Charting the Ethical Frontier in Newborn Screening Research: Insights from the NBSTRN ELSI Researcher Needs Survey.

From 2008 to 2024, the Newborn Screening Translational Research Network (NBSTRN), part of the National Institute of Child Health and Human Development (NICHD) Hunter Kelly Newborn Screening Program, served as a robust infrastructure to facilitate groundbreaking research in newborn screening (NBS), public health, rare disease, and genomics. Over its sixteen years, NBSTRN developed into a significant international network, supporting innovative research on novel technologies to screen, diagnose, treat, manage, and understand the natural history of more than 280 rare diseases. The NBSTRN tools and resources were used by a variety of stakeholders including researchers, clinicians, state NBS programs, parents, families, and policy makers. Resources and expertise for the newborn screening community in ethical, legal, and social issues (ELSI) has been an important area of focus for the NBSTRN and this includes efforts across the NBS system from pilot studies of candidate conditions to public health implementation of screening for new conditions, and the longitudinal follow-up of NBS-identified individuals to inform health outcomes and disease understanding. In 2023, the NBSTRN conducted a survey to explore ELSI issues in NBS research, specifically those encountered by the NBS community. Since NBS research involves collaboration among researchers, state NBS programs, clinicians, and families, the survey was broadly designed and disseminated to engage all key stakeholders. With responses from 88 members of the NBS community, including researchers and state NBS programs, the survey found that individuals rely most on institutional and collegial resources when they encounter ELSI questions. Most survey responses ranked privacy as extremely or very important in NBS research and identified the need for policies that address informed consent in NBS research. The survey results highlight the need for improved collaborative resources and educational programs focused on ELSI for the NBS community. The survey results inform future efforts in ELSI and NBS research in the United States (U.S.) and the rest of the world, including the development of policies and expanded ELSI initiatives and tools that address the needs of all NBS stakeholders.

Defining the Minimal Long-Term Follow-Up Data Elements for Newborn Screening.

Newborn screening (NBS) is hailed as a public health success, but little is known about the long-term outcomes following a positive newborn screen. There has been difficulty gathering long-term follow-up (LTFU) data consistently, reliably, and with minimal effort. Six programs developed and tested a core set of minimal LTFU data elements. After an iterative data collection process and the development of a data collection tool, the group agreed on the minimal LTFU data elements. The denominator captured all infants with an NBS diagnosis, accounting for children who moved or died prior to the follow-up year. They also agreed on three LTFU outcomes: if the child was still alive, had contact with a specialist, and received appropriate care specific to their diagnosis within the year. The six programs representing NBS public health programs, clinical providers, and research programs provided data across multiple NBS disorders. In 2022, 83.8% (563/672) of the children identified by the LTFU programs were alive and living in the jurisdiction; of those, 92.0% (518/563) saw a specialist, and 87.7% (494/563) received appropriate care. The core LTFU data elements can be applied as a foundation to address the impact of early diagnosis by NBS within and across jurisdictions.

Long-Term Follow-Up Cares and Check Initiative: A Program to Advance Long-Term Follow-Up in Newborns Identified with a Disease through Newborn Screening.

In the United States and around the world, newborns are screened on a population basis for conditions benefiting from pre-symptomatic diagnosis and treatment. The number of screened conditions continues to expand as novel technologies for screening, diagnosing, treating, and managing disease are discovered. While screening all newborns facilitates early diagnosis and treatment, most screened conditions are treatable but not curable. Patients identified by newborn screening often require lifelong medical management and community support to achieve the best possible outcome. To advance the long-term follow-up of infants identified through newborn screening (NBS), the Long-Term Follow-up Cares and Check Initiative (LTFU-Cares and Check) designed, implemented, and evaluated a system of longitudinal data collection and annual reporting engaging parents, clinical providers, and state NBS programs. The LTFU-Cares and Check focused on newborns identified with spinal muscular atrophy (SMA) through NBS and the longitudinal health information prioritized by parents and families. Pediatric neurologists who care for newborns with SMA entered annual data, and data tracking and visualization tools were delivered to state NBS programs with a participating clinical center. In this publication, we report on the development, use of, and preliminary results from the LTFU-Cares and Check Initiative, which was designed as a comprehensive model of LTFU. We also propose next steps for achieving the goal of a national system of LTFU for individuals with identified conditions by meaningfully engaging public health agencies, clinicians, parents, families, and communities.