Outpatient vs inpatient management of preterm prelabor rupture of membranes: A systematic review and meta-analysis.

INTRODUCTION: To compare neonatal, obstetrical, and maternal outcomes associated with outpatient vs inpatient management of pregnancies with preterm prelabor rupture of membranes (PPROM). MATERIAL AND METHODS: A search of MEDLINE, EMBASE, the Cochrane Database and Central Register from January 1, 1990 to July 31, 2023 identified randomized controlled trials (RCTs) and cohort studies comparing outpatient with inpatient management for pregnant persons diagnosed with PPROM before 37 weeks' gestation. No language restriction was applied. We applied a random effects model for meta-analysis. Trustworthiness was assessed using recently published guidance and Risk of bias using the RoB 2.0 tool for RCTs and ROBINS-I tool for cohort studies. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach was used to assess the certainty of evidence (COE). Outcomes of interest included perinatal mortality, neonatal morbidities, latency and gestational age at delivery, and maternal morbidities. RCTs and cohort studies were analyzed separately. This study was registered in the International Prospective Register of Systematic Reviewsr: CRD42022295275. RESULTS: From 2825 records, two RCTs and 10 cohort studies involving 1876 patients were included in the review and meta-analysis. Outpatient management protocols varied but generally included brief initial hospitalization, strict eligibility criteria, and surveillance with laboratory and ultrasound investigations. Outpatient management showed lower rates of neonatal respiratory distress syndrome (cohort: RR 0.63 [0.52-0.77, very low COE]), longer latency to delivery (RCT: MD 7.43 days [1.14-13.72 days, moderate COE], cohort: MD 8.78 days [2.29-15.26 days, low COE]), higher gestational age at birth (cohort: MD 7.70 days [2.02-13.38 days, low COE]), lower rates of Apgar scores <7 at 5 min of life (cohort: RR 0.66 [0.50-0.89, very low COE]), and lower rates of histological chorioamnionitis (cohort: RR 0.74 [0.62-0.89, low COE]) without increased risks of adverse neonatal, obstetrical, or maternal outcomes. CONCLUSIONS: Meta-analysis of data from RCTs and cohort studies with very low-to-moderate certainty of evidence indicates that further high-quality research is needed to evaluate the safety and potential benefits of outpatient management for selected PPROM cases, given the moderate-to-high risk of bias in the included studies.

Risk factors for high-stage histological chorioamnionitis among pregnancies with cervical incompetence.

AIM: The study aimed to identify predictive risk factor to identify high-stage histological chorioamnionitis (HCA) in pregnancies with cervical incompetence (CIC). METHODS: A retrospective cohort study was conducted by including 116 pregnant women with cervical incompetence that required prophylactical and therapeutical cerclage. The histopathology examination on placenta was conducted with informed patient consent. All the cases included in this study were divided based on the severity degree of HCA. The demographic characteristic and the parameters related to maternal and fetal outcome were all analyzed. Besides, perioperative parameters of cerclage, including cervical length, cervical morphology, and laboratory indexes were also compared between two groups. Univariate and multivariate logistic regression analysis were used to determine the risk factor of severe chorioamnionitis. RESULTS: Severe HCA was significantly associated with cervical morphology, cerclage indication, cerclage type, and cervical length measured via ultrasound and vaginal examination. After adjusted for confounders, V-type funneling and short cervix was indicated as independent risk factors of severe HCA by multivariate logistic regression analysis, respectively. CONCLUSIONS: V-type funneling and short cervix may indicate the elevated risk of high-stage HCA. Due to the negative outcomes related with high-stage HCA, appropriate prenatal treatment would improve the pregnancy outcomes in cerclaged population. To facilitate postpartum treatment, placental histological examination should be routinely recommended to identify the high-stage HCA, especially in high risk pregnancies.

Effect of chorioamnionitis on postnatal growth in very preterm infants: a population-based study in Japan.

