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Problem: The placental membranes are a key barrier to fetal and uterine infection. Inflammation of the membranes, diagnosed as maternal inflammatory response (MIR) or alternatively as acute chorioamnionitis, is associated with adverse maternal‐fetal outcomes. MIR is staged 1–3, with higher stages indicating more hazardous inflammation. However, the diagnosis relies upon subjective evaluation and has not been deeply characterized. The goal of this work is to develop a cell classifier for eight placental membrane cells and quantitatively characterize MIR1–2. Method of Study: Hematoxylin and eosin (H&E)‐stained placental membrane slides were digitized. A convolutional neural network was trained on a dataset of hand‐annotated and machine learning‐identified cells. Overall cell class‐level metrics were calculated. The model was applied to 20 control, 20 MIR1, and 23 MIR2 placental membrane cases. MIR cell composition and neutrophil distribution were assessed via density and Ripley's cross K‐function. Clinical data were compared to neutrophil density and distribution. Results: The classification model achieved a test‐set accuracy of 0.845, with high precision and recall for amniocytes, decidual cells, endothelial cells, and trophoblasts. Using this model to classify 53 073 cells from healthy and MIR1–2 placental membranes, we found that (1) MIR1–2 have higher neutrophil density and fewer decidual cells and trophoblasts, (2) Neutrophils colocalize heavily around decidual cells in healthy placental membranes and around trophoblasts in MIR1, (3) Neutrophil density impacts distribution in MIR, and (4) Neutrophil metrics correlate with features of clinical chorioamnionitis. Conclusions: This paper introduces cell classification into the placental membranes and quantifies cell composition and neutrophil spatial distributions in MIR. [ABSTRACT FROM AUTHOR]

Chorioamnionitis or intra-uterine inflammation is considered the most common infection diagnosed in labor and delivery units worldwide. It is a leading cause of maternal morbidity and mortality, as well as neonatal death and sepsis. The heterogeneity of this clinical syndrome has been recently reported. The objectives of this study were to determine: 1) placental microbiology using molecular microbiological techniques; 2) diagnostic accuracy of the clinical criteria used to identify patients with placental bacterial infection; 3) relationship between placental bacterial infection and histological chorioamnionitis. This prospective cross-sectional study included 41 women diagnosed with clinical and histological chorioamnionitis. The presence of microorganisms in the placenta was determined by conducting placental analysis using a broad range of polymerase chain reactions (PCR). Bacterial placental infection (defined as the presence of the 16S gene detected in placental tissue using the molecular technique PCR) was observed in 63% (26/41) of parturients diagnosed with histological chorioamnionitis. The traditional criteria for diagnosing clinical chorioamnionitis exhibit poor diagnostic performance in accurately identifying proven intra-amniotic infection. The molecular analysis (PCR) of the placenta has suggested that acute chorioamnionitis commonly has a bacterial origin. [ABSTRACT FROM AUTHOR]

Chorioamnionitis or intra-uterine inflammation is considered the most common infection diagnosed in labor and delivery units worldwide. It is a leading cause of maternal morbidity and mortality, as well as neonatal death and sepsis. The heterogeneity of this clinical syndrome has been recently reported. The objectives of this study were to determine: 1) placental microbiology using molecular microbiological techniques; 2) diagnostic accuracy of the clinical criteria used to identify patients with placental bacterial infection; 3) relationship between placental bacterial infection and histological chorioamnionitis. This prospective cross-sectional study included 41 women diagnosed with clinical and histological chorioamnionitis. The presence of microorganisms in the placenta was determined by conducting placental analysis using a broad range of polymerase chain reactions (PCR). Bacterial placental infection (defined as the presence of the 16S gene detected in placental tissue using the molecular technique PCR) was observed in 63% (26/41) of parturients diagnosed with histological chorioamnionitis. The traditional criteria for diagnosing clinical chorioamnionitis exhibit poor diagnostic performance in accurately identifying proven intra-amniotic infection. The molecular analysis (PCR) of the placenta has suggested that acute chorioamnionitis commonly has a bacterial origin.

The purpose of this study was to investigate the prevalence of abnormal vaginal colonization in women with cervical incompetence and to analyze its impact on obstetric and neonatal outcomes and placental inflammation. We included 138 pregnant women diagnosed with cervical incompetence and delivered in our hospital. Patients with major fetal anomaly or multifetal pregnancy were excluded. Upper vaginal culture was performed on the day of admission. A total of 60.9% (84/138) of cervical incompetence patients had abnormal bacterial colonization, and Escherichia coli (E. coli) was the most common colonized pathogen (33.3%, 46/138). The positive vaginal E. coli group had a higher rate of prior preterm birth (p = 0.021) and an earlier gestational age at which cervical incompetence was diagnosed (p < 0.01) than the negative group. The positive vaginal E. coli group had higher rates of clinical chorioamnionitis (p = 0.008) and subchorionic microabscess of the placenta (p = 0.012). Importantly, the positive vaginal E. coli group had significantly higher rates of proven early-onset neonatal sepsis (EONS) (p = 0.046), necrotizing enterocolitis (NEC) (p = 0.001), and neonatal mortality (p = 0.023). After adjusting for confounding variables, the positive vaginal E. coli group had significantly higher risk for proven EONS (OR: 3.853, 95% CI: 1.056–14.055) and NEC (OR: 12.410, 95% CI: 1.290–119.351). In conclusion, E. coli was the most common vaginal microorganism isolated from patients with cervical incompetence. Maternal vaginal E. coli colonization was associated with adverse neonatal outcomes including proven EONS and NEC and was characterized by a higher rate of placental subchorionic microabscess. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of a quality‐improvement initiative designed to increase diagnostic accuracy and adequate management of clinical chorioamnionitis (CC) at a tertiary center. Chorioamnionitis occurs in 1%–13% of term pregnancies and increases maternal and neonatal peripartum complications; often over‐diagnosed, it leads to unnecessary investigations and treatments. Methods: This was an interrupted time‐series study. In September 2017 two interventions were implemented: (1) staff training and (2) standardized clinical protocol for the management of fever in labor. All singleton term pregnancies were included. CC cases were reviewed in the pre‐intervention (2015–2016, n = 179) and post‐intervention (2017–2018, n = 142) groups. CC criteria based on the American College of Obstetricians and Gynecologists guidelines, antibiotics, maternal and neonatal outcomes, and pathology were compared. A cost–consequence analysis was performed. Results: Incidence of CC decreased from 8.2 to 5.6 per 10 person‐year (P < 0.001). This was associated with a significant increase in diagnostic accuracy from 15.7% to 73.2% (P < 0.001). Weight‐adjusted tobramycin dosage improved from 8.8% to 69.1% (P < 0.001). Maternal length of hospitalization and readmissions decreased significantly, without affecting neonatal sepsis rate. Interventions decreased yearly hospital costs associated with CC by 23.4%. Conclusion: Standardizing the management of fever in labor significantly increased the diagnostic accuracy of CC and decreased the misuse of antibiotics in term pregnancies. CC costs decreased by 23.4%. Synopsis: Education on chorioamnionitis and implementation of a standardized clinical protocol increase the diagnostic accuracy of chorioamnionitis and decrease the misuse of antibiotics in term pregnancies. [ABSTRACT FROM AUTHOR]

