Histological Chorioamnionitis Group Research Articles

Histological chorioamnionitis and pathological stages on very preterm infant outcomes.

Histological chorioamnionitis (HCA) is a condition linked to preterm birth and neonatal infection and its relationship with various pathological stages in extremely preterm neonates, and with their associated short- and long-term consequences, remains a subject of research. This study investigated the connection between different pathological stages of HCA and both short-term complications and long-term outcomes in preterm infants born at or before 32 weeks of gestational age. Preterm infants born at ≤ 32 weeks of gestation who underwent placental pathology evaluation and were followed-up at 18-24 months of corrected age were included. Neonates were classified based on their exposure to HCA and were further subdivided into different groups according to maternal inflammatory responses (MIR) and fetal inflammatory responses (FIR) stages. We compared short-term complications during their hospital stay between the HCA-exposed and -unexposed groups and examined the influence of HCA stages on long-term outcomes. The HCA group exhibited distinct characteristics such as higher rates of premature rupture of membranes > 18 h, reduced amniotic fluid, early-onset sepsis, bronchopulmonary dysplasia and intraventricular haemorrhage (IVH) grades III-IV (P < 0.05). The moderate-severe HCA group displayed lower gestational age, lower birth weight and higher incidence of IVH (grades III-IV) and preterm sepsis compared with the mild HCA group (P < 0.05). After adjusting for confounders, the MIR stages 2-3 group showed associations with cognitive impairment and cerebral palsy (P < 0.05), and the FIR stages 2-3 group also showed poor long-term outcomes and cognitive impairment (P < 0.05). Moderate-severe HCA was associated with increased early-onset sepsis, severe IVH and poor long-term outcomes, including cognitive impairment and cerebral palsy. Vigilant prevention strategies are warranted for severe HCA cases in order to mitigate poorer clinical outcomes.

Establishment of a prediction model for histological chorioamnionitis and its association with outcomes of premature infants.

This study aims to construct a prediction model for histological chorioamnionitis (HCA) and analyze the associations between the predicted risk of HCA and adverse outcomes in preterm infants. In total, 673 subjects were included in this cohort study and divided into HCA group (n = 195) and non-HCA group (n = 478). A stepwise method was used to screen the predictors for HCA, binary logistic regression was used to construct the prediction model, and the associations between the predicted risk of HCA and adverse outcomes were analyzed. HCA occurred in 195 patients, accounting for 29.0%. The sensitivity of the prediction model was 0.821 [95% confidence interval (CI): 0.767-0.874)], the specificity was 0.684 (95% CI: 0.642-0.726), the positive predictive value was 0.514 (0.459-0.570), the negative predictive value was 0.903 (95% CI: 0.873-0.934), the area under the curve was 0.821 (95% CI: 0.786-0.855), and the accuracy was 0.724 (95% CI: 0.690-0.757). The predicted risk of HCA was associated with a higher risk of bronchopulmonary dysplasia (BPD) [odds ratio (OR) = 3.48, 95% CI: 1.10-10.95)], sepsis (OR = 6.66, 95% CI: 2.17-20.43), and neonatal infections (OR = 9.85, 95% CI: 3.59-26.98), but not necrotizing enterocolitis (OR = 0.67, 95% CI: 0.24-1.88), retinopathy of prematurity (OR = 1.59, 95% CI: 0.37-6.85), and brain damage (OR = 1.77, 95% CI: 0.82-3.83). After adjusting for confounders including gestational week at birth and birth weight, the risk of neonatal infections (OR = 5.03, 95% CI: 2.69-9.41) was increased in preterm infants' exposure to HCA. The model showed good predictive performance for identifying pregnant women with a higher risk of HCA. In addition, HCA was associated with the risk of BPD, sepsis, and infections in neonates.

Predictors for histological chorioamnionitis among women with preterm prelabour rupture of membranes after dexamethasone treatment: a retrospective study.

To investigate reliable biomarkers for predicting histological chorioamnionitis (HCA) in women with preterm prelabour rupture of membranes (PPROM). A retrospective study. A maternity care hospital in Shanghai. Women with PPROM before 34+0/7 weeks of gestation. Mean values of biomarkers were compared by two-way analysis of variance (ANOVA). Log-binomial regression models were used to assess the association between biomarkers and risk of HCA. A stepwise logistic regression model was used to develop a multi-biomarker prediction model and identify the independent predictors. The area under the receiver operating characteristic curve (AUC) was used to assess prediction performance. The ability of the individual biomarker and the combination of multiple biomarkers to predict HCA. In 157 mothers with PPROM, 98 (62.42%) women had HCA and 59 (37.58%) women did not have HCA. No significant differences were observed between the two groups in white blood cell, neutrophil or lymphocyte counts, whereas both high-sensitivity C-reactive protein (hsCRP) and procalcitonin (PCT) were significantly higher in the HCA group. HsCRP and PCT were found to be independently associated with the risk of HCA, and PCT had a larger AUC value than hsCRP (p< 0.05). The optimal multi-biomarker prediction model for HCA (AUC=93.61%) included hsCRP at 72 hours and PCT at 48 and 72 hours, and PCT had a stronger prediction capacity than hsCRP. PCT could be a reliable biomarker for the early prediction of HCA in women with PPROM within 72 hours of dexamethasone treatment.

