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American Journal of Obstetrics and... May 2023Intrapartum 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... (Review)
Review
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.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Cohort Studies; Oxytocin; Postpartum Hemorrhage; Labor, Obstetric; Anti-Bacterial Agents; Randomized Controlled Trials as Topic
PubMed: 36997396
DOI: 10.1016/j.ajog.2022.11.002 -
American Journal of Obstetrics and... Sep 2022The 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...
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.
Topics: Cohort Studies; Female; Fever; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Meconium Aspiration Syndrome; Pregnancy; Prospective Studies; Retrospective Studies
PubMed: 35598690
DOI: 10.1016/j.ajog.2022.05.031 -
Journal of Clinical Medicine May 2023Maternal intrapartum fever can lead to various maternal and neonatal complications and is attributed to various etiologies including infectious and non-infectious...
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 ( < 0.05 for all). The total number of infectious-related hospitalizations was significantly higher (30.1% vs. 24.1%; OR = 1.36; = 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, = 0.016). To conclude, fever diagnosed close to delivery may influence offspring susceptibility to pediatric infections.
PubMed: 37176769
DOI: 10.3390/jcm12093329 -
Ceska Gynekologie 2021Epidural analgesia (EPA) is the most effective method of intrapartum pain relief and is considered to be very safe. Recently, it has been used in up to 34% of...
Epidural analgesia (EPA) is the most effective method of intrapartum pain relief and is considered to be very safe. Recently, it has been used in up to 34% of parturients with EPA and is also associated with maternal temperature elevations during labor. The mechanism of this epidural-associated fever remains incompletely understood. The most likely etiology seems to be non-infectious inflammation caused by an epidural catheter. However, some authors deny this association. They theorize it is caused by selection bias only, as EPA is more often required by women with more painful and prolonged or more complicated labor, where temperature elevation is due to other causes. They point out that in some studies, fever was correlated to EPA only with concurrent placental inflammation. Maternal fever, despite the cause, either infectious or non-infectious origin, carries important clinical and public health implications. Further research that evaluates maternal epidural status and its influence on maternal or neonatal fever could improve sepsis evaluation and lead to worldwide decrease of unnecessary antibio-tic exposure.
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Female; Fever; Humans; Infant, Newborn; Labor, Obstetric; Parturition; Placenta; Pregnancy
PubMed: 34736336
DOI: 10.48095/cccg2021355 -
American Journal of Obstetrics and... Dec 2020This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an... (Review)
Review
This review aimed to examine the existing evidence about interventions proposed for the treatment of clinical chorioamnionitis, with the goal of developing an evidence-based contemporary approach for the management of this condition. Most trials that assessed the use of antibiotics in clinical chorioamnionitis included patients with a gestational age of ≥34 weeks and in labor. The first-line antimicrobial regimen for the treatment of clinical chorioamnionitis is ampicillin combined with gentamicin, which should be initiated during the intrapartum period. In the event of a cesarean delivery, patients should receive clindamycin at the time of umbilical cord clamping. The administration of additional antibiotic therapy does not appear to be necessary after vaginal or cesarean delivery. However, if postdelivery antibiotics are prescribed, there is support for the administration of an additional dose. Patients can receive antipyretic agents, mainly acetaminophen, even though there is no clear evidence of their benefits. Current evidence suggests that the administration of antenatal corticosteroids for fetal lung maturation and of magnesium sulfate for fetal neuroprotection to patients with clinical chorioamnionitis between 24 0/7 and 33 6/7 weeks of gestation, and possibly between 23 0/7 and 23 6/7 weeks of gestation, has an overall beneficial effect on the infant. However, delivery should not be delayed to complete the full course of corticosteroids and magnesium sulfate. Once the diagnosis of clinical chorioamnionitis has been established, delivery should be considered, regardless of the gestational age. Vaginal delivery is the safer option and cesarean delivery should be reserved for standard obstetrical indications. The time interval between the diagnosis of clinical chorioamnionitis and delivery is not related to most adverse maternal and neonatal outcomes. Patients may require a higher dose of oxytocin to achieve adequate uterine activity or greater uterine activity to effect a given change in cervical dilation. The benefit of using continuous electronic fetal heart rate monitoring in these patients is unclear. We identified the following promising interventions for the management of clinical chorioamnionitis: (1) an antibiotic regimen including ceftriaxone, clarithromycin, and metronidazole that provides coverage against the most commonly identified microorganisms in patients with clinical chorioamnionitis; (2) vaginal cleansing with antiseptic solutions before cesarean delivery with the aim of decreasing the risk of endometritis and, possibly, postoperative wound infection; and (3) antenatal administration of N-acetylcysteine, an antioxidant and antiinflammatory agent, to reduce neonatal morbidity and mortality. Well-powered randomized controlled trials are needed to assess these interventions in patients with clinical chorioamnionitis.
