Tandem mass spectrometry (MS/MS) is the most universal platform currently available for the analysis of enzymatic activities and biomarkers in dried blood spots (DBS) for applications in newborn screening (NBS). Among the MS/MS applications in NBS, the most common is flow-injection analysis (FIA-) MS/MS, where the sample is introduced as a bolus injection into the mass spectrometer without the prior fractionation of analytes. Liquid chromatography combined with MS/MS (LC-MS/MS) has been employed for second-tier tests to reduce the false-positive rate associated with several nonspecific screening markers, beginning two decades ago. More recently, LC-MS/MS has been applied to primary screening for new conditions for which FIA-MS/MS or other methods, including genomic screening, are not yet adequate. In addition to providing a list of the currently used LC-MS/MS-based assays for NBS, the authors share their experience regarding the maintenance requirements of LC-MS/MS vs. FIA-MS/MS systems. The consensus is that the maintenance of LC-MS/MS and FIA-MS/MS instrumentation is similar, and LC-MS/MS has the advantage of allowing for a larger number of diseases to be screened for in a multiplex, cost-effective fashion with a high throughput and an adequate turnaround time.

A Utah study reveals the value of a two-screen approach in identifying congenital hypothyroidism cases in newborns.

As newborn screening programs transition from paper-based data exchange toward automated, electronic methods, significant data exchange challenges must be overcome. This article outlines a data model that maps newborn screening data elements associated with patient demographic information, birthing facilities, laboratories, result reporting, and follow-up care to the LOINC, SNOMED CT, ICD-10-CM, and HL7 healthcare standards. The described framework lays the foundation for the implementation of standardized electronic data exchange across newborn screening programs, leading to greater data interoperability. The use of this model can accelerate the implementation of electronic data exchange between healthcare providers and newborn screening programs, which would ultimately improve health outcomes for all newborns and standardize data exchange across programs.

Expansion of the newborn disorder panel requires the incorporation of new testing modalities. This is especially true for disorders lacking robust biomarkers for detection in primary screening methods and for disorders requiring genotyping or sequencing as a second-tier and/or diagnostic test. In this commentary, we discuss how next-generation sequencing (NGS) methods can be used as a secondary testing method in NBS. Additionally, we elaborate on the importance of genomic variant repositories for the annotation and interpretation of variants. Barriers to the incorporation of NGS and bioinformatics within NBS are discussed, and ideas for a regional bioinformatics model and shared variant repository are presented as potential solutions.

Myotonic dystrophy (DM) is a multisystemic disorder characterized by significant heterogeneity in symptom manifestation, progression, and severity. This variability complicates clinical trial design and implementation, thereby affecting therapeutic development. This study aimed to identify barriers to clinical trial readiness in DM and explore actionable solutions by incorporating perspectives from pharmaceutical partners, clinical trial site staff, people living with DM (PLDM), and caregivers. Focus groups, surveys, and interviews were conducted with pharmaceutical partners ( n = 65), PLDM and caregivers ( n = 35), principal investigators ( n = 12), and clinical research coordinators ( n = 12). Qualitative findings were thematically analyzed and triangulated with survey data to enhance validity. Three major barriers consistently emerged: (1) a lack of comprehensive, validated endpoints that capture outcomes meaningful to patients; (2) insufficient data sharing and coordination across industry; and (3) challenges in trial design, recruitment, and participant burden. PLDM emphasized under-studied but debilitating symptoms—such as dysphagia, fatigue, and cognitive impairment—that are rarely prioritized in clinical trials. Pharmaceutical partners cited regulatory uncertainty surrounding composite outcome measures as well as the value of quantitative myotonia indicators as informative holistic disease indicators. Limited access to natural history data, often prohibitively costly for smaller companies, reinforces competitive rather than collaborative dynamics. PLDM and caregivers also highlighted substantial financial, logistical, and accessibility challenges associated with trial participation. Participants favored several strategies to address these barriers: (1) convening a multi-stakeholder scientific session with the U.S. Food and Drug Administration (FDA) and establishing a working group to define and standardize patient-centered, clinically relevant endpoints; (2) developing a comprehensive, coordinated registry that integrates existing data sources, longitudinal health and study data, genetic diagnostic data, supports recruitment and refinement of study inclusion criteria, and enables post-market surveillance; (3) strengthening trial site preparedness and anticipating recruitment needs, including biomarker-driven cohorts; and (4) adopting patient-centered trial designs that minimize burden, with patient advocacy groups (PAGs) serving a central convening and advocacy role by bringing various groups together to discuss these topics. While barriers to DM clinical trial readiness are significant, they are addressable. Coordinated action among industry, regulators, clinicians, and advocacy groups—guided by patient priorities—will be essential. Implementing these strategies could accelerate therapeutic development, improve trial inclusivity, and ultimately enhance quality of life for individuals living with DM.