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.

Effects of epidural analgesia on intrapartum maternal fever and maternal outcomes: an updated systematic review and meta-analysis.

OBJECTIVE: Epidural-related maternal fever in women is a common clinical phenomenon that leads to adverse consequences for mothers and neonates. The meta-analysis aimed to quantify the risk for intrapartum maternal fever after epidural analgesia (EA) stratified according to parity. The secondary objective was to investigate the association between EA and maternal outcomes. METHODS: An electronic literature search of the Medline/PubMed, Embase, Cochrane Library, Wanfang Data, and China National Knowledge Infrastructure databases was performed to identify studies reporting the occurrence of intrapartum fever in parturients. Studies were reviewed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and meta-analysis was performed using Review Manager version 5.3. RESULTS: Seventeen randomized controlled trials (RCTs) (5959 parturients) were included. Odds ratios for maternal fever in the analysis were 4.17 (95% confidence interval (CI) 2.93-5.94) and 5.83 (95% CI 4.96-6.87), respectively. Results of subgroup analysis according to parity were consistent. EA significantly prolonged the length of the first stage of labor (MD 34.52 [95% CI 12.13-56.91]) and the second stage of labor (MD 9.10 [95% CI 4.51-13.68]). Parturients who received EA were more likely to undergo instrumental delivery (OR 2.03 [95% CI 1.44-2.86]) and oxytocin augmentation (OR 1.45 [95% CI 1.12-1.88]). There were no differences in cesarean delivery rates between the EA and non-EA groups. CONCLUSIONS: Parturients who received EA exhibited a higher incidence of intrapartum fever. Credibility of the subgroup analyses was low because the mixed group did not effectively represent multiparas.

Fever in childbirth: a mini-review of epidural-related maternal fever.

Fever during childbirth, which is often observed in clinical settings, is characterized by a temperature of 38°C or higher, and can occur due to infectious and non-infectious causes. A significant proportion of non-infectious causes are associated with epidural-related maternal fever during vaginal delivery. Therapeutic interventions are required because fever has adverse effects on both mother and newborn. Effective treatment options for ERMF are lacking. As it is difficult to distinguish it from intrauterine infections such as chorioamnionitis, antibiotic administration remains the only viable option. We mentioned the importance of interleukin-1 receptor antagonist in the sterile inflammatory fever pathway and the hormonal influence on temperature regulation during childbirth, an important factor in elucidating the pathophysiology of ERMF. This review spotlighted the etiology and management of ERMF, underscoring recent advancements in our understanding of hypothalamic involvement in thermoregulation and its link to sterile inflammation. We propose to deepen the understanding of ERMF within the broader context of autonomic neuroscience, aiming to foster the development of targeted therapies.

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.

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.

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.

Effects of neuraxial labor analgesia on intrapartum maternal fever in full-term pregnancy and its influence on birth outcomes.

Introduction: This study aimed to explore the relationship between neuraxial labor analgesia and intrapartum fever and to demonstrate the influence of maternal fever on perinatal outcomes within 6 weeks after birth. Methods: This was a secondary analysis of a multicenter prospective cohort study that enrolled women with single- and full-term cephalic pregnancy in northern China. Intrapartum maternal fever was defined as the highest axillary temperature during labor ≥37.5°C. Data on baseline characteristics, maternal variables, and neonatal outcomes were all collected. The association between neuraxial labor analgesia and intrapartum maternal fever was analyzed with logistic regression models, and the cutoff point was identified by the receiver operating characteristic curve. Results: Of 577 parturients, 74 (12.8%) developed intrapartum fever. Neuraxial analgesia was associated with an increased risk of maternal intrapartum fever with or without adjusting for confounding factors (adjusted OR = 2.68; 95% CI: 1.32-5.47; p = 0.007). Further analysis showed that neuraxial analgesia of <5 h did not increase the risk of intrapartum fever compared with no analgesia (OR = 1.52; 95% CI: 0.63-3.64; p = 0.35), and longer neuraxial labor analgesia time (over 5 h) significantly increased the risk of fever (OR = 3.38; 95% CI: 1.63-7.01; p = 0.001). Parturients with intrapartum fever suffered more maternal adverse outcomes compared with those without fever (p < 0.001). Neonates of women with intrapartum fever had slightly higher rates of composite adverse neonatal outcomes compared with those without fever; however, the difference was not statistically significant (p = 0.098). Conclusion: In women with low-risk pregnancies, a longer time of neuraxial labor analgesia was associated with an increased risk of intrapartum maternal fever. Intrapartum fever was related to adverse maternal outcomes but did not significantly affect neonatal outcomes within 6 weeks after delivery.

