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BACKGROUND AND OBJECTIVE: Sotrovimab 500 mg administered by a single intravenous (IV) infusion has been granted special approval for emergency use in Japan for treatment of SARS-CoV-2 infection in adults and children aged ≥ 12 years weighing ≥ 40 kg. This Phase 1, single-dose study investigated the pharmacokinetics, safety, and tolerability of IV or intramuscular (IM) sotrovimab 500 mg doses versus placebo in healthy Japanese and Caucasian volunteers. METHODS: This was a two-part, Phase 1, randomized, placebo-controlled, single-blind study. In Part 1, participants received a single sotrovimab 500 mg IV infusion or matching placebo on Day 1. In Part 2, participants received a single sotrovimab 500 mg IM dose or matching placebo on Day 1, administered as two 4 mL injections. RESULTS: There was no effect of ethnicity on the peak or total serum exposure of IV sotrovimab through Week 18; after adjusting for body weight, the point estimate and 90 % confidence interval for the ratio of total exposure between Japanese and Caucasian participants fell within conventional bioavailability bounds (80-125%). Geometric mean Cmax and AUClast following a single IM administration of sotrovimab were higher in Japanese participants compared with Caucasian participants, even after adjustment for body weight. Overall, a single IV or IM dose of sotrovimab was well tolerated by both Japanese and Caucasian participants. CONCLUSIONS: After adjusting for body weight, exposures following a single IV dose of sotrovimab 500 mg were similar between Japanese and Caucasian participants, and higher in Japanese participants following IM administration. Higher exposures were not associated with any safety signals. TRIAL REGISTRATION: ClinicalTrials.Gov: NCT04988152.
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Anticorpos Neutralizantes , COVID-19 , Adulto , Criança , Humanos , Japão/epidemiologia , Voluntários Saudáveis , Método Simples-Cego , SARS-CoV-2 , Anticorpos Monoclonais Humanizados/efeitos adversos , Peso Corporal , Método Duplo-CegoRESUMO
BACKGROUND: An intraoperative transfer of care from one anesthesia provider to another, or handover, may result in information loss and contribute to adverse patient outcomes. In 2019 the authors undertook a quality improvement effort to increase the use of a structured intraoperative handover tool incorporated in the electronic medical record. The authors hypothesized that intraoperative handovers of anesthesia care would be associated with adverse patient outcomes, and that increased use of a structured tool would attenuate this effect. METHODS: This study included adult patients undergoing noncardiac surgery of at least 1 h duration performed during the period 2016 to 2021. Cases with a handover were identified if either there was a change of attending anesthesiologist or change of nurse anesthetist or resident for more than 35 min. The primary outcome was the occurrence of a composite of postoperative mortality and major postoperative morbidity. The effect of the intervention was analyzed by examining the quarterly change in odds ratio for the primary outcome for cases with and without a handover. RESULTS: A total of 121,077 cases, 40.4% of which had a handover, were included. After weighting, the composite outcome was statistically associated with handovers (3,517 of 48,986 [7.2%] in handover cases vs. 4,470 of 72,091 [6.2%] in nonhandover cases; odds ratio, 1.08; 95% CI, 1.04 to 1.12). Time series analysis showed a marked increase in usage of the structured tool after the initial intervention. The odds ratio for the composite outcome showed a significant decrease over time after the initial intervention (t = -3.97; P < 0.001), with the slope of the odds ratio versus time curve decreasing from 0.002 (95% CI, 0.001 to 0.004; P = 0.018) to -0.011 (95% CI, -0.01 to -0.018; P < 0.001). CONCLUSIONS: Intraoperative handovers are significantly associated with adverse outcomes even after controlling for multiple confounding variables. Use of a structured handover tool during anesthesia care may attenuate the adverse effect.
