Clinical chorioamnionitis at term: definition, pathogenesis, microbiology, diagnosis, and treatment.

Clinical chorioamnionitis, the most common infection-related diagnosis in labor and delivery units, is an antecedent of puerperal infection and neonatal sepsis. The condition is suspected when intrapartum fever is associated with two other maternal and fetal signs of local or systemic inflammation (eg, maternal tachycardia, uterine tenderness, maternal leukocytosis, malodorous vaginal discharge or amniotic fluid, and fetal tachycardia). Clinical chorioamnionitis is a syndrome caused by intraamniotic infection, sterile intraamniotic inflammation (inflammation without bacteria), or systemic maternal inflammation induced by epidural analgesia. In cases of uncertainty, a definitive diagnosis can be made by analyzing amniotic fluid with methods to detect bacteria (Gram stain, culture, or microbial nucleic acid) and inflammation (white blood cell count, glucose concentration, interleukin-6, interleukin-8, matrix metalloproteinase-8). The most common microorganisms are Ureaplasma species, and polymicrobial infections occur in 70% of cases. The fetal attack rate is low, and the rate of positive neonatal blood cultures ranges between 0.2% and 4%. Intrapartum antibiotic administration is the standard treatment to reduce neonatal sepsis. Treatment with ampicillin and gentamicin have been recommended by professional societies, although other antibiotic regimens, eg, cephalosporins, have been used. Given the importance of Ureaplasma species as a cause of intraamniotic infection, consideration needs to be given to the administration of antimicrobial agents effective against these microorganisms such as azithromycin or clarithromycin. We have used the combination of ceftriaxone, clarithromycin, and metronidazole, which has been shown to eradicate intraamniotic infection with microbiologic studies. Routine testing of neonates born to affected mothers for genital mycoplasmas could improve the detection of neonatal sepsis. Clinical chorioamnionitis is associated with decreased uterine activity, failure to progress in labor, and postpartum hemorrhage; however, clinical chorioamnionitis by itself is not an indication for cesarean delivery. Oxytocin is often administered for labor augmentation, and it is prudent to have uterotonic agents at hand to manage postpartum hemorrhage. Infants born to mothers with clinical chorioamnionitis near term are at risk for early-onset neonatal sepsis and for long-term disability such as cerebral palsy. A frontier is the noninvasive assessment of amniotic fluid to diagnose intraamniotic inflammation with a transcervical amniotic fluid collector and a rapid bedside test for IL-8 for patients with ruptured membranes. This approach promises to improve diagnostic accuracy and to provide a basis for antimicrobial administration.

Effects of early- and late- neuraxial analgesia on multiparous women: a retrospective monocentric study.

BACKGROUND: The mechanism underlying maternal fever and prolonged labor progression associated with neuraxial analgesia (NA) remains elusive, raising concerns among certain pregnant women regarding the application of NA during vaginal delivery. This study aimed to investigate the impact of early and late NA on maternal and neonatal outcomes in multiparous women. METHODS: This retrospective study collected data from 1119 multiparous women with singleton pregnancies, full term and live births at our labor and delivery center between August 1st, 2021 and July 31st, 2022. Based on the timing of NA initiation, participants were categorized into three groups: no-NA, early-NA and late-NA. The no-NA group comprised of 172 women who did not receive NA during vaginal delivery; the early-NA group included 603 women in which NA was initiated when cervical dilation was between 0.5 and 2.0 cm; and the late-NA group comprising 344 cases in which NA was initiated at the cervical dilation of ≥ 2 cm. Maternal and neonatal outcomes were observed, including durations of the first, second, third and total stage of labor, the rate of intrapartum cesarean delivery (CD), intrapartum fever, postpartum hemorrhage (PPH), transfer to intensive care unit (ICU), admission to the neonatal intensive care unit (NICU), meconium-stained amniotic fluid, and neonatal Apgar scores at 1 and 5 min. RESULTS: No differences were noted in the maternal age, body mass index (BMI) on admission, gestations, parity, gestational weeks at delivery and neonatal birth weight, or the rate of gestational diabetes mellitus (GDM) and hypertension disorder did not significantly differ among the three groups (p > 0.05). The no-NA group had shorter durations of first stage, second stage of labor compared to the early-NA or late-NA group (median, 215.0 min and 10.0 min vs. 300.0 min and 12.0 min vs. 280.0 min and 13.0 min) (p < 0.05), but no differences were observed between the early-NA and late-NA group (p > 0.05). There were no differences in the rate of intrapartum CD, intrapartum fever, PPH, maternal transferred to ICU, neonatal transfer to NICU, meconium-stained amniotic fluid, and postpartum stay ≥ 7d, as well as the neonatal the Apgar scores at 1 and 5 min among the three groups (p > 0.05). CONCLUSION: NA is associated with extended durations of the first, second and total stages of labor. However, the early initiation of NA in multiparous women (cervical dilation within 0.5-2.0 cm) does not increase the risk of intrapartum CD or intrapartum fever. These findings endorse the secure utilization of early NA for pain relief during labor in multiparous women.

Intrapartum fever complicated with maternal bacteremia: prevalence, bacteriology, and risk factors.