Topics: Acetylcysteine; Adrenal Cortex Hormones; Ampicillin; Anti-Bacterial Agents; Anti-Infective Agents, Local; Antioxidants; Antipyretics; Ceftriaxone; Cesarean Section; Chorioamnionitis; Clarithromycin; Clindamycin; Delivery, Obstetric; Endometritis; Evidence-Based Medicine; Female; Gentamicins; Gestational Age; Humans; Magnesium Sulfate; Metronidazole; Practice Guidelines as Topic; Pregnancy; Puerperal Infection; Tocolytic Agents
PubMed: 33007269
DOI: 10.1016/j.ajog.2020.09.044 -
PeerJ 2022Intrapartum fever is a well-known predisposing factor for severe perinatal outcomes. Herein, we explored the intrapartum features, obstetric outcomes, and neonatal...
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 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 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 ( < 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.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Retrospective Studies; Neonatal Sepsis; Chorioamnionitis; Pregnancy Trimester, Third; Fever
PubMed: 36320562
DOI: 10.7717/peerj.14242 -
JAMA Mar 2023Neonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
Neonatal sepsis is a leading cause of neonatal mortality. New interventions are needed to decrease neonatal sepsis and mortality in regions with highest burden.
OBJECTIVE
To evaluate the efficacy of intrapartum azithromycin to reduce neonatal sepsis or mortality, as well as neonatal and maternal infections.
DESIGN, SETTING, AND PARTICIPANTS
This double-blind, placebo-controlled, randomized clinical trial enrolled and followed up birthing parents and their infants at 10 health facilities in The Gambia and Burkina Faso, West Africa, between October 2017 and May 2021.
INTERVENTIONS
Participants were assigned at random to receive oral azithromycin (2 g) or placebo (ratio 1:1) during labor.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of neonatal sepsis or mortality, with the former defined based on microbiologic or clinical criteria. Secondary outcomes were neonatal infections (skin, umbilical, eye and ear infections), malaria, and fever; postpartum infections (puerperal sepsis, mastitis), fever, and malaria; and use of antibiotics during 4-week follow-up.
RESULTS
The trial randomized 11 983 persons in labor (median age, 29.9 years). Overall, 225 newborns (1.9% of 11 783 live births) met the primary end point. The incidence of neonatal mortality or sepsis was similar in the azithromycin and placebo groups (2.0% [115/5889] vs 1.9% [110/5894]; risk difference [RD], 0.09 [95% CI, -0.39 to 0.57]), as was the incidence of neonatal mortality (0.8% vs 0.8%; RD, 0.04 [95% CI, -0.27 to 0.35]) and neonatal sepsis (1.3% vs 1.3%; RD, 0.02 [95% CI, -0.38 to 0.43]). Newborns in the azithromycin group compared with the placebo group had lower incidence of skin infections (0.8% vs 1.7%; RD, -0.90 [95% CI, -1.30 to -0.49]) and need for antibiotics (6.2% vs 7.8%; RD, -1.58 [95% CI, -2.49 to -0.67]). Postpartum parents in the azithromycin group had lower incidence of mastitis (0.3% vs 0.5%; RD, -0.24 [95% CI, -0.47 to -0.01]) and puerperal fever (0.1% vs 0.3%; RD, -0.19 [95% CI, -0.36 to -0.01]).
CONCLUSIONS AND RELEVANCE
Azithromycin administered orally during labor did not reduce neonatal sepsis or mortality. These results do not support routine introduction of oral intrapartum azithromycin for this purpose.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03199547.