PURPOSE: There is growing evidence that preterm infants born to mothers with chorioamnionitis (CAM) have increased risk of various neonatal morbidities and long-term neurological disorders; however, the effect of CAM on postnatal growth remains insufficiently investigated. This study evaluated the effect of histological CAM on postnatal growth trajectories in very preterm infants using a nationwide neonatal database in Japan. METHOD: A multicenter retrospective study was conducted using clinical data of 4220 preterm neonates who weighed ≤ 1500 g and were born at < 32 weeks of gestation between 2003-2017 (CAM group: n = 2110; non-CAM group: n = 2110). Z-scores for height and weight were evaluated at birth and 3 years of age. Univariable and multivariable analyses were conducted to evaluate the effect of histological CAM on ΔZ-scores of height and weight during the first three years with a stratification by infant sex and the stage of histological CAM. RESULTS: Multivariable analyses showed that histological CAM was associated with accelerated postnatal increase (ΔZ-score) in weight (ß coefficient [95% confidence interval]; 0.10 [0.00 to 0.20]), but not in height among females (0.06 [- 0.04 to 0.15]) and not in height and weight among males (0.04 [- 0.04 to 0.12] and 0.02 [- 0.07 to 0.11], respectively). An interaction analysis demonstrated no significant difference in the effect of histological CAM on the ΔZ-scores of height and weight during the first three years between male and female infants (height, p = 0.81; weight p = 0.25). CONCLUSIONS: Intrauterine exposure to maternal CAM contributes to accelerated postnatal weight gain in female preterm infants during the first three years.

The histologic fetal inflammatory response and neonatal outcomes: systematic review and meta-analysis.

OBJECTIVE: This study aimed to investigate the prognostic role of concomitant histological fetal inflammatory response with chorioamnionitis on neonatal outcomes through a systematic review and meta-analysis of existing literature. DATA SOURCES: The primary search was conducted on October 17, 2021, and it was updated on May 26, 2023, across 4 separate databases (MEDLINE, the Cochrane Central Register of Controlled Trials, Embase, and Scopus) without using any filters. STUDY ELIGIBILITY CRITERIA: Observational studies reporting obstetrical and neonatal outcomes of infant-mother dyads with histological chorioamnionitis and histological fetal inflammatory response vs infant-mother dyads with histological chorioamnionitis alone were eligible. Studies that enrolled only preterm neonates, studies on neonates born before 37 weeks of gestation, or studies on neonates with very low birthweight (birthweight <1500 g) were included. The protocol was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42021283448). METHODS: The records were selected by title, abstract, and full text, and disagreements were resolved by consensus. Random-effect model-based pooled odds ratios with corresponding 95% confidence intervals were calculated for dichotomous outcomes. RESULTS: Overall, 50 studies were identified. A quantitative analysis of 14 outcomes was performed. Subgroup analysis using the mean gestational age of the studies was performed, and a cutoff of 28 weeks of gestation was implemented. Among neonates with lower gestational ages, early-onset sepsis (pooled odds ratio, 2.23; 95% confidence interval, 1.76-2.84) and bronchopulmonary dysplasia (pooled odds ratio, 1.30; 95% confidence interval, 1.02-1.66) were associated with histological fetal inflammatory response. Our analysis showed that preterm neonates with a concomitant histological fetal inflammatory response are more likely to develop intraventricular hemorrhage (pooled odds ratio, 1.54; 95% confidence interval, 1.18-2.02) and retinopathy of prematurity (pooled odds ratio, 1.37; 95% confidence interval, 1.03-1.82). The odds of clinical chorioamnionitis were almost 3-fold higher among infant-mother dyads with histological fetal inflammatory response than among infant-mother dyads with histological chorioamnionitis alone (pooled odds ratio, 2.99; 95% confidence interval, 1.96-4.55). CONCLUSION: This study investigated multiple neonatal outcomes and found association in the case of 4 major morbidities: early-onset sepsis, bronchopulmonary dysplasia, intraventricular hemorrhage, and retinopathy of prematurity.

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

OBJECTIVE: To investigate reliable biomarkers for predicting histological chorioamnionitis (HCA) in women with preterm prelabour rupture of membranes (PPROM). DESIGN: A retrospective study. SETTING: A maternity care hospital in Shanghai. POPULATION: Women with PPROM before 34+0/7  weeks of gestation. METHODS: 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. MAIN OUTCOME MEASURES: The ability of the individual biomarker and the combination of multiple biomarkers to predict HCA. RESULTS: 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. CONCLUSIONS: PCT could be a reliable biomarker for the early prediction of HCA in women with PPROM within 72 hours of dexamethasone treatment.

Laboratory markers to identify acute histological chorioamnionitis in febrile parturients undergoing epidural analgesia: a retrospective study.