PURPOSE: To assess the prevalence, microbial profile, and clinical risk factors of maternal bacteremia associated with intrapartum fever (IPF). METHODS: A retrospective cohort study, in a single tertiary university-affiliated medical center between 2012 and 2018. Demographic and labor characteristics of women, who delivered at term (37+0/7-41+6/7) and developed bacteremia following IPF were compared to a control group of women with IPF but without bacteremia. RESULTS: During the study period there were 86,590 deliveries in our center. Of them, 2074 women (2.4%) were diagnosed with IPF, of them, for 2052 women (98.93%) the blood maternal cultures were available. In 26 patients (1.25%) maternal bacteremia was diagnosed. A lower rate of epidural anesthesia (84.6% vs 95.9%, p = 0.02) and a higher rate of antibiotics prophylaxis treatment prior to the onset of fever (30.8%.vs 12.1%, p = 0.006) were observed in patients who developed maternal bacteremia in comparison to those who have not. Maternal hyperpyrexia developed after initiation of antibiotics or without epidural anesthesia remained significantly associated with maternal bacteremia after applying a multivariate analysis, (Odds Ratio 3.14 95% CI 1.27-7.14, p = 0.009; 4.76 95% CI 1.35-12.5, p = 0.006; respectively). CONCLUSION: Maternal fever developing after initiation of antibiotics or without epidural is associated with maternal bacteremia.

Adverse obstetric outcomes in cases of meconium-stained amniotic fluid complicated with intrapartum fever.

PURPOSE: Meconium-stained amniotic fluid (MSAF) often signifies colonization of the amniotic sac by microorganisms. This study investigated additional adverse obstetric outcomes associated with MSAF in deliveries complicated by maternal intrapartum fever (IF). METHODS: This retrospective study included all singleton pregnancies from 2014 to 2020, with intrapartum maternal fever ≥ 38 °C during a trial of labor. In accordance with departmental protocol, all patients received intravenous antibiotic therapy consisting of ampicillin and gentamicin in the absence of allergies to these medications. Subsequent antibiotic therapy was adjusted based on the culture results. Antibiotic treatment was discontinued postpartum after 48 h without fever. Swab cultures were obtained immediately postpartum from both the maternal and fetal sides of the placenta. Maternal and fetal outcomes, along with positive placental cultures, were compared between participants with MSAF&IF and those with clear amniotic fluid &IF (control group). RESULTS: In comparison to the control group (n = 1089), the MSAF&IF group (n = 264) exhibited significantly higher rates of cesarean delivery (CD) (p = 0.001), CD due to non-reassuring fetal heart rate (p = 0.001), and cord pH ≤ 7.1 (p = 0.004). Positive swab cultures from the placental maternal and fetal sides were more prevalent among the MSAF&IF group (23.1% vs. 17.6%, p = 0.041 and 29.2% vs. 22.9%, p = 0.032, respectively). Placental cultures yielding gastrointestinal pathogens and extended spectrum beta-lactamase were notably more common in the MSAF&IF group compared to controls (p = 0.023). However, there was no significant difference between groups regarding the rate of group B streptococcus positive placental cultures. CONCLUSIONS: Women experiencing IF and MSAF during labor face an elevated risk of CD compared to those with IF alone. The presence of MSAF heightens the risk of positive placental cultures, particularly with gastrointestinal and extended spectrum beta-lactamase pathogens.

Maternal intrapartum fever during epidural labour analgesia: Incidence and influencing factors.

BACKGROUND: The management and nursing care of women's temperature during delivery is an important part of clinical obstetrics. We aimed to evaluate maternal intrapartum fever during epidural labour analgesia to provide evidence for the management and care of women in labour. METHODS: This study was conducted and reported according to the STROBE statement. Women in labour undergoing epidural labour analgesia in our hospital from 1 January 2021 to 31 August 2022 were retrospectively selected. The characteristics of women in labour with and without intrapartum fever were compared. Pearson correlation and logistic regression analysis were used to analyse the influencing factors of postpartum fever. RESULTS: A total of 196 women in labour were included, the incidence of maternal intrapartum fever in women in labour undergoing epidural analgesia was 27.5%. Pearson correlation analyses showed that BMI, oxytocin use, labour duration, number of vaginal examinations, time from rupture of the foetal membranes to the end of labour and duration of epidural analgesia were all correlated with the occurrence of intrapartum fever (all P < 0.05). Logistic regression analyses indicated that body mass index ≥28 kg/m2 (OR = 1.825), oxytocin use (OR = 2.082), labour duration ≥9.2 h (OR = 2.613), number of vaginal examinations ≥8 (OR = 2.044-3.115), the time from rupture of the foetal membranes to the end of labour ≥250 min (OR = 2.766) and duration of epidural analgesia ≥300 min (OR = 3.106) were risk factors for intrapartum fever in women in labour undergoing epidural analgesia (all P < 0.05). CONCLUSIONS: Maternal intrapartum fever in women in labour undergoing epidural analgesia is common and influenced by many factors. Nurses should take early preventive care measures according to these factors during epidural analgesia in labour.

