Vitamin D neuroimmune synaptic plasticity and precision intervention in pediatric neurodevelopmental disorders

Abstract

Vitamin D deficiency is highly prevalent in children worldwide but has long been regarded only as a risk factor for bone health. Emerging evidence indicates that vitamin D profoundly influences child brain development by regulating neuroimmune responses and synaptic plasticity, forming a “neuroimmune–synaptic plasticity axis.” Deficiency is significantly associated with the risk of multiple pediatric neurological disorders, including autism spectrum disorder (ASD), epilepsy, and attention-deficit / hyperactivity disorder (ADHD). This axis exerts irreversible regulatory effects during critical developmental windows from gestation to the preschool period, representing a core causal pathway linking vitamin D deficiency to neurodevelopmental disorders. However, the clinical benefits of vitamin D supplementation are highly heterogeneous, necessitating a move beyond the “one-size-fits-all” paradigm. This review systematically integrates causal mechanisms, molecular pathways, disease-specific associations, and clinical evidence, proposing the “neuroimmune–synaptic plasticity axis” as a central hypothesis. We critically analyze the mechanisms of vitamin D during key neurodevelopmental periods and evaluate sources of heterogeneity in existing clinical trials, including dosage, timing, VDR genotype, and co-nutrients. Finally, we propose a research roadmap for individualized supplementation strategies based on developmental stage, biomarkers, and VDR genotype, aiming to transition vitamin D use from empirical to precision intervention.