The role of upper and lower genital tract microbiota alterations in term chorionamnionitis: A prospective study.

This study aimed to compare the dynamics of lower and upper genital tract microbiota in normal term pregnancy, histological chorioamnionitis (HCA), and clinical chorioamnionitis (CCA) patients to provide a reference for the diagnosis and treatment of chorioamnionitis (CAM) patients. We prospectively collected vaginal and cervical secretions, as well as placenta tissues, fetal membranes, and amniotic fluid from normal-term pregnant women, HCA and CCA patients. Then, we performed genomic DNA extraction and PCR amplification for all samples. The eligible samples were analyzed by 16S ribosomal RNA (16S rRNA) sequencing. Additionally, all placenta tissues were histopathologically examined, and neonatal pharyngeal swabs and placenta tissues from the HCA and CCA groups were subjected to microbial culture. A total of 85 term pregnant women were enrolled in this study, including 34 in the normal group (N), 37 in the HCA group, and 14 in the CCA group. A total of 171 qualified samples were analyzed by 16S rRNA sequencing. The results suggested that the cervical microbiota was highly similar to the vaginal microbiota in normal term parturients, with Lactobacillus as the dominant bacterium. Moreover, there was no difference in the alpha and beta diversity of vaginal microbiota between the N, HCA, and CCA groups at the genus level. Besides, no significant differences were detected in cervical microbiome among the three groups. Regarding intrauterine microorganisms, the N and HCA groups had similar microbial composition but were different from the CCA group. No microbe was detected in the placental tissue of normal term parturients, while some microorganisms were found in the intrauterine amniotic fluid and fetal membrane samples. Regardless of cultivation or 16S rRNA sequencing, an extremely low microbial positive rate was detected in HCA and CCA intrauterine samples. Compared to the normal group, Lactobacillus was significantly reduced in the CCA group intrauterine, and Ureaplasma and Enterococcus increased with no statistically significant. The N, HCA and CCA groups had similar composition of vaginal and cervical microflora. Some normal-term pregnant women can harbor non-pathogenic microbiota in the uterine cavity. Sterile inflammation is more frequent than microbial-associated inflammation in term HCA and CCA parturients.

Non-invasive prediction of histologic chorioamnionitis using maternal serum markers in women with preterm prelabour rupture of membranes.

This study aimed to evaluate and compare the predictive accuracy of serum markers for histological chorioamnionitis (HCA) among women with preterm prelabour rupture of membranes (PPROM), and to develop a nomogram prediction model to minimize the damage of the disease. This case-control study included 153 pregnant women with PPROM with a gestational age of 20+0 ∼36+6 weeks. The subjects were assigned into two groups: PPROM with and without HCA. According to the results of logistic regression analysis, the predictive equation and nomogram were generated using key parameters, and the discrimination and consistency of the model were evaluated by receiver operating characteristic (ROC) curves and calibration curves. From 153 subjects with PPROM, 77 developed HCA. Compared with the PPROM without HCA group, the CRP, PCT and NLR were significantly higher in HCA group (P < 0.001), and the CRP had the highest predictive value. The area underthecurve(AUC) of the prediction model was 0.873, and the sensitivity and specificity of predicting HCA were 68.8% and 92.1%, respectively. And the calibration curves fitted well with the realistic situation. Maternal serum CRP and NLR could be used as predictive biomarkers for HCA in women with PPROM, while PCT needs to be further explored due to its slightly lower predictive value. Our serum markers and gestational age at PPROM could be used as a non-invasive and convenient method to predict HCA in women with PPROM.

Adverse Maternal and Neonatal Outcomes in Women With Elevated Intrapartum Temperature Complicated by Histological Chorioamnionitis at Term: A Propensity-Score Matched Study.

