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