• Gareth L Ackland, Stefan Van Duijvenboden, AbbottTom E FTEFTranslational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK., Gutierrez Del ArroyoAnaATranslational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK., Matthew J Wilson, Anna L David, and EPIFEVER-2 investigators.
• Translational Medicine and Therapeutics, William Harvey Research Institute, Queen Mary University of London, London, UK. Electronic address: g.ackland@qmul.ac.uk.
• Br J Anaesth. 2022 Jan 1; 128 (1): 899789-97.

BackgroundLower circulating levels of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1ra) are associated with intrapartum inflammation and epidural analgesia-related maternal fever, both of which increase the rate of obstetric interventions. We hypothesised that genetic variants determining IL-1ra levels would be associated with Caesarean delivery rates after the onset of labour.MethodsWe performed Mendelian randomisation analyses in parous women ≥16 yr old who received either non-neuraxial or neuraxial analgesia for their first two labours (UK Biobank). We used an established genetic score (calculated as 0-4, determined by the presence/absence of rs6743376 and rs1542176 alleles), in which the complete absence of both alleles causes the lowest IL-1ra levels. The primary outcome was Caesarean delivery after the onset of labour (odds ratio [OR]: 95% confidence intervals).ResultsThere were 7731 women (mean [standard deviation] age at first birth: 25 [5] yr) who had complete genetic scores and delivery data. For women who received non-neuraxial analgesia, Caesarean delivery rates were different across allele scores (χ2=12.4; P=0.015): 104/596 (17.4%) women with zero allele score underwent Caesarean delivery, compared with 654/5015 (13.0%) with allele score ≥1 (OR 1.41; 1.12-1.77). For women who had neuraxial analgesia, Caesarean delivery was not different across allele scores, ranging from 18.1% to 20.8% (χ2=0.29; P=0.99). Caesarean delivery was independent of type of analgesia for 818/7731 (10.6%) women with zero allele scores (OR 0.93; 0.63-1.39), but was higher in women receiving neuraxial analgesia with allele scores ≥1 (OR 1.55; 1.35-1.79; P<0.001).ConclusionsMendelian randomisation analysis suggests that higher IL-1ra levels are associated with reduced Caesarean delivery rate. Neuraxial analgesia appears to disrupt this link.Clinical Trial RegistrationUK Biobank study 62745.Copyright © 2021 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.

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