Background: Elevated intrapartum temperature has been widely proven to be associated with adverse clinical outcomes in both mothers and neonates. Histological chorioamnionitis (HCA), the inflammation of chorion and amniotic membranes, is commonly observed in those with elevated intrapartum temperature. Thus, we aimed to explore whether the combination of HCA would further affect the pregnancy outcomes in those with intrapartum temperature ≥ 37.5°C.Methods: This retrospective cohort study was conducted at the International Peace Maternity and Child Health Hospital (IPMCH), including all full-term women with intrapartum temperature ≥ 37.5°C from Jan 2017 to Jan 2019. Patients were divided in to HCA group or control group according to placental pathology results, and we used 1:1 propensity score matching (PSM) to reduce the effects of potential confounding factors between the two groups. Univariate and multivariable logistic regression were used to identify the association between HCA and different adverse maternal and neonatal outcomes.Results: We formed a propensity-score matched cohort containing 464 women in each group. Higher positive rate of mycoplasma (14.01% vs. 7.33%, p = 0.001) was found in the vaginal secretion culture of women in the HCA group. After adjusting for various baseline clinical characteristics, women with HCA were more likely to end their delivery by cesarean section (AOR = 1.55, 95% CI: 1.05–2.28), and puerperal morbidity (AOR = 2.77, 95% CI: 1.44–5.33) as well as prolonged hospitalization (AOR = 1.56, 95% CI: 1.12–2.17) were more likely to be observed in the HCA group. The existence of HCA might also be associated with neonatal sepsis (AOR = 2.83, 95% CI: 1.14–7.04) and NICU admission (AOR = 1.40, 95% CI: 1.04–1.87) in newborns. In the study on the impact of different stages of HCA, we found that both maternal and neonatal outcomes would not be affected by mild HCA (stage I), while HCA of stage III was associated with increased need for neonatal respiratory support and elevated likelihood of prolonged hospitalization in neonates.Conclusions: Elevated intrapartum temperature complicated by HCA might be related to the elevated occurrence of several adverse maternal and neonatal outcomes, except those with HCA of stage I. Advanced HCA stage correlated with a worse prognosis.

Prognostic Markers for Chorioamnionitis: IL-6, TNF-α, and MMP-8 in Vaginally Obtained Amniotic Fluid.

Background. Earlier chorioamnionitis diagnosis is crucial to improve maternal and neonatal health outcomes. This study was conducted to evaluate the inlerleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and matrix metalloproteinase 8 (MMP-8) levels in vaginally obtained amniotic fluid to investigate their prognostic value and to determine the most appropriate cut-off values for the prediction of chorioamnionitis. Methods. This case control study included women who were diagnosed with preterm premature rupture of the membranes before 34 weeks of gestation and were admitted to Vilnius University Hospital Santaros Klinikos. Free-leaking amniotic fluid was obtained vaginally with a sterile speculum less than 48h before delivery. Amniotic fluid IL-6, TNF-α, and MMP-8 levels were determined by the Enzyme Linked Immunosorbent Assay. Diagnosis of chorioamnionitis was confirmed by histological examination of the placenta and membranes after delivery. Results. The study included 156 women, 65 patients in the histological chorioamnionitis group (Group I) and 91 in a group without diagnosed histological chorioamnionitis (Group II). The median concentrations of IL-6, MMP-8, and TNF-α in amniotic fluid were statistically significantly higher in Group I than in Group II (p-value < 0.001). The area under the curve of TNF-α and MMP-8 were higher than the area under the curve of IL-6 (0.91, 0.89, and 0.81, respectively). No statistically significant difference was found when comparing the receiver operating characteristic (ROC) curves of TNF-α and MMP-8. The optimum cut-off values for the prediction of chorioamnionitis were found to be 1389.82 pg/mL for IL-6, 21.17 pg/mL for TNF-α, and 172.53 ng/mL for MMP-8. The sensitivity, specificity, positive prognostic value (PPV), and negative prognostic value (NPV) of the IL-6 cut-off for chorioamnionitis were 88%, 70%, 67%, and 89%, respectively. The sensitivity, specificity, PPV, and NPV of the TNF-α cut-off were 88%, 84%, 79%, and 90%, respectively. The sensitivity, specificity, PPV, and NPV of the MMP-8 cut-off were 80%, 87%, 81%, and 86%, respectively. Conclusions. The vaginally obtained amniotic fluid IL-6, MMP-8, and TNF-α seem to be good predictors for chorioamnionitis of patients with preterm premature rupture of membranes before 34 weeks of gestation. The noninvasive technique of sampling amniotic fluid could be alternative method to invasive amniocentesis.

Association of different stages of histological chorioamnionitis with respiratory distress syndrome in preterm infants with a gestational age of < 32 weeks

OBJECTIVE To study the association of different stages of histological chorioamnionitis (HCA) with the incidence rate and severity of respiratory distress syndrome (RDS) in preterm infants. METHODS Related data were collected from the infants and their mothers who were treated in the Neonatal Intensive Care Unit of Qingdao Women and Children's Hospital, Qingdao University, from January 2018 to June 2020. According to the presence or absence of HCA and its stage, the infants were divided into four groups: control (n=109), early-stage HCA (n=126), middle-stage HCA (n=105), and late-stage HCA (n=36). The four groups were compared in terms of gestational age, birth weight, sex, maternal age, placental abruption, prenatal use of antibiotics, and incidence rate of RDS. The correlation between HCA stage and RDS severity was analyzed. RESULTS Compared with the control and late-stage HCA groups, the early-stage HCA group had a significantly lower incidence rate of placental abruption and a significantly higher rate of prenatal use of antibiotics (P 0.05). CONCLUSIONS Early-, middle-, and late-stage HCA can reduce the incidence rate of RDS in preterm infants. HCA stage may not be correlated with RDS severity in preterm infants, which needs to be verified by further research.

