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.