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Anestesia , Anestesiologia , Transferência da Responsabilidade pelo Paciente , Adulto , Humanos , Melhoria de Qualidade , Estudos Retrospectivos , Anestesia/efeitos adversosRESUMO
Importance: Electronic frailty index (eFI) is an automated electronic health record (EHR)-based tool that uses a combination of clinical encounters, diagnosis codes, laboratory workups, medications, and Medicare annual wellness visit data as markers of frailty status. The association of eFI with postanesthesia adverse outcomes has not been evaluated. Objective: To examine the association of frailty, calculated as eFI at the time of the surgical procedure and categorized as fit, prefrail, or frail, with adverse events after elective noncardiac surgery. Design, Setting, and Participants: This cohort study was conducted at a tertiary care academic medical center in Winston-Salem, North Carolina. The cohort included patients 55 years or older who underwent noncardiac surgery of at least 1 hour in duration between October 1, 2017, and June 30, 2021. Exposure: Frailty calculated by the eFI tool. Preoperative eFI scores were calculated based on available data 1 day prior to the procedure and categorized as fit (eFI score: ≤0.10), prefrail (eFI score: >0.10 to ≤0.21), or frail (eFI score: >0.21). Main Outcomes and Measures: The primary outcome was a composite of the following 8 adverse component events: 90-item Patient Safety Indicators (PSI 90) score, hospital-acquired conditions, in-hospital mortality, 30-day mortality, 30-day readmission, 30-day emergency department visit after surgery, transfer to a skilled nursing facility after surgery, or unexpected intensive care unit admission after surgery. Secondary outcomes were each of the component events of the composite. Results: Of the 33â¯449 patients (median [IQR] age, 67 [61-74] years; 17 618 females [52.7%]) included, 11 563 (34.6%) were classified as fit, 15 928 (47.6%) as prefrail, and 5958 (17.8%) as frail. Using logistic regression models that were adjusted for age, sex, race and ethnicity, and comorbidity burden, patients with prefrail (odds ratio [OR], 1.24; 95% CI, 1.18-1.30; P < .001) and frail (OR, 1.71; 95% CI, 1.58-1.82; P < .001) statuses were more likely to experience postoperative adverse events compared with patients with a fit status. Subsequent adjustment for all other potential confounders or covariates did not alter this association. For every increase in eFI of 0.03 units, the odds of a composite of postoperative adverse events increased by 1.06 (95% CI, 1.03-1.13; P < .001). Conclusions and Relevance: This cohort study found that frailty, as measured by an automatically calculated index integrated within the EHR, was associated with increased risk of adverse events after noncardiac surgery. Deployment of eFI tools may support screening and possible risk modification, especially in patients who undergo high-risk surgery.
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Fragilidade , Estados Unidos , Feminino , Humanos , Idoso , Estudos de Coortes , Fragilidade/diagnóstico , Fragilidade/epidemiologia , Medicare , Centros Médicos Acadêmicos , EletrônicaRESUMO
Obstructive sleep apnea (OSA) is a prevalent disease affecting 10 to 15% of Americans and nearly one billion people worldwide. It leads to multiple symptoms including daytime sleepiness; snoring, choking, or gasping during sleep; fatigue; headaches; non-restorative sleep; and insomnia due to frequent arousals. Although polysomnography (PSG) is the gold standard for OSA diagnosis, it is expensive, not universally available, and time-consuming, so many patients go undiagnosed due to lack of access to the test. Given the incomplete access and high cost of PSG, many studies are seeking alternative diagnosis approaches based on different data modalities. Here, we propose a machine learning model to predict OSA severity from 2D frontal view craniofacial images. In a cross-validation study of 280 patients, our method achieves an average AUC of 0.780. In comparison, the craniofacial analysis model proposed by a recent study only achieves 0.638 AUC on our dataset. The proposed model also outperforms the widely used STOP-BANG OSA screening questionnaire, which achieves an AUC of 0.52 on our dataset. Our findings indicate that deep learning has the potential to significantly reduce the cost of OSA diagnosis.
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Background: Five hundred milligrams of intravenous (IV) sotrovimab has been shown to be well tolerated and efficacious against pre-Omicron strains in treating patients with mild to moderate coronavirus disease 2019 (COVID-19) at high risk for disease progression. Methods: This was an open-label, single-arm substudy of phase 3 COMET-TAIL (NCT04913675) assessing the safety and tolerability of a 2000 mg IV dose of sotrovimab. Symptomatic patients (aged ≥18 years) with COVID-19 at high risk for progression were enrolled from June 30 through July 11, 2022, when Omicron BA.5, BA.2.12.1, and BA.4 were the predominant circulating variants in the United States. The primary end point was the occurrence of adverse events (AEs), serious AEs (SAEs), AEs of special interest, and COVID-19 disease-related events (DREs) through day 8. Safety, pharmacokinetics, viral load, and hospitalization >24 hours for acute management of illness or death through day 29 were assessed. Results: All participants (n = 81) were Hispanic, 58% were female, and 51% were aged ≥55 years. Through day 8, no AEs, including infusion-related reactions or hypersensitivity, were reported; 2 participants reported DREs (mild cough, n = 2). One SAE (acute myocardial infarction), which was considered unrelated to sotrovimab or COVID-19 by the investigator, occurred on day 27 and was the only hospitalization reported. Maximum serum concentration (geometric mean) was 745.9â µg/mL. Viral load decreased from baseline through day 29; only 2 (3%) participants had a persistently high viral load (≥4.1 log10 copies/mL) at day 8. Conclusions: Two thousand milligrams of IV sotrovimab was well tolerated, with no safety signals observed. Trial registration: ClinicalTrials.gov Identifier: NCT04913675.
