Symptomatic carotid webs require aggressive intervention.

OBJECTIVE: Carotid web (CaWeb) is a rare form of fibromuscular dysplasia that can produce embolic stroke. Misdiagnosis of symptomatic CaWeb as "cryptogenic stroke" or "embolic stroke of unknown source" is common and can lead to recurrent, catastrophic neurologic events. Reports of CaWeb in the literature are scarce, and their natural history is poorly understood. Appropriate management remains controversial. METHODS: CaWeb was defined as a single, shelf-like, linear projection in the posterolateral carotid bulb causing a filling defect on computed tomography angiography (CTA) or cerebral angiography. Cases of symptomatic CaWeb at a single institution with a high-volume stroke center were identified through collaborative evaluation by vascular neurologists and vascular surgeons. RESULTS: Fifty-two patients with symptomatic CaWeb were identified during a 6-year period (2016-2022). Average age was 49 years (range, 29-73 years), 35 of 52 (67%) were African American, and 18 of 52 (35%) were African American women under age 50. Patients initially presented with stroke (47/52; 90%) or transient ischemic attack (5/52; 10%). Stenosis was <50% in 49 of 52 patients (94%) based on NASCET criteria, and 0 of 52 (0%) CaWebs were identified with carotid duplex. Definitive diagnosis was made by CTA examined in multiple planes or cerebral angiography examined in a lateral projection to adequately assess the posterolateral carotid bulb, where 52 of 52 (100%) of CaWebs were seen. Early in our institutional experience, 10 of 52 patients (19%) with symptomatic CaWeb were managed initially with dual antiplatelet and statin therapy or systemic anticoagulation; all suffered ipsilateral recurrent stroke at an average interval of 43 months (range, 1-89 months), and five were left with permanent deficits. Definitive treatment included carotid endarterectomy in 27 of 50 (56%) or carotid stenting in 23 of 50 (46%). Two strokes were irrecoverable, and intervention was deferred. Web-associated thrombus was observed in 20 of 50 (40%) on angiography or grossly upon carotid exploration. Average interval from initial stroke to intervention was 39 days. After an average follow-up of 38 months, there was no reported postintervention stroke or mortality. CONCLUSIONS: To our knowledge, this is the largest single-institution analysis of symptomatic CaWeb yet reported. Our series demonstrates that carotid duplex is inadequate for diagnosis, and that medical management is unacceptable for symptomatic CaWeb. Recurrent stroke occurred in all patients managed early in our experience with medical therapy alone. We have since adopted an aggressive interventional approach in cases of symptomatic CaWeb, with no postoperative stroke reported over an average follow-up of 38 months. In younger patients presenting with cryptogenic stroke, especially African American women, detailed review of lateral cerebral angiography or multi-planar, fine-cut CTA images is required to accurately rule out or diagnose CaWeb and avoid recurrent neurologic events.

Adaptive expression of engrams by retroactive interference.

Long-term memories are stored as configurations of neuronal ensembles, termed engrams. Although investigation of engram cell properties and functionality in memory recall has been extensive, less is known about how engram cells are affected by forgetting. We describe a form of interference-based forgetting using an object memory behavioral paradigm. By using activity-dependent cell labeling, we show that although retroactive interference results in decreased engram cell reactivation during recall trials, optogenetic stimulation of the labeled engram cells is sufficient to induce memory retrieval. Forgotten engrams may be reinstated via the presentation of similar or related environmental information. Furthermore, we demonstrate that engram activity is necessary for interference to occur. Taken together, these findings indicate that retroactive interference modules engram expression in a manner that is both reversible and updatable. Inference may constitute a form of adaptive forgetting where, in everyday life, new perceptual and environmental inputs modulate the natural forgetting process.

Anesthesia and Developing Brains: Unanswered Questions and Proposed Paths Forward.

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.

Prevalence and factors associated with advance health directives in frail older inpatients.