Objectives: Preterm premature rupture of membranes (PPROM) remote from term is an important obstetric cause of maternal and fetal adverse outcomes. The aim of our study is to examine the efficacy of ampicillin and Lactobacillus casei rhamnosus treatment in cases of PPROM remote from term. Material and methods: The study was carried out by examining the results of cases who were given Ampicillin and Lactobacillus casei rhamnosus treatment. The patients were divided into two groups. Group 1 who didn't develop clinical chorioamnionitis and Group 2 who developed clinical chorioamnionitis. Obstetric characteristics, neonatal outcomes, adverse events were recorded. Results: A total of 46 pregnant women, 40 in Group 1 and six in Group 2, were included in the study. The frequency of clinical chorioamnionitis developing during the treatment was found to be 13.0%. Mean gestational age at diagnosis was 28.43 ± 2.38 and 28.17 ± 1.33 for Groups 1 and Group 2, respectively. Mean gestational age at the time of delivery was 32.38 ± 2.07 31.33 ± 1.63 for Group 1 and Group 2, respectively. The mean latency period for Group 1 and Group 2 was 27.45 ± 1.71 days, 23.66 ± 4.53, respectively. Sepsis developed in six newborns (15%) in Group 1, while it developed in three newborns (50%) in Group 2. While 90% of the babies in Group 1 were discharged from the hospital, this rate was 66.7% in Group 2. Conclusions: Ampicillin + Lactobacillus casei rhamnosus is an effective treatment method in PPROM cases and positively affects perinatal outcomes. [ABSTRACT FROM AUTHOR]

We discuss a case where the blood cultures of a patient with clinical chorioamnionitis and elevated D-dimer levels enabled early diagnosis of infective endocarditis. A 31-year-old female with a 39-week pregnancy presented to the obstetrics department with a fever. Cardiotocography revealed fetal tachycardia and severe late deceleration. Preoperative examinations revealed a leukocyte count of 15,900/μL and D-dimer levels of 86.2 μg/mL. She was diagnosed with a non-reassuring fetal status due to clinical chorioamnionitis; accordingly, an emergency cesarean section was performed. Imaging studies ruled out the possibility of a thromboembolism. Subsequent maternal blood cultures were positive for Staphylococcus aureus . Echocardiography revealed vegetation on the aortic valve, leading to a diagnosis of infective endocarditis. Blood cultures can be useful in evaluating for sepsis in cases of clinical chorioamnionitis with elevated D-dimer levels as they may facilitate early diagnosis of infective endocarditis during pregnancy., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yamano et al.)

Purpose of review: The criteria for the diagnosis of intra-amniotic infection (IAI) were derived from a study of women at term in labor but is currently used as the main diagnostic tool for clinical chorioamnionitis. Regarding the inconsistent usage of the term, the diagnostic utility of clinical chorioamnionitis needs to be revisited. In this review, we addressed the critical issues on why the diagnostic criteria of suspected clinical chorioamnionitis should be changed.Recent findings: Overall, the accuracy of clinical chorioamnionitis to detect intra-amniotic infection (IAI) is not high, around 50%. The accuracy of each diagnostic criteria to diagnose IAI is, for example, 51.1% with maternal tachycardia, 57.8% with fetal tachycardia, and 55.6% with maternal leukocytosis. However, it needs to be reminded that these diagnostic performances had been obtained from term pregnancies but not from preterm pregnancies. Since there is a difference between clinical chorioamnionitis and histologic chorioamnionitis or even IAI, the diagnostic criteria of clinical chorioamnionitis would be ideal if it could directly predict the development of neonatal infectious outcomes. In fact, multiple definitions of clinical chorioamnionitis either in more lenient or stringent manner are currently used, which is responsible for inconsistent association of clinical chorioamnionitis with long-term neonatal outcomes. Whereas the diagnosis of clinical chorioamnionitis in preterm is followed by expeditious delivery, the diagnosis of clinical chorioamnionitis at term pregnancy is usually conducted in laboring women and requires additional neonatal evaluation for sepsis, which suggests different implications of clinical chorioamnionitis in preterm and term pregnancy.Summary: Current diagnostic criteria of clinical chorioamnionitis should be revised, specifically in terms of sensitivity in preterm pregnancy and specificity in term pregnancy. [ABSTRACT FROM AUTHOR]

Background: Preterm birth is the leading cause of perinatal morbidity and mortality. Preterm prelabor rupture of membranes (pPROM) occurs in 30% of preterm births; thus, this complication is a major contributor to maternal and neonatal morbidity. However, the cellular immune responses in amniotic fluid of women with pPROM have not been investigated. Methods: Amniotic fluid samples were obtained from women with pPROM and a positive (n = 7) or negative (n = 10) microbiological culture. Flow cytometry was performed to evaluate the phenotype and number of amniotic fluid leukocytes. The correlation between amniotic fluid immune cells and an interleukin-6 (IL-6) concentration or a white blood cell (WBC) count in amniotic fluid was calculated. Results: Women with pPROM and a positive amniotic fluid culture had (1) a greater number of total leukocytes in amniotic fluid, including neutrophils and monocytes/macrophages and (2) an increased number of total T cells in amniotic fluid, namely CD4+ T cells and CD8+ T cells, but not B cells. The numbers of neutrophils and monocytes/macrophages were positively correlated with IL-6 concentrations and WBC counts in amniotic fluid of women with pPROM. Conclusion: Women with pPROM and a positive amniotic fluid culture exhibit a more severe cellular immune response than those with a negative culture, which is associated with well-known markers of intra-amniotic inflammation. [ABSTRACT FROM AUTHOR]

