Post-Analytical Tools for the Triage of Newborn Screening Results in Follow-up Can Reduce Confirmatory Testing and Guide Performance Improvement

Abstract

Georgia uses post-analytical tools through Collaborative Laboratory Integrated Reports (CLIR) to triage abnormal newborn screening (NBS) results for follow-up. Condition specific tools are used to assign each case a risk level, which is used to guide follow-up recommendations. Follow-up recommendations include assessment by the child’s primary care provider as well as testing, either a repeat NBS or confirmatory testing. Triaging abnormal cases using these tools has been advantageous in managing the workflow for the follow-up team, as well as prioritizing cases that appropriately require more attention and resources. The initial goal in utilizing these tools was to reduce the amount of confirmatory testing, particularly for disorders where there are many false positives. We assessed the performance of these tools retrospectively for three of the most commonly detected conditions by tandem mass spectrometry in Georgia: phenylketonuria, medium chain acyl-CoA dehydrogenase deficiency and very long chain dehydrogenase deficiency. The post-analytical tools appropriately assigned all true positive cases to the higher levels of follow-up testing and reduced the level of intervention for a significant number of cases as well. Based on the experience gained from our utilization of the tools in the follow-up program, we are well situated to move forward with using the tools in a more prospective manner, and reduce the number of cases that will be reported, rather than just assigning resources appropriately at follow-up. Post-analytical tools are an improvement over trying to capture the variation in the newborn population using multiple cutoffs. It also easily identifies significant abnormalities that are unrelated to inherited disease, such as large amino acid elevations due to total parenteral nutrition.

Digital Microfluidics in Newborn Screening for Mucopolysaccharidoses: A Progress Report

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Utilizing augmented artificial intelligence for aminoacidopathies using collaborative laboratory integrated reporting- A cross-sectional study

“…CLIR has an extensive database of confirmed cases and reference data which can be utilized to identify abnormal PAA profiles by comparison to confirmed cases rather than by simple deviation from the reference range [ 10 , 12 ]. Its technique is based on the principles of worldwide laboratory collaboration, data sharing, comparison with peers, and post-analytical interpretive update tools that will be personalized according to the needs of clinicians and laboratory technicians [ 13 , 14 ]. This software allows patient values to be adjusted based on covariates such as age at the time of sample collection and compares them to continuously moving percentiles, instead of traditional discrete benchmarks [ 12 , 15 ].…”

Newborn screening research sponsored by the NIH: From diagnostic paradigms to precision therapeutics

“…Additional requirements during the second 5‐year funding cycle beginning in 2013 included development of common data elements (CDEs; see https://cde.nlm.nih.gov/cde/search?q=newborn%20screening) for NBS conditions and maintenance of a data repository to securely house genomic data, such as variant call files from genome and exome sequencing, and phenotypic data from subjects in the LPDR. The R4S system for collecting laboratory‐based information from state programs and establishing cutoffs by comparing with the results of other states and international partners is now subsumed by the Collaborative Laboratory Integrative Reports (CLIR) project (Hall, Wittenauer, & Hagar, 2020). Several of the work products of the NBSTRN have been developed by its working groups, and in particular, the Bioethics and Legal Workgroup has developed a platform to address ELSI questions (“Ask ELSA!”) and integrate key ELSI questions into pilot studies (Goldenberg et al, 2019).…”