• Int J Obstet Anesth · May 2022

    IL-1ra polymorphisms and risk of epidural-related maternal fever (EPIFEVER-2): study protocol for a multicentre, observational mechanistic cohort study.

    • A Ali, V Weber, S J Thompson, AbbottT E FTEFTranslational Medicine and Therapeutics, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK., R Harmston, A L David, G L Ackland, and EPIFEVER-2 investigators.
    • Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
    • Int J Obstet Anesth. 2022 May 1; 50: 103540.

    BackgroundLaboratory data suggest that insufficient circulating levels of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) are associated with intrapartum inflammation and epidural-related maternal fever, both of which increase the rate of obstetric interventions and antibiotic use during labour. Genetic polymorphisms strongly influence IL-1ra levels in the general population. We aim to examine the association between IL-1ra polymorphisms and epidural-related maternal fever using Mendelian randomization analysis.MethodsEPIFEVER-2 is a multicentre UK trial enrolling 637 women receiving epidural analgesia for labour. Blood samples obtained no later than four hours after epidural insertion will provide deoxyribonucleic acid for Taqman single-nucleotide polymorphism genotyping for presence/absence of rs6743376, rs1542176 alleles for IL-1ra, to establish the genetic score. The absence of both alleles is associated with the lowest IL-1ra levels. The primary outcome is pyrexia (>38°C) or intrapartum antibiotic administration. Secondary outcomes include mode of delivery, maternal and neonatal healthcare interventions.ResultsThe EPIFEVER-2 study was prospectively registered (ISRCTN99641204) following ethical approval. Participant recruitment began in May 2021, with 221 women recruited across three centres as of November 21, 2021.ConclusionsEPIFEVER-2 will generate the largest prospective dataset detailing the incidence and consequences of epidural-related maternal fever. Using Mendelian randomisation analysis, a causative role for lower IL1-ra levels in determining the risk of epidural-related maternal fever and/or antibiotic administration before delivery will be examined.Copyright © 2022 Elsevier Ltd. All rights reserved.

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