Objective  To identify single nucleotide polymorphisms (SNPs) associated with clinical chorioamnionitis among preterm infants. Study Design  We reanalyzed a genome-wide association study (GWAS) from preterm newborns at less than 30 weeks' gestation. Cases and control definitions were determined using administrative records. There were 213 clinical chorioamnionitis cases and 707 clinically uninfected controls. We compared demographic and clinical outcomes of cases and controls. We performed a GWAS and compared the distribution of SNPs from the background genes and from the immunome genes. We used a Wilcoxon's rank-sum test to compare the SNPs normalized odds ratio and used odds ratios and p -values to determine candidate genes. Results  Infants affected by clinical chorioamnionitis were more likely to have periventricular leukomalacia, high-grade retinopathy, and high-grade intraventricular hemorrhage (IVH). Although a GWAS did not identify SNPs associated with clinical chorioamnionitis at the genome-wide significance level, a direct test on the exonic variants in the human immunome revealed their significant increase of risk in clinical chorioamnionitis. Conclusion  Among very preterm infants, clinical chorioamnionitis was associated with periventricular leukomalacia, high-grade retinopathy, and IVH. Our analysis of variants in the human immunome indicates an association with clinical chorioamnionitis in very preterm pregnancies. [ABSTRACT FROM AUTHOR]

Rectovaginal colonization with Group B Streptococcus during pregnancy has historically been shown to be associated with an increased risk of clinical chorioamnionitis and peripartum infectious morbidity. Newer observational data in the era of intrapartum antibiotic prophylaxis suggest a possible reversal of this association; however, it is unclear if this is related to differences in labor management for those with and without Group B Streptococcus colonization. We therefore sought to assess the association between intrapartum antibiotic prophylaxis for Group B Streptococcus colonization and clinical chorioamnionitis within the context of a randomized induction of labor trial with a standardized labor protocol. We performed an exploratory secondary analysis of a randomized trial of patients undergoing term induction at a tertiary care center. Patients received third trimester Group B Streptococcus screening and intrapartum antibiotic prophylaxis as routine care. Group B Streptococcus detection was performed using a carrot broth-enhanced subculture to Group B Streptococcus Detect approach (Hardy Diagnostics, Santa Maria, CA). Labor management was protocolized per the trial. Patients with unknown Group B Streptococcus status or who did not receive intrapartum antibiotic prophylaxis, if indicated, were excluded. The primary outcome was diagnosis of clinical chorioamnionitis, compared between patients who received intrapartum antibiotic prophylaxis for known Group B Streptococcus positive status (by culture, history, or Group B Streptococcus bacteriuria) and those who were Group B Streptococcus negative and did not receive intrapartum antibiotic prophylaxis. Secondary outcomes included postpartum endometritis, wound infection, a composite maternal peripartum infectious morbidity, and neonatal outcomes. A total of 491 patients were enrolled in the trial. Of these, 466 had a known Group B Streptococcus status and received or did not receive intrapartum antibiotic prophylaxis accordingly and were included in this analysis: 292 (62.7%) were Group B Streptococcus negative and did not receive intrapartum antibiotic prophylaxis, and 174 (37.3%) were Group B Streptococcus positive and received intrapartum antibiotic prophylaxis. The majority of patients were Non-Hispanic Black (78.1%) and nulliparous (59.7%). There were no differences in demographic, clinical, induction or labor characteristics between groups. Patients who were Group B Streptococcus positive had a 49% lower rate of clinical chorioamnionitis (8.1% vs 14.7%, odds ratio, 0.51; P =.03) and a lower rate of peripartum infectious morbidity (8.1% vs 15.8%, odds ratio, 0.47; P =.02) compared to those who were Group B Streptococcus negative. Infants born to patients who were Group B Streptococcus positive were significantly less likely to be admitted to the neonatal intensive care unit (3.4% vs 15.1%, P <.001). Although Group B Streptococcus colonization has historically been considered a risk factor for clinical chorioamnionitis, in the era of universal antibiotic prophylaxis for Group B Streptococcus positive patients, our findings support the point that intrapartum antibiotic prophylaxis for Group B Streptococcus positivity is associated with lower rates of clinical chorioamnionitis and peripartum infectious morbidity among patients undergoing induction with protocolized labor management. These findings demonstrate that intrapartum antibiotic prophylaxis for Group B Streptococcus may protect against perinatal infectious morbidity, a phenomenon that warrants further investigation. [ABSTRACT FROM AUTHOR]

Gloria Mercedes Galán Henríquez, Fermín García-Muñoz Rodrigo Service of Neonatalogy, Complejo Hospital Universitario Insular Materno Infantil de Canarias, Las Palmas de Gran Canaria, Spain Abstract: The term chorioamnionitis (CA) is commonly used to refer to different clinical or pathological conditions characterized by an infectious and/or inflammatory process that affects primarily the chorioamniotic membranes, but also the amniotic fluid, vessels of the chorionic plate, and, eventually, the umbilical cord (funisitis) and the fetus. Its incidence is higher at lower gestational ages, and the main mechanism is believed to be the ascending bacterial infection from the maternal genital tract. It can be diagnosed by clinical criteria, amniotic fluid examination for inflammatory mediators, and/or isolation of microorganisms, or by histopathological examination of the placenta. CA is an important cause of stillbirth and is related to an increased incidence of premature rupture of membranes, preterm delivery, and adverse maternal and neonatal outcomes such as early-onset neonatal sepsis and necrotizing enterocolitis. An independent causal association to other neonatal morbidities is more controversial. The heterogeneity in the diagnostic criteria and in the operative definitions for morbidity makes comparison of studies difficult, and results are inconsistent. In addition, the intensity and duration of the process are usually not considered. For all these reasons, evidence-based recommendations for the management of mother and infant under these circumstances are difficult to establish, and clinical practice varies widely. Keywords: clinical chorioamnionitis, histological chorioamnionitis, stillbirth, prematurity, morbidity, mortality

