Friday, May 9, 2025
5/9/2025
Enhancing Disease Detection in NYS Newborns by Reducing the Rate of False Positive Results - Newborn screening (NBS) relies on early detection and intervention to prevent significant morbidity and mortality. In the absence of a family history, these infants would otherwise go undiagnosed until symptomatic, when treatment is less/not effective. NBS programs aim to identify all affected infants to the extent practicable, thus, cutoffs are set conservatively, so that infants with borderline results are also identified. However, by maximizing algorithm sensitivity, there are appreciable false positive (FP) rates for some conditions due to low specificity. The psychosocial impact of FP screens on families can be substantial. Parents may experience anxiety and distress when they learn of abnormal results for life-altering or life-limiting conditions and must wait for repeat NBS or diagnostic results. This project fills current gaps in the New York State (NYS) NBS Program and the United States by increasing the specificity of newborn screening tests. First, we will decrease the FP rate by validating and implementing second-tier biochemical screening for congenital adrenal hyperplasia, maple syrup urine disease, isovaleric acidemia, propionic acidemia, methylmalonic acidemia and cobalamin C/D deficiency by adding analytes screened after the initial testing. These conditions have a high FP rate when assessing risk by a single or few analytes/ratios, due to interferents/isomers. Implementation of these new second-tier tests and utilization of analytic tools under development at the CDC are expected to decrease the anxiety for 100s of families and decrease burden to follow-up staff in programs. Second, we will expand use of digital droplet PCR to: (1) distinguish variants in cis v. in trans enabling release of babies from referral when 2 or more variants are in cis (carriers) and (2) distinguish SMN2 copy number more precisely (4 v. >5 copies); this information impacts treatment decisions. Third, we will further improve NBS specificity by completing validation of an expanded molecular panel targeting an additional 14 genes (plus GALT), which account for 9 additional panel conditions. By project end, 17 conditions (22 genes) are expected to have second-tier analysis as part of the screen. Further, the NYS comprehensive variant database will be expanded for these conditions and made available to the NBS community, permitting consistent, accurate interpretation of genetic data. These activities will promote genetic data harmonization nationally, allow Programs implementing sequencing to use information gathered for this project and assist the CDC in the ED3N project. Lastly, to continue our longstanding tradition of knowledge sharing, we will continue to assist other programs by convening a workshop for NBS professionals at the NYS NBS lab in Albany each year. This tailored, intensive workshop will include educational modules, detailed overviews of NBS technology, algorithms and follow-up, and hands-on training in NBS methods, including biochemical analysis using tandem mass spectrometry (MS/MS) and molecular analysis using sequencing, real-time quantitative PCR, and digital droplet PCR. All methods, including biochemical and molecular assays, NGS panel design and genetic variant databases will be shared with the NBS community. This project will fulfill major gaps and priorities for the NYS NBS Program and nationally including building NBS capability, quality improvement, training and education.
HHS’ Tracking Accountability in Government Grants System (TAGGS) website provides access to detailed descriptions of grants, loans, aggregated direct payments and other types of financial assistance awarded by the HHS Operating Divisions (OPDIVs) and the Office of the Secretary Staff Divisions (STAFFDIVs).