Epidural-related maternal fever: incidence, pathophysiology, outcomes, and management.

Epidural-related maternal fever affects 15% to 25% of patients who receive a labor epidural. Two meta-analyses demonstrated that epidural-related maternal fever is a clinical phenomenon, which is unlikely to be caused by selection bias. All commonly used neuraxial techniques, local anesthetics with or without opioids, and maintenance regimens are associated with epidural-related maternal fever, however, the impact of each component is unknown. Two major theories surrounding epidural-related maternal fever development have been proposed. First, labor epidural analgesia may lead to the development of hyperthermia through a sterile (noninfectious) inflammatory process. This process may involve reduced activation of caspase-1 (a protease involved in cell apoptosis and activation of proinflammatory pathways) secondary to bupivacaine, which impairs the release of the antipyrogenic cytokine, interleukin-1-receptor antagonist, from circulating leucocytes. Detailed mechanistic processes of epidural-related maternal fever remain to be determined. Second, thermoregulatory mechanisms secondary to neuraxial blockade have been proposed, which may also contribute to epidural-related maternal fever development. Currently, there is no prophylactic strategy that can safely prevent epidural-related maternal fever from occurring nor can it easily be distinguished clinically from other causes of intrapartum fever, such as chorioamnionitis. Because intrapartum fever (of any etiology) is associated with adverse outcomes for both the mother and baby, it is important that all parturients who develop intrapartum fever are investigated and treated appropriately, irrespective of labor epidural utilization. Institution of treatment with appropriate antimicrobial therapy is recommended if an infectious cause of fever is suspected. There is currently insufficient evidence to warrant a change in recommendations regarding provision of labor epidural analgesia and the benefits of good quality labor analgesia must continue to be reiterated to expectant mothers.

Maternal fever in labor: etiologies, consequences, and clinical management.

Intrapartum fever is common and presents diagnostic and treatment dilemmas for the clinician. True maternal sepsis is rare; only an estimated 1.4% of women with clinical chorioamnionitis at term develop severe sepsis. However, the combination of inflammation and hyperthermia adversely impacts uterine contractility and, in turn, increases the risk for cesarean delivery and postpartum hemorrhage by 2- to 3-fold. For the neonate, the rates of encephalopathy or the need for therapeutic hypothermia have been reported to be higher with a maternal fever >39°C when compared with a temperature of 38°C to 39°C (1.1 vs 4.4%; P<.01). In a large cohort study, the combination of intrapartum fever and fetal acidosis was particularly detrimental. This suggests that intrapartum fever may lower the threshold for fetal hypoxic brain injury. Because fetal hypoxia is often difficult to predict or prevent, every effort should be made to reduce the risk for intrapartum fever. The duration of exposure to epidural analgesia and the length of labor in unmedicated women remain significant risk factors for intrapartum fever. Therefore, paying careful attention to maintaining labor progress can potentially reduce the rates of intrapartum fever and the risk for cesarean delivery if fever does occur. A recent, double-blind randomized trial of nulliparas at >36 weeks' gestation demonstrated that a high-dose oxytocin regimen (6×6 mU/min) when compared with a low-dose oxytocin regimen (2×2 mU/min) led to clinically meaningful reductions in the rate of intrapartum fever (10.4% vs 15.6%; risk rate, 0.67; 95% confidence interval, 0.48-0.92). When fever does occur, antibiotic treatment should be initiated promptly; acetaminophen may not be effective in reducing the maternal temperature. There is no evidence that reducing the duration of fetal exposure to intrapartum fever prevents known adverse neonatal outcomes. Therefore, intrapartum fever is not an indication for cesarean delivery to interrupt labor with the purpose of improving neonatal outcome. Finally, clinicians should be ready for the increased risk for postpartum hemorrhage and have uterotonic agents on hand at delivery to prevent delays in treatment.

Antibiotic treatment of women with isolated intrapartum fever vs clinical chorioamnionitis: maternal and neonatal outcomes.

