Genetic and Genomic Technologies in Newborn Screening: Current Applications and Future Directions

Dear Colleagues,

Newborn screening (NBS) is one of the most successful public health interventions, enabling early identification and treatment of serious congenital disorders before the onset of irreversible clinical symptoms. Traditionally, NBS programs have relied primarily on biochemical screening methods, which have evolved substantially with the introduction of multiplex technologies such as tandem mass spectrometry.

In recent years, genetic technologies have become increasingly integrated into newborn screening systems. Molecular testing is now widely used as a second-tier test, for confirmatory diagnostics or targeted detection of specific genetic conditions included in screening panels. These approaches improve screening specificity, support rapid diagnosis, and contribute to a better understanding of genotype–phenotype correlations in screened disorders.

Simultaneously, rapid advances in next-generation sequencing (NGS) technologies are enabling exploration of genomic newborn screening (gNBS) as a potential extension of current screening paradigms. Targeted gene panels, whole-exome sequencing, and whole-genome sequencing are being evaluated in several large pilot programs worldwide. These initiatives aim to assess the feasibility, clinical validity, and potential public health impact of genomic technologies when applied at the population level in newborn screening.

As these developments unfold, it is vital to consider genetic and genomic technologies within the broader context of newborn screening as a public health system. Integration of molecular and genomic approaches requires careful alignment of laboratory workflows, bioinformatics pipelines, diagnostic pathways, and program organization.

This Special Issue aims to provide a comprehensive overview of the evolving role of genetic and genomic technologies in newborn screening, addressing both current molecular applications within established NBS programs and emerging genomic approaches that may shape the future of screening.

To reflect this evolving landscape, the Special Issue will address two complementary dimensions.

1. Current Genetic Applications within Newborn Screening Systems: This section focuses on the existing role of molecular testing within current NBS programs. Genetic methods are increasingly being incorporated into screening algorithms to improve test performance and support confirmatory diagnostics.

Topics may include second-tier genetic testing, targeted mutation analysis for specific screened conditions, variant interpretation in the context of newborn screening, genotype–phenotype correlations, and the integration of molecular methods with biochemical screening strategies.

2. Emerging Genomic Approaches and Genomic Newborn Screening: The second focus area addresses the development of genomic screening approaches based on next-generation sequencing technologies. Contributions may explore targeted sequencing panels, exome or genome sequencing strategies, disease selection frameworks, pilot program results, and bioinformatics pipelines designed for population-scale genomic screening.

Particular attention will be given to the integration of genomic technologies into existing newborn screening systems, including laboratory implementation, data management, and program organization.

The Special Issue welcomes submissions addressing, but not limited to, the following topics.

1. Genetic Applications in Current NBS Programs:

• Second-tier genetic testing in newborn screening algorithms.
• Molecular confirmation of positive screening results.
• Targeted gene testing in specific NBS conditions (e.g., CFTR, SMN1, GALT).
• Genotype–phenotype correlations in screened disorders.
• Variant interpretation in the context of newborn screening.
• Integration of molecular methods with biochemical screening approaches.
• Laboratory workflows and quality assurance for molecular testing in NBS laboratories.
• Role of genetic testing in improving screening specificity and diagnostic pathways.

2. Emerging Genomic Approaches in Newborn Screening:

• Targeted gene panels for genomic newborn screening.
• Whole-exome and whole-genome sequencing in newborn screening.
• Disease selection frameworks for genomic screening panels.
• Evidence from genomic newborn screening pilot programs.
• Bioinformatics pipelines and variant filtering strategies for genomic screening.
• Clinical validity and utility of genomic screening in newborns.
• Integration of genomic approaches with existing biochemical NBS programs.
• Implementation within Newborn Screening Systems.
• Integration of genomic technologies into established NBS infrastructures.
• Laboratory and bioinformatics capacity for genomic NBS.
• Data management and informatics pipelines in genomic screening programs.
• Program design and operational models for genomic screening.
• Health system readiness for implementation of genomic approaches in NBS.
• International experiences and comparisons in genomic NBS programs.

Dr. Urh Groselj
Dr. Peter C. J. I. Schielen
Dr. Natasha Heather
Dr. Jernej Kovač
Dr. Alexander D. Rowe
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Neonatal Screening is an international peer-reviewed open access quarterly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

• newborn screening
• next-generation sequencing
• genomic newborn screening
• genetic and genomic technologies
• molecular testing
• second-tier genetic testing