An Age-Based Framework for Evaluating Genome-Scale Sequencing Results in Newborn Screening


      To assess the performance of a standardized, age-based metric for scoring clinical actionability to evaluate conditions for inclusion in newborn screening and compare it with the results from other contemporary methods.

      Study design

      The North Carolina Newborn Exome Sequencing for Universal Screening study developed an age-based, semiquantitative metric to assess the clinical actionability of gene–disease pairs and classify them with respect to age of onset or timing of interventions. This categorization was compared with the gold standard Recommended Uniform Screening Panel and other methods to evaluate gene–disease pairs for newborn genomic sequencing.


      We assessed 822 gene–disease pairs, enriched for pediatric onset of disease and suspected actionability. Of these, 466 were classified as having childhood onset and high actionability, analogous to conditions selected for the Recommended Uniform Screening Panel core panel. Another 245 were classified as having childhood onset and low to no actionability, 25 were classified as having adult onset and high actionability, 19 were classified as having adult onset and low to no actionability, and 67 were excluded due to controversial evidence and/or prenatal onset.


      This study describes a novel method to facilitate decisions about the potential use of genomic sequencing for newborn screening. These categories may assist parents and physicians in making informed decisions about the disclosure of results from voluntary genomic sequencing in children.



      ASQM ( Age-based, semiquantitative metric), NBS ( Newborn screening), NC NEXUS ( The North Carolina Newborn Exome Sequencing for Universal Screening), NGS ( Next-generation sequencing), NGS-NBS ( Next-generation sequencing for newborn screening), PCD ( Primary ciliary dyskinesia), RUSP ( Recommended Uniform Screening Panel), SQM ( Semiquantitative metric)
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      Linked Article

      • Large Scale Next Generation Sequencing and Newborn Screening: Are We Ready?
        The Journal of PediatricsVol. 209
        • In Brief
          Newborn screening (NBS) is a public health program that aims to identify children with medically actionable conditions prior to becoming symptomatic and provide interventions that result in improvement of long-term outcomes. Over the past decades, a number of conditions have been gradually added to the screening panels. Significant expansion of NBS happened in the mid-1990s to early 2000s when tandem mass spectrometry became available and was applied to detecting biochemical genetic conditions. Several organizations were established to ensure that NBS is standardized and uniformed.
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