465 Histologic chorioamnionitis in pregnancies complicated by preeclampsia and the effect on neonatal outcomes

Inflammation plays a major role in the development of preeclampsia. Histological chorioamnionitis (HC) is a common placental finding, that can represent acute or chronic inflammation and can influence neonatal outcomes. We aimed to examine the added effect of HC on neonatal outcomes in pregnancies complicated by preeclampsia. The computerized medical files of all pregnancies with the diagnosis of preeclampsia at 24-42 weeks of gestation between 2008 and 2019 were reviewed. Cases with overt clinical chorioamnionitis were excluded. Placental lesions were classified according to “Amsterdam” criteria. The composite adverse neonatal outcome included ≥ 1 of the following: Apgar at 5 min < 7, respiratory support, respiratory distress syndrome (RDS), neurological morbidity, NEC, sepsis, or death. The maternal and neonatal outcomes were compared between cases of preeclampsia with and without HC. Multivariable regression analysis was performed to identify independent associations with adverse neonatal outcomes. As compared to the preeclampsia without HC group (n=517), the preeclampsia with HC group (n=55) was characterized by a more advanced gestational age (GA) at delivery (37.7±3.4 vs. 36.13.3 weeks, p<0.001), and a lower rate of a history of previous preeclampsia (p=0.04). Neonates in the preeclampsia with HC group had a higher rate of composite adverse neonatal outcome (p<0.001) despite a higher mean birth weight (p=0.005)- Table 1. By multivariate analysis, HC was found to be independently associated with adverse neonatal-outcome (aOR 1.33, 95% CI 1.11-3.09)- Table 2. In placental pathology preeclampsia without HC was associated with a higher rate of MVM lesions (p=0.01) – the "classical" placental findings of preeclampsia. In pregnancies complicated by preeclampsia concomitant placental HC was associated with a higher rate of adverse neonatal outcome despite a more advanced GA at delivery. This inflammatory mechanism plays a role in a subgroup of preeclampsia cases, causing an additional risk for the developing fetus.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

Histologic Chorioamnionitis in Pregnancies Complicated by Preeclampsia and the Effect on Neonatal Outcomes.

Histological chorioamnionitis (HC) is a common placental finding that represents acute/chronic inflammation and can affect neonatal outcomes. We aimed to examine the effect of HC on neonatal outcomes in pregnancies complicated by preeclampsia. All pregnancies with the diagnosis of preeclampsia at 24-42weeks between 2008 and 2019 were reviewed. Placental lesions were classified according to the "Amsterdam" criteria. Composite adverse neonatal outcome included ≥1 early complication. Maternal and neonatal outcomes were compared between cases with and without HC. Multivariable regression analysis was performed to identify independent associations with adverse neonatal outcome. Compared to preeclampsia without HC (n=517), preeclampsia with HC (n=55) was characterized by a more advanced gestational age (p<0.001) and a higher rate of nulliparity (p=0.02). Diabetes was more prevalent in preeclampsia without HC (p=0.039) as was a history of previous preeclampsia (p=0.048). Neonates in the preeclampsia with HC group had higher rates of adverse neonatal outcome (p<0.001) and Apgar scores <7 at 5min (p=0.034) despite a higher birthweight (p=0.005). Preeclampsia without HC was associated with smaller placentas and a higher rate of placental maternal vascular malperfusion lesions (p=0.014 and p<0.001 respectively). By multivariate analysis, gestational age and HC were independently associated with adverse neonatal outcome (aOR 0.88 95% CI 0.76-0.96, and aOR 1.33, 95% CI 1.11-3.09, respectively). In preeclampsia, concomitant HC was associated with adverse neonatal outcome despite a more advanced gestational age and higher neonatal birthweight. This inflammatory mechanism probably plays a role in a more severe subgroup of preeclampsia cases, causing an additional risk for the developing fetus.

Impact of chorioamnionitis on maternal and fetal levels of proinflammatory S100A12.

