Interpretation
Labor-associated inflammasome activation in the intrauterine compartment, mainly in the choriodecidual interphase, might correlates with the progressive concentration increase of IL-1β in the CVF.9,18 This cytokine has been proposed as a key signal for the amplification cascade leading to the production of secondary labor mediators such as PGs16, 19–21 and, in conjunction with IL-6, inducing the expression of oxytocin receptors on myometrial cells22 and the secretion and activation of MMPs in the chorioamniotic membranes and cervix.23An effort to discard the presence of cervicovaginal or intrauterine infection in participating women, allowed us to propose that concentrations of danger signals or alarmins and cytokines are associated with sterile inflammation.24–28Interestingly, cytokine concentrations were similar between term deliveries and preterm deliveries, highlighting the concept of a common labor-associated inflammatory response in both conditions.
A multitude of maternal biomarkers, including cytokines, have been shown to be associated with the occurrence of spontaneous preterm birth (sPTB), but their predictive accuracy has only moderately good, thus precluding their use as a screening test in clinical practice.29,30 The great heterogeneity in inclusion criteria and gestational age at the time of evaluation represent other peculiar limitations to most studies.31 In this setting, it has been difficult to quantify the strength of the association between a given marker and sPTB and the diagnostic performance of that marker in identifying women at risk of childbirth. We explored the possibility of using CVF cytokines or a combination of them to improve our knowledge and understanding between the inflammatory response associated with childbirth and the clinical manifestations of childbirth. An initial approach resulted in the pro-inflammatory profile extracted by PCA, pointing out the importance of multiple biomarker modeling for optimal predictive efficacy and the coherence of the statistical results with the proposed biological phenomenon.32
IL-6 by itself has proved to be a good marker to diagnose and predict spontaneous labor regardless of gestational age, highlighting the importance of being an independent predictor. IL-6 is one of the most studied biomarkers in sPTB and preterm premature rupture of membranes (pPROM),33,34 however, multiple cutoffs have been proposed for both clinical entities.29,30 Therefore, cutoffs for normal and abnormal cytokines in disease states need to be better established to support and distinguish diagnoses, as well as estimate prognoses more accurately. Evidence that IL-6 is a helpful marker to identify spontaneous labor was found and must be followed by a clinical trial evaluating it as a diagnostic tool for characterization of labor progression and furthermore, to identify women at risk of delivering in a limited window of time. The characterization of IL-6 reference values can be better accomplished with an easily accessible compartment such as CVF.