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BACKGROUND: Many students elect to take gap years in between graduating college and matriculating into medical school. At an academic institution, investigators can be limited in conducting research due to clinical endeavors. Utilizing a structured, clinical research, gap-year program with students called clinical research technicians (CRTs) can aid both investigators conducting research and students applying to graduate health programs. In this original article, we sought to understand CRT and investigator perceptions of and experiences in the program. METHODS: We distributed a survey to past and present CRTs and the investigators with whom they worked at Atrium Health Wake Forest Baptist Medical Center. We conducted thematic and sentiment analyses of the survey results. We also collected data on grant approvals, research funding awards, and CRT, clinical research nurse, and clinical research coordinator salaries. RESULTS: We received responses from 20/29 investigators and 21/22 CRTs. We identified five themes for the investigator survey, including research accuracy and precision; research output; alleviating responsibilities; cost; and likelihood of referral. We identified five themes for the CRT survey, including future career assistance; physician career insights; mentorship; likelihood of referral; and other. The majority of respondents strongly agreed or agreed with the survey statements. The majority of comments were coded as positive. All of CRTs were accepted into a graduate health profession program. CONCLUSIONS: Our program's success demonstrates how a structured, clinical research, gap-year program for premedical students can serve as a new educational tool and important research infrastructure resource for hospitals.
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STUDY OBJECTIVE: We sought to determine changes in continuous mean and systolic blood pressure and heart rate in a cohort of non-cardiac surgical patients recovering on the postoperative ward. Furthermore, we estimated the proportion of vital signs changes that would remain undetected with intermittent vital signs checks. DESIGN: Retrospective cohort. SETTING: Post-operative general ward. PATIENTS: 14,623 adults recovering from non-cardiac surgical procedures. INTERVENTIONS & MEASUREMENTS: Using a wireless, noninvasive monitor, we recorded postoperative blood pressure and heart rate at 15-s intervals and encouraged nursing intervention as clinically indicated. MAIN RESULTS: 7% of our cohort of 14,623 patients spent >15 sustained minutes with a MAP <65 mmHg, and 23% had MAP <75 mmHg for 15 sustained minutes. Hypertension was more common, with 67% of patients spending at least 60 sustained minutes with MAP >110 mmHg. Systolic pressures <90 mmHg were present for 15 sustained minutes in about a fifth of all patients, and 40% of patients had pressures >160 mmHg sustained for 30 min. 40% of patients were tachycardic with heart rates >100 beats/min for at least continuous 15 min and 15% of patients were bradycardic at a threshold of <50 beats/min for 5 sustained minutes. Conventional vital sign assessments at 4-h intervals would have missed 54% of mean pressure episodes <65 mmHg sustained >15 min, 20% of episodes of mean pressures >130 mmHg sustained >30 min, 36% of episodes of heart rate > 120 beats/min sustained <10 min, and 68% of episodes of heart rate sustained <40 beats per minute for >3 min. CONCLUSIONS: Substantial hemodynamic disturbances persisted despite implementing continuous portable ward monitoring coupled with nursing alarms and interventions. A significant proportion of these changes would have gone undetected using traditional intermittent monitoring. Better understanding of effective responses to alarms and appropriate interventions on hospital wards remains necessary.
