Lab Matters Summer 2018 | Page 81

APHL 2018 Annual Meeting Poster Abstracts

Newborn Screening

Playing with Building Blocks: The Newborn Screening Health IT Implementation Guide and Toolkit

M. K. Yost-Daljev 1, S. Downer 1, A. Padgett 1, J. Miller 2, W. Andrews 3; 1 J Michael Consulting, Atlanta, GA, 2 Colorado School of Public Health, Denver, CO, 3 Virginia Division of Consolidated Laboratory Services, Richmond, VA

Background: Health information technology( HIT) continues to play a crucial role in improving newborn screening( NBS) processes. A key component of HIT is utilizing Health Level 7( HL7) to send laboratory orders and test results between providers and the NBS laboratory. Several NBS programs have implemented, or are in the process of implementing, HL7 messaging using program-specific methodologies with varying levels of success. This disparate nature of implementation has produced inconsistent results and served as the impetus for the development of a NBS HIT resource guide and toolkit to provide guidance for programs implementing electronic messaging. Objective: To introduce the NBS HIT Resource Guide and Toolkit to the NBS community, educate them on the value of the guide and facilitate an interactive discussion of it. Next steps for expanding the guide to other areas of HIT beyond electronic messaging will also be discussed.

Methods: The NewSTEPs 360 project, funded by the Health Resources and Services Administration( HRSA), works with NBS programs to improve timeliness of NBS from birth to results reporting. This includes activities to implement HIT solutions including electronic messaging. NewSTEPs 360 partnered with the Virginia Division of Consolidated Laboratory Services( DCLS) and J Michael Consulting( JMC) to bring together NBS programs, at various stages of electronic messaging implementation and several national partners to author a NBS HIT Resource Guide and Toolkit.

Results: Representatives met for an in-person meeting in February 2017, which resulted in a detailed outline of NBS electronic messaging processes based on their diverse experiences. This outline will be developed into a resource guide planned for release by the end of August 2017. This first version will lead a NBS program through the steps needed to plan, implement and maintain an electronic messaging project including details on such activities as establishing partnerships, workflow mapping and message validation among others. The modular nature of the guide will allow the reader to utilize the sections that are important for their project status while setting aside the sections that are not relevant. The guide will also provide descriptions of the tasks needed to meet milestones, tools for accomplishing those tasks and case studies from programs that have completed milestones highlighting lessons learned.

Conclusion: This poster will introduce participants to the NBS HIT Resource Guide and Toolkit, walk them through the layout and explain its utility.

Presenter: Willie Andrews, Virginia Division of Consolidated Laboratory Services, Richmond, VA, Phone 804.648.4480, Email: willie. andrews @ dgs. virginia. gov

Validation of a Six-Gene Next Generation Sequencing( NGS) Panel for Second-Tier Newborn Screening

H. Schwab, R. Sicko, C. Stevens, D. Kay, C. Saavedra-Matiz and M. Caggana, Wadsworth Center, New York State Department of Health, Albany, NY

Background: The New York State( NYS) newborn screening( NBS) program has developed a six-gene next generation sequencing( NGS) panel to replace Sanger sequencing as a second-tier test for Pompe disease, Krabbe disease, mucopolysaccharidosis type I( MPS-I), X-linked adrenoleukodystrophy( X-ALD), very long-chain acyl- CoA dehydrogenase deficiency( VLCADD) and medium-chain acyl- CoA dehydrogenase deficiency( MCADD). These inherited metabolic disorders often result in death in infancy or childhood. With timely diagnosis, treatment may improve morbidity and / or mortality. In NYS, the current testing algorithm involves first-tier tandem mass spectrometry followed by second-tier Sanger sequencing. Sanger assays are expensive, labor intensive and cannot detect large, heterozygous deletions and duplications( del / dup). Since these conditions are autosomal recessive( except for X-ALD), all infants with a single mutation must be referred for diagnostic testing and clinical evaluation, as they may carry an undetected del / dup. Many infants who are carriers and will never develop disease are referred, leading to unnecessary follow-up testing and undue emotional stress for families. In 2016, 125 infants were referred for confirmatory testing for these six conditions, though only 21 infants were confirmed to have disease.

Objective: The aim of this project is to validate the six-gene panel and to replace the individual Sanger sequencing assays that are currently in place for these six conditions. The validation will include testing to assess the analytical and clinical validity of the panel, including accuracy and reproducibility testing. Turnaround time and cost will also be assessed.

Methods: A TruSeq Custom Amplicon( TSCA) panel, which uses 178 amplicons to target regions of the GAA, IDUA, GALC, ABCD1, ACADVL and ACADM genes was designed. DNA from a well-characterized genomic DNA( Coriell cell line NA12878) and 30 dried blood spot( DBS) samples previously screened by the NYS program will be run on the panel. DNA will be extracted from a single 3-mm punch DBS per sample and 10 ng will be used to prepare sequencing libraries, which will be run on an Illumina MiSeq using a version 2 flow cell with 300 cycles. A bioinformatics pipeline will be developed and variant calling and analysis will allow for the identification of genetic variants, including the detection of del / dups with copy number algorithms. The panel will be assessed by comparison to Sanger results and evaluation of the Coriell DNA.

Conclusions: Implementation of this panel may improve the current algorithms used in NYS by decreasing false positive referral rates, if only infants with two mutations can be referred. It will also be possible to expand the panel to include additional conditions, allowing for additional cost-savings.

Presenter: Holly Schwab, Wadsworth Center, New York State Department of Health, Albany, NY, Phone: 518.705.0417, Email: schwabh4444 @ gmail. com

Newborn Screening