Applications of nuclear magnetic resonance spectroscopy in pediatric clinical metabolomics: From research to future perspectives.

Metabolomics studies small-molecule metabolites to provide insights into health and disease, supporting early diagnosis and personalized medicine. Advances in mass spectrometry and nuclear magnetic resonance (NMR) have expanded its use in metabolic, cancer, and cardiovascular diseases. In pediatrics, high-resolution NMR metabolomics has been instrumental in identifying age-related metabolic changes during early childhood and their associations with growth, nutrition, and disease risk. However, a comprehensive review of its clinical applications and future potential remains limited. This review highlights how utilizing specific NMR pulse sequences, such as CPMG and NOESY, allows for precise and non-destructive metabolic profiling of diverse biofluids, supported by minimal sample preparation and high-throughput automated analysis. Data processing tools like NMRProcFlow and MetaboAnalyst facilitate spectral preprocessing, statistical analysis, and biological interpretation, streamlining metabolomics workflows. Clinically, NMR-based metabolomics has elucidated metabolic alterations in pediatric growth, prematurity, nutrition-related sensitizations, allergic diseases, lipid metabolism, infectious conditions, and neurobehavioral disorders. In particular, metabolomics has been applied to identify specific metabolic signatures underlying the molecular mechanisms of childhood allergic asthma. Despite limitations in detecting low-abundance metabolites, NMR's ability to preserve sample integrity and integrate multi-omics data, especially gut microbiota-derived metabolites, shows great promise in advancing precision pediatric medicine, early disease screening, and personalized therapeutic strategies.