Ali, A; Noblett, J; Usman, N; Wray, S; Blake, H; Gutierrez del Arroyo, A; Abbott, TEF; ... Phull, M; + view all Ali, A; Noblett, J; Usman, N; Wray, S; Blake, H; Gutierrez del Arroyo, A; Abbott, TEF; Begum, S; Dias, P; Weber, V; Papoutsos, C; Ackland, G; Black, R; Khan, A; Stretch, B; Wikner, M; Wong, R; Warrington, A; Bruce-Hickman, K; Verma, P; Rodriguez Sierra, EP; Coulter, C; Al-Maiyah, F; Barrett, A; Razzaque, M; Patrick, A; Martin, T; Das, A; Costa, AV; Palfreeman, C; George, D; Raja, J; Stephenson, L; Kwok, S; Quereshi, N; Chapman, A; Tsun, J; Patel, A; Smith, C; Arumugaum, A; Hoe, M; Thompson, C; Singh, A; Sritharan, P; Valori, L; Collins, E; Kennedy, N; Longbottom, R; Meroz, MR; Tanqueray, T; Canclini, L; Noakes, I; Frowd, R; Sharp, T; Leary, R; Nicklin, A; Sousi, E; Mazzoli, I; Berger, P; De Freixo, L; Vishwanathan, A; Eiben, P; Hoodless, S; Carey, A; Pinder, A; Wilson, M; Waspe, J; Bramley, P; Wilson, V; David, AL; Weist, S; Newth, O; Folorunsho, M; Ali, J; Achempong, Y; Bourke, M; Brunnen, D; Kim, J; Mak, K; Odor, P; Sarmiento, L; Ciechanowicz, S; Borg, LX; Tripurneni, V; Phull, M; - view fewer (2025) Interleukin-1 receptor antagonist polymorphisms in women receiving epidural analgesia who develop maternal intrapartum fever: a prospective, multicentre Mendelian randomised study. British Journal of Anaesthesia , 135 pp. 134-140. 10.1016/j.bja.2025.03.037.

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Abstract

BACKGROUND: Genetically predicted higher levels of the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL1-Ra) might reduce the risk of developing epidural-related maternal fever, a phenomenon that occurs exclusively in women having epidural analgesia in labour. We hypothesised that in women having epidural analgesia, the absence of specific alleles that lower circulating levels of IL1-Ra would be associated with the development of epidural-related maternal fever, administration of intrapartum antibiotics, or both. METHODS: We prospectively enrolled women ≥18 yr of age receiving epidural analgesia during labour, excluding those with pre-existing fever, antibiotic therapy, or immunodeficiency. Allele scores were constructed from genotyping the C-allele frequency at variants rs6743376 and rs1542176; more copies of each allele independently raise IL-1Ra. The composite primary outcome was maternal intrapartum fever (>38°C) or administration of intrapartum antibiotics after epidural placement. The exposure of interest was the IL1-Ra allele score, comparing 0 (lowest genetically predicted IL-1Ra levels) with ≥1 allele scores. Maternal fever and antibiotic administration were compared in women with 0 or ≥1 allele scores. RESULTS: Of 624 women genotyped, 155 (24.8%) developed maternal fever or received antibiotics. Fever or antibiotic administration occurred in 19/74 (25.7%) labouring women with an IL-1Ra allele score of 0, compared with 136/550 (24.7%) women with IL-1Ra allele scores ≥1 (odds ratio 1.05, 95% confidence interval 0.60–1.83; P=0.89). Conclusions In women who receive epidural analgesia during labour, genetically predicted (higher) interleukin-1 receptor antagonist levels do not alter the incidence of maternal intrapartum fever or use of intrapartum antibiotics. CLINICAL TRIAL REGISTRATION: ISRCTN99641204.

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