BACKGROUND: Advance health directives (AHD) can be used to explore and document patient preferences for treatment and are therefore an important aspect of care planning. AIMS: To investigate the prevalence and factors associated with AHD among older inpatients. METHODS: This retrospective study included 6449 patients, aged ≥65 years referred for specialist geriatric consultation between 2007 and 2018 in Queensland, Australia. The interRAI-Acute Care Comprehensive Geriatric Assessment tool was used to calculate a frailty index (FI), range 0-1, based on 52 possible deficits, and categorised into intervals of 0.1 for analysis. FI was also grouped according to previously reported cut points: fit (FI ≤0.25), moderately frail (FI >0.25-0.4), frail (FI >0.4-0.6) and severely frail (FI >0.6). RESULTS: An AHD was present in 1032 (16.0%) of 6449 patients. Those with an AHD were significantly frailer than those without an AHD (mean FI 0.52 vs 0.45; P < 0.001). Higher frailty (odds ratio (OR): 1.34 (1.27-1.40)), older age (OR: 1.04 (1.03-1.05)), living in an institution (OR: 1.33 (1.01-1.73)) and recent hospitalisation (OR: 1.42 (1.23-1.62)) were significantly associated with higher prevalence of AHD. Prevalence of AHD increased over time, from 7.6% (n = 66) in 2008 to 35.4% (n = 99) in 2017. CONCLUSIONS: The presence of AHD is associated with sociodemographic factors, as well as higher frailty levels. Prevalence of AHD among inpatients has increased over the past decade but remains modest.

Short-Term Pre-Operative Protein Caloric Restriction in Elective Vascular Surgery Patients: A Randomized Clinical Trial.

(1) Background: Vascular surgery operations are hampered by high failure rates and frequent occurrence of peri-operative cardiovascular complications. In pre-clinical studies, pre-operative restriction of proteins and/or calories (PCR) has been shown to limit ischemia-reperfusion damage, slow intimal hyperplasia, and improve metabolic fitness. However, whether these dietary regimens are feasible and safe in the vascular surgery patient population remains unknown. (2) Methods: We performed a randomized controlled trial in patients scheduled for any elective open vascular procedure. Participants were randomized in a 3:2 ratio to either four days of outpatient pre-operative PCR (30% calorie, 70% protein restriction) or their regular ad-libitum diet. Blood was drawn at baseline, pre-operative, and post-operative day 1 timepoints. A leukocyte subset flow cytometry panel was performed at these timepoints. Subcutaneous/perivascular adipose tissue was sampled and analyzed. Follow-up was one year post-op. (3) Results: 19 patients were enrolled, of whom 11 completed the study. No diet-related reasons for non-completion were reported, and there was no intervention group crossover. The PCR diet induced weight loss and BMI decrease without malnutrition. Insulin sensitivity was improved after four days of PCR (p = 0.05). Between diet groups, there were similar rates of re-intervention, wound infection, and cardiovascular complications. Leukocyte populations were maintained after four days of PCR. (4) Conclusions: Pre-operative PCR is safe and feasible in elective vascular surgery patients.

Association Between Cyanosis, Transfusion, and Thrombotic Complications in Neonates and Children Undergoing Cardiac Surgery.

OBJECTIVE: Children with congenital heart defects are at increased risk for perioperative bleeding and postoperative thrombosis. In this study, the authors sought to develop a predictive model for postoperative thrombotic complications that integrates intraoperative bleeding and the requirement for allogenic blood products in addition to known patient and surgical characteristics. DESIGN: Retrospective cohort. SETTING: Pediatric hospital. PARTICIPANTS: Neonates and children who underwent surgery with cardiopulmonary bypass (CPB). INTERVENTIONS: None MEASUREMENTS AND MAIN RESULTS: Demographic, laboratory, point-of-care coagulation, surgical, and perioperative transfusion data were collected. Among the 369 participants included in the study, 67 (18%) developed postoperative thrombotic complications. From multivariable logistic regression analyses, preoperative oxygen saturation <85% (odds ratio [OR] 2.06, 95% confidence interval [CI] 1.10-3.85; p = 0.024), surgery in the neonatal period (OR 2.16, 95% CI 1.02-4.55; p = 0.044), use of preoperative antiplatelet or anticoagulation therapy (OR 3.34, 95% CI 1.61-6.96; p = 0.001), and the volume of blood product transfused post-CPB (>80 mL/kg [OR 5.72, 95% CI 1.73-18.91; p = 0.004] and 15-80 mL/kg [OR 3.06, 95% CI 1.24-7.53; p = 0.015]) were independently associated with an increased incidence of thrombotic complications. No statistical differences were observed in available preoperative coagulation tests between children who developed postoperative thrombosis and those who did not. CONCLUSION: This observational cohort study found that cyanosis, surgery in neonates, preoperative anticoagulation or antiplatelet therapy, and the volume of post-CPB transfusion are important predictors of postoperative thrombotic complications in children undergoing cardiac surgery. Additional studies are required to explore the relationship between hypoxia, coagulopathy, and postoperative thrombosis.

