Association Between Serum Zinc Level and Comorbid Orthostatic Intolerance in Pediatric Patients with Migraine

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Abstract
Background/Objectives: Migraine affects approximately 10% of school-aged children, and frequently co-occurs with orthostatic intolerance (OI). However, although low serum zinc levels have been linked to migraine in adults, yet evidence in pediatric populations remains scarce. We aimed to investigate the association of serum zinc levels with comorbid OI in pediatric patients with migraine. Methods: We retrospectively analyzed medical records of 57 patients (26 male, 31 female; median age 13 years) newly diagnosed with migraine between December 2017 and March 2022. Diagnosis was made according to the International Classification of Headache Disorders, third edition criteria. Serum zinc, iron, copper, and ferritin concentrations were measured at initial presentation. Zinc deficiency was defined as serum concentration < 80 μg/dL. OI diagnosis required ≥2 characteristic symptoms based on modified Japanese diagnostic criteria. Results: The median serum zinc concentration was 80.7 μg/dL, with 40% of patients exhibiting zinc deficiency. Patients without comorbid OI (54%) demonstrated significantly lower serum zinc levels than those with OI (77.5 vs. 84.7 μg/dL, p < 0.001). Linear mixed model analysis identified comorbid OI as the only clinical factor significantly associated with serum zinc concentrations (p = 0.019). Conclusions: Pediatric patients with migraine without comorbid OI exhibit lower serum zinc levels than those with OI, suggesting differences in the underlying pathophysiology. Further large-scale, prospective studies including healthy control groups are warranted to validate these results.

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