Calcitonin Gene‐Related Peptide ( CGRP ) Levels of Children and Adolescents With Migraine: A Systematic Review and Meta‐Analysis of Observational Studies

ABSTRACT Background and Objective Although calcitonin gene‐related peptide (CGRP) has emerged as a promising therapeutic target in migraine management, current clinical evidence regarding its dynamic variations in paediatric migraine populations remains inconclusive. We conducted a meta‐analysis to explore the relationship between blood CGRP levels and paediatric migraine. Databases and Data Treatment We systematically searched for observational studies that reported CGRP levels in paediatric migraine published in English from the PubMed, Web of Science, and Embase electronic databases, or in Chinese from the Chinese National Knowledge Infrastructure and the WanFang Med database. The Newcastle–Ottawa Quality Assessment Scale was used to assess the quality of the included studies. The quality of evidence for each outcome was assessed according to the Grading of Recommendations, Assessment, Development, and Evaluation guidelines. Results Of the 1134 identified studies, eight were eligible for inclusion. There was a ‘Moderate’ level of evidence demonstrating significantly elevated CGRP levels in children with migraine compared to controls (standardised mean difference [SMD] = 1.44, 95% CI 0.61–2.31). Stratification analysis showed the ‘Low’ level of evidence revealed higher levels during both ictal (SMD = 2.39, 95% CI 0.59–4.19) and interictal phases (SMD = 1.27, 95% CI 0.54–1.99). ‘Very low’ quality of evidence supported paediatric migraine patients with (SMD = 1.47, 95% CI 0.67–2.27) and without (SMD = 1.11, 95% CI 0.50–1.72) aura had higher CGRP levels than non‐migraine controls. Conclusions Our findings suggest that CGRP levels may be a potential diagnostic biomarker and prophylactic therapeutic target for paediatric migraine, but need high‐quality longitudinal studies to validate. Significance Statement This systematic review and meta‐analysis provides significant evidence that CGRP levels serve as a potential diagnostic biomarker for migraine in children and adolescents. Future research should further explore the diagnostic value of CGRP levels in this population. However, the current evidence does not confirm CGRP as an acute‐phase therapeutic target for pediatric and adolescent migraine, necessitating validation through higher‐quality studies. Trial Registration PROSPERO number: CRD42025635332