BACKGROUND: This study aimed to investigate the effect of the pathological staging of acute histological chorioamnionitis (HCA) on laboratory indicators and to conduct further studies to reassess the threshold values used by clinicians to identify acute HCA in febrile parturients undergoing epidural analgesia. METHODS: A retrospective study of febrile mothers receiving epidural analgesia at Nanjing Maternal and Child Health Care Hospital from January 1, 2018 to December 31, 2018. The participants were grouped by the progression of acute HCA, and the laboratory parameters were compared between groups. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and monocyte-leukocyte ratio (M%), alone or in combination, to identify acute HCA in febrile parturients undergoing epidural analgesia was assessed using logistic regression and ROC curves. RESULTS: The area under the curve (AUC) of the best logistic regression model predicting HCA climbed to 0.706 (CRP + MLR). Maternal CRP, NLR, and MLR significantly and progressively increased with the progression of acute HCA (p < 0.0001). Based on the ROC curves, the following thresholds were selected to define increased laboratory indicators for identifying acute HCA: CRP ≥ 6.90 mg/L, NLR ≥ 11.93, and MLR ≥ 0.57. In addition, the AUC of the best logistic regression model predicting HCA ≥ stage 2 was 0.710, so these inflammatory markers were more precise in predicting HCA ≥ stage 2. CONCLUSION: Increased CRP (≥ 6.90 mg/L), NLR (≥ 11.93), and MLR (≥ 0.57) may help clinicians to identify early potential acute HCA in febrile parturients receiving epidural analgesia and to monitor progression to optimize clinical treatment options. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry on November 24, 2021 ( http://www.chictr.org.cn , ChiCTR2100053554).

Placental Pathology and Its Importance in Preterm Infants.

OBJECTIVE: We evaluated what placental pathologies were associated with adverse preterm births. MATERIALS AND METHODS: Placental findings, classified according to the Amsterdam criteria, were correlated with infant outcomes. The fetal vascular lesions, inflammatory responses other than histological chorioamnionitis (HCA), and placentas with combined maternal vascular malperfusion (MVM) and HCA were excluded. RESULTS: A total of 772 placentas were evaluated. MVM was present in 394 placentas, HCA in 378. Early neonatal sepsis, retinopathy of prematurity, necrotizing enterocolitis, and neonatal death occurred more often in the MVM-only group than HCA-only group. The frequency of bronchopulmonary dysplasia (BPD) was 38.6% in the HCA-only group, and it was 20.3% in the MVM-only group (p < 0.001). HCA was the most important independent risk factor for BPD (OR 3.877, 95% CI 2.831-5.312). CONCLUSION: Inflammation in the placenta influences fetal and neonatal outcomes. HCA is an independent risk factor for BPD.

Labor dystocia and risk of histological chorioamnionitis and funisitis: a study from a single tertiary referral center.

BACKGROUND: Intrauterine inflammation affects short- and long-term neonatal outcomes. Histological chorioamnionitis and funisitis are acute inflammatory responses in the fetal membranes and umbilical cord, respectively. Although labor dystocia includes a potential risk of intrauterine inflammation, the risk of histological chorioamnionitis and funisitis of labor dystocia has not been evaluated yet. This study aimed to examine the association between labor dystocia and risk of histological chorioamnionitis and funisitis. METHODS: In this retrospective cohort study, the cases who underwent histopathological examinations of the placenta and umbilical cord at Fukushima Medical University Hospital, Japan, between 2015 and 2020, were included. From the dataset, the pathological findings of the patients with labor dystocia and spontaneous preterm birth were reviewed. Based on the location of leukocytes, the inflammation in the placenta (histological chorioamnionitis) and umbilical cord (funisitis) was staged as 0-3. Multiple logistic regression analysis was performed to evaluate the risk of histological chorioamnionitis, histological chorioamnionitis stage ≥2, funisitis, and funisitis stage ≥2. RESULT: Of 317 women who met the study criteria, 83 and 144 women had labor dystocia and spontaneous preterm birth, respectively, and 90 women were included as controls. Labor dystocia was a risk factor for histological chorioamnionitis (adjusted odds ratio, 6.3; 95% confidential interval, 1.9-20.5), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 6.0; 95% confidence interval, 1.7-21.8), funisitis (adjusted odds ratio, 15.4; 95% confidence interval, 2.3-101.3), and funisitis stage ≥2 (adjusted odds ratio, 18.5; 95% confidence interval, 2.5-134.0). Spontaneous preterm birth was also a risk factor for histological chorioamnionitis (adjusted odds ratio, 3.7; 95% confidence interval, 1.7-7.8), histological chorioamnionitis stage ≥2 (adjusted odds ratio, 3.0; 95% confidence interval, 1.2-7.9), and funisitis (adjusted odds ratio, 6.6; 95% confidence interval, 1.4-30.6). However, the adjusted odds ratio was smaller in spontaneous preterm births than in labor dystocia. CONCLUSION: Labor dystocia is a risk factor for severe histological chorioamnionitis and funisitis. Further studies are required to evaluate the effects of histological chorioamnionitis and funisitis on long-term neonatal outcomes.

