Neonatal Genomic Screening
Genomic newborn screening is moving from targeted biochemical assays to whole genome analysis. This shift demands interpretation tools that can process millions of variants under time pressure, with incomplete phenotype information, and deliver clinically actionable results to neonatal teams.
Under 60 minutes
Full genome interpretation
No phenotype required
Pathogenicity-first analysis
The Neonatal Interpretation Challenge
Neonatal intensive care represents the most demanding clinical context for genomic interpretation -- where time, phenotype specificity, and diagnostic scope all work against traditional approaches.
Time-Critical Decisions
In neonatal intensive care, treatment decisions cannot wait for weeks of manual variant interpretation. A newborn with unexplained seizures or metabolic crisis needs actionable genomic information within hours, not days.
Non-Specific Presentations
Newborns present with non-specific symptoms -- respiratory distress, hypotonia, seizures, metabolic acidosis. These presentations overlap across hundreds of genetic conditions, making phenotype-guided gene panel selection unreliable.
Evolving Clinical Picture
A newborn's phenotype changes rapidly in the first days and weeks of life. Features that could narrow the differential diagnosis may not yet be apparent. Interpretation must work with incomplete and evolving clinical information.
Genome-Wide Scope
Targeted gene panels risk missing diagnoses outside their scope. For critically ill neonates, whole genome or exome analysis is increasingly the first-line approach -- but it produces millions of variants that need systematic evaluation.
Phenotype-Agnostic Analysis
Traditional variant interpretation starts with phenotype and works backward to genes. In neonatal care, where phenotype is incomplete and evolving, Helix Insight starts with pathogenicity and works forward to clinical relevance.
No Phenotype Required to Start
Helix Insight performs genome-wide pathogenicity-first prioritization. Every variant is classified and scored based on population frequency, functional predictions, gene constraint, and clinical databases -- independent of phenotypic input. When HPO terms are available, phenotype matching adds a correlation layer. When they are not yet available (common in NICU), the system still produces a clinically useful prioritized variant list.
Phenotype Matching as Evolving Layer
As the newborn's clinical picture develops, HPO terms can be updated and the case reprocessed. New phenotype information immediately re-ranks variants based on genotype-phenotype correlation, surfacing candidates that were classified but not initially prioritized. The underlying classification does not change -- only the clinical prioritization adapts.
Unexpected Diagnoses Surface
Phenotype-constrained analysis can only find what it looks for. Phenotype-agnostic interpretation identifies all pathogenic and likely pathogenic variants across the genome, including findings in genes not initially suspected. This is particularly important in neonates where the differential diagnosis is broad and multi-system involvement is common.
Age-Aware Screening Profiles
Variant prioritization adapts to the clinical context. A newborn in the NICU and a child in a developmental genetics clinic have different urgent gene lists and different clinical priorities.
Neonatal
0 -- 28 daysHighest priority for conditions with neonatal onset and available treatment. Gene weighting emphasizes disorders where early intervention changes outcomes -- metabolic conditions (PKU, galactosemia, MCAD deficiency), cystic fibrosis, spinal muscular atrophy, congenital adrenal hyperplasia, and early-onset epilepsies.
Key genes: CFTR, SMN1, GAA, GBA, HEXA, PAH, GALT, ACADM, CYP21A2, and curated neonatal-onset gene lists
Pediatric
29 days -- 18 yearsBroader scope including childhood-onset conditions. Weight profiles shift toward developmental disorders, childhood-onset metabolic conditions, immunodeficiencies, and genetic epilepsies. Lower urgency than neonatal but still requires efficient evidence gathering for timely clinical decisions.
Key genes: Expanded panels including developmental delay, intellectual disability, epilepsy, and immunodeficiency gene lists
Proactive
Any agePopulation-scale screening for actionable genetic conditions regardless of current clinical presentation. Focuses on conditions where early knowledge enables preventive action -- hereditary cancer syndromes, cardiac conditions (LQTS, HCM), pharmacogenomic variants, and carrier status.
Key genes: ACMG SF v3.2 secondary findings list, pharmacogenomic panels, carrier screening panels
Platform Capabilities
Processing Speed
Gene panel VCF: 1-2 minutes. Whole exome: 2-5 minutes. Whole genome: under 15 minutes. Classification, annotation, and phenotype matching run in parallel across the full variant set.
Neonatal Gene Curation
Age-aware scoring profiles weight neonatal-onset conditions with available treatment higher than adult-onset conditions. Gene lists are curated from OMIM, GeneReviews, and newborn screening program publications.
ACMG Classification
Every variant receives full ACMG/AMP classification with Bayesian point framework, not just a pass/fail screen. The geneticist sees the complete evidence basis for each finding, enabling informed clinical decisions under time pressure.
Tiered Clinical Output
Results are presented in clinical tiers: Tier 1 (actionable findings requiring immediate attention), Tier 2 (potentially actionable, warranting further evaluation), and incidental findings flagged separately. The NICU team sees what matters first.
Reprocessing Without Re-Upload
As clinical information evolves, cases can be reprocessed with updated HPO terms or different screening profiles without re-uploading the VCF. Updated reference databases are applied automatically, and previous results are preserved for comparison.
GDPR-Native EU Infrastructure
Neonatal genomic data is among the most sensitive categories of personal data. All processing occurs on dedicated infrastructure in Helsinki, Finland. No variant data leaves the EU. No external API calls are made during analysis.
See Neonatal Screening in Action
Request a demo to see how Helix Insight processes a neonatal case -- from whole genome VCF to age-aware clinical prioritization.