| Title: | Interleukin-1 receptor antagonist, mode of analgesia and risk of Caesarean delivery after onset of labour: a Mendelian randomisation analysis |
| Journal: | British Journal of Anaesthesia |
| Published: | 19 Nov 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/34802694/ |
| DOI: | https://doi.org/10.1016/j.bja.2021.09.039 |
Publication 13812
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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.</p>
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).</p>
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).</p>
CONCLUSIONS: Mendelian randomisation analysis suggests that higher IL-1ra levels are associated with reduced Caesarean delivery rate. Neuraxial analgesia appears to disrupt this link.</p>
CLINICAL TRIAL REGISTRATION: UK Biobank study 62745.</p>
16 Keywords
- Adult
- Analgesia, Epidural
- Analgesia, Obstetrical
- Cesarean Section
- Cohort Studies
- Female
- Genetic Variation
- Humans
- Interleukin 1 Receptor Antagonist Protein
- Labor, Obstetric
- Mendelian Randomization Analysis
- Pregnancy
- Prospective Studies
- Risk
- United Kingdom
- Young Adult
45 Authors
- Gareth L. Ackland
- Stefan Van Duijvenboden
- Tom E.F. Abbott
- Ana Gutierrez del Arroyo
- Matthew J. Wilson
- Anna L. David
- the EPIFEVER-2 investigators
- Amaan Ali
- Matt Wikner
- James Noblett
- Nusrat Usman
- Sarah Wray
- Holly Blake
- Ana G. del Arroyo
- Tom E.F. Abbott
- Valentin Weber
- Constantinos Papoutsos
- Rebecca Black
- Kara Bruce-Hickman
- Parvesh Verma
- Chris Sadler
- Alice Barrett
- Laura Fulton
- Tim Martin
- Tabitha Tanqueray
- Rebecca Longbottom
- Lisa Cancili
- India Nokes
- Rachel Frowd
- Natasha Kennedy
- Matt Wilson
- Vicki Wilson
- Anna L. David
- Sarah Weist
- Olivia Newth
- Morenike Folorunsho
- Jihana Ali
- Yaa Achaempong
- Miriam Bourke
- Derek Brunnen
- Jennifer Kim
- Kei Mak
- Pete Odor
- Laura Sarmiento
- Sarah Ciechanowicz
1 Application
| Application ID | Title |
|---|---|
| 62745 | EPIFEVER-2: single nucleotide polymorphisms in the IL-1Ra gene and outcomes in labour following epidural analgesia. |
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