Histologic chorioamnionitis (HCA) may lead to the fetal inflammatory response syndrome (FIRS). The aim of this pilot study was to evaluate S100A12, a marker of innate immune activation, in mothers with or without HCA and in their infants. Concentrations of S100A12, interleukin 6 (IL-6), and C-reactive protein (CRP) were evaluated in maternal, cord, and neonatal blood of very preterm infants. Histologic examinations of the placenta and umbilical cords were performed. The 48 mother-neonate pairs enrolled were subdivided into two groups: HCA group (N = 15) and control group without HCA (N = 33). Maternal S100A12 levels were similar between HCA and control group. Similarly, S100A12 concentrations in cord and neonatal blood did not differ between the groups. However, high S100A12 concentrations were detected in cord and neonatal blood of two out of three neonates exposed to HCA associated with advanced funisitis. Concentrations of IL-6 and CRP were higher in maternal blood of the HCA group compared with controls (p < 0.05, p < 0.001; respectively), but no differences in cord or neonatal blood was found.Conclusion:S100A12 did neither identify mothers with HCA nor very preterm infants exposed to HCA. It is currently unknown if S100A12 may identify neonates with FIRS. What is known: • Histologic chorioamnionitis (HCA) may lead to the fetal inflammatory response syndrome (FIRS). • S100A12 represents an early, sensitive, and specific diagnostic marker of inflammatory processes. What is new: • S100A12 did neither identify mothers with HCA nor very preterm infants exposed to HCA. • It is currently still unclear if S100A12 has a potential in identifying preterm infants with FIRS.

Clinical Predictors of Histologic Chorioamnionitis at Term [06N

INTRODUCTION: The objective of this study was to determine the diagnostic criteria for clinical chorioamnionitis (CC) that best predict histologic chorioamnionitis (HC). METHODS: This is an IRB-approved retrospective cohort study of women diagnosed with CC over a 5-year period. Inclusion criteria were: gestational age 37 to 42 weeks, diagnosis of CC as determined and documented by the provider, and available placental pathology records. CC diagnostic criteria (maternal temperature, maternal or fetal tachycardia, leukocytosis, fundal tenderness, and purulent amniotic fluid) were compared between those with and without HC. RESULTS: 223 women met inclusion criteria; 159 (71.3%) had HC. Prostaglandin use, diabetes, epidural use, and duration from initiation of antibiotics to delivery were similar. Mean maximum body temperature and presence of other diagnostic criteria were similar between the groups. Those with HC were more likely to have a peak white blood cell count greater than or equal to 25.0x10^9cells/L (13.2 vs 3.1%, P=.03). Twenty-one (13.2%) women in the HC group and 12 (18.8%) in the normal pathology group had no documented fever despite a diagnosis of CC. Of the women without a fever, 64% had HC. CONCLUSION: Normal placental pathology was found in a large proportion of women with CC. Although none of the assessed clinical findings predicted HC, a significant leukocytosis was more frequent in women with HC. For women diagnosed with CC without fever, the majority had findings of HC. This study highlights the challenge of diagnosing CC. Providers should consider the diagnosis of CC in the absence of fever when other clinical criteria are present.

Histologic chorioamnionitis concomitant placental abruption and its effects on pregnancy outcome

IntroductionTwo possible causative pathways have been suggested to participate in the development of placental abruption (PA), an acute inflammatory pathway and placental vascular derived, a chronic pathway. We aimed to study the impact of the inflammatory pathway on maternal and neonatal outcome. MethodsThe computerized medical files and placental reports of all pregnancies diagnosed with PA, between 11/2008-1/2019, at 24–42 weeks, were reviewed. Placental lesions were classified according to “Amsterdam” criteria into maternal and fetal vascular malperfusion lesions, acute inflammatory responses and chronic villitis. Composite neonatal morbidity included ≥1 of the following: seizures, intra-ventricular hemorrhage (IVH), hypoxic-ischemic encephalopathy, periventricular leukomalacia (PVL), blood transfusion, necrotizing enterocolitis (NEC), neonatal sepsis, respiratory distress syndrome, or neonatal death. Maternal and neonatal outcome were compared between PA with and without histologic chorioamnionitis (HC). ResultsAs compared to the PA without HC group (n = 267), the PA with HC group (n = 77) was characterized by lower gestational age (GA) at delivery (32.9 ± 5.5 vs. 35.6 ± 4.1 weeks, p < 0.001), higher rates of oligohydramnios (p < 0.001), bloody amniotic fluid at labor (p < 0.001), maternal postpartum fever (p < 0.001), longer maternal hospitalization (<0.001), and increased composite adverse neonatal morbidity (41.6% vs. 22.8%, p = 0.002). By multivariate analysis, GA and HC were found to be independently associated with adverse neonatal outcome, aOR 0.63 95% CI 0.43–0.78, p < 0.001, and aOR1.12, 95% CI 1.02–3.87, p = 0.04, respectively. DiscussionThe involvement of the inflammatory causative pathway in the development of placental abruption, is associated with increased maternal and neonatal morbidity.

Subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis in women with spontaneous preterm delivery.

ObjectiveTo compare subsequent pregnancy outcomes according to the presence of acute histologic chorioamnionitis (HCA) in women with spontaneous preterm delivery (SPTD).MethodsAmong 1,706 women who gave birth twice or more at our institution, 138 women delivered spontaneously at preterm (<37.0 weeks). Subsequent deliveries occurred at our institution and placental biopsy results were available. The study population was categorized into 2 groups based on the presence of acute HCA at the time of SPTD: HCA group (n=52) and non-HCA group (n=86). The primary outcome measures were gestational age at delivery, birthweight, and frequency of preterm delivery in subsequent pregnancies.ResultsThe median gestational age at the time of SPTD was 34.0 weeks (interquartile range [IQR], 28.9–35.3 weeks), and the frequency of acute HCA was 52/138 (38%). There were no differences in gestational age at delivery, birthweight, and frequency of preterm delivery between the HCA group and non-HCA group (median gestational age at delivery, 38.0 weeks (IQR, 36.7–38.8 weeks) in the HCA group vs. 37.9 weeks (IQR, 35.7–39.0 weeks) in the non-HCA group; frequency of preterm delivery, 14/52 (27%) in the HCA group vs. 33/86 (38%) in the non-HCA group; and median birthweight, 3.14 kg (IQR, 2.64–3.45 kg) in the HCA group vs. 2.95 kg (IQR, 2.44–3.36 kg) in the non-HCA group; P>0.1 for all.ConclusionThe presence of acute HCA in women at prior SPTD did not significantly affect their subsequent pregnancy outcomes.

Maternal peripheral blood platelet-to-white blood cell ratio and platelet count as potential diagnostic markers of histological chorioamnionitis-related spontaneous preterm birth.

BackgroundHistological chorioamnionitis (HCA) is one of the leading causes of spontaneous preterm birth, thus, to identify novel biomarkers for the early diagnosis of HCA is in a great need.ObjectiveTo investigate the diagnostic value of maternal peripheral blood platelet‐to‐white blood cell ratio (PLT/WBC) and platelet (PLT) counts in HCA‐related preterm birth.MethodsA total of 400 patients with preterm birth were enrolled in this study: non‐HCA group (n = 193) and HCA group (n = 207), and 87 full‐term pregnancies were enrolled as the control. The peripheral blood of the participators was collected, and the neutrophil count, WBC count, platelet count, and levels of C‐reactive protein (CRP) and procalcitonin were recorded, and the platelet‐to‐white blood cell ratio (PLT/WBC) of the participators was calculated. Receiver operating characteristic (ROC) curve has been drawn to show the sensitivity and specificity of PLT/WBC and PLT count for the diagnosis of HCA‐related spontaneous preterm birth patients.ResultsThe neutrophil count, WBC count, and procalcitonin show no significant differences among the three groups, and the PLT count, PLT/WBC, and CRP (P < 0.05) were significantly increased in HCA group compared with non‐HCA group; moreover, the area under the curve (AUC) of PLT/WBC, PLT, and CRP was 0.744 (95% confidence interval [CI], 0.6966‐0.7922), 0.8095 (95% CI, 0.7676‐0.8514), and 0.5730 (95% CI, 0.5173‐0.6287), respectively.ConclusionPlatelet count and PLT/WBC may become a potential biomarker of HCA‐related spontaneous preterm birth.

Diagnostic efficacy of inflammatory markers in maternal and umbilical cord blood in histologic chorioamnionitis

