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Infection/inflammation-associated preterm delivery within 14 days of presentation with symptoms of preterm labour: A multivariate predictive model


Autoři: Emmanuel Amabebe aff001;  Steven Reynolds aff002;  Xiaoya He aff001;  Robyn Wood aff001;  Victoria Stern aff001;  Dilly O. C. Anumba aff001
Působiště autorů: Academic Unit of Reproductive and Developmental Medicine, University of Sheffield, Sheffield, England, United Kingdom aff001;  Academic Unit of Radiology, University of Sheffield, Sheffield, England, United Kingdom aff002
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pone.0222455

Souhrn

Multi-marker tests hold promise for identifying symptomatic women at risk of imminent preterm delivery (PTD, <37 week’s gestation). This study sought to determine the relationship of inflammatory mediators and metabolites in cervicovaginal fluid (CVF) with spontaneous PTD (sPTD) and delivery within 14 days of presentation with symptoms of preterm labour (PTL). CVF samples from 94 (preterm = 19, term = 75) singleton women with symptoms of PTL studied between 19+0–36+6 weeks’ gestation were analysed for cytokines/chemokines by multiplexed bead-based immunoassay, while metabolites were quantified by enzyme-based spectrophotometry in a subset of 61 women (preterm = 16, term = 45). Prevalence of targeted vaginal bacterial species was determined for 70 women (preterm = 14, term = 66) by PCR. Overall, 10 women delivered within 14 days of sampling. Predictive capacities of individual biomarkers and cytokine-metabolite combinations for sPTD and delivery within 14 days of sampling were analysed by logistic regression models and area under the receiver operating characteristic curve. Fusobacterium sp., Mubiluncus mulieris and Mycoplasma hominis were detected in more preterm-delivered than term women (P<0.0001), while, M. curtisii was found in more term-delivered than preterm women (P<0.0001). RANTES (0.91, 0.65–1.0), IL-6 (0.79, 0.67–0.88), and Acetate/Glutamate ratio (0.74, 0.61–0.85) were associated with delivery within 14 days of sampling (AUC, 95% CI). There were significant correlations between cytokines and metabolites, and several cytokine-metabolite combinations were associated with sPTD or delivery within 14 days of sampling (e.g. L/D-lactate ratio+Acetate/Glutamate ratio+IL-6: 0.84, 0.67–0.94). Symptomatic women destined to deliver preterm and within 14 days of sampling express significantly higher pro-inflammatory mediators at mid to late gestation. In this cohort, IL-6, Acetate/Glutamate ratio and RANTES were associated with delivery within 14 days of sampling, consistent with their roles in modulating infection-inflammation-associated preterm labour in women presenting with symptoms of preterm birth. Replication of these observations in larger cohorts of women could show potential clinical utility.

Klíčová slova:

Biology and life sciences – Biochemistry – Organisms – Research and analysis methods – Enzymology – Neuroscience – Developmental biology – Medicine and health sciences – Microbiology – Medical microbiology – Microbial pathogens – Bacterial pathogens – Bacteria – Pathology and laboratory medicine – Pathogens – Physiology – Women's health – Maternal health – Birth – Obstetrics and gynecology – Pregnancy – Immunology – Immune system – Innate immune system – Cytokines – Immune physiology – Molecular development – Metabolism – Carbohydrate metabolism – Glucose metabolism – Spectrum analysis techniques – Spectrophotometry – Neurochemistry – Gut bacteria – Neurotransmitters – Glutamate – Metabolites – Enzyme chemistry – Enzyme metabolism – Fusobacteria – Preterm birth – Pregnancy complications


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