BACKGROUND: Clinical chorioamnionitis refers to the presence of maternal fever (≥38°C) and at least 2 clinical signs: (1) maternal tachycardia (>100 bpm), (2) fetal tachycardia (>160 bpm), (3) maternal leukocytosis >15,000/mm2, (4) purulent vaginal discharge, and (5) uterine tenderness. Few data exist to guide the appropriate management of women with isolated intrapartum fever in the absence of other clinical signs suggesting chorioamnionitis. OBJECTIVE: This study compared maternal and neonatal infectious outcomes and microbiological outcomes between women with isolated intrapartum fever and women with clinical chorioamnionitis. STUDY DESIGN: This 10-year retrospective study included all the laboring women at our institution, at ≥34 weeks of gestation, with a singleton pregnancy and body temperature of ≥38.0°C, with or without other evidences of infection. According to our department protocol, women with isolated intrapartum fever received intravenous ampicillin, whereas women with clinical chorioamnionitis received intravenous ampicillin plus gentamicin. The primary outcome was puerperal endometritis, compared between women with isolated intrapartum fever (treated with ampicillin) and women with clinical chorioamnionitis (treated with ampicillin plus gentamicin). The secondary maternal outcomes consisted of (1) maternal clinical outcomes, such as cesarean delivery, surgical site infection, postpartum hemorrhage, and postpartum length of stay, and (2) microbiological studies, including positive chorioamniotic membrane swabs and blood culture. Among the secondary neonatal outcomes were early-onset sepsis, neonatal intensive care unit admission, and length of stay. Of note, 2 multivariate logistic regression models were created. A model aimed to predict puerperal endometritis controlled for gestational age of >41 weeks, diabetes mellitus, obesity, positive group B streptococcus status, rupture of membrane ≥18 hours, meconium staining, positive chorioamniotic membrane swabs, cesarean delivery, and empiric postdelivery antibiotic administration. A model aimed to predict neonatal early-onset sepsis controlled for gestational age of 34 to 37 weeks, positive group B streptococcus status, rupture of membrane ≥18 hours, and positive chorioamniotic membrane swabs. RESULTS: Overall, 458 women met the inclusion criteria. Compared with women with clinical chorioamnionitis (n=231), women with isolated intrapartum fever (n=227) had higher rates of puerperal endometritis (3.9% vs 8.8%; P=.03), early-onset sepsis (0.4% vs 4.4%; P=.005), positive chorioamniotic membrane swabs (46.3% vs 63.9%; P<.001), and ampicillin-resistant Escherichia coli (35.5% vs 48.9%; P=.033). The rate of group B streptococcus-positive chorioamniotic membrane swabs was similar between the groups. In a subanalysis of women with negative or unknown group B streptococcus status, the puerperal endometritis and neonatal early-onset sepsis rates were higher among women with isolated intrapartum fever than women with suspected chorioamnionitis (8.7% vs 3.3% [P=.041] and 4.1% vs 0% [P<.001], respectively). In 2 multivariate analysis models, among women with isolated intrapartum fever treated with ampicillin compared with those with clinical chorioamnionitis treated with ampicillin and gentamicin, the odds ratio of antibiotic treatment of endometritis was 2.65 (95% confidence interval, 1.06-6.62; P=.036), and the odds ratio of neonatal early-onset sepsis was 8.33 (95% confidence interval, 1.04-60.60; P=.045). CONCLUSION: Women with intrapartum fever, with or without other signs of infection, were at increased risk of maternal and neonatal complications. The use of ampicillin as a sole agent in isolated intrapartum fever might promote ampicillin-resistant E coli growth in the chorioamniotic membranes and consequently lead to puerperal endometritis and early-onset sepsis. In this context, a broad-range antibiotic should be considered.

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OBJECTIVES: To investigate influencing factors of intrapartum fever during vaginal delivery and to construct a prediction model for infectious intrapartum fever. METHODS: A total of 444 patients with intrapartum fever admitted in Ningbo Women and Children's Hospital from January 2020 to December 2021 were enrolled. The clinical data and laboratory findings were compared between patients with infectious intrapartum fever and non-infectious intrapartum fever, and the factors associated with intrapartum fever were analyzed with a multivariate logistic regression model. A prediction nomogram model was constructed based on the factors of intrapartum fever and its predictive efficiency was evaluated by correction curve and receiver operator characteristic curve. RESULTS: In the 444 cases, 182 (41.0%) had definite intrauterine infection and 262 (59.0%) had no infectious intrapartum fever. Univariate analysis showed that the length of hospital stay before induced labor, the time of induced abortion, misoprostol administration, autoimmune diseases, white blood cell count (WBC) and hypersensitive C-reactive protein (hs-CRP) levels were significantly different between the two groups (all P<0.05). Multivariate analysis showed that misoprostol administration and autoimmune diseases were protective factors (OR=0.31 and 0.36, both P<0.05) for infectious intrapartum fever, while high WBC and hs-CRP were risk factors (OR=1.20 and 1.09, both P<0.05). The area under the curve of nomogram model for predicting infectious intrapartum fever was 0.823, and the calibration curve validation showed that the predicted and measured values were in general agreement. CONCLUSIONS: Multiple factors cause intrapartum fever. The nomogram model constructed in this study has good predictive accuracy for infectious intrapartum fever.

Severity of intrapartum fever and neonatal outcomes.

