Disrupting the Clock: Meta-Analysis of Irregular Night Shifts and Migraine, Proposing Shift Work Migraine Disorder with Chronobiology Strategies

Background Migraine is linked to circadian rhythm disruptions, with morning attack peaks, circadian variations in trigeminal pain sensitivity, anterior hypothalamus involvement, and core circadian clock gene activity. Irregular night shift work, affecting up to 50% of the population, including new parents and students, causes significant circadian disruption. We hypothesize that irregular night shifts increase migraine prevalence compared to fixed schedules.

A systematic review and meta-analysis of observational studies up to March 27, 2025, assessed migraine prevalence in irregular versus fixed night shift workers, searching Web of Science and PubMed with terms like “shift work” and “migraine” (PRISMA/MOOSE-compliant, PROSPERO: CRD420250654865). Study quality was evaluated using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis calculated weighted odds ratios (ORs) for migraine prevalence.

From 203 records, 13 high-quality cross-sectional studies (N=38,798,271, 77% female, NOS 9–10) showed irregular night shifts significantly increased migraine odds (OR=1.61, 95% CI: 1.27–2.04, p<0.0001, I²=73%), with females at higher odds (OR=2.02–4.21). Meta-regression linked higher female representation to increased migraine odds (β=0.70, p=0.0003, R²=50%). Irregular night shifts showed no association with tension-type headache (OR=0.79, 95% CI: 0.43–1.45).

Irregular night shifts disrupt circadian rhythms, elevating migraine odds but not tension-type headache, suggesting fixed schedules may reduce the burden. Chronobiology- informed management, including slow-rotating schedules (≥5 days with rest days), delay- directed rotations, timed light exposure, and ambient temperature regulation, needs testing to prevent ‘Shift Work Migraine Disorder,’ a proposed distinct migraine subgroup. Competing Interest Statement YWW: Chief Medical Officer, Ex-Amplify Therapeutics; Consultant, Advanced Clinical and Research Center, Ethiopia; Consultant, Atheneum. Funding Statement This research was funded by the National Institute of Neurological Diseases and Stroke, National Institutes of Health, grant number K01NS124911 to YWW. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study used ONLY openly available human data from published observational studies, located via systematic searches in Web of Science (https://www.webofscience.com/wos/) and PubMed, adhering to PRISMA guidelines (PROSPERO: CRD420250654865). These databases provide access to the full text or abstracts of the 13 included studies through their search interfaces, with some articles available via PubMed Central (https://www.ncbi.nlm.nih.gov/pmc/) or publisher websites linked from the citations. The links and the studies included in the meta-analysis are as below, as included in the manuscript references section. National Institute for Occupational Safety and Health. 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Al Maqwashi LS, Sufyani AM, Bichara MM, et al. The Association Between Shift Work and Migraine Attacks Among Healthcare Workers in the Kingdom of Saudi Arabia. Cureus. 2024;16:e53315. Affatato O, Miguet M, Schioth HB, Mwinyi J. Major sex differences in migraine prevalence among occupational categories: a cross-sectional study using UK Biobank. J Headache Pain. 2021;22:145. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability Data supporting the findings of this study are available within the paper. Should any raw data files be needed in another format, they are available from the corresponding author upon reasonable request.