In the past 20 years, several policy activities were undertaken that shaped today’s newborn screening (NBS) programs and their associated NBS research activities: the Newborn Screening Task Force Report; the Child Health Act of 2000, Screening for Heritable Disorders; the American College of Medical Genetics and Genomics’ (ACMG’s) Newborn Screening Uniform Panel; and the ACMG expert panel to examine the development of a national collaborative study system for rare genetic diseases. These activities helped conceptualize the Newborn Screening Translational Research Network (NBSTRN) infrastructure and lay the foundation for its current activities. After 10 years, NBSTRN has grown into an organization that provides tools and resources for researchers to conduct research relevant to NBS programs for rare diseases for which data has been siloed locally. Infrastructure includes tools for the analytical and clinical validation of screening tests; the collection, analysis, sharing, and reporting of longitudinal laboratory and clinical data on newborn-screened individuals; and a web-based tool that allows researchers to acquire dried blood spots available for use in research from state NBS programs. NBSTRN also provides tools for researchers such as informed consent templates, disease registries, state NBS profiles, and consultation on planning pilot studies. In time, the growing data will become a resource itself.
Bibliographical noteFunding Information:
Research efforts supported by the Hunter Kelly Newborn Screening Research Program through grants and contracts were encouraged to use NBSTRN resources and infrastructure for their projects. Twenty-three published papers have mentioned the use of NBSTRN resources and/or tools (27% LPDR, 23% pilots, 23% NBSTRN, 10% VRDBS, 7% policy, 5% R4S, 5% ELSI) and two recent papers reference the availability of data sets in the LPDR.19–33 While not inclusive of all of the projects funded under Hunter Kelly NIH or other programs funded by the federal Department of Health and Human Services (HHS), the examples listed illustrate how the NBSTRN-CC resources are being exploited and the benefits of creating a network of experts across disciplines and venues. Additional projects and publications from these projects can be seen at the NBSTRN website.11 All of these efforts were reviewed by the NBSTRN steering committee and various workgroups with guidance provided where needed: Inborn Errors of Metabolism Collaborative (IBEMC): The IBEMC investigators collaborated with NBSTRN in generating and deploying the LPDR for use in their project designed to collect longitudinal data on the clinical progress of persons a/presymptomatic or affected with conditions identified by newborn screening, focusing on inborn errors of metabolism.34 Every week thousands of data points were collected from 22 clinics in 14 states using the LPDR module. This project illustrates the use of LPDR to (1) investigate the relationship among newborn screen data, genotype, and early manifestations as well as complications of inborn errors of metabolism; (2) evaluate the impact of early identification and intervention on metabolic conditions; (3) inform decision making about optimal public health investment in newborn screening; (4) clarify the previously undefined clinical history of treated and untreated very rare metabolic conditions; and (5) identify the current nutritional and therapeutic interventions for children with metabolic conditions and evaluation of their effectiveness. The complete IBEMC data set is available for secondary research through the NBSTRN. SCID Pilot Study: From 2010 to 2011, NBSTRN provided the administrative core for this project and used its convening power to bring participants and experts together to define parameters for data collection while a contract supplement to New York State supported screening costs in participating states.35 The project used both the LPDR and R4S. The inclusion of diagnostic information was an expansion of the R4S system that enabled clinical validation and furthered scientific understanding of the immunological disorders identified by SCID NBS. The analytical and clinical definitions are now being used by states as they implement SCID newborn screening and were included in a Clinical and Laboratory Standards Institute (CLSI) guidance document.36 During the 8-month study, 654,053 babies were screened, and 307 were referred for diagnostic assessment. A total of 12 babies were confirmed with SCID, 3 babies were confirmed with a SCID variant, and 38 babies were confirmed with an immunodeficiency related to another condition.37 LSDs: This was a 5-year effort to conduct a pilot newborn screening for several LSDs in approximately 80,000 infants born in New York City hospitals to validate the screening assay for LSDs and to define the natural history of these disorders.38 NBSTRN coordinated a workgroup chaired by the lead researcher to develop the LPDR to enable longitudinal studies and data aggregation for pilots of these disorders. These data sets are now in use by several state-based NBS programs as nationwide screening for several of these conditions is implemented. In addition, the NBSTRN has been an explicit part of NIH/ NICHD efforts to promote research in NBS. For example, in 2016 the NIH/NICHD created a pool of three states to conduct NBS pilots to facilitate the implementation of conditions recently added to routine newborn screening by ACHDNC, utilizing the coordinating infrastructure of NBSTRN. These projects are implementing NBS for Pompe (glycogen storage disease type II), mucopolysaccharidosis (MPS) type I, and X-linked adrenoleukodystrophy. NBSTRN-CC coordinates monthly conference calls, facilitating adoption of R4S/CLIR and LPDR for use in the pilots and clinical outcome studies. These implementation pilots generate valued resources to accelerate and support the adoption of screening for these conditions and reduce the potential for disparity for both the early identification of disease and the initiation of life-saving treatment across the United States. Finally, NBSTRN-CC also has served in an administrative capacity for NIH/NICHD-NHGRI cofunded Newborn Sequencing in Genomic Medicine and Public Health program (NSIGHT) grantees.39 NSIGHT was established to explore the implications, challenges, and opportunities associated with the use of genomic sequence information in the newborn period. Three research approaches were used: (1) acquisition and analysis of genomic data sets that expand considerably the scale of data available for analysis in the newborn period, (2) clinical research that will advance understanding of specific disorders identifiable via newborn screening through promising new DNA-based analysis, and (3) research related to ELSI issues in genomic sequencing of newborns. The NSIGHT teams plan to utilize LPDR to house clinical and genomic data to conduct cross-cohort analysis of newborns from the accumulated populations of healthy newborns, newborns with a RUSP condition, newborns with atypical SCID, and newborns in the neonatal intensive care unit.
© 2018, American College of Medical Genetics and Genomics.
Copyright 2019 Elsevier B.V., All rights reserved.
- newborn screening
- public health
- translational research