The return of genetic research results after death in the pediatric setting comes with unique complexities. Researchers must determine which results and through which processes results are returned. This paper discusses the experience over 15 years in pediatric cancer genetics research of returning research results after the death of a child and proposes a preventive ethics approach to protocol development in order to improve the quality of return of results in pediatric genomic settings.

Psychiatric disorders present distinct clinical challenges which are partly attributable to their multifactorial aetiology and the absence of laboratory tests that can be used to confirm diagnosis or predict risk. Psychiatric disorders are highly heritable, but also polygenic, with genetic risk conferred by interactions between thousands of variants of small effect that can be summarized in a polygenic risk score. We discuss four areas in which the use of polygenic risk scores in psychiatric research and clinical contexts could have ethical (...) implications. First, there is concern that clinical use of polygenic risk scores may exacerbate existing health inequities. Second, research findings regarding polygenic risk could be misinterpreted in stigmatising or discriminatory ways. Third, there are concerns associated with testing minors as well as eugenics concerns elicited by prenatal polygenic risk testing. Fourth, potential challenges that could arise with the feedback and interpretation of high polygenic risk for a psychiatric disorder would require consideration. While there would be extensive overlap with the challenges of feeding back genetic findings in general, the potential clinical use of polygenic risk scoring warrants discussion in its own right, given the recency of this possibility. To this end, we discuss how lay interpretations of risk and genetic information could intersect. Consideration of these factors would be necessary for ensuring effective and constructive communication and interpretation of polygenic risk information which, in turn, could have implications for the uptake of any therapeutic recommendations. Recent advances in polygenic risk scoring have major implications for its clinical potential, however, care should be taken to ensure that communication of polygenic risk does not feed into problematic assumptions regarding mental disorders or support reductive interpretations. (shrink)

There may be compelling reasons to return to parents a limited subset of results from research conducted using residual newborn screening dried blood samples. This article explores the circumstances under which research results might be returned, as well as the mechanisms by which state newborn screening programs might facilitate the return of research results. The scope of any responsibility to return results of research conducted using DBS should be assessed in light of the potential impact on the primary mission of (...) state newborn screening programs. (shrink)

In debates about genetic testing of children, as well as about disclosing unsolicited findings (UFs) of pediatric exome sequencing, respect for future autonomy should be regarded as a prima facie consideration for not taking steps that would entail denying the future adult the opportunity to decide for herself about what to know about her own genome. While the argument can be overridden when other, morally more weighty considerations are at stake, whether this is the case can only be determined in (...) concrete cases. Importantly, when children grow into adolescents, respect for future autonomy will have to give way to respecting their emerging autonomy. When pediatric exome sequencing is done for complex conditions not involving developmental delay, respect for the child’s future or emerging autonomy should be a primary consideration for those charged with deciding on behalf of the child. Building on what Emanuel and Emanuel have termed the ‘deliberative model’ of shared decision making, we argue that if parents fail to give these considerations their due, professionals should actively invite them to do so. Taking a directive stance may be needed in order to make sure that the future or emerging autonomy of the child are duly considered in the decision-making process, but also to help the parents and themselves to shape their respective roles as responsible care-givers. (shrink)

Background Massively parallel sequencing techniques, such as whole exome sequencing (WES) and whole genome sequencing (WGS), may reveal unsolicited findings (UFs) unrelated to the diagnostic aim. Such techniques are frequently used for diagnostic purposes in pediatric cases of developmental delay (DD). Yet policy guidelines for informed consent and return of UFs are not well equipped to address specific moral challenges that may arise in these children’s situations. Discussion In previous empirical studies conducted by our research group, we found that it (...) is sometimes uncertain how children with a DD will develop and whether they could come to possess capacities for autonomous decision-making in the future. Parents sometimes felt this brought them into a Catch-22 like situation when confronted with choices about UFs before undergoing WES in trio-analysis (both the parents’ and child’s DNA are sequenced). An important reason for choosing to consent to WES was to gain more insight into how their child might develop. However, to make responsible choices about receiving or declining knowledge of UFs, some idea of their child’s future development of autonomous capacities is needed. This undesirable Catch-22 situation was created by the specific policy configuration in which parents were required to make choices about UFs before being sequencing (trio-analysis). We argue that this finding is relevant for reconfiguring current policies for return of UFs for WES/WGS and propose guidelines that encompass two features. First, the informed consent process ought to be staged. Second, differing guidelines are required for withholding/disclosing a UF in cases of DD appropriate to the level of confidence there is about the child’s future developmental of autonomous capacities. Conclusion When combined with a dynamic consent procedure, these two features of our guidelines could help overcome significant moral challenges that present themselves in the situations of children undergoing genomic sequencing for clarifying a DD. (shrink)

Adolescents may often have opinions about whether they want genetic and genomic testing in both the clinic and research and about who should have access to the results. This legal analysis demonstrates that the law provides very little protection to minors' wishes.