Chronic intrahippocampal interleukin-1ß overexpression in adolescence impairs hippocampal neurogenesis but not neurogenesis-associated cognition.

Both neuroinflammation and adult hippocampal neurogenesis (AHN) are implicated in many neurodegenerative disorders as well as in neuropsychiatric disorders, which often become symptomatic during adolescence. A better knowledge of the impact that chronic neuroinflammation has on the hippocampus during the adolescent period could lead to the discovery of new therapeutics for some of these disorders. The hippocampus is particularly vulnerable to altered concentrations of the pro-inflammatory cytokine interleukin-1ß (IL-1ß), with elevated levels implicated in the aetiology of neurodegenerative disorders such as Alzheimer's and Parkinson's, and stress-related disorders such as depression. The effect of acutely and chronically elevated concentrations of hippocampal IL-1ß have been shown to reduce AHN in adult rodents. However, the effect of exposure to chronic overexpression of hippocampal IL-1ß during adolescence, a time of increased vulnerability, hasn't been fully interrogated. Thus, in this study we utilized a lentiviral approach to induce chronic overexpression of IL-1ß in the dorsal hippocampus of adolescent male Sprague Dawley rats for 5 weeks, during which time its impact on cognition and hippocampal neurogenesis were examined. A reduction in hippocampal neurogenesis was observed along with a reduced level of neurite branching on hippocampal neurons. However, there was no effect of IL-1ß overexpression on performance in pattern separation, novel object recognition or spontaneous alternation in the Y maze. Our study has highlighted that chronic IL-1ß overexpression in the hippocampus during the adolescent period exerts a negative impact on neurogenesis independent of cognitive performance, and suggests a degree of resilience of the adolescent hippocampus to inflammatory insult.

Emergency intraoperative vascular surgery consultations at a tertiary academic center.

OBJECTIVE: Vascular surgeons are frequently called on to provide emergency assistance to surgical colleagues. Whereas previous studies have included elective preoperative vascular consultations, we sought to characterize the breadth of assistance provided during unplanned intraoperative consultations at a single tertiary academic center. METHODS: We queried our institutional billing department during a 15-year period and reviewed the records (January 1, 2002-December 31, 2016) and identified unanticipated unplanned vascular surgery intraoperative consultations from all surgical services. Patients' demographics and comorbidities were recorded along with the consulting services, type of index operation, reasons for vascular consultation, regions of anatomic interventions, type of vascular interventions performed, and outcomes achieved. RESULTS: There were 419 emergency intraoperative consultations identified. Patients were 51% male, with an average age of 57 years and body mass index of 28.3 kg/m2. The most frequently consulting subspecialties included surgical oncology (n = 139 [33.2%]), cardiac surgery (n = 82 [19.6%]), and orthopedics (n = 44 [10.5%]). Index cases were elective/nonurgent (n = 324 [77.3%]), urgent (n = 27 [6.4%]), and emergent (n = 68 [16.2%]), with a majority involving tumor resection (n = 240 [57.3%]). The primary reasons for vascular consultation were revascularization (n = 213 [50.8%]), control of bleeding (n = 132 [31.5%]), assistance with dissection or exposure (n = 46 [11%]), embolic protection (n = 24 [5.7%]), and other (n = 4 [1.1%]). The primary blood vessel and anatomic field of intervention were categorized. Most cases (n = 264 [63%]) included preservation of blood flow, including primary arterial repair (n = 181 [43.2%]), patch angioplasty (n = 83 [19.8%]), bypass (n = 63 [15%]), and thrombectomy (n = 38 [9.1%]). Postoperative mean length of stay was 15 days, with 30-day and 1-year mortality of 7.2% and 26.5%. CONCLUSIONS: Vascular surgeons are called on to provide unplanned open surgical consultations for a wide variety of specialties over wide-ranging anatomic regions, employing a variety of skills and techniques. This study testifies to the essential services supplied to hospitals and our surgical colleagues along with the broad skills and training necessary for modern vascular surgeons.

Human Studies of Anesthesia-Related Neurotoxicity in Children: A Narrative Review of Recent Additions to the Clinical Literature.

In 2017, the US Food and Drug Administration warned that exposure to anesthetic medicines for lengthy periods of time or over multiple surgeries may affect brain development in children aged less than 3 years. Since then, the clinical literature continues to find mixed evidence of pediatric anesthesia-related neurotoxicity. However, several new human studies provide strong evidence that a single short exposure to general anesthesia in young children does not cause detectable neurocognitive injury by neuropsychological testing. These newer findings are reassuring, but cannot be extrapolated to children who are deemed to be at highest risk of neurologic injury after anesthesia.

