Significance of Cervicovaginal Inflammatory Cytokines During Spontaneous Onset of First Stage of Labor: A Data-Driven Approach from a Pseudo-Longitudinal Study

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Objective: To evaluate the ability of cervicovaginal cytokines to describe and predict the inflammatory processes associated to spontaneous labor onset both, term and preterm. Design: Pseudo-longitudinal study. Setting: Two Ministry of Health-affiliated hospitals in Mexico City from 2018 to 2020. Population or Sample: Women with singleton pregnancies at different moments during spontaneous onset of first stage of labor between 12 and 41 weeks of gestation. Methods: Women were grouped in five stages going from the absence of uterine activity and cervical changes (Stage 0) to the regular uterine contractions with cervix dilation >3 cm (Stage 4 or established labor). Main Outcome Measures: Cervicovaginal cytokine concentrations between term and preterm labor, cytokine trajectories throughout spontaneous labor onset and predictive accuracy of IL-6 for spontaneous labor. Results: Of 144 women with spontaneous labor 96 delivered at term and 48 preterm, both groups displayed similar cytokine concentrations. We found positive correlations between pro-inflammatory cytokines and clinical manifestations of labor (study stages) using individual cytokines and score-based data by principal-component analysis (IFN-ϒ, TNF-α, IL-1β, IL-6) as dependent variables. The risk of delivery increased as IL-6 concentrations increased (HR 202.09, 95% CI 24.57-1662.49, P<0.001). IL-6 was a significant predictor for spontaneous labor within 12 days (AUC=0.785, 95% CI 0.693-0.877) regardless of gestational age. Conclusions: Cervicovaginal cytokines, particularly IL-6, reflect and predict the intrauterine inflammatory sequence associated to initial labor progression. This study provides a new insight into cervicovaginal inflammatory biomarkers usability for labor diagnosis and birth prediction. Keywords: Labor, cytokines, preterm birth, IL-6.

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