Tandem mass spectrometry in newborn screening for inherited metabolic diseases: A comprehensive review

Zhihui Wan; Jiaqi Han; He S. Yang; Ruben Y. Luo; Jie Xie; Yanhong Zhai; Yuanyuan Kong; Zheng Cao

doi:10.59717/j.xinn-med.2026.100215

The Innovation Medicine > 2026 Vol. 4 > No. 2 > 100215

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Tandem mass spectrometry in newborn screening for inherited metabolic diseases: A comprehensive review

1.
Department of Laboratory Medicine, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
2.
Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York 10021, USA
3.
Department of Pathology, Stanford University 3375 Hillview Ave, Palo Alto CA 94304, USA
4.
Technology Innovation Center of Mass Spectrometry for State Market Regulation, Center for Advanced Measurement Science, National Institute of Metrology, Beijing 100029, China
5.
Department of Newborn Screening Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing Maternal and Child Health Care Hospital, Beijing 100026, China
6.
These authors contributed equally

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Corresponding authors: zhengcao2011@ccmu.edu.cn (Z.C.); kongyuanyuan1971@mail.ccmu.edu.cn (Y.K.); zhaiyanhong2006@ccmu.edu.cn (Y.Z.)
Received Date: December 19, 2025

Accepted Date: April 17, 2026

Published Online: April 18, 2026

The Innovation Medicine 4(2), https://doi.org/10.59717/j.xinn-med.2026.100215 | Cite this article

GRAPHICAL ABSTRACT

GRAPHICAL ABSTRACT

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PUBLIC SUMMARY

PUBLIC SUMMARY
1. Newborn screening is a key public health strategy for preventing childhood diseases and deaths.
  
  MS/MS has revolutionized screening by detecting dozens of metabolic disorders in a single run.
  
  This review outlines MS/MS principles and evidence of improved detection, early treatment, and outcomes.
  
  Challenges remain, including false-positive results, clinical relevance confirmation, and ethical concerns.
  
  Future directions include AI, expanded panels, and genomics for precise diagnosis and personalized care.

ABSTRACT

ABSTRACT

Newborn screening represents a critical public health strategy for preventing childhood morbidity and mortality. The introduction of tandem mass spectrometry (MS/MS) has revolutionized the screening landscape for inherited metabolic diseases, shifting the paradigm from single-disease assays to a high-throughput, integrated platform capable of detecting dozens of disorders in a single run. This review systematically outlines the applications and challenges of MS/MS in newborn screening. It begins by outlining the technical principles underlying MS/MS, highlighting its unique capacity to simultaneously quantify multiple amino acids, organic acids, and fatty acid oxidation metabolites. Then, it summarizes global implementation experiences and overviews evidence to demonstrate that MS/MS significantly enhances disease detection rates, enables early intervention, and substantially improves clinical outcomes. However, its widespread adoption introduces new challenges, such as the interpretation of false-positive results, confirmation of clinical relevance for newly screened conditions, and accompanying ethical concerns. Future directions include leveraging artificial intelligence to refine interpretive workflows, expanding the screening panel, and integrating genomic technologies with MS/MS to achieve more precise diagnosis and personalized management. This review aims to offer public health policymakers, clinicians, and laboratory specialists a comprehensive interdisciplinary overview to advance the next developmental phase of newborn screening systems.

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Wan Z., Han J., Yang H., et al. (2026). Tandem mass spectrometry in newborn screening for inherited metabolic diseases: A comprehensive review. The Innovation Medicine 4:100215. https://doi.org/10.59717/j.xinn-med.2026.100215

Wan Z., Han J., Yang H., et al. (2026). Tandem mass spectrometry in newborn screening for inherited metabolic diseases: A comprehensive review. The Innovation Medicine 4:100215. https://doi.org/10.59717/j.xinn-med.2026.100215

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Tandem mass spectrometry in newborn screening for inherited metabolic diseases: A comprehensive review

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