Background: Monocytes, after neutrophils, are the most abundant white blood cells found in the amniotic cavity of women with intra-amniotic inflammation/infection. However, the origin of such cells has not been fully investigated. Herein, we determined (1) the origin of amniotic fluid monocytes/macrophages from women with intra-amniotic inflammation/infection, (2) the relationship between the origin of amniotic fluid monocytes/macrophages and preterm or term delivery and (3) the localization of monocytes/macrophages in the placental tissues. Methods: Amniotic fluid samples (n = 16) were collected from women with suspected intra-amniotic inflammation or infection. Amniotic fluid monocytes/macrophages were purified by fluorescence-activated cell sorting, and DNA fingerprinting was performed. Blinded placental histopathological evaluations were conducted. Immunohistochemistry was performed to detect CD14+ monocytes/macrophages in the placental tissues. Results: DNA fingerprinting revealed that (1) 56.25% (9/16) of amniotic fluid samples had mostly fetal monocytes/macrophages, (2) 37.5% (6/16) had predominantly maternal monocytes/macrophages and (3) one sample (6.25% [1/16]) had a mixture of fetal and maternal monocytes/macrophages. (4) Most samples with predominantly fetal monocytes/macrophages were from women who delivered early preterm neonates (77.8% [7/9]), whereas all samples with mostly maternal monocytes/macrophages or a mixture of both were from women who delivered term or late preterm neonates (100% [7/7]). (5) Most of the women included in this study presented acute maternal and fetal inflammatory responses in the placenta (85.7% [12/14]). (6) Women who had mostly fetal monocytes/macrophages in amniotic fluid had abundant CD14+ cells in the umbilical cord and chorionic plate, whereas women with mostly maternal amniotic fluid monocytes/macrophages had abundant CD14+ cells in the chorioamniotic membranes. Conclusion: Amniotic fluid monocytes/macrophages can be of either fetal or maternal origin, or a mixture of both, in women with intra-amniotic inflammation or infection. These immune cells could be derived from the fetal and maternal vasculature of the placenta. [ABSTRACT FROM AUTHOR]

To predict the presence of histological funisitis at term, we examined the symptoms of clinical chorioamnionitis in 251 cases of maternal fever of 38 degrees or higher during labor at term. The examined symptoms in this study were clinical maternal findings (uterine fundal tenderness, maternal tachycardia, purulent or foul amniotic fluid or cervical discharge, and maternal white blood cell count) and fetal tachycardia. In these cases, microscopic histopathological analysis of the placenta was performed after delivery. The positive predictive value for histological funisitis in cases of maternal fever of 38 degrees or higher was only 15.5%. In cases of maternal fever with uterine fundal tenderness and purulent or foul amniotic fluid or cervical discharge at term, the positive predictive value for histological chorioamnionitis was 100%. Therefore, uterine fundal tenderness and amniotic fluid or cervical discharge with a foul odor are important symptoms to predict the presence of funisitis in cases of maternal fever of 38 degrees or higher. [ABSTRACT FROM AUTHOR]

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal–fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition.

Preterm birth is the leading cause of neonatal morbidity and mortality worldwide. Inflammation is causally linked to preterm birth; therefore, finding an intervention that dampens maternal and fetal inflammatory responses may provide a new strategy to prevent adverse pregnancy and neonatal outcomes. Using animal models of systemic maternal inflammation [intraperitoneal injection of lipopolysaccharide (LPS)] and fetal inflammation (intra-amniotic administration of LPS), we found that (1) systemic inflammation induced adverse pregnancy and neonatal outcomes by causing a severe maternal cytokine storm and a mild fetal cytokine response; (2) fetal inflammation induced adverse pregnancy and neonatal outcomes by causing a mild maternal cytokine response and a severe fetal cytokine storm; (3) exendin-4 (Ex4) treatment of dams with systemic inflammation or fetal inflammation improved adverse pregnancy outcomes by modestly reducing the rate of preterm birth; (4) Ex4 treatment of dams with systemic, but not local, inflammation considerably improved neonatal outcomes, and such neonates continued to thrive; (5) systemic inflammation facilitated the diffusion of Ex4 through the uterus and the maternal–fetal interface; (6) neonates born to Ex4-treated dams with systemic inflammation displayed a similar cytokine profile to healthy control neonates; and (7) treatment with Ex4 had immunomodulatory effects by inducing an M2 macrophage polarization and increasing anti-inflammatory neutrophils, as well as suppressing the expansion of CD8+ regulatory T cells, in neonates born to dams with systemic inflammation. Collectively, these results provide evidence that dampening maternal systemic inflammation through novel interventions, such as Ex4, can improve the quality of life for neonates born to women with this clinical condition. [ABSTRACT FROM AUTHOR]

Objective: Intra-amniotic infection is associated with spontaneous preterm labor. In most cases, the infection is subclinical and bacteria are detected in the amniotic cavity rather than in the chorioamniotic membranes. The aims of this study were to establish a model of intra-amniotic lipopolysaccharide (LPS)-induced preterm labor/birth that resembles the subclinical syndrome and to compare this model to two established models of LPS-induced preterm labor/birth.Methods: Pregnant B6 mice received an intra-amniotic, intra-uterine, or intra-peritoneal injection of LPS (100 ng/amniotic sac, 15 μg/25 μL, and 15 μg/200 μL respectively) or PBS (control). Following injection, body temperature (every two hours for a 12-h period), gestational age, and the rate of preterm labor/birth were recorded.Results: An intra-amniotic injection of LPS resulted in preterm labor/birth [LPS 80 ± 24.79% (8/10) versus PBS 0% (0/8); p = 0.001] without causing maternal hypothermia. Intra-peritoneal [LPS 100% (8/8) versus PBS 0% (0/8); p < 0.001)] and intra-uterine [LPS 100% (8/8) versus PBS 28.57 ± 33.47% (2/7); p =0 .007] injections of LPS induced preterm labor/birth; yet, maternal hypothermia was observed.Conclusion: Intra-amniotic injection of LPS induces preterm labor/birth in the absence of a body temperature change, which resembles the subclinical syndrome. [ABSTRACT FROM AUTHOR]

