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. Additionally, in the genes analyzed, only pathogenic and likely pathogenic variants are reported. Variants of uncertain significance are NOT reported.
● 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 which reports pathogenic and likely pathogenic variants, but not variants of uncertain significance. | Biochemical assays measure enzyme activity/analytes, which has a different detection threshold than DNA sequencing. A patient may have clinical diagnosis and/or biochemical signs of disease, but not have a genetic risk identified through genomic screening. |
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.