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Hospitais , Sinais Vitais , Adulto , Humanos , Pressão Sanguínea , Frequência Cardíaca , Incidência , Estudos RetrospectivosRESUMO
This case report was written with the assistance of the large language model known as ChatGPT, a form of generative artificial intelligence that can write grammatically correct and semantically meaningful prose on a multitude of topics. Here, it has assisted us in presenting a case of anesthetic management for a case of Juvenile Hyaline Fibromatosis (JHF), an extremely rare genetic disorder that is part of a spectrum of diseases presently characterized as Hyaline Fibromatosis Syndrome (HFS), which also includes a more severe variant presenting in infancy. HFS is caused by autosomal recessive mutations in the ANTXR2 (anthrax toxin receptor cell adhesion molecule 2) gene, which binds collagen IV and laminin, suggesting that it may be involved in extracellular matrix adhesion. Defects in this molecule lead to abnormal deposition of hyaline material in perivascular areas, presenting as cutaneous lesions, joint contractures, and in some cases internal organ dysfunction. Anesthetic management of patients with JHF may present difficulties with patient positioning and airway management. Most reports of anesthetic management concern children with severe disease and adult reports are uncommon. We present a case of JHF in a 39-year-old woman managed for resection of a lower extremity cutaneous lesion. The anesthetic management of this relatively minor case was uneventful, but the process of drafting this report with the assistance of the new software tool ChatGPT was informative of both its strengths and limitations.
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STUDY OBJECTIVE: The hypothesis that the exclusive use of the commonly used vasopressor phenylephrine during the intraoperative period in noncardiac surgery is associated with postoperative acute kidney injury (AKI) was tested. DESIGN: A retrospective cohort analysis of 16,306 adults undergoing major noncardiac surgery who either did or did not receive phenylephrine was conducted. The primary outcome was the association of the use of phenylephrine with the risk of postoperative AKI defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. Logistic regression models with all independently associated potential confounders, and an exploratory model considering only patients with no untreated minutes of hypotension (post-phenylephrine in the exposed cohort, or entire case in the unexposed cohort) were used in the analysis. SETTING: The study was conducted in a tertiary care university hospital where a total of 8,221 patients were exposed to phenylephrine, and 8,085 were not. RESULTS: In unadjusted analysis, phenylephrine exposure was associated with an increased risk of AKI (OR 1.615, 95% CI [1.522-1.725], p < 0.001). In an adjusted model including several variables associated with AKI, phenylephrine remained associated with AKI (OR 1.325 [1.153-1.524]), as did post-phenylephrine exposure lengths of hypotension. Exclusion of patients with >1 min of post-phenylephrine exposure hypotension, also demonstrated that phenylephrine use was associated with AKI (OR 1.478, [1.245-1.753]). CONCLUSIONS: The exclusive use of intraoperative phenylephrine is associated with an increased risk of postoperative renal injury. Anesthesiologists must consider a balanced approach to correct hypotension under anesthesia, including judicious choices for fluids, inotropic support when indicated, and an appropriate adjustment of the plane of anesthesia.
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Injúria Renal Aguda , Hipotensão , Adulto , Humanos , Estudos Retrospectivos , Fenilefrina/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Hipotensão/tratamento farmacológico , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Fatores de RiscoRESUMO
BACKGROUND: Perioperative hyperglycemia is associated with adverse outcomes in surgical patients, and major societies recommend intraoperative monitoring and treatment targeting glucose <180-200 mg/dL. However, compliance with these recommendations is poor, in part due to fear of unrecognized hypoglycemia. Continuous Glucose Monitors (CGMs) measure interstitial glucose with a subcutaneous electrode and can display the results on a receiver or smartphone. Historically CGMs have not been utilized for surgical patients. We investigated the use of CGM in the perioperative setting compared to current standard practices. METHOD: This study evaluated the use of Abbott Freestyle Libre 2.0 and/or Dexcom G6 CGMs in a prospective cohort of 94 participants with diabetes mellitus undergoing surgery of ≥3 h duration. CGMs were placed preoperatively and compared to point of care (POC) BG checks obtained by capillary samples analyzed with a NOVA glucometer. Frequency of intraoperative blood glucose measurement was at the discretion of the anesthesia care