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

BACKGROUND: Histological 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. OBJECTIVE: To 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. METHODS: A 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. RESULTS: The 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. CONCLUSION: Platelet count and PLT/WBC may become a potential biomarker of HCA-related spontaneous preterm birth.

Noninvasive Sampling of the Intrauterine Environment in Women with Preterm Labor and Intact Membranes.

Spontaneous preterm birth has enormous consequences for newborns, children, and families. Intra-amniotic inflammation (IAI) is the leading cause of spontaneous preterm delivery, mainly at earlier gestational ages. Amniocentesis is the only method used to identify IAI in clinical practice. Although it is an invasive procedure with a very low risk of complications, many women and physicians are hesitant about amniocentesis on this indication. This has been an incentive to explore IAI and the intra-amniotic environment through noninvasive techniques, such as sampling cervical mucus, vaginal fluid, or maternal blood. With this overview, we aim to provide a concise update on the state of the art of the noninvasive sampling of the intrauterine environment in women with preterm labor and intact membranes. So far, it is unknown whether this screening helps improve our knowledge about the impact of IAI on the neonatal and long-term outcome, but we believe it merits this review.

Mean gestation at delivery and histological chorioamnionitis correlates with early-onset neonatal sepsis following expectant management in pPROM.

This prospective observational study was carried out in India among 100 women with preterm pre-labour rupture of membranes (pPROM) between 26(0/7)-33(0/7) weeks on expectant management in order to correlate early-onset neonatal sepsis (EONS) with various features of chorioamnionitis. The incidence of pPROM during the study period of 1.5 years was 7%. The mean gestation at pPROM was 30(6/7) ± 1.8 weeks and at delivery was 32(1/7) ± 1 weeks. Features of chorioamnionitis in the form of clinical, microbiological, histological or a combination of these were observed in 70/100 women. Clinical chorioamnionitis was seen in 16%, bacterial isolates were present in 30% on cervical swab and in 39% on placental membrane culture and 19% had histological chorioamnionitis. EONS was present in 23/97 (24%). Clinical chorioamnionitis (p = 0.069), bacterial isolates on cervical swab (p = 0.56) or placental membranes (p = 0.39) were not found to predict EONS; whereas histological chorioamnionitis (p = 0.002) and lower gestation at delivery (p = 0.013) were significantly associated with EONS.

Bedside assessment of amniotic fluid interleukin-6 in preterm prelabor rupture of membranes.

OBJECTIVE: The objective of the study was to determine the diagnostic indices and predictive values by bedside assessment of amniotic fluid interleukin-6 (IL-6) concentration in the identification of microbial invasion of the amniotic cavity (MIAC) and/or histological chorioamnionitis (HCA) in patients with preterm prelabor rupture of membranes. STUDY DESIGN: One hundred twenty-four women with singleton pregnancies were included in this study. The amniotic fluid was sampled by transabdominal amniocentesis at the time of admission. IL-6 concentrations were assessed with an immunoassay. RESULTS: The presence of MIAC, HCA, or the coexistence of both was associated with higher amniotic fluid concentrations of IL-6 in both a crude and adjusted analysis. The amniotic fluid concentration of IL-6 of 1000 pg/mL was determined to be the best cutoff value for the prediction of MIAC (sensitivity of 50%, specificity of 95%, positive predictive value of 82%, negative predictive value of 81%, and likelihood ratio of 8.4) or both MIAC and HCA (sensitivity of 60%, specificity of 94%, positive predictive value of 75%, negative predictive value of 88%, and likelihood ratio of 9.4). CONCLUSION: The bedside assessment of amniotic fluid IL-6 seems to be an easy, rapid, and inexpensive method for the prediction of MIAC or both MIAC and HCA in pregnancies complicated by preterm prelabor rupture of membranes.

