Prenatal and perinatal anesthesia and the long-term cognitive sequelae: a review (original) (raw)
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Translational Pediatrics
Background: Multiple human studies have shown no significant long-term results of anesthesia exposure during early childhood compared to the general population; however, reports on short-term neurodevelopmental assessment before and after anesthesia exposure are limited. This study aimed to evaluate the short-term characteristics of neurocognitive function post-anesthesia in noncardiac surgery compared with baseline. Methods: This prospective case-control pilot study recruited healthy participants in the control group and hospitalized children in the anesthesia group. Children aged 1-36 months without previous anesthesia were included. Neurocognitive function was assessed at baseline and seven days after anesthesia administration using a cognitive scale of the Bayley Scales of Infant and Toddler Development, third edition. The control group received only a baseline assessment. The cognitive composite score had a mean of 100 and a standard deviation (SD) of 15, with a difference of score >1/3 SD (5 points) defined as clinically significant. Results: Twenty and 39 participants in the control and anesthesia groups, respectively, were included in the final analysis. The baseline cognitive scale score of the anesthesia group was statistically and clinically lower than that of the control group. The mean (SD) cognitive composite scores in the control and anesthesia group were 111.50 (11.71) and 97.13 (9.88), P<0.001. The mean difference [95% confidence interval (CI)] was −14.37 (−8.28 to −20.47). In the anesthesia group, the post-anesthesia cognitive composite score was statistically higher than that at baseline, but without clinical significance. The mean (SD) of baseline and post-anesthesia cognitive composite scores were 97.05 (9.85) and 101.28 (10.87), P=0.039, respectively. The mean difference (95% CI) was 4.23 (0.23-8.23). However, 7 (17.9%) participants had decreased cognitive composite scores after anesthesia exposure. Conclusions: Children in the anesthesia group had lower baseline cognitive composite scores than those ^ ORCID:
Pediatric Anesthesia and Neurodevelopmental Impairments
Journal of Neurosurgical Anesthesiology, 2012
Experimental evidence of anesthesia-induced neurotoxicity has caused serious concern about the long-term effect of commonly used volatile anesthetic agents on young children. Several observational studies based on existing data have been conducted to address this concern with inconsistent results. We conducted a meta-analysis to synthesize the epidemiologic evidence on the association of anesthesia/surgery with neurodevelopmental outcomes in children. Using Bayesian meta-analytic approaches, we estimated the synthesized odds ratios (OR) and 95% credible interval (CrI) as well as the predictive distribution of a future study given the synthesized evidence. Data on 7 unadjusted and 6 adjusted measures of association were abstracted from 7 studies. The synthesized OR based on the 7 unadjusted measures for the association of anesthesia/ surgery with an adverse behavioral or developmental outcome was 1.9 (95% CrI 1.2, 3.0). The most likely unadjusted OR from a future study was estimated to be 2.2 (95% CrI 0.6, 6.1). The synthesized OR based on the 6 adjusted measures for the association of anesthesia/surgery with an adverse behavioral or developmental outcome was 1.4 (95% CrI 0.9, 2.2). The most likely adjusted OR from a future study was estimated to be 1.5 (95% Cr I 0.5, 4.0). We conclude that the existent epidemiologic evidence suggests a modestly elevated risk of adverse behavioral or developmental outcomes in children who were exposed to anesthesia/surgery during early childhood. The uncertainty with the existent epidemiologic evidence, however, is considerable, implying that the value of additional research using existent data sources to enhance the evidence base is diminishing. Keywords anesthesia; neurocognitive; meta-analysis; Bayesian Among the initial clinical investigations, a population-based retrospective cohort study found a 60% increased risk of learning disorders following more than one anesthetic
JAMA, 2016
Exposure of young animals to commonly used anesthetics causes neurotoxicity including impaired neurocognitive function and abnormal behavior. The potential neurocognitive and behavioral effects of anesthesia exposure in young children are thus important to understand. To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. Sibling-matched cohort study conducted between May 2009 and April 2015 at 4 university-based US pediatric tertiary care hospitals. The study cohort included sibling pairs within 36 months in age and currently 8 to 15 years old. The exposed siblings were healthy at surgery/anesthesia. Neurocognitive and behavior outcomes were prospectively assessed with retrospectively documented anesthesia exposure data. A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibli...
The effects of anaesthesia on the developing brain: a summary of the clinical evidence
F1000Research, 2013
Introduction: There is data amassing in the literature regarding the potentially adverse effects of anaesthesia exposure on the developing human brain. The purpose of this article is to summarise current relevant data from clinical studies in this area. Methods: Articles from journals written in English were searched for using PubMed, Ovid and Medline. Keywords used included: brain (newborn, infant, child and neonate), neurodegeneration, apoptosis, toxicity, neurocognitive impairment (developmental impairment and learning disorders) and anaesthesia (intravenous, inhalational and sedation). Results: From the initial search, 23 articles were identified as potentially relevant, with publication dates spanning from 1978 to 2012. Twelve studies were deemed irrelevant to the research questions. The results of neurocognitive assessment from eight of the remaining eleven studies had showed some differences in the performances of children exposed to anaesthesia. The control population in th...
