Feasibility and Pilot Study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) Project (original) (raw)
Related papers
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...
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...
British Journal of Anaesthesia, 2019
Background: We hypothesised that exposure to multiple, but not single, procedures requiring general anaesthesia before age 3 yr is associated with a specific pattern of deficits in processing speed and fine motor skills. Methods: A secondary analysis (using factor and cluster analyses) of data from the Mayo Anesthesia Safety in Kids study was conducted, in which unexposed, singly exposed, and multiply exposed children born in Olmsted County, MN, USA from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8e12 or 15e20 yr. Results: In the factor analysis, the data were well fit to a five factor model. For subjects multiply (but not singly) exposed to anaesthesia, a factor reflecting motor skills, visual-motor integration, and processing speed was significantly lower [standardised difference of e0.35 (95% confidence interval {CI} e0.57 to e0.13)] compared with unexposed subjects. No other factor was associated with exposure. Three groups were identified in the cluster analysis, with 106 subjects (10.6%) in Cluster A (lowest performance in most tests), 557 (55.9%) in Cluster B, and 334 (33.5%) in Cluster C (highest performance in most tests). The odds of multiply exposed children belonging to Cluster A was 2.83 (95% CI: 1.49e5.35; PĀ¼0.001) compared with belonging to Cluster B; there was no other significant association between exposure status and cluster membership. Conclusions: Multiple, but not single, exposures to procedures requiring general anaesthesia before age 3 yr are associated with a specific pattern of deficits in neuropsychological tests. Factors predicting which children develop the most pronounced deficits remain unknown.
BJA: British Journal of Anaesthesia, 2018
Background: Neurotoxicity of anaesthetics in developing brain cells is well documented in preclinical studies, yet results are conflicting in humans. The use of many and different outcome measures in human studies may contribute to this disagreement. Methods: We conducted a systematic review to identify all measures used to assess long-term neurocognitive outcomes following general anaesthesia (GA) and surgery in children. The quality of studies was assessed according to the Newcastle-Ottawa Scale (NOS) for observational studies. PubMed/MEDLINE, EMBASE, Cinahl, Web of Science, and the Cochrane Library were searched for studies investigating neurocognitive outcome after GA in children <18 yr. Results: Sixty-seven studies were identified from 19 countries during 1990e2017. Most assessments were performed within cognition, sensory-motor development, academic achievement or neuropsychological diagnosis. Few studies assessed other outcomes (magnetic resonance imaging, serum-biomarkers, mortality, neurological examination, measurement of head circumference, impairment of vision). Rating according to the NOS rewarded a mean of six stars out of nine. Some concerns prevail regarding potential inter-rater variability because of equivocal description of rating criteria. Specific features such as stability over lifetime and interrelations of outcomes (e.g. prediction of subsequent development or diagnosis of neuropsychological conditions) are discussed. The importance of validity and reliability of the various test instruments are described. The studies vary immensely in important characteristics. Conclusions: Future observational studies should be more consistent in the choice of study population, age at exposure, follow-up, indication for and type of surgery, and outcomes. Assessment of sensory-motor development seems feasible in young children (age <4 yr), and intelligence/cognition in older children.
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
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 ā14.37 (ā8.28 to ā20.47). 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:
Anesthesia & Analgesia, 2011
Introduction: In vitro and in vivo studies of anesthetic agents have demonstrated serious neurotoxic effects on the developing brain. However the clinical relevance of these findings to children undergoing anesthesia remains unclear. Using data from a sibling birth cohort, we assessed the association between exposure to anesthesia in the setting of surgery under three years of age and the risk of developmental and behavioral disorders. Methods: We constructed a retrospective cohort of 10,450 siblings who were born between 1999 and 2005 and who were enrolled in the New York State Medicaid program. The exposed group was 304 children without prior history of developmental or behavioral disorders who underwent surgery under three years of age. The unexposed group was 10,146 children who did not receive any surgical procedures under three years of age. Exposed children were entered into analysis at the date of surgery. Unexposed children were entered into analysis at age 10 months (the mean age at which exposed children underwent surgery). Both exposed and unexposed children were followed until diagnosis with a developmental or behavioral disorder, loss to follow up, or the end of 2005. The association of exposure to anesthesia with subsequent developmental and behavioral disorders was assessed with both proportional hazards modeling, and pair-matched analysis. Results: The incidence of developmental and behavioral disorders was 128.2 diagnoses per 1000 person-years for the exposed cohort and 56.3 diagnoses per 1000 person-years for the unexposed cohort. With adjustment for sex and history of birth-related medical complications, and clustering by sibling status, the estimated hazard ratio of developmental or behavioral disorders associated with any exposure to anesthesia under three years of age was 1.6 (95% CI 1.4, 1.8). The risk increased from 1.1 (95% CI 0.8, 1.4) for one surgery to 2.9 (94% CI 2.5, 3.1) for two surgeries and 4.0 (95% CI 3.5, 4.5) for three or more surgeries. The risk in a matched analysis of 138 sibling pairs was 0.9 (95% CI 0.6, 1.4) Conclusion: The risk of being subsequently diagnosed with developmental and behavioral disorders in children who are enrolled in a state Medicaid program and who undergo surgery under three years of age is 60% greater than that of a similar group of siblings who do not undergo surgery. More tightly-matched pairwise analyses indicate that the extent to which the excess risk is causally attributable to anesthesia or mediated by unmeasured factors remains to be determined.
Anesthetic neurotoxicity in the pediatric population: a systematic review of the clinical evidence
Acta anaesthesiologica Belgica, 2020
Background : Exposure to general anesthesia (GA) in early life is known to be neurotoxic to animals. Objectives : To evaluate the risk of GA inducing longterm neurodevelopmental deficits in human children. Design : Systematic review. Methods : We included observational and randomized studies that compared the long-term neurodevelopment of postnatal children exposed to GA to the long-term neurodevelopment of children not exposed to GA. We searched MEDLINE, Embase and Web of Science for relevant studies published in the year 2000 or later. We screened all the identified studies on predetermined inclusion and exclusion criteria. A risk of bias assessment was made for each included study. We identified 9 neurodevelopmental domains for which a sub-analysis was made: intelligence; memory; learning; language/ speech; motor function; visuospatial skills; development/ emotions/behavior; ADHD/attention; autistic disorder. Results : We included 26 studies involving 605.391 participants. Based on AHRQ-standards 11 studies were of poor quality, 7 studies were of fair quality and 8 studies were of good quality. The major causes of potential bias were selection and comparability bias. On 2 neurodevelopmental domains (visuospatial skills and autistic disorder), the available evidence showed no association with exposure to GA. On 7 other neurodevelopmental domains, the available evidence showed mixed results. The 4 studies that used a randomized or sibling-controlled design showed no association between GA and neurodevelopmental deficits in their primary endpoints. Limitations : The absence of a meta-analysis and funnel plot. Conclusions : Based on observational studies, we found an association between GA in childhood and neurodevelopmental deficits in later life. Randomized and sibling-matched observational studies failed to show the same association and therefore no evidence of a causal relationship exists at present. Since GA seems to be a marker, but not a cause of worse neurodevelopment, we argue against delaying or avoiding interventional or diagnostic procedures requiring GA in childhood based on the argument of GA-induced neurotoxicity.