Early postnatal immature-to-total neutrophil ratio in the histological chorioamnionitis among neonatal intensive care unit infants.

OBJECTIVE: Histological chorioamnionitis (hCAM) is a major risk factor for early-onset sepsis. Predictive methods for hCAM are needed in clinical practice during the early postnatal period. To examine the relationship between hCAM and perinatal variables including early postnatal immature-to-total neutrophil ratio (ITR). STUDY DESIGN: A single-center study was undertaken at Ohta Nishinouchi Hospital between April 1, 2016 and June 30, 2023. Blood samples and placenta collected from study candidate infants admitted to the neonatal intensive care unit were assessed by univariate analyses and multivariate logistic regression analysis. We also assessed the test performance of ITR and maternal white blood cell (WBC) counts by area under a receiver operating characteristic (ROC) curves. RESULTS: A total of 725 infants were analyzed (496 in the non-hCAM group and 229 in the hCAM group). Significant relationships were observed between hCAM and ITR (p < 0.001, odds ratio (OR), 1.067; 95% confidence interval (CI), 1.041 to 1.093). Per the ROC curves, an ITR (%) of 7.15 could predict hCAM at a sensitivity of 55.9% and specificity of 71.9% [area under the curve (AUC) = 0.691, p < 0.001, 95% CI, 0.649 to 0.733]. Further, maternal WBC counts of 9.85 ( × 109/L) predicted hCAM with 69.0% sensitivity and 67.3% specificity (AUC = 0.710, p < 0.001, 95%CI, 0.669 to 0.750). CONCLUSIONS: Early postnatal ITR was high in cases with greater leukocyte invasion into the placenta tissue, which may be a biomarker of the presence and/or severity of hCAM. Histological CAM should be considered when the early neonatal ITR (%) is 7.15 or higher.

Novel Biomarkers: Soluble Urokinase-Type Plasminogen Activator Receptor and Procalcitonin- and Histological Chorioamnionitis after Preterm Premature Rupture of Membranes.

Fetal inflammatory response syndrome or infection after preterm premature rupture of membranes (PPROM) increases neonatal morbidity in preterm deliveries. Biochemical markers from the amniotic fluid (AF) have been used to evaluate possible intra-amniotic infection during the asymptomatic phase after PPROM. This study aimed to describe whether soluble urokinase-type plasminogen activator receptor (suPAR) or procalcitonin (PCT) from AF or maternal sera could reveal fetal inflammatory response or infection after PPROM. AF and maternal serum samples were collected weekly after PPROM (23+ 0 - 34+ 6 gestational weeks) until delivery from twenty women and two women with possible chorioamnionitis with intact membranes. Levels of suPAR, PCT, interleukin-6 (IL-6), glucose, lactate dehydrogenase (LDH), and bacterial PCR were determined from AF and suPAR and PCT and IL-6 from maternal sera. Fetal infection or inflammation response were determined by the histology of the placenta after delivery. AF glucose was significantly lower and AF LDH higher in the fetal site histologic chorioamnionitis (HCA) group, while AF suPAR concentrations tended to be higher in this group. AF suPAR correlated significantly with AF glucose and LDH. Based on receiver operating characteristic (ROC) analysis, AF glucose had the best predictability for fetal site histological chorioamnionitis. The findings of AF PCT were insignificant considering HCA. AF glucose had the highest accuracy in predicting fetal site histologic chorioamnionitis. AF suPAR may be a promising marker; however, our findings were limited by a small study population.

In premature rupture of membranes, maternal serum delta neutrophil index may be a predictive factor for histological chorioamnionitis and affect fetal inflammatory markers: A retrospective cross-sectional study.