BACKGROUND: The few studies that have addressed the relationship between severity of intrapartum fever and neonatal and maternal morbidity have had mixed results. The impact of the duration between reaching maximum intrapartum temperature and delivery on neonatal outcomes remains unknown. OBJECTIVE: To test the association of severity of intrapartum fever and duration from reaching maximum temperature to delivery with neonatal and maternal morbidity. STUDY DESIGN: This was a secondary analysis of a prospective cohort of term, singleton patients admitted for induction of labor or spontaneous labor who had intrapartum fever (≥38°C). Patients were divided into 3 groups according to maximum temperature during labor: afebrile (<38°C), mild fever (38°C-39°C), and severe fever (>39°C). The primary outcome was composite neonatal morbidity (umbilical artery pH <7.1, mechanical ventilation, respiratory distress, meconium aspiration with pulmonary hypertension, hypoglycemia, neonatal intensive care unit admission, and Apgar <7 at 5 minutes). Secondary outcomes were composite neonatal neurologic morbidity (hypoxic-ischemic encephalopathy, hypothermia treatment, and seizures) and composite maternal morbidity (postpartum hemorrhage, endometritis, and maternal packed red blood cell transfusion). Outcomes were compared between the maximum temperature groups using multivariable logistic regression. Cox proportional-hazards regression modeling accounted for the duration between reaching maximum intrapartum temperature and delivery. RESULTS: Of the 8132 patients included, 278 (3.4%) had a mild fever and 74 (0.9%) had a severe fever. The incidence of composite neonatal morbidity increased with intrapartum fever severity (afebrile 5.4% vs mild 18.0% vs severe 29.7%; P<.01). After adjusting for confounders, there were increased odds of composite neonatal morbidity with severe fever compared with mild fever (adjusted odds ratio, 1.93 [95% confidence interval, 1.07-3.48]). Severe fevers remained associated with composite neonatal morbidity compared with mild fevers after accounting for the duration between reaching maximum intrapartum temperature and delivery (adjusted hazard ratio, 2.05 [95% confidence interval, 1.23-3.43]). Composite neonatal neurologic morbidity and composite maternal morbidity were not different between patients with mild and patients with severe fevers. CONCLUSION: Composite neonatal morbidity correlated with intrapartum fever severity in a potentially dose-dependent fashion. This correlation was independent of the duration from reaching maximum intrapartum temperature to delivery, suggesting that clinical management of intrapartum fever, in terms of timing or mode of delivery, should not be affected by this duration.

Interventions for the prevention or treatment of epidural-related maternal fever: a systematic review and meta-analysis.

BACKGROUND: Epidural-related maternal fever in women in labour has consequences for the mother and neonate. There has been no systematic review of preventive strategies. METHODS: RCTs evaluating methods of preventing or treating epidural-related maternal fever in women in active labour were eligible. We searched MEDLINE, EMBASE, CINAHL, Web of Science, CENTRAL, and grey literature sources were searched from inception to April 2021. Two review authors independently undertook study selection. Data extraction and quality assessment was performed by a single author and checked by a second. The Cochrane Risk of Bias 2 tool was used. Meta-analyses for the primary outcome, incidence of intrapartum fever, were performed using the DerSimonian and Laird random effects model to produce summary risk ratios (RRs) with 95% confidence intervals (95% CIs). RESULTS: Forty-two records, representing 34 studies, were included. Methods of reduced dose epidural reduced the incidence of intrapartum fever, but this was not statistically significant when six trials at high risk of bias were removed (seven trials; 857 participants; RR=0.83; 95% CI, 0.41-1.67). Alternative methods of analgesia and high-dose prophylactic systemic steroids reduced the risk of intrapartum fever compared with epidural analgesia. Prophylactic paracetamol was not effective. CONCLUSIONS: There is no clear evidence to support the use of any individual preventative or therapeutic intervention for epidural-related maternal fever. Further research should focus on understanding the mechanism of fever development to enable RCTs of potential interventions to reduce the incidence of intrapartum fever development and the subsequent disease burden felt by the neonate. CLINICAL TRIAL REGISTRATION: CRD42021246929.

Study on perinatal-related factors of maternity and newborn in parturients with intrapartum fever in part of Eastern China: A cross-sectional study.

BACKGROUND: Maternal intrapartum fever has a serious impact on mother and child. However, the corresponding study seems to be in short. METHODS: The role of inflammatory cells in patients who were diagnosed with intrapartum fever lived in part of Eastern China was evaluated. The obstetrics outcomes, complete blood cell count (CBC) and thereby converted neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio, monocyte to lymphocyte ratio (MLR), and vaginal secretion were compared in different groups. RESULTS: Prepartum values of white blood cell (WBC), red blood cell (RBC), and hemoglobin (Hb) were all a little higher in the febrile group than in the afebrile group, and postpartum WBC in the afebrile group was still higher while postpartum RBC and Hb were inferior to non-fever maternity. Postpartum NLR and MLR were all higher in the fever group but not preferred overtly difference before delivery. Additionally, the comparison of WBC, RBC, Hb, platelets, neutrophils, and monocytes in prepartum and postpartum all showed significant differences. CONCLUSION: The parturition could bring about the value change of CBC and intrapartum fever might aggravate or alleviate this change. Besides, the intrapartum fever might not be caused mainly by infection and the difference between bacteria and fungus could reflect in the CBC.

Risk factors of maternal intrapartum fever and the effect of fever duration on neonatal morbidity in different temperature.