Prediction of intrapartum fever using continuously monitored vital signs and heart rate variability.

Objectives: Neonatal early onset sepsis (EOS), bacterial infection during the first seven days of life, is difficult to diagnose because presenting signs are non-specific, but early diagnosis before birth can direct life-saving treatment for mother and baby. Specifically, maternal fever during labor from placental infection is the strongest predictor of EOS. Alterations in maternal heart rate variability (HRV) may precede development of intrapartum fever, enabling incipient EOS detection. The objective of this work was to build a predictive model for intrapartum fever. Methods: Continuously measured temperature, heart rate, and beat-to-beat RR intervals were obtained from wireless sensors on women (n = 141) in labor; traditional manual vital signs were taken every 3-6 hours. Validated measures of HRV were calculated in moving 5-minute windows of RR intervals: standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD) between normal heartbeats. Results: Fever (>38.0 °C) was detected by manual or continuous measurements in 48 women. Compared to afebrile mothers, average SDNN and RMSSD in febrile mothers decreased significantly (p < 0.001) at 2 and 3 hours before fever onset, respectively. This observed HRV divergence and raw recorded vitals were applied to a logistic regression model at various time horizons, up to 4-5 hours before fever onset. Model performance increased with decreasing time horizons, and a model built using continuous vital signs as input variables consistently outperformed a model built from episodic vital signs. Conclusions: HRV-based predictive models could identify mothers at risk for fever and infants at risk for EOS, guiding maternal antibiotic prophylaxis and neonatal monitoring.

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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.

Intrapartum Maternal Fever and Long-Term Infectious Morbidity of the Offspring.

Maternal intrapartum fever can lead to various maternal and neonatal complications and is attributed to various etiologies including infectious and non-infectious processes. In this study, we evaluated whether intrapartum fever affects the offspring's tendency to long-term infectious morbidity. A population-based cohort analysis including deliveries between 1991 and 2021 was conducted. The incidence of hospitalizations of the offspring up to the age of 18 years, due to various infectious conditions, was compared between pregnancies complicated by intrapartum fever and those that were not. A Kaplan-Meier survival curve was used to assess cumulative hospitalization incidence. A Cox proportional hazards model was used to control for confounders. Overall, 538 of the 356,356 included pregnancies were complicated with fever. A higher rate of pediatric hospitalizations due to various infectious conditions was found among the exposed group, which was significant for viral, fungal and ENT infections (p < 0.05 for all). The total number of infectious-related hospitalizations was significantly higher (30.1% vs. 24.1%; OR = 1.36; p = 0.001), as was the cumulative incidence of hospitalizations. This association remained significant after controlling for confounders using a Cox proportional hazards model (adjusted HR = 1.21; 95% CI 1.04-1.41, p = 0.016). To conclude, fever diagnosed close to delivery may influence offspring susceptibility to pediatric infections.

Single versus dual antibiotic regimen in women with term prolonged rupture of membranes and intrapartum fever: a retrospective study.

OBJECTIVES: The impact of E. coli in causing peripartum infections has been increasing due to rising ampicillin resistance. In this study, we compared maternal and neonatal outcomes of women with prolonged rupture of membranes (ROM >18h) and intrapartum fever, according to two antibiotic regimens they received, and describe the bacterial distribution focusing on risk factors for Enterobacteriaceae-related infectious morbidity. STUDY DESIGN: This 10-year retrospective study of women with ROM >18h and intrapartum fever included 62 women who were treated with ampicillin and gentamicin due to suspected intraamniotic infection and 79 without these signs who were treated with ampicillin alone. The primary outcomes were endometritis and neonatal early-onset sepsis (EOS) rates. Outcomes were compared using univariate and multivariate analyses. RESULTS: Among women who received ampicillin alone compared with dual therapy, rates were higher of endometritis (16.5% vs. 3.2%, p<0.001), neonatal early onset sepsis (7.5% vs. 0%, p=0.03), Enterobacteriaceae positive placental swab culture (67.9% vs. 15.7%, p<0.001), and histopathological subchorionitis (25.3% vs. 8.0%, p=0.008). Over 83% of Enterobacteriaceae isolates were ampicillin-resistant. Gestational age at delivery >41 weeks, meconium at delivery, ROM >24h and treatment with a single antibiotic agent were associated with the presence of a positive Enterobacteriaceae placental swab culture. CONCLUSION: Ampicillin compared to dual treatment in women with prolonged ROM and fever might promote the growth of ampicillin-resistant Enterobacteriaceae (including E.coli) and increase risks of maternal and neonatal infectious morbidity.

