Magnetic Resonance Spectroscopy in Developmental Delay: Current Applications, Limitations, and Future Directions: Review article

Background: Developmental delay (DD) encompasses a wide range of neurodevelopmental disorders characterized by impairments in cognitive, motor, language or social domains. The underlying etiologies are diverse, including genetic disorders, metabolic abnormalities, hypoxic-ischemic injury and environmental factors. While conventional imaging provides structural information, it frequently fails to detect subtle biochemical abnormalities that precede overt morphological changes, underscoring the need for advanced techniques such as proton Magnetic Resonance Spectroscopy (¹H-MRS), which can non-invasively assess neuronal integrity, myelination and metabolic activity. Objectives: This review aimed to synthesize current evidence on the clinical application of MRS in pediatric DD, highlighting diagnostic utility, characteristic metabolite patterns, technical limitations, and future research directions. Methods: A narrative review of studies evaluating single-voxel and multivoxel ¹H-MRS in children with DD was performed. We used PubMed, Google Scholar and Scopus with keywords including Paediatric, Neurodevelopmental Disorders, Metabolic activity and Neuronal integrity. The writers evaluated relevant literature references as well. Only the most recent or thorough investigations, from 2002 to 2024, were taken into account. Documents written in languages other than English were ignored. Papers that were not regarded as significant scientific research included dissertations, oral presentations, conference abstracts, and unpublished manuscripts were excluded. Outcomes included metabolite concentrations, ratios (e.g., NAA/Cr, Cho/Cr), regional patterns, and correlations with clinical phenotypes across populations with idiopathic, metabolic, hypoxic-ischemic and autism spectrum disorders. Conclusion: ¹H-MRS is a valuable adjunct to conventional MRI in paediatric developmental delay, providing metabolic insights that can detect neuronal integrity, glial activity and energy metabolism that cannot be captured by conventional structural MRI alone. Technical challenges, age-dependent variability and heterogeneous acquisition protocols limited its routine use. Future directions include standardized acquisition, development of age-specific normative databases, integration with multimodal imaging and clinical data, and targeted application in high-risk or clinically enriched populations to maximize its diagnostic utility.