PROBLEM: We aimed to investigate the predictive value of delta neutrophil index (DNI) for histological choriomanionitis (HCAM) and the effect of maternal inflammatory markers on neonatal outcomes and fetal inflammatory parameters. METHOD OF STUDY: In this retrospective cross-sectional study, 68 pregnant women without HCAM (group 1) and 46 pregnant women diagnosed with HCAM (group 2) were divided into two groups. Demographic stories of the groups; maternal hematological parameters; maternal DNI and systemic inflammatory index (SII) values; outcomes of newborns; fetal inflammatory markers were recorded and compared between groups. RESULTS: Maternal DNI, and SII levels were significantly higher in group 2 (p value < .05 for all). Admission to the neonatal unit (NICU) was higher in group 2 than in group 1 (p = .0001). We found that fetal inflammatory markers were significantly higher in group 2 (p values .001 for CRP, .0001 for DNI, and .002 for leukocyte). Maternal DNI was determined to be significantly diagnostic at a value of ≥1.3 in HCAM (p = .001). We observed that SII had a significant predictive value of 953036.6 (p = .019) for NICU admission. There is also a positive correlation between fetal inflammatory markers and maternal inflammatory markers. CONCLUSIONS: We found that maternal inflammatory markers are high in HCAM, maternal DNI can predict patients who will develop HCAM, maternal SII value can predict NICU admission, fetal inflammatory markers are high in HCAM, and these markers are affected by maternal inflammatory markers.

Association Analysis Between Maternal Neutrophil Ratio and the Risk of Histological Chorioamnionitis in Pregnant Women with Premature Rupture of Membranes in Late Pregnancy.

Background: We aimed to investigate the association between maternal neutrophil ratio and histological chorioamnionitis (HCA) risk in pregnant women with premature rupture of membranes (PROM) in late pregnancy. Methods: A retrospective analysis was conducted on 95 cases of women with PROM in their late pregnancy between March 2018 and August 2021. These women were divided into two groups based on the presence of HCA. General clinical data and laboratory indicators were compared between the two groups. A generalized additive model was used for curve fitting, and a segmented regression model was used to explain further the non-linear relationship between neutrophil ratio and HCA risk. Results: After adjusting for confounding factors, the curve fitting showed a "U"-shaped curve relationship between the neutrophil ratio and the risk of HCA. When the neutrophil ratio was <76.3%, the risk of HCA exhibited a decreasing trend, but the difference was not statistically significant (adjusted OR = 0.884, 95% CI: 0.781-1.001, P = 0.053). However, when the neutrophil ratio was >76.3%, the HCA risk was significantly increased (adjusted OR = 1.339, 95% CI: 1.067-1.680, P = 0.012). Furthermore, we equally divided the neutrophil ratio into three groups. The risk of HCA was significantly increased in the low-ratio group (OR = 4.292, 95% CI: 1.247-14.706, P = 0.021) compared with the middle-ratio group, which was used as the reference group. Similarly, the HCA risk of the high-ratio group (OR = 13.145, 95% CI: 1.796-96.233, P = 0.011) was also significantly enhanced. However, there was no significant difference in HCA risk between the high-ratio and low-ratio groups (OR = 1.182, 95% CI: 0.357-3.909, P = 0.784). Conclusion: There was a significant "U"-shaped relationship between maternal neutrophil ratio and HCA risk in women with PROM in late pregnancy.

Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants.

OBJECTIVE: To test the hypothesis that increasing severity of the fetal inflammatory response (FIR) would have a dose-dependent relationship with severe neurodevelopmental impairment or death in extremely preterm infants. STUDY DESIGN: We report 347 infants of 23-28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or neurodevelopmental impairment at the 18- to 22-month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1, phlebitis; stage 2, arteritis with or without phlebitis; stage 3, subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis). RESULTS: A FIR was detected in 110 placentas (32%). The rate of severe neurodevelopmental impairment/death was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs 35%; P < .05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with a higher rate of severe neurodevelopmental impairment/death (47% vs 23%; P < .05). After adjustment for confounding factors, only subacute necrotizing funisitis (risk ratio, 1.87; 95% CI, 1.04-3.35; P = .04) and chorionic plate vasculitis with thrombosis (risk ratio, 2.21; 95% CI, 1.10-4.46; P = .03) were associated with severe neurodevelopmental impairment/death. CONCLUSION: Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.

The neutrophil-to-lymphocyte ratio: A low-cost antenatal indicator of placental chorioamnionitis in women who deliver preterm without clinical signs and symptoms of infection.