Risk factors for retained placenta in a first pregnancy-A clinical trial.

OBJECTIVE: To evaluate potential risk factors for retained placenta in a first pregnancy. METHOD: This retrospective case-control study included all primigravida with a singleton, live, vaginal birth at 24 weeks or later, at a tertiary hospital, 2014-2020. The cohort was divided into those with retained placenta versus controls. Retained placenta was defined as the need for manual extraction of the placenta or portions of it, immediately postpartum. Maternal and delivery characteristics, and obstetric and neonatal adverse outcomes, were compared between groups. Multivariable regression was performed to reveal potential risk factors for retained placenta. RESULTS: Among 10 796 women, 435 (4.0%) had retained placenta and 10 361 (96.0%) controls did not. Multivariable logistic regression revealed nine potential risk factors for retained placenta: abruption (adjusted odds ratio [aOR] 3.58, 95% confidence interval [CI] 2.36-5.43), hypertensive disorders (aOR 1.74, 95% CI 1.17-2.57), prematurity (<37 weeks, aOR 1.63, 95% CI 1.13-2.35), maternal age older than 30 years (aOR 1.55, 95% CI 1.27-1.90), intrapartum fever (aOR 1.48, 95% CI 1.03-2.11), lateral placentation (aOR 1.39, 95% CI 1.01-1.91), oxytocin administration (aOR 1.39, 95% CI 1.11-1.74), diabetes mellitus (aOR 1.35, 95% CI 1.01-1.79), and female fetus (aOR 1.26, 95% CI 1.03-1.53). CONCLUSION: Retained placentas in first deliveries are associated with obstetric risk factors, some of which could be related to abnormal placentation.

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.

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.

Retrospective study of intrapartum fever in term pregnancies and adverse obstetric and neonatal outcomes.

Background: Intrapartum fever is a well-known predisposing factor for severe perinatal outcomes. Herein, we explored the intrapartum features, obstetric outcomes, and neonatal outcomes in relation to the extent of intrapartum fever via three group analyses. Methods: A retrospective cohort analysis consisting of 575 term, singleton live births in one medical center from January 1st to December 31st, 2020 was carried out. Parturients who had experienced a maximal intrapartum fever of <38.0 °C were compared with two sub-groups of parturients who had experienced respective maximal fevers of 38.0-38.9 °C and ≥39.0 °C. We computed the adjusted risks for adverse perinatal outcomes via multiple logistic regression models to control for confounders. Results: There were statistically remarkable differences among the three groups in 13 items including body mass index, epidural, and WBC before delivery (p < 0.05). In contrast with intrapartum fevers of 37.5-37.9 °C, intrapartum fevers of 38.0-38.9 °C were linked to an elevated risk of neonatal sepsis and neonatal intensive care unit admission with an odds ratio (OR) of 4.28 (95% CI 2.162-8.479) and 1.73 (95% CI 1.125-2.666), nonetheless, the relationship was remarkably higher for intrapartum fever ≥39.0 °C, with an OR of 6.40 (95% CI 2.450-16.725) and 2.23 (95% CI 1.021-4.854). Additionally, intrapartum fevers of 38.0-38.9 °C and ≥39.0 °C were related to remarkably higher risk for operative deliveries (OR 2.24, 95% CI 1.373-3.648; OR 3.59, 95% CI 1.398-9.226; respectively) and histological chorioamnionitis (OR 3.77, 95% CI 2.261-6.271; OR 19.24, 95% CI 7.385-50.111, respectively). Conclusions: Intrapartum fever is an important indicator of adverse perinatal outcomes. The higher the temperature, the higher risk of histological chorioamnionitis, as well as the risk of neonatal sepsis and neonatal intensive care unit admission.

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.

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.

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.

Fetal and maternal inflammatory response in the setting of maternal intrapartum fever with and without clinical and histologic chorioamnionitis.

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-É£, interleukin-1ß, 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-É£, interleukin-1ß, 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.