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

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

“…Although the study design benefits from minimising many limitations associated with observational databases, the sample size is informed using UK Biobank genetic data derived from just two racial backgrounds, with more than 93% of women with British or Irish white race. 17 We cannot exclude that IL-1 signaling by IL-1Ra influences the quality of analgesia, but we will be able to rule out that IL-1Ra signaling impacts upon potential confounders such as duration of labour. 28 Induction of labour will likely be common in labouring women requesting epidural analgesia, so a planned subgroup analysis will assess whether there is any relationship between induction of labour and the study exposure of interest and/or outcomes.…”

“…13 Our previous analysis of over 250,000 women from the UK Biobank showed that approximately 11% of UK white women have a zero genetic (allele) score for IL-1Ra (i.e., the lowest genetically determined amount of IL1-ra). 17 The overall incidence of ERMF in EPIFEVER was 13.4%. 25 Our original sample size estimate was based on the single outcome of ERMF-(temperature > 38ºC), assuming that women with 0-1 allele scores are more likely to develop temperature > 38ºC (approximately 22%) compared with with IL-1Ra allele scores >1.…”

“…16 Mendelian randomisation analysis of UK Biobank data suggests that genetic IL-1ra levels are associated with a reduced risk of an unplanned caesarean section after the onset of labour; this association is disrupted by the use of neuraxial analgesia. 17 In EPIFEVER-2 trial, we hypothesise that the absence of rs6743376 and rs1542176 alleles for IL1-ra, which results in the lowest circulating levels of IL-1ra, are associated with ERMF and/or the administration of intrapartum antibiotics (Figure 1).…”

Interleukin-1 Receptor Antagonist, Mode of Analgesia and Risk of Cesarean Delivery After Onset of Labor: A Mendelian Randomization Analysis

“…5 Labor activates the release of cytokines, specifically IL-1β and concurrently a release of IL-1ra prevents the effects of IL-1-induced preterm labor. 5 As demonstrated by del Arroyo et al, there is a modulation of IL-1β and the receptor antagonist that takes place when tissue is exposed to bupivacaine. 6 Local anesthetics may favor the proinflammatory cytokines by the change in the IL-1ra/IL-1β ratio.…”

Effect of Continuous Infusion of a Subhypnotic Dose of Propofol on Nausea and Vomiting after Carboprost Administration at Cesarean Delivery: A Randomized, Double-blind, Placebo-controlled Trial

“…The interleukin receptor antagonist (IL-1ra) directly inhibits the pro-inflammatory impacts of IL-1β. 5 Labor activates the release of cytokines, specifically IL-1β and concurrently a release of IL-1ra prevents the effects of IL-1-induced preterm labor. 5 As demonstrated by del Arroyo et al, there is a modulation of IL-1β and the receptor antagonist that takes place when tissue is exposed to bupivacaine.…”