jump to: Research, Other

9 pages, 217 KiB  
Review
The Future of Newborn Genomic Testing
by John D. Lantos
Children 2023, 10(7), 1140; https://doi.org/10.3390/children10071140 - 30 Jun 2023
Viewed by 924
Abstract
Genome sequencing (GS) provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. Nevertheless, there are reasons to remain cautious about the use of GS. Studies to date have been mostly in highly selected populations [...] Read more.
Genome sequencing (GS) provides exciting opportunities to rapidly identify a diagnosis in critically ill newborns and children with rare genetic conditions. Nevertheless, there are reasons to remain cautious about the use of GS. Studies to date have been mostly in highly selected populations of babies with unusual clinical presentations. GS leads to diagnoses in many such infants. More rarely, it leads to beneficial changes in management. Parents and physicians whose babies meet these criteria and for whom GS is performed both find these results useful. The concern is this: we do not know how useful such testing will be in the general population. We can speculate that a number of problems will arise as the use of GS expands. First, the percentage of cases in which a valid molecular diagnosis is made will likely go down. The number of ambiguous results or false positives will rise. Genetic counseling will become more complex and challenging. We do not know the relative cost-effectiveness of whole genome, whole exome, or targeted panels in different populations. We do not know the relative contribution of a molecular diagnosis to the decision to withdraw life support. We will have to carefully evaluate the use of such testing in order to understand whether it truly improves outcome and survival or reduces symptoms in babies who are tested. Each of these concerns will require careful study of both the technology and the ethical issues to allow us to harness the potential of these new technologies while avoiding foreseeable problems. Studies are underway to see how the tests are used in general populations. These studies should generate important information to guide clinicians and policymakers. As part of informed consent, doctors should explain to parents that genetic results are not always straightforward. Sometimes, they confirm a diagnosis that was already suspected. Sometimes, they rule out a possible diagnosis. Sometimes, the results are ambiguous and difficult to interpret. Anticipatory discussions should try to give parents a realistic understanding of the likely impact of a genetic diagnosis. Diagnostic genomic testing for newborns is a science that is still in its infancy. More research is essential in order to establish how to personalize this promising but sometimes problematic tool. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
21 pages, 1248 KiB  
Review
Translating Precision Health for Pediatrics: A Scoping Review
by Mathushan Subasri, Celine Cressman, Danielle Arje, Leighton Schreyer, Erin Cooper, Komal Patel, Wendy J. Ungar, Melanie Barwick, Avram Denburg and Robin Z. Hayeems
Children 2023, 10(5), 897; https://doi.org/10.3390/children10050897 - 17 May 2023
Viewed by 1577
Abstract
Precision health aims to personalize treatment and prevention strategies based on individual genetic differences. While it has significantly improved healthcare for specific patient groups, broader translation faces challenges with evidence development, evidence appraisal, and implementation. These challenges are compounded in child health as [...] Read more.
Precision health aims to personalize treatment and prevention strategies based on individual genetic differences. While it has significantly improved healthcare for specific patient groups, broader translation faces challenges with evidence development, evidence appraisal, and implementation. These challenges are compounded in child health as existing methods fail to incorporate the physiology and socio-biology unique to childhood. This scoping review synthesizes the existing literature on evidence development, appraisal, prioritization, and implementation of precision child health. PubMed, Scopus, Web of Science, and Embase were searched. The included articles were related to pediatrics, precision health, and the translational pathway. Articles were excluded if they were too narrow in scope. In total, 74 articles identified challenges and solutions for putting pediatric precision health interventions into practice. The literature reinforced the unique attributes of children and their implications for study design and identified major themes for the value assessment of precision health interventions for children, including clinical benefit, cost-effectiveness, stakeholder values and preferences, and ethics and equity. Tackling these identified challenges will require developing international data networks and guidelines, re-thinking methods for value assessment, and broadening stakeholder support for the effective implementation of precision health within healthcare organizations. This research was funded by the SickKids Precision Child Health Catalyst Grant. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
Show Figures

Figure 1

Other

Jump to: Research, Review

9 pages, 249 KiB  
Essay
Managing Prognosis in Precision Medicine: Utility, Imagination, and Communication
by Rebecca Mueller, Brittany M. Lee and Katharine Press Callahan
Children 2023, 10(4), 664; https://doi.org/10.3390/children10040664 - 31 Mar 2023
Cited by 1 | Viewed by 1315
Abstract
Research on how physicians predict and communicate prognosis focuses primarily on end-of-life care. Unsurprisingly, as genomic technology gains traction as a prognostic tool, the focus has also been on terminality, with research focused on how genetic results may be used to terminate pregnancies [...] Read more.
Research on how physicians predict and communicate prognosis focuses primarily on end-of-life care. Unsurprisingly, as genomic technology gains traction as a prognostic tool, the focus has also been on terminality, with research focused on how genetic results may be used to terminate pregnancies or redirect care towards palliation for neonates. However, genomic results also have powerful impacts on how patients who live prepare for their futures. Genomic testing provides broad-reaching and early—albeit complex, uncertain, and shifting—prognostic information. In this essay, we argue that as genomic testing occurs earlier and increasingly in a screening context, researchers and clinicians must strive to understand and manage the prognostic implications of results. While our understanding of the psychosocial and communicational aspects of prognosis in symptomatic populations is incomplete, it has progressed further than our understanding in a screening context and therefore provides useful lessons and feasible opportunities for further research. By providing an interdisciplinary and inter-specialty perspective on the psychosocial and communicational aspects of prognosis in genetics, we discuss prognostication with respect to genetics from the neonatal period through adulthood, highlighting medical specialties and patient populations that are especially informative for considering the longitudinal management of prognostic information in genomic medicine. Full article
(This article belongs to the Special Issue Genomic Sequencing in Maternal and Child Health)
Show Figures

Graphical abstract

Back to TopTop