Controversy exists about the relationship between maternal inflammation and the development of different morbidities and mortality in the newborn. We aimed to establish the incidence of clinical chorioamnionitis in our Neonatal Intensive Care Unit and its relation to morbidity and mortality among very-low-birth-weight infants. Methods: This was an observational study of a cohort of very-low-birth-weight neonates admitted to our Neonatal Intensive Care Unit, between January 2008 and December 2012. Demographic characteristics and outcomes were analyzed and a comparison between exposed and non-exposed infants was carried out. Results: During the study period, 451 very-low-birth-weight infants were admitted to our Neonatal Intensive Care Unit, and 31 (6.87%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower gestational ages: 13.2% (23–26 weeks), 8.1% (27–30 weeks), and 2.6% (31–34 weeks) (p = 0.022). After correcting by gestational age and birth weight, early-onset neonatal sepsis (adjusted relative risk = 6.13; 95% confidence interval = 1.67–22.58; p = 0.006) and periventricular leukomalacia (adjusted relative risk = 24.62; 95% confidence interval = 1.87–324.28; p = 0.015) were significantly associated with maternal clinical chorioamnionitis. There were no differences in mortality or in survival without major morbidity. Conclusion: Clinical chorioamnionitis confers an increased risk of early-onset neonatal sepsis and periventricular leukomalacia to exposed very-low-birth-weight infants.

Problem Neutrophils are capable of performing phagocytosis, a primary mechanism for microbial killing. Intra-amniotic infection is characterized by an influx of neutrophils into the amniotic cavity. Herein, we investigated whether amniotic fluid neutrophils could phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection. Methods Amniotic fluid neutrophils from women with intra-amniotic infection were visualized by transmission electron microscopy (n=6). The phagocytic activity of amniotic fluid neutrophils from women with intra-amniotic infection and/or inflammation (n=10) or peripheral neutrophils from healthy individuals (controls, n=3) was tested using ex vivo phagocytosis assays coupled with live imaging. Phagocytosis by amniotic fluid neutrophils was also visualized by confocal microscopy (n=10) as well as scanning and transmission electron microscopy (n=5). Results (i) Intra-amniotic infection-related bacteria including cocci (eg Streptococcus agalactiae), bacilli (eg Bacteriodes fragilis and Prevotella spp.), and small bacteria without a cell wall (eg Ureaplasma urealyticum) were found inside of amniotic fluid neutrophils; (ii) peripheral neutrophils (controls) rapidly phagocytized S. agalactiae, U. urealyticum, Gardnerella vaginalis, and Escherichia coli; (iii) amniotic fluid neutrophils rapidly phagocytized S. agalactiae and G. vaginalis; and (iv) amniotic fluid neutrophils slowly phagocytized U. urealyticum and E. coli; yet, the process of phagocytosis of the genital mycoplasma was lengthier. Conclusion Amniotic fluid neutrophils can phagocytize bacteria found in the amniotic cavity of women with intra-amniotic infection, namely S. agalactiae, U. urealyticum, G. vaginalis, and E. coli. Yet, differences in the rapidity of phagocytosis were observed among the studied microorganisms. These findings provide a host defense mechanism whereby amniotic fluid neutrophils can kill microbes invading the amniotic cavity. [ABSTRACT FROM AUTHOR]

Objective To re-evaluate the utility of the conventional criteria for clinical chorioamnionitis in the prediction of early-onset neonatal sepsis ( EONS) in preterm birth. Design Retrospective cohort study. Setting Seoul, Republic of Korea. Sample A total of 1468 singleton births between 24 and 34 weeks due to preterm labour ( n = 713) or preterm prelabour rupture of membranes ( n = 755). Method We evaluated three diagnostic categories of clinical chorioamnionitis: Criteria 1, conventional criteria; Criteria 2, combination of any three conventional parameters without prerequisite fever; Criteria 3, Criteria 1 plus positive maternal C-reactive protein and neutrophil left-shift into minor criteria. EONS included proven or suspected sepsis within 7 days following birth. Neonatal morbidity and mortality of EONS were also reviewed. Main outcome measures Diagnostic performance of three combinations. Results The prevalence of EONS was 13.8%. Among 203 cases of EONS, maternal manifestation of clinical chorioamnionitis by criteria 1 was evident in only one out of seven, indicating 15.3% sensitivity for EONS prediction. However, with application of criteria 2, sensitivity significantly increased to 34.0%, while compromising specificity from 92.3% to 78.7%. Criteria 3 showed similar diagnostic performance compared with criteria 1 (sensitivity 16.7%, specificity 91.6%). Overall, neonatal mortality and neonatal composite morbidity in EONS were 14.9% and 67.8%, respectively, and there was no difference in neonatal morbidity and mortality between neonates whose mothers showed fever as a sign of clinical chorioamnionitis and those whose mothers did not. Conclusion The renouncement of fever as a prerequisite for the criteria of clinical chorioamnionitis could increase sensitivity for the identification of EONS, a serious outcome of preterm birth. Tweetable abstract The renouncement of fever as an essential can increase sensitivity for prediction of neonatal sepsis. [ABSTRACT FROM AUTHOR]