Chorioamnionitis is present in up to 70% of spontaneous preterm births and is associated with poor maternal, fetal and neonatal outcomes. OBJECTIVE: To explore the relationship between the neutrophil-to-lymphocyte ratio and histological chorioamnionitis in women who delivered preterm with no clinical signs or symptoms of infection. STUDY DESIGN: This was a retrospective analysis of a cohort of women who delivered spontaneously between 16 and 36+6 weeks at a tertiary UK hospital. Only women with placental histology and no signs of clinical infection were included. The neutrophil-to-lymphocyte ratio was calculated from a full blood count sample taken routinely within 24 h of delivery. The neutrophil-to-lymphocyte ratio was also calculated from first trimester booking bloods (<13 + 6 weeks) in a subgroup. Placental histopathology was categorised as either inflammatory (i.e. histologic chorioamnionitis, with or without evidence of fetal inflammatory response) or non-inflammatory (vascular pathology or a normal placenta). RESULTS: 169 women had available placental pathology and were included in the analysis. 70 % (118/169) had confirmed placental inflammation. The mean neutrophil-to-lymphocyte ratio was significantly raised in this group compared to those with normal (n = 24) or vascular (n = 27) pathology (inflammatory neutrophil-to-lymphocyte ratio 9.81 vs non-inflammatory neutrophil-to-lymphocyte ratio 6.53, p = 0.002. The delivery neutrophil-to-lymphocyte ratio had an area under the receiver operating characteristic curve of 0.69 (0.60 to 0.78) for predicting placental inflammation. A raised neutrophil-to-lymphocyte ratio (>6) was associated with an odds ratio of 5.2 (95 % CI 2.55 to 10.56) for histological chorioamnionitis, with a sensitivity of 80 % and negative predictive value of 86 %. A higher cut-off of 9 had a negative predictive value of 79 % for fetal inflammatory response. CONCLUSIONS: A raised neutrophil-to-lymphocyte ratio is associated with a 5-fold increased risk of histological chorioamnionitis in women who delivered early without signs or symptoms of infection. It was also raised at the time of preterm labour compared to the first trimester. A full blood count is an almost universal investigation in women admitted in preterm labour, often repeated, making this inexpensive and non-invasive ratio a useful additional antenatal biomarker in women admitted in spontaneous preterm labour at risk of subclinical chorioamnionitis and its associated poor outcomes.

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

Aim: 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. Methods: 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. Results: 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. Conclusion: 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.

Predictive value of serum inflammatory markers for histological chorioamnionitis among women with preterm premature rupture of membranes after undergoing cervical cerclage.

PURPOSE: To determine the predictive value of maternal White Blood Cells (WBC), neutrophils, and C-Reactive Protein (CRP) for diagnosing Histological Chorioamnionitis (HCA) among women with Preterm Premature Rupture of Membranes (PPROM) who underwent cervical cerclage. METHODS: A retrospective cross-sectional study was conducted among women with singleton pregnancy and PPROM, who underwent cervical cerclage during 2018-2020. RESULTS: A total of 55 eligible women were included in the final analysis, including 36 (61.02%) cases with HCA and 19 (38.98%) without HCA. Women with HCA had higher WBC count (12.31 ± 2.80) × 109/L and neutrophil count (9.67 ± 2.90)×109/L than those without HCA (10.35 ± 2.53) × 109/L and 7.82 ± 2.82 × 109/L, respectively) (both p < 0.05). The cut-off value of WBC count at 10.15×109/L was found to be the most effective in identifying HCA, with an Area Under Curve (AUC) of 0.707 (95% CI: 0.56-0.86; p = 0.012), sensitivity of 86.11%, specificity of 57.90%, Positive Predictive Value (PPV) of 79.49%, Negative Predictive Value (NPV) of 68.75%, and Youden index of 0.44. The combination of WBC + neutrophil had a slightly higher (AUC = 0.711, 95% CI: 0.57-0.86; p = 0.011), specificity (68.42%), and PPV (81.25%), but lower sensitivity (72.22%), than the WBC count alone. A cut-off value of neutrophil at 7.46 × 109/L was effective in identifying HCA, with an AUC of 0.689 (95% CI: 0.53-0.84; p = 0.022). DISCUSSION: Combination use of WBC+neutrophil was found to be the most accurate predictor of HCA among women with PPROM after surgery of cervical cerclage.