Chorioamnionitis is defined as inflammation or infection of the placenta and placental membranes after 20 weeks of gestation. It is one of the primary causes of perinatal morbidity and mortality, which seriously negatively affects the prognosis of the perinatal infant. According to the different stages of its clinical manifestations, it is divided into histological chorioamnionitis and clinical chorioamnionitis. Histological chorioamnionitis, also known as subclinical chorioamnionitis, has hidden clinical manifestations and requires confirmation by a thorough pathological examination of the placenta. Clinical chorioamnionitis is the final stage of histological chorioamnionitis progression. At this stage, the fetus in utero has been exposed to the inflammatory environment for an extended time period, which greatly impacts the prognosis of the newborn.
Prior studies have reported the different incidence of chorioamnionitis in pregnant women with cervical cerclage. Lee et al. reported that 81% (42/52) of patients with cervical insufficiency have evidence of intraamniotic inflammation [1, 2]. In the present study, the diagnosis rate of clinical chorioamnionitis is only 23.8% and tissue chorioamnionitis incidence is 70%. For pregnant women with cervical cerclage, it often indicates potential chorioamnionitis when signs of labor appear. The removal or retention of cervical cerclage suture and the time for expected continued treatment are clinically controversial issues. Clinical decision-making is necessary to balance the potential benefits of prolonged pregnancy with risk of intrauterine infection. Amniocentesis is an invasive test, and if maternal serum markers can be obtained non-invasively to predict tissue chorioamnionitis, management after cervical cerclage could be improved.
At present, many studies describe predictive indicators of tissue chorioamnionitis, and the results of clinical studies are also quite different. There are currently no recommended clinical or laboratory indicators. In particular, the predictive value of amniotic fluid inflammatory factors is highly debatable. Yoneda et al. reported that the IL-8 level in amniotic fluid can more accurately predict tissue chorioamnionitis . Park et al. reported that maternal plasma IL-6 can independently predict intraamniotic infection in preterm women. However, its diagnostic value is inferior to assessing IL-6 levels in amniotic fluid and similar to that of serum CRP . Horinouchi et al. found that the IL-6 and PCT levels in umbilical vein can predict histological chorioamnionitis . Another prospective study found no connection between inflammatory markers in amniotic fluid and preterm birth . Kim et al. found that for patients with preterm premature rupture of fetal membranes, non-invasive parameters (serum CRP) and invasive parameters (amniotic fluid IL-6 levels) were not significantly different in predictive ability for histological chorioamnionitis . A recent systematic review and meta-analysis of diagnostic indicators for histological chorioamnionitis indicated that simply using CRP and maternal leukocytosis as predictive indicators shows low sensitivity and specificity. In a combination of 13 studies, CRP sensitivity was 68.7% (95% CI 58–77%) and specificity was 77.1% (95% CI 67–84%). A combination of 4 studies to evaluate the quantity of maternal white blood cells revealed that the combinatorial sensitivity was 51% (95% CI 40–62%) and specificity was 65% (95% CI 50–78%) . In light of these findings, current recommendations support a combination of maternal blood and amniotic fluid biomarkers for improved accuracy in predicting histological chorioamnionitis .
Recent data suggest complete blood count (CBC) and its derived parameters including neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and platelet to white blood cell ratio are recognized inflammatory markers for low-grade inflammation [10, 11]. These non-invasive inflammatory markers are highly correlated with neonatal outcomes, suggesting a poor neonatal prognosis . Our research on the prediction of preterm birth found that the combination of three parameters of blood cell components such as NLR, PDW (platelet distribution width) and HGB (hemoglobin) can better predict preterm birth, and the predictive sensitivity of the combined diagnostic markers is 88.6% and the specificity is 40.5% [13, 14]. Another of our studies on the prediction of preterm birth found that platelets and PLT/WBC as a potential marker have certain significance in predicting the occurrence of histological chorioamnionitis . Using blood cell-related parameters to predict preterm labor requires no concomitant drug therapy to promote lung maturity. However, Winkler et al. suggest that the dose of corticosteroids used to prevent respiratory distress syndrome does not affect early prediction of asymptomatic infections in preterm labor .
The findings presented here indicate that the number of platelets in patients with cervical cerclage before surgery is a risk factor for chorioamnionitis. The post-surgery risk of histological chorioamnionitis for pregnant women with cervical cerclage whose preoperative platelets ≥ 229.5 × 109/L was 7.692 times greater than those with preoperative platelets < 229.5 × 109/L. Multivariate regression analysis also indicated that preoperative platelet count is a potential serum marker of histological chorioamnionitis. Multiple studies have confirmed that platelet activation participates in the pre-inflammatory response and can be used as a predictor of inflammation. In the course of inflammation, platelets rapidly participate in inflammatory pathogenesis through the secretion of cytokines, chemokines and other inflammatory mediators . Our team’s prospective study on spontaneous preterm birth also found that the platelet count of histological chorioamnionitis (HCA) patients was significantly higher than that of the non-HCA and control groups (P < 0.001). In addition, the AUC of the PLT count was 0.8095, indicating that the PLT count is a sensitive predictor of HCA in preterm patients.
The platelet/white blood cell ratio (PLT/WBC) as a hematological marker of systemic inflammation has been widely used to predict postoperative infection and disease prognosis [18, 19]. We have found that PLT/WBC are sensitive biomarkers for the diagnosing HCA. Our data also attempts to verify that the PLT/WBC ratio can be used as an index to predict histological chorioamnionitis during onset of labor following cervical cerclage. The data in this study also confirms that the number of white blood cells and platelet/white blood cell ratio during onset of labor are risk factors for subclinical chorioamnionitis are also likely risk factors after multivariate logistic regression analysis. After further grouping the platelets before cervical cerclage, the number of white blood cells and the platelet/white blood cell ratio during onset of labor according to the cut-off values, a joint screening system was established. When these three indicators have 2 or more values greater than or equal to the corresponding cut-off value, the sensitivity for predicting subclinical chorioamnionitis is 87.5%, and the specificity is 45.5%.
Park et al. reported that non-invasive parameters, including maternal white blood cell count, CRP level, parity and gestational age, can strongly predict intraamniotic infection in women with preterm premature rupture of membranes (PPROM) . The present study attempted to find appropriate clinical and laboratory indicators to predict chorioamnionitis. However, no clinical indicators such as parity, cervical cerclage gestational age, and cervical dilatation were found to be risk factors for chorioamnionitis. This difference may be due to the different sample sources in different studies.
Our research has certain limitations that must be mentioned. One limitation is that this study is retrospective and was conducted in a single center. The small sample size limits the widespread application of our results. Secondly, we will further verify the effectiveness of the noninvasive prediction model through prospective studies in future clinical studies.