Objective: Various prophylactic antibiotic regimens are used in the management of preterm premature rupture of membranes. We investigated the efficacy and safety of these regimens in terms of maternal and neonatal outcomes., Data Sources: We searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials from inception to July 20, 2021., Study Eligibility Criteria: We included randomized controlled trials involving pregnant women with preterm premature rupture of membranes before 37 weeks of gestation and a comparison of ≥2 of the following 10 antibiotic regimens: control/placebo, erythromycin, clindamycin, clindamycin plus gentamicin, penicillins, cephalosporins, co-amoxiclav, co-amoxiclav plus erythromycin, aminopenicillins plus macrolides, and cephalosporins plus macrolides., Methods: Two investigators independently extracted published data and assessed the risk of bias with a standard procedure following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Network meta-analysis was conducted using the random-effects model., Results: A total of 23 studies that recruited a total of 7671 pregnant women were included. Only penicillins (odds ratio, 0.46; 95% confidence interval, 0.27-0.77) had significantly superior effectiveness for maternal chorioamnionitis. Clindamycin plus gentamicin reduced the risk of clinical chorioamnionitis, with borderline significance (odds ratio, 0.16; 95% confidence interval, 0.03-1.00). By contrast, clindamycin alone increased the risk of maternal infection. For cesarean delivery, no significant differences were noted among these regimens., Conclusion: Penicillins remain the recommended antibiotic regimen for reducing maternal clinical chorioamnionitis. The alternative regimen includes clindamycin plus gentamicin. Clindamycin should not be used alone., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Bioactive lipids derived from the metabolism of polyunsaturated fatty acids are important mediators of the inflammatory response. Labor per se is considered a sterile inflammatory process. Intra-amniotic inflammation (IAI) due to microorganisms (i.e., intra-amniotic infection) or danger signals (i.e., sterile IAI) has been implicated in the pathogenesis of preterm labor and clinical chorioamnionitis at term. Early and accurate diagnosis of microbial invasion of the amniotic cavity (MIAC) requires analysis of amniotic fluid (AF). It is possible that IAI caused by microorganisms is associated with a stereotypic lipidomic profile, and that analysis of AF may help in the identification of patients with this condition. To test this hypothesis, we analyzed the fatty acyl lipidome of AF by liquid chromatography--mass spectrometry from patients in spontaneous labor at term and preterm gestations. We report that the AF concentrations of proinflammatory lipid mediators of the 5-lipoxygenase pathway are significantly higher in MIAC than in cases of sterile IAI. These results suggest that the concentrations of 5-lipoxygenase metabolites of arachidonic acid, 5-hydroxyeicosatetraenoic acid, and leukotriene B4 in particular could serve as potential biomarkers of MIAC. This finding could have important implications for the rapid identification of patients who may benefit from anti-microbial treatment. [ABSTRACT FROM AUTHOR]

Objective: To examine the association of clinical chorioamnionitis on cesarean delivery in a national sample of hospital discharges.Data Source: Hospital discharge data from the 1998-2010 Nationwide Inpatient Sample.Study Design: We performed a cross-sectional study and general linear modeling was used to determine the association of clinical chorioamnionitis on risk of cesarean delivery.Principal Findings: A total of 10,843,682 deliveries and 51,799,431 nationally weighted deliveries were identified. Clinical chorioamnionitis was present in 2.9 percent of cesarean and 1.3 percent of vaginal deliveries (p < .001). In multivariate analysis, clinical chorioamnionitis was associated with a 1.39-fold increased risk of cesarean delivery. Compared with women without clinical chorioamnionitis at an urban/teaching hospital, women with clinical chorioamnionitis at an urban/teaching, urban/nonteaching, and rural hospital were 1.4-1.5 times more likely to have cesarean delivery. Compared with women without clinical chorioamnionitis in the Midwest, the relative risk for cesarean in women with clinical chorioamnionitis was 1.54 for women in the South, 1.47 in the Northeast, 1.39 in the Midwest, and 1.34 in the West.Conclusions: Women with clinical chorioamnionitis were more likely to have cesarean delivery than those without clinical chorioamnionitis, and the risk of cesarean delivery varied significantly by hospital location, teaching status, and U.S. region. [ABSTRACT FROM AUTHOR]

Objective: To investigate dynamic changes in myometrial thickness during the third stage of labor. Methods: Myometrial thickness was measured using ultrasound at one-minute time intervals during the third stage of labor in the mid-region of the upper and lower uterine segments in 151 patients including: women with a long third stage of labor (n = 30), postpartum hemorrhage (n = 4), preterm delivery (n = 7) and clinical chorioamnionitis (n = 4). Differences between myometrial thickness of the uterine segments and as a function of time were evaluated. Results: There was a significant linear increase in the mean myometrial thickness of the upper uterine segments, as well as a significant linear decrease in the mean myometrial thickness of the lower uterine segments until the expulsion of the placenta (p < 0.001). The ratio of the measurements of the upper to the lower uterine segments increased significantly as a function of time (p < 0.0001). In women with postpartum hemorrhage, preterm delivery, and clinical chorioamnionitis, an uncoordinated pattern among the uterine segments was observed. Conclusion: A well-coordinated activity between the upper and lower uterine segments is demonstrated in normal placental delivery. In some clinical conditions this pattern is not observed, increasing the time for placental delivery and the risk of postpartum hemorrhage. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: The umbilical arterial pH (UApH) in cases of clinically apparent chorioamnionitis (CAM) in which the infant later develop severe cerebral palsy (CP) has not yet been fully investigated. The objective of this study was to determine the UApH in CAM cases in which the infant later develop severe CP. Methods: A review was conducted unti1 April 2014 among 324 infants with CP diagnosed to be caused by antenatal and/or intrapartum conditions, as determined by the Japan Council for Quality Health Care. Eighty-six infants born at over 34 weeks of gestation with an abnormal FHR pattern during labor were selected. The subjects were divided into the following two groups: cases with (Group I, n = 19) and those without (Group II, n = 67) clinical CAM. Severe fetal acidemia was defined as a pH of less than 7.0. Results: The frequency of severe acidemia in Groups 1 and II was 26.3 and 74.6 %, respectively. In addition, the frequency of severe acidemia was significantly less in Group I (odds ratio (OR) 0.12, 95 % confidence interval (CI) 0.03-0.53) than in Group II, while the frequency of fetal tachycardia was greater in Group I (OR 7.61, 95 % CI 1.82-31.7) than in Group II, after adjusting for confounding effects. Conclusions: The frequency of severe acidemia was lower in the cases of clinical CAM in which the infant later developed severe cerebral palsy than in the cases without clinical CAM. The relation of fetal tachycardia to CP with clinical CAM, but not to acidemia, should be reevaluated in such cases. [ABSTRACT FROM AUTHOR]