Topics: Adult; Female; Humans; Infant, Newborn; Pregnancy; Anti-Bacterial Agents; Azithromycin; Labor, Obstetric; Neonatal Sepsis; Double-Blind Method; Administration, Oral; Postpartum Period
PubMed: 36881034
DOI: 10.1001/jama.2022.24388 -
Obstetrical & Gynecological Survey Mar 2012Intrauterine infection is a serious complication during labor at term and is associated with adverse neonatal outcome. Early and accurate diagnosis is of great concern... (Review)
Review
UNLABELLED
Intrauterine infection is a serious complication during labor at term and is associated with adverse neonatal outcome. Early and accurate diagnosis is of great concern for both obstetrician and pediatrician with the use of current diagnostics. Clinical symptoms are often regarded as the main sign of intrauterine infection but this approach is highly unreliable and leads to both under- and overtreatment. Currently, no distinct fetal heart rate (FHR) patterns have been found that reliably identify neonates with intrauterine infection. Using a systematic literature search, this article reviews possible markers for the early detection of intrauterine or neonatal infection in maternal serum, amniotic fluid, and umbilical cord blood during labor at term. Maternal serum markers, with the possible exception of interleukin (IL)-8, are unreliable for the detection of intrauterine infection. In contrast, amniotic fluid levels of especially IL-6 and IL-8 are significantly associated with intrauterine infection. Umbilical cord blood IL-6 has been extensively investigated and is usually elevated in case of intrauterine or neonatal infection but shows only modest positive and negative predictive values (NPVs) for clinical use. Umbilical cord IL-8 concentration could be a valuable addition in the diagnostic process, as it has shown to have an NPV of 84% to 92% in the detection of neonatal infection and histological chorioamnionitis. Future research is essential and should focus on the combination of different markers and on the development of a prediction model, to improve the positive and NPVs of our arsenal to detect intrauterine and neonatal infections. Amniotic fluid and umbilical cord values of IL-6 and IL-8 levels are likely candidates for such a prediction model.
TARGET AUDIENCE
Obstetricians & Gynecologists and Family Physicians
LEARNING OBJECTIVES
After the completing the CME activity, physicians should be better able to evaluate the use of clinical chorioamnionitis with regard to histological evidence and as a diagnostic tool in early diagnosis of intra-amniotic infection. Asses the use of amniotic fluid IL-6 and IL-8 as diagnostic tools to detect early intra-amniotic infection and assess umbilical cord blood IL-8 in case of intrauterine- or neonatal infection using positive (PPV) and negative predictive values (NPV).
Topics: Amniotic Fluid; Biomarkers; Chorioamnionitis; Female; Fetal Blood; Fetal Diseases; Fever; Humans; Infant, Newborn; Interleukin-6; Interleukin-8; Labor, Obstetric; Pregnancy; Pregnancy Complications, Infectious; Risk Factors
PubMed: 22901952
DOI: 10.1097/OGX.0b013e31824bb5f1 -
Journal of Clinical Anesthesia Sep 2022To assess whether pulse perfusion index (PI) values could be employed to predict intrapartum fever and to provide a cut-off PI value for predicting intrapartum fever... (Observational Study)
Observational Study
STUDY OBJECTIVE
To assess whether pulse perfusion index (PI) values could be employed to predict intrapartum fever and to provide a cut-off PI value for predicting intrapartum fever occurrence.
DESIGN
We conducted a single-center, prospective, observational study.
SETTING
Delivery room at the Department of Obstetrics, Affiliated Hospital of Jiangsu University.
PATIENTS
117 parturients who intended to have a vaginal delivery.
INTERVENTIONS
Each parturient received epidural analgesia.
MEASUREMENTS
We checked each parturient's tympanic temperature before analgesia (T), at 1 h (T) and 2 h (T) after analgesia, immediately at the end of the second (T) and third (T) stages of labor, and at 1 h postpartum (T). A temperature of ≥38°C was defined as fever. PI, measured on the right second toe, was recorded before analgesia (PI) and at 10 min (PI), 20 min (PI), and 30 min (PI) after analgesia. The PI change rate was calculated as the incremental change in PI from PI, divided by the PI. Receiver operating characteristic (ROC) curves were used to verify the utility of the PI and PI change rate values for predicting intrapartum fever.
MAIN RESULTS
We found that peak temperature (T) occurred at the end of the second or the third stage of labor. Within 30 min after analgesia, the PI showed a significant increase over time and there was a linear correlation between PI and T values (P < 0.001, r = 0.544). The PI, PI, PI and PI change rate in febrile parturients were higher than those in afebrile parturients (P < 0.001). The area under the ROC (AUROC) for PI was 0.818 (P < 0.001) with a cut-off of 9.30. The AUROC of the PI change rate was 0.738 (P < 0.001) with a cut-off of 3.45.
CONCLUSIONS
PI and PI change rate values could be used to predict intrapartum fever in parturients after epidural analgesia.
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Female; Fever; Humans; Labor, Obstetric; Perfusion Index; Pregnancy; Prospective Studies
PubMed: 35489302
DOI: 10.1016/j.jclinane.2022.110852 -
The Journal of Obstetrics and... Mar 2021Previous 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...
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 37 to 41 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.
Topics: Analgesia, Epidural; Analgesia, Obstetrical; Female; Fever; Humans; Infant, Newborn; Obstetric Labor Complications; Placenta; Pregnancy; Retrospective Studies
PubMed: 33438353
DOI: 10.1111/jog.14651