AIM: To investigate the clinical risk factors of intrapartum fever and explore the relationship between fever duration and neonatal morbidity of different fever peak. METHODS: A case-control study was conducted, and 714 pregnant women were divided into fever and nonfever group. Multivariable logistic regression model was estimated to evaluate the risk factors for maternal intrapartum fever. Receiver operating characteristic curve was adopted to explore the relationship between fever duration and fetal distress of different fever peak to find the cut-off point, then the neonatal outcomes of women with fever ≥38°C in two groups of different fever duration were compared. RESULTS: Epidural analgesia (odds ratio [OR]: 6.89, p < 0.001), longer time of membrane rupture (OR: 1.06, p < 0.001) and longer time of first stage of labor (OR: 1.04, p = 0.03) were considered as independent risk factors for maternal fever. For women with temperature <38°C, fever duration was not associated with fetal distress, whereas the women with temperature ≥38°C, fever duration longer than 93.5 min was a good predictor of fetal distress (Area under curve (AUC) = 0.82, p < 0.05). Further analysis showed that infants of women with fever peak ≥38°C and fever duration longer than 90 min had a higher rate of 1 min Apgar score <7 (15.5% vs. 2.2%, p = 0.03), assisted ventilation (29.6% vs. 11.1%, p = 0.02), and admission to neonatal ward (87.3% vs. 60.0%, p = 0.001). CONCLUSIONS: Epidural analgesia, longer time of membrane rupture, and longer time of first stage of labor were considered as independent risk factors for maternal intrapartum fever. For women with fever ≥38°C, controlling fever time less than 90 min might be helpful to reduce neonatal morbidity.

Nomogram for perinatal prediction of intrapartum fever: a retrospective case-control study.

OBJECTIVE: To explore the risk factors for intrapartum fever and to develop a nomogram to predict the incidence of intrapartum fever. METHODS: The general demographic characteristics and perinatal factors of 696 parturients who underwent vaginal birth at the Affiliated Hospital of Xuzhou Medical University from May 2019 to April 2020 were retrospectively analysed. Data was collected from May 2019 to October 2019 on 487 pregnant women who formed a training cohort. A multivariate logistic regression model was used to identify the independent risk factors associated with intrapartum fever during vaginal birth, and a nomogram was developed to predict the occurrence. To verify the nomogram, data was collected from January 2020 to April in 2020 from 209 pregnant women who formed a validation cohort. RESULTS: The incidence of intrapartum fever in the training cohort was found in 72 of the 487 parturients (14.8%), and the incidence of intrapartum fever in the validation cohort was 31 of the 209 parturients (14.8%). Multivariate logistic regression analysis showed that the following factors were significantly related to intrapartum fever: primiparas (odds ratio [OR] 2.43; 95% confidence interval [CI] 1.15-5.15), epidural labour analgesia (OR 2.89; 95% CI 1.23-6.82), premature rupture of membranes (OR 2.37; 95% CI 1.13-4.95), second stage of labour ≥ 120 min (OR 4.36; 95% CI 1.42-13.41), amniotic fluid pollution degree III (OR 10.39; 95% CI 3.30-32.73), and foetal weight ≥ 4000 g (OR 7.49; 95% CI 2.12-26.54). Based on clinical experience and previous studies, the duration of epidural labour analgesia also appeared to be a meaningful factor for intrapartum fever; therefore, these seven variables were used to develop a nomogram to predict intrapartum fever in parturients. The nomogram achieved a good area under the ROC curve of 0.86 and 0.81 in the training and in the validation cohorts, respectively. Additionally, the nomogram had a well-fitted calibration curve, which also showed excellent diagnostic performance. CONCLUSION: We constructed a model to predict the occurrence of fever during childbirth and developed an accessible nomogram to help doctors assess the risk of fever during childbirth. Such assessment may be helpful in implementing reasonable treatment measures. TRIAL REGISTRATION: Clinical Trial Registration: ( www.chictr.org.cn ChiCTR2000035593 ).

Clinical chorioamnionitis at term X: microbiology, clinical signs, placental pathology, and neonatal bacteremia - implications for clinical care.

OBJECTIVES: Clinical chorioamnionitis at term is considered the most common infection-related diagnosis in labor and delivery units worldwide. The syndrome affects 5-12% of all term pregnancies and is a leading cause of maternal morbidity and mortality as well as neonatal death and sepsis. The objectives of this study were to determine the (1) amniotic fluid microbiology using cultivation and molecular microbiologic techniques; (2) diagnostic accuracy of the clinical criteria used to identify patients with intra-amniotic infection; (3) relationship between acute inflammatory lesions of the placenta (maternal and fetal inflammatory responses) and amniotic fluid microbiology and inflammatory markers; and (4) frequency of neonatal bacteremia. METHODS: This retrospective cross-sectional study included 43 women with the diagnosis of clinical chorioamnionitis at term. The presence of microorganisms in the amniotic cavity was determined through the analysis of amniotic fluid samples by cultivation for aerobes, anaerobes, and genital mycoplasmas. A broad-range polymerase chain reaction coupled with electrospray ionization mass spectrometry was also used to detect bacteria, select viruses, and fungi. Intra-amniotic inflammation was defined as an elevated amniotic fluid interleukin-6 (IL-6) concentration ≥2.6 ng/mL. RESULTS: (1) Intra-amniotic infection (defined as the combination of microorganisms detected in amniotic fluid and an elevated IL-6 concentration) was present in 63% (27/43) of cases; (2) the most common microorganisms found in the amniotic fluid samples were Ureaplasma species, followed by Gardnerella vaginalis; (3) sterile intra-amniotic inflammation (elevated IL-6 in amniotic fluid but without detectable microorganisms) was present in 5% (2/43) of cases; (4) 26% of patients with the diagnosis of clinical chorioamnionitis had no evidence of intra-amniotic infection or intra-amniotic inflammation; (5) intra-amniotic infection was more common when the membranes were ruptured than when they were intact (78% [21/27] vs. 38% [6/16]; p=0.01); (6) the traditional criteria for the diagnosis of clinical chorioamnionitis had poor diagnostic performance in identifying proven intra-amniotic infection (overall accuracy, 40-58%); (7) neonatal bacteremia was diagnosed in 4.9% (2/41) of cases; and (8) a fetal inflammatory response defined as the presence of severe acute funisitis was observed in 33% (9/27) of cases. CONCLUSIONS: Clinical chorioamnionitis at term, a syndrome that can result from intra-amniotic infection, was diagnosed in approximately 63% of cases and sterile intra-amniotic inflammation in 5% of cases. However, a substantial number of patients had no evidence of intra-amniotic infection or intra-amniotic inflammation. Evidence of the fetal inflammatory response syndrome was frequently present, but microorganisms were detected in only 4.9% of cases based on cultures of aerobic and anaerobic bacteria in neonatal blood.