Background: Preterm premature rupture of membranes complicates approximately 3% of pregnancies. Currently, in the absence of chorioamnionitis or placental abruption, expectant management, including antenatal steroids for lung maturation and prophylactic antibiotic treatment, is recommended. The benefits of individualized management have not been adequately explored.Objective: This study aimed to compare the impact of 2 different management strategies of preterm premature rupture of membranes in 2 tertiary obstetrical centers on latency of >7 days, latency to birth, chorioamnionitis, funisitis, and short-term adverse maternal and neonatal outcomes.Study Design: This was a multicenter retrospective study of women with singleton pregnancies with preterm premature rupture of membranes from 23 0/7 to 33 6/7 weeks of gestation between 2014 and 2018 and undelivered within 24 hours after hospital admission managed at Sunnybrook Health Sciences Center, Toronto, Canada (standard management group), and BCNatal (Hospital Clínic of Barcelona and Hospital Sant Joan de Déu Barcelona), Barcelona, Spain (individualized management group), following local protocols. The standard management group received similar management for all patients, which included a standard antibiotic regimen and routine maternal and fetal surveillance, whereas the individualized management group received personalized management on the basis of amniocentesis at hospital admission (if possible), to rule out microbial invasion of the amniotic cavity and targeted treatment. The exclusion criteria were cervical dilatation >2 cm, active labor, contraindications to expectant management (acute chorioamnionitis, placental abruption, or abnormal fetal tracing), and major fetal anomalies. The primary outcome was latency of >7 days, and the secondary outcomes included latency to birth, chorioamnionitis, and short-term adverse maternal and neonatal outcomes. Statistical comparisons between groups were conducted with propensity score weighting.Results: A total of 513 pregnancies with preterm premature rupture of membranes were included in this study: 324 patients received standard management, and 189 patients received individualized management, wherein amniocentesis was performed in 112 cases (59.3%). After propensity score weighting, patients receiving individualized management had a higher latency of >7 days (76.0% vs 41.6%; P<.001) and latency to birth (18.1±14.7 vs 9.7±9.7 days; P<.001). Although a higher rate of clinical chorioamnionitis was suspected in the individualized management group than the standard group (34.5% vs 22.0%; P<.01), there was no difference between the groups in terms of histologic chorioamnionitis (67.2% vs 73.4%; P=.16), funisitis (57.6% vs 58.1%; P=.92), or composite infectious maternal outcomes (9.1% vs 7.9%; P=.64). Prolonged latency in the individualized management group was associated with a significant reduction of preterm birth at <32 weeks of gestation (72.1% vs 90.5%; P<.001), neonatal intensive care unit admission (75.6% vs 83.0%; P=.046), and neonatal respiratory support at 28 days of life (16.1% vs 26.1%; P<.01) compared with that in the standard management group. Moreover, prolonged latency was not associated with neonatal severe morbidity at discharge (survival without severe morbidity, 80.4% vs 73.5%; P=.09).Conclusion: Individualized management of preterm premature rupture of membranes may prolong pregnancy and reduce preterm birth at <32 weeks of gestation, the need for neonatal support, and neonatal intensive care unit admissions, without an increase in histologic chorioamnionitis, funisitis, neonatal infection-related morbidity, and short-term adverse maternal and neonatal outcomes. [ABSTRACT FROM AUTHOR]

Background Controversy exists about the relationship between maternal inflammation and the development of different morbidities and mortality in the newborn. We aimed to establish the incidence of clinical chorioamnionitis in our Neonatal Intensive Care Unit and its relation to morbidity and mortality among very-low-birth-weight infants. Methods This was an observational study of a cohort of very-low-birth-weight neonates admitted to our Neonatal Intensive Care Unit, between January 2008 and December 2012. Demographic characteristics and outcomes were analyzed and a comparison between exposed and non-exposed infants was carried out. Results During the study period, 451 very-low-birth-weight infants were admitted to our Neonatal Intensive Care Unit, and 31 (6.87%) were exposed to maternal clinical chorioamnionitis. The incidence was higher at lower gestational ages: 13.2% (23–26 weeks), 8.1% (27–30 weeks), and 2.6% (31–34 weeks) ( p = 0.022). After correcting by gestational age and birth weight, early-onset neonatal sepsis (adjusted relative risk = 6.13; 95% confidence interval = 1.67–22.58; p = 0.006) and periventricular leukomalacia (adjusted relative risk = 24.62; 95% confidence interval = 1.87–324.28; p = 0.015) were significantly associated with maternal clinical chorioamnionitis. There were no differences in mortality or in survival without major morbidity. Conclusion Clinical chorioamnionitis confers an increased risk of early-onset neonatal sepsis and periventricular leukomalacia to exposed very-low-birth-weight infants. [ABSTRACT FROM AUTHOR]

Objective:To evaluate the association between maternal interleukin (IL)-6 G(−174)C polymorphism and cystic periventricular leukomalacia (cPVL) of the preterm newborn.Study Design:After searching a local database, we recruited 132 preterm infants with diagnosis of cPVL, 44 Caucasian mothers were also recruited to participate in this candidate gene-association study at a single teritary care center. Data related to maternal IL-6 G(−174)C polymorphisms were compared with 41 controls, and furthermore compared with data from umbilical cord blood samples from a consecutive birth cohort of 395 healthy newborns, and published data from Caucasian populations including 1104 adults, respectively. In addition, subgroup analysis was performed in cases with either history of preterm premature rupture of the membranes (PPROM) or clinical chorioamnionitis (CCA). IL-6 genotyping was performed using an allele-specific polymerase chain reaction technique.Result:Frequencies of the IL-6 G(−174)C polymorphisms did not differ between cases (GG, 29.5%; GC, 54.5% and CC, 15.9%) and controls (GG, 34.2; GC, 51.2 and CC, 14.6%). Subgroup analysis of 31 cases with history of PPROM (GG, 25.8; GC, 54.8 and CC 19.4%) and controls did not reveal significant differences, but a significantly higher frequency of the CC genotype was found in 23 cases with a history of CCA (34.8%) compared with controls by either univariate (P=0.032; odds ratio 3.11, 95% confidence interval (CI) 1.11 to 8.68) or multivariate analysis (P=0.049, odds ratio 2.54, 95% CI 1.01 to 6.45). These data were confirmed by a comparing the CC genotype frequency to 395 term controls (CC 14.7%, P=0.005) and to the mean CC genotype frequency of 1104 Caucasian adults (CC 15.6%, P<0.0001).Conclusion:Frequencies of the IL-6 G(−174)C polymorphisms did not differ between groups. Subgroup analysis revealed an association of the CC genotype with CCA and cPVL in the preterm newborn. [ABSTRACT FROM AUTHOR]