Neurodevelopmental implications of the general anesthesia in neonate and infants
Experimental Neurology, 2015
Each year, about six million children, including 1.5 million infants, in the United States undergo surgery with general anesthesia, often requiring repeated exposures. However, a crucial question remains of whether neonatal anesthetics are safe for the developing central nervous system (CNS). General anesthesia encompasses the administration of agents that induce analgesic, sedative, and muscle relaxant effects. Although the mechanisms of action of general anesthetics are still not completely understood, recent data have suggested that anesthetics primarily modulate two major neurotransmitter receptor groups, either by inhibiting N-methyl-D-aspartic acid (NMDA) receptors, or conversely by activating γ-aminobutyric acid (GABA) receptors. Both of these mechanisms result in the same effect of inhibiting excitatory activity of neurons. In developing brains, which are more sensitive to disruptions in activity-dependent plasticity, this transient inhibition may have longterm neurodevelopmental consequences. Accumulating reports from preclinical studies show that anesthetics in neonates cause cellular toxicity including apoptosis and neurodegeneration in the developing brain. Importantly, animal and clinical studies indicate that exposure to general anesthetics may affect CNS development, resulting in long-lasting cognitive and behavioral deficiencies, such as learning and memory deficits, as well as abnormalities in social memory and social activity. While the casual relationship between cellular toxicity and neurological impairments is still not clear, recent reports in animal experiments showed that anesthetics in neonates can affect neurogenesis, which could be a possible mechanism underlying the chronic effect of anesthetics. Understanding the cellular and molecular mechanisms of anesthetic effects will help to define the scope of the problem in humans and may lead to preventive and therapeutic strategies. Therefore, in this review, we summarize the current evidence on neonatal anesthetic effects in the developmental CNS and discuss how factors influencing these processes can be translated into new therapeutic strategies.
Anesthetic Exposure During Childhood and Neurodevelopmental Outcomes
JAMA Network Open
IMPORTANCE Clinical studies of neurodevelopmental outcomes after anesthetic exposure have evaluated a range of outcomes with mixed results. OBJECTIVE To examine via meta-analyses the associations between exposure to general anesthesia and domain-specific neurodevelopmental outcomes in children.
Anesthesia-induced Developmental Neurotoxicity in Pediatric Population
Anesthetics and sedatives may cause long-term negative neurocognitive consequences in children. Many clinical reports on this subject have had a profound impact on the field of clinical pediatric anesthesiology. Findings from animal models suggest that early exposure to anesthesia might cause neurocognitive impairment and apoptotic cell death in the brain. Even though the findings from the experimental animals cannot be directly translated to the use of anesthesia in pediatric population due to many variable factors, parents and government regulatory bodies have become sensitive and attentive to the potential adverse effects of anesthesia in children. Multiple epidemiological investigations in human have added to the growing body of evidence showing neurological impairment and cognitive decline after early anesthetic exposure.
Anesthesiology, 2018
Few studies of how exposure of children to anesthesia may affect neurodevelopment employ comprehensive neuropsychological assessments. This study tested the hypothesis that exposure to multiple, but not single, procedures requiring anesthesia before age 3 yr is associated with adverse neurodevelopmental outcomes. Unexposed, singly exposed, and multiply exposed children born in Olmsted County, Minnesota, from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8 to 12 or 15 to 20 yr. The primary outcome was the Full-Scale intelligence quotient standard score of the Wechsler Abbreviated Scale of Intelligence. Secondary outcomes included individual domains from a comprehensive neuropsychological assessment and parent reports. In total, 997 children completed testing (411, 380, and 206 unexposed, singly exposed, and multiply exposed, respectively). The primary outcome of intelligence quotient did not differ significantly accordin...
General anesthesia and neurotoxicity on the developing brain
2018
With the evolution of surgical techniques and technology an increasing number of infants, neonates, and fetuses are exposed to general anesthesia. Despite the acknowledged safety of general anesthesia, a considerable amount of preclinical evidence shows that the developing brain is highly vulnerable to anesthetic drugs. Early-age anesthesia may impair the fine tuning of neurotransmitters and growth factors that orchestrate the replication, differentiation and organization of neural cells into functional networks. In order to translate these insights from animal models to human patients, large trials and observational studies have been published or are currently ongoing. The aim of this narrative review is to provide an update on the pathophysiologic mechanisms and published evidence of anesthesia-related neurotoxicity in pediatric patients.