Migraine in pediatric population: the role of biochemical markers
Abstract
BACKGROUND: Diagnosis of migraine remains primarily clinical, and objective biological markers are lacking. Although biomarker research has expanded considerably in adults, evidence in pediatric populations remains fragmented and heterogeneous. This systematic review aimed to synthesize current data on biochemical markers in pediatric migraine and to evaluate their potential diagnostic, monitoring, prognostic, and treatment-response roles. METHODS: The review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. PubMed, Embase and Scopus were searched up to January 1st, 2026. Studies investigating biochemical markers in individuals younger than 18 years diagnosed with episodic or chronic migraine according to International Classification of Headache Disorders 3rd edition (ICHD-3) criteria were included. Biomarkers assessed in blood, saliva, urine, cerebrospinal fluid, or stool were considered. Due to substantial heterogeneity in study design, sampling timing and laboratory methods, findings were synthesized narratively. RESULTS: Twenty-eight studies met inclusion criteria. Neuropeptides were the most extensively investigated biomarkers. Ictal elevation of calcitonin gene-related peptide (CGRP) was the most reproducible finding, supporting a disease-activity monitoring role, whereas interictal levels showed inconsistent results. Pituitary adenylate cyclase–activating polypeptide 38 (PACAP-38) and vasoactive…
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