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

Abstract

Newborn screening (NBS) is a successful public health initiative that effectively identifies pre-symptomatic neonates so that treatment can be initiated before the onset of irreversible morbidity and mortality. Legislation passed in 2008 has supported a system of state screening programs, educational resources, and an evidence-based review process to add conditions to a recommended universal newborn screening panel (RUSP). The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), NIH, has promoted NBS research to advance legislative goals by supporting research that will uncover fundamental mechanisms of disease, develop treatments for NBS disorders, and promote pilot studies to test implementation of new conditions. NICHD's partnerships with other federal agencies have contributed to activities that support nominations of new conditions to the RUSP. The NIH's Newborn Sequencing In Genomic Medicine and Public Health (NSIGHT) initiative funded research projects that considered how genomic sequencing could be integrated into NBS and its ethical ramifications. Recently, the workshop, "Gene Targeted Therapies: Early Diagnosis and Equitable Delivery," has explored the possibility of expanding NBS to include genetic diagnosis and precision, gene-based therapies. Although hurdles remain to realize such a vision, broad engagement of multiple stakeholders is essential to advance genomic medicine within NBS.

Keywords: genomic sequencing; newborn screening; pilot studies; public health; research.

Figure 1.

Elements of the Hunter Kelly Newborn Screening Research Program as outlined in the Newborn Screening Saves Lives Act (NBSSLA) of 2007 and its 2014 reauthorization and NICHD mechanisms used to achieve its goals. The four articulated NIH responsibilities under the NBSSLA are described in the gray boxes. Funding mechanisms and programs used to address the goals are indicated underneath the elements. ACHDNC, Advisory Committee for Heritable Disorders in Newborns and Children; IDIQ, Indefinite Delivery, Indefinite Quantity; NBS, newborn screening; PARs, Program Announcement with special Review. *Dedicated NBS PARs include Innovative Therapies and Clinical Studies/Tools for Screenable Disorders and Natural History of Disorders Identifiable by Newborn Screening

Figure 2.

Core functions of the Newborn Screening Translational Research Network (NBSTRN). The NBSTRN provides 3 newly created knowledgebases to assist investigators with understanding the framework of NBS across conditions and states and address their ethical, legal, and social issues (left large box). Researchers can participate in a variety of collaboration tools and activities and forums (middle large box). The Longitudinal Pediatric Data Resource (LPDR) provides a suite of data tools to collect, analyze, visualize, and share genomic and phenotypic data for NBS project (right large box). dbGaP, database of Genotypes and Phenotypes; ELSI, ethical, legal, and social issues; NBS, newborn screening.

Figure 3.

The Road to the RUSP with federal agency support. The circles above the black funnel represent preparatory work prior to submission of a nomination package for a new condition to the ACHDNC. The 8 arrow-bars underneath represent the steps in considering, approving, and implementing a new condition that has been nominated to the ACHDNC and approved. ACHDNC, Advisory Committee on Heritable Disorders in Newborns and Children; AHRQ, Agency for Healthcare Research and Quality; CDC, Centers for Disease Control and Prevention; Epi, epidemiological; FDA, Food and Drug Administration; HHS, U.S. Department of Health and Human Services; HRSA, Health Resources and Services Administration; NBS, Newborn Screening; NIH, National Institutes of Health; NSMBB, Newborn Screening and Molecular Biology Branch; RUSP, Recommended Uniform Screening Panel; Secretary, Secretary of HHS; QA, Quality Assurance; TA, Technical Assistance.