Clinician Guide to Negative & Discrepant Screening Results
What is BRIDGES-NBS?
BRIDGES-NBS is an NIH-funded research study assessing the feasibility of incorporating Genome Sequencing into routine newborn screening.
Scope of BRIDGES-NBS
BRIDGES-NBS screens for a select panel of genes (~800 genes) that are connected to conditions that are actionable within the first year of life. BRIDGES-NBS only reports pathogenic/likely pathogenic (P/LP) variants (i.e. variants expected to cause genetic disease).
What is excluded and not reported:
● Variants of Uncertain Significance (VUS)
● Adult-onset conditions
● Carrier status
Click here to view our complete condition list.
Implications of a Negative Result
A Negative (Screen-Normal) BRIDGES-NBS result means that no reportable P/LP variants were identified among the specific genes analyzed on the study’s targeted panel.
● Reduces, But Does Not Eliminate, Risk: Genomic Sequencing has technical limitations; it may not detect 100% of pathogenic/likely pathogenic variants or structural anomalies.
● Limited to Panel Scope: Participants were only screened for the conditions on the BRIDGES-NBS panel, we did not look for variants in their entire genome.
● Clinical Presentation Supersedes Screening: If you suspect that a baby may have a genetic condition due to medical symptoms, developmental delay, or a positive family history, perform a typical standard of care medical work-up, regardless of a negative screening result. You also have the option to contact GeneDx (GenomicsNBS@genedx.com, 888-729-1206), the laboratory performing the BRIDGE-NBS testing, to ask more about the technical details of testing or order additional testing. GeneDx will store the baby’s genetic sequence data for 5 years in case additional clinical testing is needed.
Discrepancies between State Newborn Screening and BRIDGES-NBS Screening
There may be discrepancies between state newborn screening (NBS) results and BRIDGES-NBS results.
| Cause of discrepancy | Why it happens | Clinical context and example |
|---|---|---|
| Non-overlapping panels | Routine state NBS panels and BRIDGES-NBS screen for different conditions. | State NBS panels screen for conditions which are not included in BRIDGES-NBS. |
| Carrier status | BRIDGES-NBS does not report carrier status. | An infant flagged as a carrier for a condition such as Cystic Fibrosis on state NBS will receive a negative BRIDGES-NBS result. |
| Different screening methods | State NBS uses biochemical markers; BRIDGES-NBS uses DNA sequencing. | Biochemical assays measure enzyme activity/analytes, which have different detection thresholds than DNA sequencing. |
Clinical Support
The BRIDGES-NBS Genome Resource Center (GRC) is available to provide healthcare providers with assistance with result interpretation and testing pathways. If needed, 1:1 assistance from study medical geneticists and genetic counselors is also available. Click here to fill out a brief form to request to talk with a Medical Geneticist or Genetic Counselor from the BRIDGES-NBS team.