Objective: To predict maternal and neonatal clinical infection at admission in women hospitalized for preterm labour (PTL) with intact membranes. Study Design: Prospective study of 371 women hospitalized for preterm labour with intact membranes. The primary outcome was clinical infection, defined by clinical chorioamnionitis at delivery or early-onset neonatal infection. Results: Clinical infection was identified in 21 cases (5.7%) and was associated with earlier gestational age at admission for PTL, elevated maternal C-reactive protein (CRP) and white blood cell count (WBC), shorter cervical length, and a cervical funnelling on ultrasound. We used ROC curves to determine the cut-off values that minimized the number of false positives and false negatives. The cut-off points chosen were 30 weeks for gestational age at admission, 25 mm for cervical length, 8 mg/l for CRP and 12,000 c/mm(3) for WBC. Each of these variables was assigned a weight on the basis of the adjusted odds ratios in a clinical infection risk score (CIRS). We set a threshold corresponding to a specificity close to 90%, and calculated the positive and negative predictive values and likelihood ratios of each marker and of the CIRS. The CIRS had a sensitivity of 61.9%, while the sensitivity of the other markers ranged from 19.0% to 42.9%. Internal cross-validation was used to estimate the performance of the CIRS in new subjects. The diagnostic values found remained close to the initial values. Conclusion: A clinical infection risk score built from data known at admission for preterm labour helps to identify women and newborns at high risk of clinical infection. [ABSTRACT FROM AUTHOR]

Background: Both infectious and noninfectious causes of maternal fever have been linked to adverse neonatal outcomes including low Apg0ar scores, respiratory distress, hypotonia, and neonatal seizures. Even in the absence of infection, the occurrence of intrapartum fever is a strong risk factor for poor long-term neonatal developmental outcomes, including encephalopathy, cerebral palsy, and neonatal death., Objective: The primary objective of this study was to compare intrapartum and postpartum maternal and fetal umbilical cord serum levels of cytokines RANTES, interferon-ɣ, interleukin-1β, interleukin-2, interleukin-4, interleukin-6, interleukin-8, interleukin-10, interleukin-13, and tumor necrosis factor-α among nonfebrile patients, febrile patients without clinical chorioamnionitis, and febrile patient with clinical chorioamnionitis., Study Design: This study was conducted at the Richmond University Medical Center from May 15, 2020 to July 16, 2019. During this time, we recruited 30 nonfebrile patients at >36 gestational weeks who were in labor and collected umbilical cord and pre- and postdelivery maternal serum samples to evaluate the cytokine levels. Placentas were collected for pathologic review and to evaluate the histopathologic findings. These results were compared with 121 patients who developed a fever of >38°C during labor. The febrile patients were further divided based on the presence or absence of clinical chorioamnionitis. A secondary analysis was performed based on the presence of absence of histologic chorioamnionitis. Statistical analysis was performed using IBM Statistical Package for the Social Sciences version 25.0. For the 3 group comparisons, a P value of <.017 was considered statistically significant after application of a Bonferroni correction., Results: A total of 151 patients were included in the study; 30 were nonfebrile patients, 46 were febrile patients with a diagnosis of clinical chorioamnionitis, and 75 were febrile patients without clinical chorioamnionitis. Compared with nonfebrile patients, umbilical cord serum interferon-ɣ, interleukin-1β, interleukin-6, interleukin-8, RANTES, and tumor necrosis factor-α levels were elevated in the presence of maternal hyperthermia irrespective of the diagnosis of clinical chorioamnionitis. Interleukin-6 umbilical cord levels were more than doubled from 63.60 pg/mL (6.09-1769.03 pg/mL) in febrile patients with no clinical chorioamnionitis to 135.77 pg/mL (1.86-6004.78 pg/mL) in febrile patients with clinical chorioamnionitis, making it the only cytokine that was significantly different between these 2 groups. When comparing the intrapartum maternal serum, we found a significant elevation in the interleukin-10, RANTES, and tumor necrosis factor-α levels in the febrile group irrespective of the presence of clinical chorioamnionitis when compared with the nonfebrile group. In the postpartum maternal blood evaluations, tumor necrosis factor-α was the only cytokine that was significantly higher in febrile patients than in nonfebrile controls., Conclusion: In the setting of intrapartum fever, maternal cytokine profiles were similar irrespective of the diagnosis of clinical chorioamnionitis. Even in the absence of clinical or histologic chorioamnionitis, maternal hyperthermia induced elevations in fetal cytokines., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Clinical chorioamnionitis is associated with significant maternal and neonatal morbidity, yet there is no clear evidence on the association between cervical examinations and infection., Objective: We sought to assess the association between the number of cervical examinations performed during term labor management and the risk of clinical chorioamnionitis., Study Design: This is a retrospective cohort study of term (≥37 weeks of gestation), singleton pregnancies who labored at our tertiary care center from 2014 to 2018. The primary outcome of clinical chorioamnionitis was defined as maternal intrapartum fever (single oral temperature of >39°C or 38°C-38.9°C for 30 minutes) and 1 or more of the following: maternal leukocytosis, purulent cervical drainage, or fetal tachycardia. The primary exposure was the number of digital cervical exams documented in the medical record. Log-binomial regression was used to model the effect of cervical examinations on the risk of clinical chorioamnionitis while adjusting for potential confounders., Results: A total of 20,029 individuals met the inclusion criteria and 1028 (5%) patients experienced clinical chorioamnionitis. The number of cervical exams was associated with increased risk of developing infection after adjusting for potential confounders. Individuals with ≥8 cervical exams had 1.7 times the risk of developing clinical chorioamnionitis compared with those with 1 to 3 exams. Prolonged rupture time, nulliparity, Black race, Medicaid insurance, higher gestational age, and higher body mass index were associated with increased risk of clinical chorioamnionitis, whereas smoking and group B Streptococcus colonization were associated with a lower risk., Conclusion: Our study found that the number of cervical exams performed during labor is an independent risk factor for developing clinical chorioamnionitis. Unnecessary cervical exams should be avoided during labor management at term., (Copyright © 2021 Elsevier Inc. All rights reserved.)