team, with a recommendation of once per hour targeting BG of 140-180 mg/dL. Of those consented, 18 were excluded due to lost sensor data, surgery cancellation, or rescheduling to a satellite campus resulting in 76 enrolled subjects. There were zero occurrences of failure with sensor application. Paired POC BG and contemporaneous CGM readings were compared with Pearson product-moment correlation coefficients, and Bland-Altman plots. RESULTS: Data for use of CGM in perioperative period was analyzed for 50 participants with Freestyle Libre 2.0, 20 participants with Dexcom G6, and 6 participants with both devices worn simultaneously. Lost sensor data occurred in 3 participants (15%) wearing Dexcom G6, 10 participants wearing Freestyle Libre 2.0 (20%) and 2 of the participants wearing both devices simultaneously. The overall agreement of the two CGM's utilized had a Pearson correlation coefficient of 0.731 in combined groups with 0.573 in Dexcom arm evaluating 84 matched pairs and 0.771 in Libre arm with 239 matched pairs. Modified Bland-Altman plot of the difference of CGM and POC BG indicated for the overall dataset a bias of -18.27 (SD 32.10). CONCLUSIONS: Both Dexcom G6 and Freestyle Libre 2.0 CGMs were able to be utilized and functioned well if no sensor error occurred at time of initial warmup. CGM provided more glycemic data and further characterized glycemic trends more than individual BG readings. Required time of CGM warm up was a barrier for intraoperative use as well as unexplained sensor failure. CGMs had a fixed warm of time, 1 h for Libre 2.0 and 2 h for Dexcom G6 CGM, before glycemic data obtainable. Sensor application issues did not occur. It is anticipated that this technology could be used to improve glycemic control in the perioperative setting. Additional studies are needed to evaluate use intraoperatively and assess further if any interference from electrocautery or grounding devices may contribute to initial sensor failure. It may be beneficial in future studies to place CGM during preoperative clinic evaluation the week prior to surgery. Use of CGMs in these settings is feasible and warrants further evaluation of this technology on perioperative glycemic management.
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Diabetes Mellitus Tipo 1 , Hiperglicemia , Hipoglicemia , Humanos , Estudos Prospectivos , Estudos de Viabilidade , Glicemia , Hipoglicemia/diagnóstico , Hipoglicemia/etiologia , Hipoglicemia/prevenção & controle , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Hiperglicemia/prevenção & controleRESUMO
With the onset of the global coronavirus disease 2019 pandemic in early 2020, it became apparent that routine administration of the ABR Qualifying and Certifying Exams would be disrupted. Initial intent for postponement was later altered to a recognition that replacement of the existing delivery methodologies was essential. Herein, the authors describe the conceptualization, development, administration, and future implications of the new remote examination delivery platforms.
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COVID-19 , Internato e Residência , Radioterapia (Especialidade) , Certificação , Avaliação Educacional , Previsões , Humanos , Radioterapia (Especialidade)/educação , Conselhos de Especialidade Profissional , Estados UnidosRESUMO
Failure to identify difficult intubation is the leading cause of anesthesia-related death and morbidity. Despite preoperative airway assessment, 75-93% of difficult intubations are unanticipated, and airway examination methods underperform, with sensitivities of 20-62% and specificities of 82-97%. To overcome these impediments, we aim to develop a deep learning model to identify difficult to intubate patients using frontal face images. We proposed an ensemble of convolutional neural networks which leverages a database of celebrity facial images to learn robust features of multiple face regions. This ensemble extracts features from patient images (n = 152) which are subsequently classified by a respective ensemble of attention-based multiple instance learning models. Through majority voting, a patient is classified as difficult or easy to intubate. Whereas two conventional bedside tests resulted in AUCs of 0.6042 and 0.4661, the proposed method resulted in an AUC of 0.7105 using a cohort of 76 difficult and 76 easy to intubate patients. Generic features yielded AUCs of 0.4654-0.6278. The proposed model can operate at high sensitivity and low specificity (0.9079 and 0.4474) or low sensitivity and high specificity (0.3684 and 0.9605). The proposed ensembled model outperforms conventional bedside tests and generic features. Side facial images may improve the performance of the proposed model. The proposed method significantly surpasses conventional bedside tests and deep learning methods. We expect our model will play an important role in developing deep learning methods where frontal face features play an important role.
