The rapid development of genomic sequencing technologies has decreased the cost of genetic analysis to the extent that it seems plausible that genome-scale sequencing could have widespread availability in pediatric care. Genomic sequencing provides a powerful diagnostic modality for patients who manifest symptoms of monogenic disease and an opportunity to detect health conditions before their development. However, many technical, clinical, ethical, and societal challenges should be addressed before such technology is widely deployed in pediatric practice. This article provides an overview of the Newborn Sequencing in Genomic Medicine and Public Health Consortium, which is investigating the application of genome-scale sequencing in newborns for both diagnosis and screening.

BackgroundThe greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The “BabySeq Project” is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.MethodsFamilies of newborns are enrolled from Boston Children’s Hospital and Brigham and Women’s Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.DiscussionThe BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns.Trial registrationThe study is registered in ClinicalTrials.gov Identifier: NCT02422511. Registration date: 10 April 2015.

Background Increasing numbers of healthy individuals are undergoing predispositional personal genome sequencing. Here we describe the design and early outcomes of the PeopleSeq Consortium, a multi-cohort collaboration of predispositional genome sequencing projects, which is examining the medical, behavioral, and economic outcomes of returning genomic sequencing information to healthy individuals. Methods Apparently healthy adults who participated in four of the sequencing projects in the Consortium were included. Web-based surveys were administered before and after genomic results disclosure, or in some cases only after results disclosure. Surveys inquired about sociodemographic characteristics, motivations and concerns, behavioral and medical responses to sequencing results, and perceived utility. Results Among 1395 eligible individuals, 658 enrolled in the Consortium when contacted and 543 have completed a survey after receiving their genomic results thus far (mean age 53.0 years, 61.4% male, 91.7% white, 95.5% college graduates). Most participants (98.1%) were motivated to undergo sequencing because of curiosity about their genetic make-up. The most commonly reported concerns prior to pursuing sequencing included how well the results would predict future risk (59.2%) and the complexity of genetic variant interpretation (56.8%), while 47.8% of participants were concerned about the privacy of their genetic information. Half of participants reported discussing their genomic results with a healthcare provider during a median of 8.0 months after receiving the results; 13.5% reported making an additional appointment with a healthcare provider specifically because of their results. Few participants (< 10%) reported making changes to their diet, exercise habits, or insurance coverage because of their results. Many participants (39.5%) reported learning something new to improve their health that they did not know before. Reporting regret or harm from the decision to undergo sequencing was rare (< 3.0%). Conclusions Healthy individuals who underwent predispositional sequencing expressed some concern around privacy prior to pursuing sequencing, but were enthusiastic about their experience and not distressed by their results. While reporting value in their health-related results, few participants reported making medical or lifestyle changes. Electronic supplementary material The online version of this article (10.1186/s13073-019-0619-9) contains supplementary material, which is available to authorized users.

Low interest in research and study logistics were major initial barriers to postpartum enrollment and are likely generic to many postpartum research efforts. Concerns over privacy and result implications were most commonly cited in decliners after ES. Understanding parental concerns around research nGS may inform future integration of nGS into newborn screening, predictive testing, and pediatric diagnostics.

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Various stakeholders have issued recommendations regarding the use of genomics in pediatrics. These guidelines are driven in part by concerns about psychosocial risks of disclosing predictive genomic information during childhood. As genomic sequencing becomes more commonly used in pediatric settings, it is important to systematically study the psychosocial impact of genomic sequencing of newborns, including the impact on family dynamics. Through review of the psychological and genetic counseling literature, we identify the following 3 domains of family dynamics that have potential to be impacted by the return of genomic results during the newborn period: perceived child vulnerability, parent-child bonding, and self and partner blame. In this article, we outline the complexity of studying these psychosocial outcomes and our plan to examine them in the BabySeq Project, a randomized controlled trial in both healthy and sick infants, in which the return of genomic information will be compared with standard of care. This trial has been registered at https:// clinicaltrials. gov/ ct2/ show/ NCT02422511 (identifier NCT02422511).

BACKGROUND AND OBJECTIVES: There is interest in applying genomic sequencing (GS) to newborns’ clinical care. Here we explore parents’ and clinicians’ attitudes toward and perceptions of the risks, benefits, and utility of newborn GS compared with newborn screening (NBS) prior to receiving study results. METHODS: The BabySeq Project is a randomized controlled trial used to explore the impact of integrating GS into the clinical care of newborns. Parents (n = 493) of enrolled infants (n = 309) and clinicians (n = 144) completed a baseline survey at enrollment. We examined between-group differences in perceived utility and attitudes toward NBS and GS. Open-ended responses about risks and benefits of each technology were categorized by theme. RESULTS: The majority of parents (71%) and clinicians (51%) agreed that there are health benefits of GS, although parents and clinicians agreed more that there are risks associated with GS (35%, 70%) than with NBS (19%, 39%; all P < .05), Parents perceived more benefit and less risk of GS than did clinicians. Clinicians endorsed concerns about privacy and discrimination related to genomic information more strongly than did parents, and parents anticipated benefits of GS that clinicians did not. CONCLUSIONS: Parents and clinicians are less confident in GS than NBS, but parents perceive a more favorable risk/benefit ratio of GS than do clinicians. Clinicians should be aware that parents’ optimism may stem from their perceived benefits beyond clinical utility.

The return of information from genomic sequencing in children, especially in early life, brings up complex issues around parental autonomy, the child’s future autonomy, the best interest standard, and the best interests of the family. These issues are particularly important in considering the return of genomic results for adult-onset-only conditions in children. The BabySeq Project is a randomized trial used to explore the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of newborns who are healthy or sick. We discuss a case in which a variant in a gene for an actionable, adult-onset- only condition was detected, highlighting the ethical issues surrounding the return of such finding in a newborn to the newborn’s parents.