Insights From a Short-Term Protein-Calorie Restriction Exploratory Trial in Elective Carotid Endarterectomy Patients.

BACKGROUND: Open vascular surgery interventions are not infrequently hampered by complication rates and durability. Preclinical surgical models show promising beneficial effects in modulating the host response to surgical injury via short-term dietary preconditioning. Here, we explore short-term protein-calorie restriction preconditioning in patients undergoing elective carotid endarterectomy to understand patient participation dynamics and practicalities of robust research approaches around nutritional/surgical interventions. METHODS: We designed a pilot prospective, multicenter, randomized controlled study in patients undergoing carotid endarterectomy. After a 3:2 randomization to a 3-day preoperative protein-calorie restriction regimen (30% calorie/70% protein restriction) or ad libitum group, blood, clinical parameters, and stool samples were collected at baseline, pre-op, and post-op days 1 and 30. Subcutaneous and perivascular adipose tissues were harvested periprocedurally. Samples were analyzed for standard chemistries and cell counts, adipokines. Bacterial DNA isolation and 16S rRNA sequencing were performed on stool samples and the relative abundance of bacterial species was measured. RESULTS: Fifty-one patients were screened, 9 patients consented to the study, 5 were randomized, and 4 completed the trial. The main reason for non-consent was a 3-day in-hospital stay. All 4 participants were randomized to the protein-calorie restriction group, underwent successful endarterectomy, reported no compliance difficulties, nor were there adverse events. Stool analysis trended toward increased abundance of the sulfide-producing bacterial species Bilophila wadsworthia after dietary intervention (P = .08). CONCLUSIONS: Although carotid endarterectomy patients held low enthusiasm for a 3-day preoperative inpatient stay, there were no adverse effects in this small cohort. Multidisciplinary longitudinal research processes were successfully executed throughout the nutritional/surgical intervention. Future translational endeavors into dietary preconditioning of vascular surgery patients should focus on outpatient approaches.

Differential effects of adolescent and adult-initiated exercise on cognition and hippocampal neurogenesis.

Adolescence is a critical period for postnatal brain maturation and thus a time when environmental influences may affect cognitive processes in later life. Exercise during adulthood has been shown to increase hippocampal neurogenesis and enhance cognition. However, the impact of exercise initiated in adolescence on the brain and behavior in adulthood is not fully understood. The aim of this study was to compare the impact of voluntary exercise that is initiated during adolescence or early adulthood on cognitive performance in hippocampal-dependent and -independent processes using both object-based and touchscreen operant paradigms. Adult (8 week) and adolescent (4 week) male Sprague-Dawley rats had access to a running wheel (exercise) or were left undisturbed (sedentary control) for 4 weeks prior to behavioral testing and for the duration of the experiment. Results from touchscreen-based tasks showed that reversal learning was enhanced by both adult and adolescent-initiated exercise, while only exercise that began in adolescence induced a subtle but transient increase in performance on a location discrimination task. Spontaneous alternation in the Y-maze was impaired following adolescent onset exercise, while object memory was unaffected by either adult or adolescent-initiated exercise. Adolescent-initiated exercise increased the number of hippocampal DCX cells, an indicator of neurogenesis. It also promoted the complexity of neurites on DCX cells, a key process for synaptic integration, to a greater degree than adult-initiated exercise. Together the data here show that exercise during the adolescent period compared to adulthood differentially affects cognitive processes and the development of new hippocampal neurons in later life.

Developmental Neurotoxicity: An Update.

In the section of "Developmental Neurotoxicity: An Update" of the Pediatric Anesthesia Neurodevelopmental Assessment (PANDA) symposium 2018 the speakers presented the current literature in translational and clinical research. Dr. Brambrink spoke about translational research in anesthetic neurotoxicity, beginning with discovery in the rodent model, then focusing on evidence from nonhuman primates. Dr. Waspe applied the methodology of Adverse Outcome Pathways from the field of toxicology to developmental neurotoxicity of anesthetics. Dr. O'Leary presented relevant clinical studies that were published in 2017 divided by a focus on academic performance, clinical outcomes or diagnoses, or neuropsychological testing.

Hospital admission on weekends for patients who have surgery and 30-day mortality in Ontario, Canada: A matched cohort study.