Degree of intrapartum fever and associated factors: Three group analysis of no fever, borderline and overt fever.

AIM: Previous studies analyzing intrapartum fever by dichotomization of fever just above 38.0°C or not may lead to overlook clinical significance of borderline fever. We aimed to investigate the maternal baseline and intrapartum characteristics, neonatal outcomes, and inflammatory placental pathology in relation to the degree of intrapartum fever by three group analysis. METHODS: We performed a retrospective analysis of consecutive singleton deliveries between 370/7 to 410/7 weeks divided into three groups based on the peak body temperature during labor: No fever (< 37.5°C), borderline fever (≥ 37.5°C and < 38.0°C), and overt fever (≥ 38.0°C). Maternal and intrapartum characteristics, neonatal outcomes, and inflammatory placental pathology were compared by trend analysis, intergroup difference analysis, and multivariable analysis. RESULTS: The degree of intrapartum fever was significantly associated with younger maternal age, nulliparity, longer duration of rupture of membrane, and epidural analgesia (p < 0.001). And the incidence of neonatal proven sepsis and mortality were not significantly different among the groups. The degree of intrapartum fever was associated with the stage of acute chorioamnionitis and funisitis (p < 0.001). Multivariate analysis revealed that the association with epidural analgesia was stronger in borderline fever than overt fever (adjusted odds ratio [95% confidence interval], borderline fever = 18.487 [11.447-29.857]; overt fever = 11.068 [4.874-25.133]) after controlling for maternal age, parity, induction or augmentation, duration of ROM, birth weight, and meconium staining. CONCLUSION: Our data support that both epidural analgesia and inflammation of the placenta may contribute to the development of intrapartum fever at term.

The correlation between the number of vaginal examinations during active labor and febrile morbidity, a retrospective cohort study.

BACKGROUND: The association between the number of vaginal examinations (VEs) performed during labor and the risk of infection is unclear. The literature regarding this issue is not consensual, and the available studies are relatively small. Therefore, we aimed to study the association between the number of VEs during labor, and maternal febrile morbidity, in a very large cohort. METHODS: This is a retrospective cohort study. All women who delivered vaginally ≥37 weeks, at our institute, between 2008 and 2017 were included. Patients who underwent cesarean delivery or who were treated with prophylactic antibiotics, or had a fever ≥38.0 °C prior to the first VE were excluded. Cases of intrauterine fetal death, known malformations, or missing data were excluded as well. The cohort was divided according to the number of VEs performed: up to 4 VEs (n = 9716), 5-6 VEs (n = 4624), 7-8 VEs (n = 2999), and 9 or more VEs (n = 4844). The rates of intrapartum febrile morbidity (intrapartum fever and chorioamnionitis), postpartum febrile morbidity (postpartum fever and endometritis), and peripartum febrile morbidity (any of the mentioned complications) were compared. RESULTS: Overall, 22,183 women were included in the study. On multivariate analysis, we found that performing 5 VEs or more during labor was independently associated with intrapartum febrile morbidity (5-6 VEs: aOR = 1.83, 95% CI (1.29-2.61), 7-8 VEs: aOR = 2.65 95% CI (1.87-3.76), 9 or more VEs aOR = 3.47 95% CI (2.44-4.92)), postpartum febrile morbidity (5-6 VEs: aOR = 1.29, 95% CI (1.09-1.86), 7-8 VEs: aOR = 1.94 95% CI (1.33-2.83), 9 or more VEs aOR = 1.91 95% CI (1.28-2.82)), and peripartum morbidity (5-6 VEs: aOR = 1.48, 95% CI (1.15-1.91), 7-8 VEs: aOR = 2.15 95% CI (1.66-2.78), 9 or more VEs: aOR = 2.57 95% CI (1.97-3.34)). CONCLUSION: The number of VEs performed during labor is directly correlated with febrile morbidity. Performing five or more VEs during labor is independently associated with febrile morbidity; For intrapartum and peripartum febrile morbidity the risk rises as more VEs are performed.