Objective To explore the clinical value of maternal and umbilical blood inflammatory markers, interleukin-6 (IL-6), neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) and pro-calcitonin (PCT), in the diagnosis of histologic chorioamnionitis (HCA). Methods A total of 102 suspected chorioamnionitic cases were enrolled from January 2014 to July 2017. They were assigned into two groups based upon postpartum histopathological examination of placenta: HCA group (48 cases) and control group (54 cases). Maternal and umbilical blood samples were collected for routine blood test and tested for IL-6, NLR, CRP and PCT levels. T, Mann-Whitney U or Chi-square (or Fisher's exact) test was used for data comparison. Meaningful indicators in maternal and umbilical cord blood were analyzed by logistic regression analysis and correlation analysis. At the same time, receiver operating characteristic (ROC) curve was drawn to evaluate their diagnostic values. Results (1) IL-6 level and NLR in maternal blood in HCA group were higher than those in control group [6.95 (2.40-13.50) vs 3.90 (2.30-9.20) pg/ml, Z=-5.147; 5.03 (1.92-9.20) vs 3.94 (1.85-11.17), Z=-3.097; both P<0.05], and the levels of white blood cells, neutrophile granulocytes, CRP and IL-6 as well as NLR in umbilical cord blood were also higher [(9.4±2.0)×109/L vs (8.6±1.4)×109/L, t=-2.522; (6.87±1.62)×109/L vs (5.99±1.26)×109/L, t=-3.071; 12.30 (0.50-89.04) vs 3.18 (0.50-88.93) mg/L, Z=-4.519; (8.78±2.56) vs (4.78±1.45) pg/ml, t=-7.025; (4.45±1.36) vs (3.78±1.22), t=-3.020; all P<0.05]. (2) Logistic regression analysis showed that elevated levels of IL-6 and NLR in maternal blood and CRP and IL-6 in umbilical cord blood were independent risk factors for HCA [OR (95%CI): 1.65 (1.32-2.06), 1.34 (1.02-1.77), 1.05 (1.00-1.11) and 2.39 (1.72-3.32), all P<0.05]. Positive correlations were found between the levels of IL-6 in maternal and umbilical cord blood, and between NLR in maternal blood and CRP level in umbilical cord blood (correlation coefficient: 0.680 and 0.230, both P<0.05). (3) IL-6 level in umbilical blood was of the greatest value in the diagnosis of HCA among all single markers, followed by IL-6 in maternal blood, CRP in umbilical blood and NLR in maternal blood [area under the ROC curve (AUC): 0.904, 0.796, 0.760 and 0.678]. When two indexes were combined, NLR in maternal blood+IL-6 in umbilical cord blood showed the highest diagnostic value, followed by, IL-6 in maternal blood+CRP in umbilical cord blood, IL-6+NLR in maternal blood and NLR in maternal blood+CRP in umbilical cord blood (AUC: 0.917, 0.870, 0.823 and 0.791). When three indexes was used in combination, the diagnostic value of IL-6 in maternal and umbilical cord blood+NLR in maternal blood was higher than that of IL-6 and NLR in maternal blood+CRP in umbilical cord blood (AUC: 0.919 and 0.836). (4) There were 13 cases (27.1%) with neonatal complications in HCA group and two (3.7%) in control group (P<0.05). Conclusions Changes in NLR and IL-6 levels in maternal blood and NLR, IL-6 and CRP levels, and white blood cells and neutrophile granulocytes counts in umbilical cord blood are associated with HCA. The diagnostic efficacy of two indexes combined is superior to that of single index, while the combination of three indexes can significantly improve the diagnostic accuracy and authenticity. Key words: Chorioamnionitis; Interleukin-6; C-reactive protein; Calcitonin; Leukocyte count

Impact of histologic chorioamnionitis on pulmonary hypertension and respiratory outcomes in preterm infants.

We aimed to evaluate the association between the presence of histologic chorioamnionitis (HC) and development of pulmonary hypertension (PH) during neonatal intensive care unit (NICU) stay. Data of preterm infants born at 32 weeks of gestation or less were reviewed. The development of PH and other respiratory outcomes were compared according to the presence of HC. Potential risk factors associated with the development of PH during NICU stay were used for multivariable logistic regression analysis. A total of 188 infants were enrolled: 72 in the HC group and 116 in the no HC group. The HC group infants were born at a significantly shorter gestational age and lower birthweight, with a greater proportion presenting preterm premature rupture of membrane (pPROM) > 18 h before delivery. More infants in the HC group developed pneumothorax (P = 0.008), and moderate and severe bronchopulmonary dysplasia (BPD; P = 0.001 and P = 0.006, respectively). PH in the HC group was significantly more frequent compared to the no HC group (25.0% versus 8.6%, P = 0.002). Based on a multivariable logistic regression analysis, birthweight (P = 0.009, odds ratio [OR] = 0.997, 95% confidence interval [CI] = 0.995–0.999), the presence of HC (P = 0.047, OR = 2.799, 95% CI = 1.014–7.731), and duration of invasive mechanical ventilation (MV) > 14 days (P = 0.015, OR = 8.036, 95% CI = 1.051–43.030) were significant factors. The presence of HC and prolonged invasive MV in infants with lower birthweight possibly synergistically act against preterm pulmonary outcomes and leads to the development of PH. Verification of this result and further investigation to establish effective strategies to prevent or ameliorate these adverse outcomes are needed.

Chorioamnionitis following preterm premature rupture of membranes and fetal heart rate variability.