BACKGROUND: Healthcare interventions on weekends have been associated with increased mortality and adverse clinical outcomes, but these findings are inconsistent. We hypothesized that patients admitted to hospital on weekends who have surgery have an increased risk of death compared with patients who are admitted and have surgery on weekdays. METHODS AND FINDINGS: This matched cohort study included 318,202 adult patients from Ontario health administrative and demographic databases, admitted to acute care hospitals from 1 January 2005 to 31 December 2015. A total of 159,101 patients who were admitted on weekends and underwent noncardiac surgery were classified by day of surgery (weekend versus weekday) and matched 1:1 to patients who both were admitted and had surgery on a weekday (Tuesday to Thursday); matching was based on age (in years), anesthesia basic unit value for the surgical procedure, median neighborhood household income quintile, resource utilization band (a ranking system of overall morbidity), rurality of home location, year of admission, and urgency of admission. Of weekend admissions, 16.2% (25,872) were elective and 53.9% (85,744) had surgery on the weekend of admission. The primary outcome was all-cause mortality within 30 days of the date of hospital admission. The 30-day all-cause mortality for patients admitted on weekends who had noncardiac surgery was 2.6% (4,211/159,101) versus 2.5% (3,901/159,101) for those who were admitted and had surgery on weekdays (adjusted odds ratio [OR] 1.05; 95% CI 1.00 to 1.11; P = 0.03). However, there was significant heterogeneity in the increased odds of death according to the urgency of admission and when surgery was performed (weekend versus weekday). For urgent admissions on weekends (n = 133,229), there was no significant increase in odds of mortality when surgery was performed on the weekend (adjusted OR 1.02; 95% CI 0.95 to 1.09; P = 0.7) or on a subsequent weekday (adjusted OR 1.05; 95% CI 0.98 to 1.12; P = 0.2) compared to urgent admissions on weekdays. Elective admissions on weekends (n = 25,782) had increased risk of death both when surgery was performed on the weekend (adjusted OR 3.30; 95% CI 1.98 to 5.49; P < 0.001) and when surgery was performed on a subsequent weekday (adjusted OR 2.70; 95% CI 1.81 to 4.03; P < 0.001). The main limitations of this study were the lack of data regarding reason for admission and cause of increased time interval from admission to surgery for some cases, the small number of deaths in some subgroups (i.e., elective surgery), and the possibility of residual unmeasured confounding from increased illness severity for weekend admissions. CONCLUSIONS: When patients have surgery during their hospitalization, admission on weekends in Ontario, Canada, was associated with a small but significant proportional increase in 30-day all-cause mortality, but there was significant heterogeneity in outcomes depending on the urgency of admission and when surgery was performed. An increased risk of death was found only for elective admissions on weekends; whether this is a function of patient-level factors or represents a true weekend effect needs to be further elucidated. These findings have potential implications for resource allocation in hospitals and the redistribution of elective surgery to weekends.

Differential effects of adolescent and adult-initiated voluntary exercise on context and cued fear conditioning.

Adolescence is a critical period for postnatal brain maturation and a time during which there is increased susceptibility to developing emotional and cognitive-related disorders. Exercise during adulthood has been shown to increase hippocampal plasticity and enhance cognition. However, the impact of exercise initiated in adolescence, on brain and behaviour in adulthood is not yet fully explored or understood. The aim of this study was to compare the impact of voluntary exercise that was initiated either during adolescence or early adulthood on cognitive performance in hippocampal and amygdala-dependent fear conditioning tasks in adulthood. Adult (eight weeks old) and adolescent (four weeks old) male Sprague Dawley rats had access to a running wheel (exercise) or were left undisturbed (sedentary control) for seven weeks. Adult-initiated exercise enhanced both contextual and cued fear conditioning, while conversely, exercise that began in adolescence did not affect performance in these tasks. These behaviours were accompanied by differential expression of plasticity-related genes in the hippocampus and amygdala in adulthood. Specifically, adolescent-initiated exercise increased the expression of an array of plasticity related genes in the hippocampus including BDNF, synaptophysin, Creb, PSD-95, Arc, TLX and DCX, while adult-initiated exercise did not affect hippocampal plasticity related genes. Together results show that exercise initiated during adolescence has a differential effect on hippocampal and amygdala-dependent behaviour and neuronal plasticity compared to when exercise was initiated in adulthood. These findings reinforce adolescence as a period during which environmental influences have a distinct impact on neuronal plasticity and cognition. This article is part of the Special Issue entitled "Neurobiology of Environmental Enrichment".