A cohort study of the impact of epidural analgesia on maternal and neonatal outcomes.

AIM: To explore the impact of epidural analgesia on maternal and neonatal outcomes, especially the relation between epidural analgesia and intrapartum fever. METHODS: A retrospective cohort study was conducted in a tertiary hospital for all deliveries from November 2017 to December 2017. A total of 506 women were divided into epidural and non-epidural group by whether to receive analgesia or not. Univariate and multivariate analyses were performed with P < 0.05 as significant. RESULTS: Epidural analgesia was associated with higher risk of maternal intrapartum fever (relative risk [RR] = 3.28, 95% confidence interval, 1.55-6.95), more intravenous use of antibiotics (36.66% vs 17.04%, P<0.001), longer time of second stage (58.55 ± 33.75 vs 47.39 ± 28.36 min，P = 0.001) and longer total duration of labor (790.32 ± 433.71 vs 461.33 ± 270.39 min，P<0.001), but had no influence on mode of delivery, the amount of post-partum hemorrhage or hospital stay after delivery and all the neonatal outcomes we studied. Further time effect analysis found that epidural analgesia less than 6 h did not increase the risk of intrapartum fever (RR = 1.73, P = 0.15), however, when epidural analgesia lasted over 6 h, it significantly increased the risk of fever (RR = 5.23, P<0.001) but did not increase more adverse outcomes. CONCLUSION: Having epidural anesthesia 6 h or more increases the risk of developing fever, but the prognosis of mothers and children is less affected.

Intrapartum cardiotocography patterns observed in suspected clinical and subclinical chorioamnionitis in term fetuses.

AIM: To evaluate the cardiotocography (CTG) features observed in suspected intrapartum chorioamnionitis in term fetuses according to the recently suggested criteria for the pathophysiological interpretation of the fetal heart rate and their correlation with perinatal outcomes. METHODS: Retrospective analysis of nonconsecutive CTG traces. 'CTG chorioamnionitis' was diagnosed either based on a persistent rise in the baseline for the given gestation or on a persistent increase in the baseline fetal heart rate during labor >10% without preceding CTG signs of hypoxia and in the absence of maternal pyrexia. Perinatal outcomes were compared among cases with no sign of chorioamnionitis, in those with only CTG features suspicious for chorioamnionitis and in those who developed clinical chorioamnionitis. RESULTS: Two thousand one hundred and five CTG traces were analyzed. Of these, 356 fulfilled the criteria for "CTG chorioamnionitis". Higher rates of Apgar <7 at 1 and 5 min (21.6% vs 9.0% and 9.8% vs 2.0%, respectively, P < 0.01 for both) and lower umbilical artery pH (7.14 ± 0.11 vs 7.19 ± 0.11, P < 0.01) and an over fivefold higher rate of neonatal intensive care unit admission (16.6% vs 2.9%, P < 0.01) were noted in the 'CTG chorioamnionitis' group. Differences in the incidence of abnormal CTG patterns were noted between cases who eventually had clinical evidence of chorioamnionitis (89/356) and those showing CTG features suspicious for chorioamnionitis in the absence of clinical evidence of chorioamnionitis (267/356). CONCLUSION: Intrapartum CTG features of suspected chorioamnionitis are associated with adverse perinatal outcomes.

Incidence of early-onset sepsis in infants born to women with clinical chorioamnionitis.

Objective To determine the frequency of sepsis and other adverse neonatal outcomes in women with a clinical diagnosis of chorioamnionitis. Methods We performed a secondary analysis of a multi-center placebo-controlled trial of vitamins C/E to prevent preeclampsia in low risk nulliparous women. Clinical chorioamnionitis was defined as either the "clinical diagnosis" of chorioamnionitis or antibiotic administration during labor because of an elevated temperature or uterine tenderness in the absence of another cause. Early-onset neonatal sepsis was categorized as "suspected" or "confirmed" based on a clinical diagnosis with negative or positive blood, urine or cerebral spinal fluid cultures, respectively, within 72 h of birth. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression. Results Data from 9391 mother-infant pairs were analyzed. The frequency of chorioamnionitis was 10.3%. Overall, 6.6% of the neonates were diagnosed with confirmed (0.2%) or suspected (6.4%) early-onset sepsis. Only 0.7% of infants born in the setting of chorioamnionitis had culture-proven early-onset sepsis versus 0.1% if chorioamnionitis was not present. Clinical chorioamnionitis was associated with both suspected [OR 4.01 (3.16-5.08)] and confirmed [OR 4.93 (1.65-14.74)] early-onset neonatal sepsis, a need for resuscitation within the first 30 min after birth [OR 2.10 (1.70-2.61)], respiratory distress [OR 3.14 (2.16-4.56)], 1 min Apgar score of ≤3 [OR 2.69 (2.01-3.60)] and 4-7 [OR 1.71 (1.43-2.04)] and 5 min Apgar score of 4-7 [OR 1.67 (1.17-2.37)] (vs. 8-10). Conclusion Clinical chorioamnionitis is common and is associated with neonatal morbidities. However, the vast majority of exposed infants (99.3%) do not have confirmed early-onset sepsis.