Whole-genome sequencing in newborn screening? A statement on the continued importance of targeted approaches in newborn screening programmes

Abstract

The advent and refinement of sequencing technologies has resulted in a decrease in both the cost and time needed to generate data on the entire sequence of the human genome. This has increased the accessibility of using whole-genome sequencing and whole-exome sequencing approaches for analysis in both the research and clinical contexts. The expectation is that more services based on these and other high-throughput technologies will become available to patients and the wider population. Some authors predict that sequencing will be performed once in a lifetime, namely, shortly after birth. The Public and Professional Policy Committee of the European Society of Human Genetics, the Human Genome Organisation Committee on Ethics, Law and Society, the PHG Foundation and the P3G International Paediatric Platform address herein the important issues and challenges surrounding the potential use of sequencing technologies in publicly funded newborn screening (NBS) programmes. This statement presents the relevant issues and culminates in a set of recommendations to help inform and guide scientists and clinicians, as well as policy makers regarding the necessary considerations for the use of genome sequencing technologies and approaches in NBS programmes. The primary objective of NBS should be the targeted analysis and identification of gene variants conferring a high risk of preventable or treatable conditions, for which treatment has to start in the newborn period or in early childhood.

Responsible Implementation of Expanded Screening Programs for Genetic Diseases at the Beginning of Life

“…A potential future driver of expansions is sequencing techniques, either whole genome sequencing, whole exome sequencing or targeted panels [16]. For the moment, the cost is much higher than that for regular neonatal screening programs, and the test properties, such as sensitivity and positive predictive value, are insufficiently characterized; however, it is conceivable that these technologies will be used in the near future as a second tier test to limit the number of false positives.…”

“…If more disorders can be diagnosed, a decision must be made regarding the benefits, or whether the targets should remain those where a clear health benefit can be achieved by earlier diagnosis [16]. Some have argued that earlier diagnosis of "untreatable" conditions is beneficial by avoiding a long diagnostic odyssey.…”

The Use of Next-Generation Sequencing for Research and Diagnostics for Intellectual Disability

“…Finally, ethical concerns need also be considered for the application of NGS to ID in both clinical and research settings, in particular, the possibility of incidental findings as had been discussed in many articles (e.g., see Knoppers et al 2014;Howard et al 2015). For gene-panel approaches, issues of incidental findings are obviously much less of a concern.…”

Psychosocial effects in parents and children 12 years after newborn genetic screening for type 1 diabetes

“…This study employed the parent measure consisting of 42 items presented with a 5-point Likert-type endorsement scale. The items are divided into five subscales: Involvement (minimum score 10-maximum score 50), Positive Parenting (6-30), Poor Monitoring/Supervision (10-50), Inconsistent Discipline (6-30), Corporal Punishment (4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Other Discipline Practices is not a scale, but provides information on an item-by-item basis.…”

“…4 While there are many issues to consider (including the child's future autonomy, confidentiality of medical data and informed consent), understanding the potential impact that knowledge of genetic disorders and health risks might have on the psychosocial wellbeing of parents and children is a key element of such discussions. 4,5 This latter issue is amenable to empirical investigation and although relatively under-researched, two recent systematic reviews have assessed the available evidence. 6,7 These early data, largely confined to effects of testing for carrier status or predicting single gene disorders, suggest that serious impacts on traditional psychological parameters such as anxiety and depression are uncommon.…”