Highlights
– In a prospective cohort of 1,000 newborns (BabyScreen+), whole‑genome sequencing (WGS) targeted to 605 genes from dried blood spot cards identified 16 infants (1.6%) with high‑chance actionable variants.
– Average time to genomic newborn result was 13 days; only one of these infants would have been detected by standard newborn screening.
– Clinical consequences ranged from surveillance and preventive measures to active treatments including transplantation; cascade testing led to 20 relative diagnoses.
– Parental decisional regret was very low (median 0, IQR 0–10) and >99% of participants supported universal availability of genomic newborn screening.
Background
Traditional newborn screening (NBS) programs, using biochemical assays and point‑of‑care tests, have established population‑level benefit by detecting a defined set of metabolic, endocrine and hematologic conditions for which early intervention reduces morbidity and mortality. Advances in genomic sequencing make it possible to detect a substantially larger number of monogenic conditions early in life—particularly early‑onset, severe, and treatable disorders that are not captured by conventional assays. However, whether genomic newborn screening is feasible, acceptable to parents, clinically useful, and implementable within routine public health programs remains a central policy question.
Study design
BabyScreen+ is a prospective cohort study conducted in Victoria, Australia, enrolling 1,000 newborns to evaluate the feasibility, acceptability and clinical outcomes of genomic newborn screening integrated with existing NBS infrastructure. Whole‑genome sequencing was performed on dried blood spot cards and analyzed against a pre‑specified panel of 605 genes associated with early‑onset, severe, treatable conditions. Results with a high predicted likelihood of clinical impact (“high‑chance” results) were returned to families, with confirmatory testing and clinical follow‑up as indicated. The principal endpoints reported include the frequency of clinically actionable findings, time to result, downstream clinical interventions, cascade testing outcomes in relatives, and parental psychosocial measures including decisional regret and attitudes toward population availability of genomic newborn screening. Laboratory analysis was done in a clinically accredited setting and the study reported operational metrics relevant to scalability and integration with public health NBS.
Key findings and interpretation
Detection yield and relation to standard NBS
Of 1,000 screened newborns, 16 (1.6%) had high‑chance genomic findings. Only one of these would have been identified by the standard newborn screening program, indicating that genomic screening substantially increases the number of detectable actionable conditions beyond current NBS panels. The absolute detection rate (1.6%) equates to roughly 1–2 per 100 births for this selected 605‑gene actionable panel, a magnitude that is clinically meaningful at a population level when scaled.
Turnaround time and operational feasibility
The average time to return a genomic newborn screening result was 13 days. This timeline demonstrates that WGS from routine dried blood spots can produce actionable information within a timeframe compatible with many forms of early preventive and surveillance interventions but is slower than the ultra‑rapid genomic protocols used to guide decisions in neonatal intensive care units (NICUs). Crucially, the study was performed in a clinically accredited laboratory and used an approach designed for scale, supporting operational feasibility within public‑health laboratory systems.
Clinical impact and cascade benefits
Clinical actions ranged from instituting surveillance or preventive measures to urgent therapeutic interventions including transplantation. This breadth of impact illustrates that genomic newborn results can alter care trajectories soon after birth for a subset of infants. Notably, cascade testing following index infant diagnoses identified 20 affected relatives, demonstrating immediate family health benefits beyond the newborn and highlighting one of the key potential public‑health values of genomic newborn screening: detection of at‑risk family members who can benefit from early diagnosis or surveillance.
Parental acceptability and psychosocial outcomes
Parental decisional regret at follow‑up was very low (median 0, IQR 0–10), and more than 99% of participating families reported that genomic newborn screening should be available to all parents. High acceptability in this cohort supports the argument that with appropriate consent and counseling processes, parents are willing to receive genomic screening for their newborns. However, acceptability in a research cohort may not fully predict uptake or attitudes in broader, more diverse populations.
Safety, specificity and unreported metrics
The published summary does not provide granular false positive rates, numbers of variants of uncertain significance (VUS) encountered, or long‑term psychosocial outcomes beyond decisional regret. While the study returned only “high‑chance” actionable results—minimizing immediate harm from uncertain findings—population implementation will require clear policies on variant interpretation thresholds, reporting of incidental findings, and management of uncertainty to avoid overdiagnosis and unnecessary interventions.