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Aprendizado Profundo , Bases de Dados Factuais , Face/diagnóstico por imagem , Humanos , Redes Neurais de ComputaçãoRESUMO
Because up to 12% of obstetric patients meet criteria for the diagnosis of thrombocytopenia in pregnancy, it is not infrequent that the anesthesiologist must decide whether to proceed with a neuraxial procedure in an affected patient. Given the potential morbidity associated with general anesthesia for cesarean delivery, thoughtful consideration of which patients with thrombocytopenia are likely to have an increased risk of spinal epidural hematoma with neuraxial procedures, and when these risks outweigh the relative benefits is important to consider and to inform shared decision making with patients. Because there are substantial risks associated with withholding a neuraxial analgesic/anesthetic procedure in obstetric patients, every effort should be made to perform a bleeding history assessment and determine the thrombocytopenia etiology before admission for delivery. Whereas multiple other professional societies (obstetric, interventional pain, and hematologic) have published guidelines addressing platelet thresholds for safe neuraxial procedures, the US anesthesia professional societies have been silent on this topic. Despite a paucity of high-quality data, there are now meta-analyses that provide better estimations of risks. An interdisciplinary taskforce was convened to unite the relevant professional societies, synthesize the data, and provide a practical decision algorithm to help inform risk-benefit discussions and shared decision making with patients. Through a systematic review and modified Delphi process, the taskforce concluded that the best available evidence indicates the risk of spinal epidural hematoma associated with a platelet count ≥70,000 × 106/L is likely to be very low in obstetric patients with thrombocytopenia secondary to gestational thrombocytopenia, immune thrombocytopenia (ITP), and hypertensive disorders of pregnancy in the absence of other risk factors. Ultimately, the decision of whether to proceed with a neuraxial procedure in an obstetric patient with thrombocytopenia occurs within a clinical context. Potentially relevant factors include, but are not limited to, patient comorbidities, obstetric risk factors, airway examination, available airway equipment, risk of general anesthesia, and patient preference.
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Anestesia Obstétrica/normas , Consenso , Perinatologia/normas , Sociedades Médicas/normas , Trombocitopenia/terapia , Comitês Consultivos/normas , Anestesia Obstétrica/métodos , Feminino , Humanos , Perinatologia/métodos , Gravidez , Trombocitopenia/diagnósticoRESUMO
Importance: Although the safety of labor epidural analgesia (LEA) for neonates has been well documented, the long-term health effects of LEA on offspring remain to be investigated. Objective: To assess the association between maternal LEA exposure and risk of autism spectrum disorders (ASDs) in offspring. Design, Setting, and Participants: Data for this retrospective longitudinal birth cohort study were derived from electronic medical records from a population-based clinical birth cohort. A total of 147â¯895 singleton children delivered vaginally between January 1, 2008, and December 31, 2015, in a single integrated health care system were included. Children were followed up from the age of 1 year until the first date of the following occurrences: clinical diagnosis of ASD, last date of health plan enrollment, death, or the study end date of December 31, 2018. Exposures: Use and duration of LEA. Main Outcomes and Measures: The main outcome was clinical diagnosis of ASD. Cox proportional hazards regression analysis was used to estimate the hazard ratio (HR) of ASD associated with LEA exposure. Results: Among the cohort of 147â¯895 singleton children (74â¯425 boys [50.3%]; mean [SD] gestational age at delivery, 38.9 [1.5] weeks), 109â¯719 (74.2%) were exposed to maternal LEA. Fever during labor was observed in 13â¯055 mothers (11.9%) in the LEA group and 510 of 38â¯176 mothers (1.3%) in the non-LEA group. Autism spectrum disorders were diagnosed in 2039 children (1.9%) in the LEA group and 485 children (1.3%) in the non-LEA group. After adjusting for potential confounders, including birth year, medical center, maternal age at delivery, parity, race/ethnicity, educational level, household income, history of comorbidity, diabetes during pregnancy, smoking during pregnancy, preeclampsia or eclampsia, prepregnancy body mass index, gestational weight gain, gestational age at delivery, and birth weight, the HR associated with LEA vs non-LEA exposure was 1.37 (95% CI, 1.23-1.53). Relative to the unexposed group, the adjusted HR associated with LEA exposure of less than 4 hours was 1.33 (95% CI, 1.17-1.53), with LEA exposure of 4 to 8 hours was 1.35 (95% CI, 1.20-1.53), and with LEA exposure of more than 8 hours was 1.46 (95% CI, 1.27-1.69). Within the LEA group, there was a significant trend of ASD risk associated with increasing duration of LEA exposure after adjusting for covariates (HR for linear trend, 1.05 [95% CI, 1.01-1.09] per 4 hours). Adding fever to the model did not change the HR estimate associated with LEA exposure (adjusted HR for LEA vs non-LEA, 1.37 [95% CI, 1.22-1.53]). Conclusions and Relevance: This study suggests that maternal LEA may be associated with increased ASD risk in children. The risk appears to not be directly associated with epidural-related maternal fever.