Interleukin-1 receptor antagonist polymorphisms in women receiving epidural analgesia who develop maternal intrapartum fever: a prospective, multicentre Mendelian randomised study

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.