Expert commentary
BabyScreen+ delivers three major messages to clinicians, laboratorians and policy makers. First, clinically accredited WGS from standard dried blood spot cards is operationally feasible and can be integrated with existing NBS logistics. Second, a targeted, actionable gene list can identify infants who would otherwise be missed by standard approaches and whose care can be altered to prevent morbidity. Third, substantial family health benefits accrue through cascade testing.
Important caveats remain. The cohort was drawn from a single jurisdiction and participants self‑selected for the study, introducing potential selection bias in both uptake and acceptability metrics. The study’s gene panel selection, variant curation and reporting thresholds drove the risk–benefit profile; other panel definitions would yield different yields and false positive rates. Furthermore, median turnaround of 13 days—while adequate for many conditions—may be too slow for acute neonatal presentations where hours matter; dedicated rapid genomic pathways in NICUs will still be needed.
From a policy perspective, implementation will require attention to equity (ensuring access across socio‑economic and geographic groups), workforce capacity (genetic counseling, clinical genetics, lab bioinformatics), data governance (storage and secondary use of genomic data), and cost‑effectiveness (including long‑term health economic modeling). Ethical issues such as informed consent in the newborn context, reporting of adult‑onset conditions, and management of uncertain findings must be resolved through transparent, community‑engaged policy processes.
Limitations and generalizability
Key limitations include the single‑jurisdiction study population and the research setting of recruitment, which may not reflect outcomes in universal public health rollouts where uptake could be lower and participant demographics different. The 605‑gene panel is a study‑specific construct; differing gene selections and interpretation frameworks across jurisdictions will change detection yields. The report focuses on early clinical actions and cascade testing but cannot yet speak to long‑term clinical outcomes, natural history modification, or downstream healthcare utilization and costs. Finally, detailed metrics on VUS reporting, confirmatory testing false positives/negatives, and rates of unnecessary interventions were not reported in the primary summary and are essential for comprehensive evaluation.
Implications for practice and policy
BabyScreen+ supports the technical and operational feasibility of integrating genomic sequencing into newborn screening programs, and provides early evidence of acceptability and clinical utility for a subset of conditions. For health systems considering policy change, the study suggests a pragmatic pathway: start with a carefully curated, actionability‑focused gene list, perform sequencing in a clinically accredited laboratory with robust variant curation pipelines, ensure confirmatory testing and clinical follow‑up, and embed evaluation of health outcomes, equity, and cost. Pilot programs aligned to implementation science principles and inclusive recruitment strategies will be critical before population‑wide adoption.
Future research priorities
– Randomized or controlled implementation studies comparing outcomes with and without genomic newborn screening, including long‑term morbidity, mortality and quality of life metrics.
– Health economic analyses that incorporate costs of sequencing, confirmatory testing, counseling, and downstream care, balanced against avoided disability and family health benefits from cascade testing.
– Equity‑focused implementation studies to define barriers and facilitators for access across diverse populations.
– Standardization of gene lists, variant interpretation thresholds, and reporting policies to harmonize practice and permit cross‑jurisdictional comparisons.
– Longitudinal psychosocial research on families receiving genomic results, including potential harms from actionable and uncertain findings.
Conclusion
The BabyScreen+ study provides compelling early evidence that clinically accredited genomic newborn screening using whole‑genome sequencing from dried blood spots is feasible, acceptable to parents, and clinically actionable for a small but important fraction of newborns. The approach identifies conditions not captured by standard electrophoretic or biochemical newborn screens and yields immediate family benefits through cascade diagnoses. Nonetheless, translation to population programs requires careful attention to equity, workforce capacity, data governance, variant interpretation policy, and robust evaluation of long‑term clinical and economic outcomes.
Funding and trial registration
Funding sources and trial registration details are reported in the primary publication: Lunke S et al., Nat Med. 2025. Please consult that report for precise funding acknowledgements and registry identifiers.
References
1. Lunke S, Downie L, Caruana J, et al. Feasibility, acceptability and clinical outcomes of the BabyScreen+ genomic newborn screening study. Nat Med. 2025 Oct 9. doi:10.1038/s41591-025-03986-z. Epub ahead of print. PMID: 41068466.
Additional literature regarding genomic sequencing and newborn screening, ethical frameworks, and implementation considerations can be found in recent reviews and policy statements from professional bodies; readers should consult these alongside the BabyScreen+ primary report when making clinical or policy decisions.
