Genomic sequencing in newborn screening: balancing consent with the right of the asymptomatic at-risk child to be found

The paper addresses how consent should be designed and implemented when genomic sequencing is incorporated into newborn screening (NBS) programs, while safeguarding children’s health rights. It situates NBS as a public health initiative that has expanded since the 1960s from a few treatable conditions (e.g., PKU, congenital hypothyroidism) to 50–60 conditions in many jurisdictions, driven by technologies such as tandem mass spectrometry (MS/MS), new treatments, advocacy, and evolving screening criteria. Genomic sequencing can identify hundreds of conditions and store data for future interrogation, raising distinctive consent challenges compared to MS/MS. The central research question is how to balance the complexities of genomic information and consent at population scale with the child’s interests, articulated as a right of the asymptomatic at-risk child to be found through screening.

The authors review core screening principles (Wilson and Jungner criteria) emphasizing recognized need, seriousness, effective treatment, and identifiable early stages, while noting contemporary expansions to include equity and access. They examine public health ethics as a framing for NBS and genomic population screening, highlighting values of solidarity, reciprocity, equity, common goods, and intergenerational connectedness. They summarize global consent practices for NBS: approaches range from implied consent, verbal consent, and opt-out to written consent or mandated participation, with substantial variability across Europe, North America, and Latin America. Prior literature cautioned against premature expansion of genomic sequencing into NBS due to cost, ethics, social implications, and risks to universal accessibility; it also documented challenges to fully informed consent given the complexity and uncertainty of genomic results. The authors reference existing and completed genomic NBS research (e.g., NC Nexus, BabySeq 1) and emerging moves toward global consensus on condition selection, while noting departures from traditional criteria in projects offering optional panels for untreatable conditions or polygenic risk scores.

This is a normative legal-ethical analysis informed by a targeted review of ongoing and recent research programs piloting genomic sequencing in newborn screening. The authors: (1) synthesize public health ethics and legal frameworks (including the UN Convention on the Rights of the Child) relevant to consent and children’s health rights; (2) review two completed genomic NBS studies (NC Nexus; BabySeq 1) and summarize seven ongoing or imminent projects using genomic sequencing via virtual panels, drawing on information collected at ICNOS 2023 and project websites; and (3) analyze consent approaches (timing, modality, content) across these projects to assess feasibility and proportionality at population scale. The approach is conceptual rather than empirical or systematic; it integrates legal norms, ethical principles, and descriptive information about pilot studies to argue for an ‘appropriate consent’ model in genomic NBS.

- Genomic sequencing in NBS intensifies consent challenges due to the complexity, breadth, and future reusability of genomic data, shifting consent from condition-specific to category- or rationale-based information. - As a population screening program, NBS should be framed within public health ethics, emphasizing solidarity, reciprocity, equity, and common goods; consent must be feasible, comprehensible, and scalable to preserve universality and equity. - The authors articulate a novel right of the asymptomatic at-risk child to be found, grounded in children’s health rights under the UN Convention on the Rights of the Child (e.g., best interests, highest attainable standard of health, preventive care). This right supports identifying children with actionable conditions, including rare disorders detectable primarily through genomic methods. - Completed genomic NBS research (e.g., NC Nexus and BabySeq 1) used WES assessing up to 822 and 954 genes, respectively. Seven ongoing/imminent projects use genomic sequencing analyzed via virtual panels, with condition counts typically between ~180 and ~604, reflecting heterogeneity in inclusion principles and movement toward global consensus. - Some projects (e.g., Early Check, GUARDIAN) offer optional panels for early-onset conditions lacking treatments but with potential preventive interventions; Early Check additionally offers an optional polygenic risk score for type 1 diabetes, marking a departure from traditional treatability criteria. - Consent in current research pilots is explicit and often prenatal, frequently facilitated by healthcare professionals or online platforms with educational content. Result return pathways often deliver negative results online or by letter; positive results involve genetic counseling. Scaling such models to universal programs would require substantial counseling and follow-up resources. - Given these pressures, fully informed clinical-style consent is impractical for population-scale genomic NBS. The authors advocate for ‘appropriate consent’ (e.g., PROMICE-inspired), emphasizing promotion of child well-being, proportionality, and core information delivery rather than exhaustive detail. - To maintain proportionality and universality, genomic NBS should prioritize carefully curated virtual panels aligned with established screening criteria (seriousness, treatability, evidence of benefit). Broader disclosures (late-onset, carrier status, untreatable conditions) would necessitate substantially different consent processes and may threaten program feasibility. - Rigorous evidence of screening effectiveness (beyond diagnostic yield) remains limited; effectiveness demonstrated in clinical contexts (e.g., NICU sequencing) cannot be extrapolated to population screening of healthy newborns.

The analysis addresses how to reconcile the demands of consent with the goals of population health screening when introducing genomic sequencing into NBS. Positioning NBS within public health ethics reframes consent as a means to support equitable, universal case-finding rather than individualized, exhaustive disclosure. The proposed ‘right of the asymptomatic at-risk child to be found’ anchors the moral and legal imperative to identify children with actionable conditions, guiding the scope of genomic applications and consent design. Appropriate consent—focusing on core, comprehensible elements and program rationale—balances the child’s interests, feasibility at scale, and respect for parental decision-making. Implementing genomic sequencing via curated virtual panels that meet established screening criteria can minimize consent burdens while maximizing population benefit. Expansions to include untreatable, late-onset, or carrier findings would require rethinking consent and raise risks to program sustainability and equity. The authors underscore the need for professional training, public co-designed education, and robust follow-up pathways to avoid undermining universality and to manage the counseling and resource demands of expanded screening.

Genomic sequencing can augment newborn screening but substantially complicates consent. Framed as a public health program, NBS should prioritize the child’s health interests, articulated as the right of the asymptomatic at-risk child to be found. The authors recommend adopting an ‘appropriate consent’ approach—grounded in proportionality and well-being—for genomics in NBS, especially for curated virtual panels aligned with established screening criteria. Clear, publicly co-designed communication about program goals, potential outcomes, and subsequent choices is essential. Given limited evidence of screening effectiveness, cautious, evidence-led implementation is warranted, alongside investment in workforce training, counseling capacity, and equitable access. Future work should develop consensus on condition selection, evaluate consent models at scale, generate robust effectiveness data (beyond diagnostic yield), and clarify policies on data storage, reinterpretation, and recontact.

The work is a normative legal-ethical analysis rather than an empirical study; its conclusions depend on ethical framing and legal interpretation, which may vary across jurisdictions. Descriptions of ongoing research projects rely on conference reports and public websites and may be incomplete or subject to change. The paper does not fully address data governance issues such as long-term storage, future research use, reinterpretation, and recontact obligations. Evidence for the effectiveness of genomic sequencing as a population screening tool in healthy newborns remains limited, constraining generalizability and policy recommendations.