IntroductionThe objective of this study was to identify prenatal markers of histological chorioamnionitis (HC) during pPROM using fetal computerized cardiotocography (cCTG).Materials and methodsRetrospective review of medical records from pregnant women referred for pPROM between 26 and 34 weeks, in whom placental histology was available, in a tertiary level obstetric service over a 5-year period. Fetal heart rate variability was assessed using cCTG. Patients were included if they were monitored at least six times in the 72 hours preceding delivery. Clinical and biological cCTG parameters during the pPROM latency period were compared between cases with or without HC.ResultsIn total, 222 pPROM cases were observed, but cCTG data was available in only 23 of these cases (10 with and 13 without HC) after exclusion of co-morbidities which may potentially perturb fetal heart rate variability measures. Groups were comparable for maternal age, parity, gestational age at pPROM, pPROM duration and neonatal characteristics (p>0.1). Baseline fetal heart rate was higher in the HC group [median 147.3 bpm IQR (144.2–149.2) vs. 141.3 bpm (137.1–145.4) in no HC group; p = 0.02]. The number of low variation episodes [6.4, (3.5–15.3) vs. 2.3 (1–5.2); p = 0.04] was also higher in the HC group, whereas short term variations were lower in the HC group [7.1 ms (6–7.4) vs. 8.1 ms (7.4–9); p = 0.01] within 72 hours before delivery. Differences were especially discriminant within 24 hours before delivery, with less short-term variation [5 ms (3.7–5.9) vs. 7.8 ms (5.4–8.7); p = 0.007] and high variation episodes [3.9 (4.9–3.2) vs. 0.8 (1.5–0.2); p < 0.001] in the HC group.ConclusionThese results show differences in fetal heart rate variability, suggesting that cCTG could be used clinically to diagnoses chorioamnionitis during the pPROM latency period.

The Delta Neutrophil Index as a predictive marker of histological chorioamnionitis in patients with preterm premature rupture of membranes: A retrospective study.

BackgroundHistological chorioamnionitis (HCA) is related to perinatal morbidity. However, there is no definite diagnostic method for detecting chorioamnionitis before delivery.MethodsWe evaluated whether the delta neutrophil index (DNI) was an effective early marker of HCA in patients with preterm premature rupture of membranes (PPROM). We retrospectively evaluated 149 women diagnosed with PPROM (gestational age, 20+0 to 36+6 weeks) at Severance Hospital from January 2013 to December 2014. The women were categorized into the following two groups: (a) PPROM without HCA and (b) PPROM with HCA. The maternal white blood cell (WBC) count, neutrophil-to-lymphocyte ratio (NLR), C-reactive protein (CRP) level, and DNI were measured at admission. The DNI has been reported to reflect the fraction of circulating immature granulocytes associated with infection.ResultsOf the 149 patients, 87 were included in the PPROM without HCA group and 62 were included in the PPROM with HCA group. The interval between admission and delivery was significantly shorter in the PPROM with HCA group than in the PPROM without HCA group. There was no significant difference in the maternal WBC count. The serum CRP level, NLR, and DNI were significantly lower in the PPROM without HCA group than in the PPROM with HCA group, while the lymphocyte count was significantly lower in the PPROM with HCA group than in the PPROM without HCA group. A predictive equation was generated by combining the DNI, lymphocyte count, and CRP level, and the sensitivity and specificity for predicting a placental inflammatory response were 69.1% and 70.5%, respectively.ConclusionsThe DNI could be a predictive marker for HCA in patients with PPROM. Our predictive equation involving the DNI, lymphocyte count, and CRP level may be helpful for predicting the placental inflammatory response in patients with PPROM.

Clinical significance of histologic chorioamnionitis with a negative amniotic fluid culture in patients with preterm labor and premature membrane rupture.

ObjectiveTo evaluate the effect of histological chorioamnionitis (HCA) with a negative amniotic fluid (AF) culture on adverse pregnancy and neonatal outcomes and inflammatory status in the AF compartment in women with preterm labor or preterm premature rupture of membranes (PPROM).MethodsThis is a retrospective cohort study of 153 women diagnosed as having a preterm labor or PPROM (20–34 weeks) who delivered singleton gestations within 48 hours of amniocentesis. AF obtained through amniocentesis was cultured, and interleukin (IL)-6, IL-8, and metalloproteinase-9 (MMP-9) levels were determined. The placentas were examined histologically.ResultsThe prevalence of HCA with negative AF culture was 23.5% (36/153). The women with HCA but with a negative AF culture (group 2) and those with a positive AF culture (group 3) had a significantly lower mean gestational age at amniocentesis and delivery than those with a negative AF culture and without HCA (group 1). Women in group 3 had the highest levels of AF IL-6, IL-8, and MMP-9, followed by those in group 2, and those in group 1. Composite neonatal morbidity was significantly higher in groups 2 and 3 than in group 1, but this was no longer significant after adjusting for confounders caused mainly by the impact of gestational age.DiscussionIn the women who delivered preterm neonates, HCA with a negative AF culture was associated with increased risks of preterm birth, intense intra-amniotic inflammatory response, and prematurity-associated composite neonatal morbidity, and its risks are similar to the risk posed by positive AF culture.