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Interleukin-1 receptor antagonist, mode of analgesia and risk of Caesarean delivery after onset of labour: a Mendelian randomisation analysis

Ackland, GL; Van Duijvenboden, S; Abbott, TEF; Gutierrez Del Arroyo, A; Wilson, MJ; David, AL; EPIFEVER-2 investigators; (2022) Interleukin-1 receptor antagonist, mode of analgesia and risk of Caesarean delivery after onset of labour: a Mendelian randomisation analysis. British Journal of Anaesthesia , 128 (1) pp. 89-97. 10.1016/j.bja.2021.09.039.

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Abstract

BACKGROUND: Lower 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. METHODS: We 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). RESULTS: There 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). CONCLUSIONS: Mendelian randomisation analysis suggests that higher IL-1ra levels are associated with reduced Caesarean delivery rate. Neuraxial analgesia appears to disrupt this link. CLINICAL TRIAL REGISTRATION: UK Biobank study 62745.

Type: Article
Title: Interleukin-1 receptor antagonist, mode of analgesia and risk of Caesarean delivery after onset of labour: a Mendelian randomisation analysis
Location: England
DOI: 10.1016/j.bja.2021.09.039
Publisher version: https://doi.org/10.1016/j.bja.2021.09.039
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Caesarean delivery, inflammation, interleukin-1 receptor antagonist, labour, newborn
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL EGA Institute for Womens Health > Maternal and Fetal Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10141598
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