Preoperative anemia increases the risk of red blood cell transfusion and prolonged hospital length of stay in children undergoing spine arthrodesis surgery.

BACKGROUND: Preoperative anemia is an important modifiable risk factor for red blood cell (RBC) transfusion in a variety of surgical populations. The primary objective of this study was to examine the association between preoperative anemia and i) transfusion of RBCs within 72 hours of surgery and ii) postoperative clinical outcomes in children undergoing spine arthrodesis surgery. STUDY DESIGN AND METHODS: We assembled a retrospective cohort of children included in the American College of Surgeons National Quality Improvement Program Pediatric database who underwent spine arthrodesis surgery from 2012 to 2016. Anemia was defined using age- and sex-specific hematocrit thresholds. Data collected included demographic and surgical characteristics, RBC transfusion within 72 hours, and 30-day postoperative outcomes (postoperative mechanical ventilation, infection, readmission, hospital length of stay, mortality). Multivariable logistic regression analyses were used to identify independent predictors of RBC transfusion and postoperative outcomes. RESULTS: We included 9,095 patients in the analysis. Preoperative anemia was present in 14% (n = 1,233) of the population and 67% (n = 6,135) of patients were transfused. Our multivariable logistic regression showed anemia, surgical time > 350 minutes, > 7 vertebral levels fused, neuromuscular disease, and cerebral palsy were all independent predictors of RBC transfusion. Preoperative anemia was also associated with prolonged hospital LOS (adjusted OR: 1.31, 95%CI: 1.11-1.54, p = 0.002). CONCLUSIONS: In this study of 9,095 children undergoing spine surgery, preoperative anemia was associated with an increased risk of RBC transfusion and prolonged LOS. Further studies are needed to determine if treatment of preoperative anemia can effectively reduce intraoperative RBC transfusion.

Influence of Surgical Procedures and General Anesthesia on Child Development Before Primary School Entry Among Matched Sibling Pairs.

Importance: Substantial preclinical evidence suggests that the developing brain is susceptible to injury from anesthetic drugs. Findings from clinical studies of the neurotoxic effects of anesthesia are mixed, but these effects can be influenced by unmeasured confounding from biological and environmental risk and protective factors on child development. Objective: To examine the association between surgical procedures that require general anesthesia before primary school entry and child development in biological siblings. Design, Setting, and Participants: This retrospective sibling-matched cohort study included sibling pairs aged 5 to 6 years with the same birth mother who had Early Development Instrument (EDI) data completed. The EDI is a population-based measure of child development that assesses children's readiness to learn in 5 major domains (physical health and well-being, social knowledge and competence, emotional health and maturity, language and cognitive development, and communication skills and general knowledge). All eligible children in public and Catholic schools in Ontario, Canada, from 2004 through 2012 were included. Data were analyzed from December 13, 2017, through July 27, 2018. Exposures: Surgical procedures that require general anesthesia from the date of birth to EDI completion. Main Outcomes and Measures: Early developmental vulnerability, defined as any major domain of the EDI in the lowest 10th percentile of the Ontario population. Results: Of the 187 226 eligible children for whom the EDI was completed, a total of 10 897 sibling pairs (21 794 children; 53.8% female; mean [SD] age, 5.7 [0.3] years) were subsequently identified, including 2346 with only 1 child exposed to surgery. No significant differences were found between exposed and unexposed children in early developmental vulnerability (697 of 3080 [22.6%] vs 3739 of 18 714 [20.0%]; adjusted odds ratio [aOR], 1.03; 95% CI, 0.98-1.14; P = .58) or for each of the 5 major EDI domains (aOR for language and cognitive development, 0.96 [95% CI, 0.80-1.14]; aOR for physical health and well-being, 1.09 [95% CI, 0.96-1.24]; aOR for social knowledge and competence, 0.98 [95% CI, 0.84-1.14]; aOR for emotional health and maturity, 0.98 [95% CI, 0.84-1.14]; and aOR for communication skills and general knowledge, 0.90 [95% CI, 0.77-1.05]), after adjusting for confounding factors (age at EDI completion, sex, mother's age at birth, and eldest sibling status). Conclusions and Relevance: In this provincial cohort study, children who had surgical procedures that require general anesthesia before primary school entry were not found to be at increased risk of adverse child development outcomes compared with their biological siblings who did not have surgery. These findings further support that anesthesia exposure in early childhood is not associated with detectable adverse child development outcomes.