Report on the Fifth PANDA Symposium on "Anesthesia and Neurodevelopment in Children".

On April 16 and 17, 2016, the Pediatric Anesthesia and Neurodevelopment Assessment (PANDA) study held its fifth biennial symposium at the Morgan Stanley Children's Hospital of New York. The PANDA symposium has served as a key forum for clinicians, researchers, and other major stakeholders to gather and review the current state of preclinical and clinical research related to anesthetic neurotoxicity in children. Goals of the meeting included assessing how current knowledge has translated and impacted clinical care of patients who may be at risk, and future directions for research and policy. The program participants represented a diverse group with a shared concern of potential anesthetic neurotoxicity in children. It included clinicians, preclinical and clinical researchers as well as representatives from government organizations (FDA [Food and Drug Administration] and National Institutes of Health). A total of 135 attended the symposium.

Association Between a Single General Anesthesia Exposure Before Age 36 Months and Neurocognitive Outcomes in Later Childhood.

IMPORTANCE: 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. OBJECTIVE: To examine if a single anesthesia exposure in otherwise healthy young children was associated with impaired neurocognitive development and abnormal behavior in later childhood. DESIGN, SETTING, AND PARTICIPANTS: 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. EXPOSURES: A single exposure to general anesthesia during inguinal hernia surgery in the exposed sibling and no anesthesia exposure in the unexposed sibling, before age 36 months. MAIN OUTCOMES AND MEASURES: The primary outcome was global cognitive function (IQ). Secondary outcomes included domain-specific neurocognitive functions and behavior. A detailed neuropsychological battery assessed IQ and domain-specific neurocognitive functions. Parents completed validated, standardized reports of behavior. RESULTS: Among the 105 sibling pairs, the exposed siblings (mean age, 17.3 months at surgery/anesthesia; 9.5% female) and the unexposed siblings (44% female) had IQ testing at mean ages of 10.6 and 10.9 years, respectively. All exposed children received inhaled anesthetic agents, and anesthesia duration ranged from 20 to 240 minutes, with a median duration of 80 minutes. Mean IQ scores between exposed siblings (scores: full scale = 111; performance = 108; verbal = 111) and unexposed siblings (scores: full scale = 111; performance = 107; verbal = 111) were not statistically significantly different. Differences in mean IQ scores between sibling pairs were: full scale = -0.2 (95% CI, -2.6 to 2.9); performance = 0.5 (95% CI, -2.7 to 3.7); and verbal = -0.5 (95% CI, -3.2 to 2.2). No statistically significant differences in mean scores were found between sibling pairs in memory/learning, motor/processing speed, visuospatial function, attention, executive function, language, or behavior. CONCLUSIONS AND RELEVANCE: Among healthy children with a single anesthesia exposure before age 36 months, compared with healthy siblings with no anesthesia exposure, there were no statistically significant differences in IQ scores in later childhood. Further study of repeated exposure, prolonged exposure, and vulnerable subgroups is needed.

Report of the fourth PANDA Symposium on "Anesthesia and Neurodevelopment in Children".

On April 12, 2014, the Pediatric Anesthesia and NeuroDevelopment Assessment (PANDA) study team held its fourth biennial scientific symposium at Morgan Stanley Children's Hospital of New York (MS-CHONY). The symposium was organized by the PANDA study team and co-sponsored by the Morgan Stanley Children's Hospital of New York-Presbyterian and the Department of Anesthesiology of Columbia University. The PANDA symposium has become a platform to review current preclinical and clinical data related to anesthetic neurotoxicity, to discuss relevant considerations in study design and approaches to future research among clinicians and researchers, and finally to engage key stakeholders in this controversial public health topic. Program attendants and speakers represented many of the most active investigators in the area of pediatric anesthetic neurotoxicity as well as stakeholders from many different backgrounds outside of anesthesia that provided their own unique perspectives, concerns, and input regarding anesthetic-related neurotoxicity in children.

Report of the third PANDA symposium on "Anesthesia and Neurodevelopment in Children".

The Pediatric Anesthesia and NeuroDevelopment Assessment (PANDA) Project team organized its third biennial scientific symposium on "Anesthesia and Neurodevelopment in Children" at the Children's Hospital of New York on April 21, 2012. The event was co-sponsored by the New York-Presbyterian/Morgan Stanley Children's Hospital (MS-CHONY) and the Department of Anesthesiology of Columbia University. The day-long program included updates of recent research in anesthetic neurotoxicity in the developing brain from preclinical studies to clinical and patient-oriented outcome research. It also provided a forum for discussion among many different stakeholders in this important public health issue.

Feasibility and pilot study of the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project.

BACKGROUND: Animal studies have documented that exposure of the developing brain to commonly used anesthetic agents induces neurotoxicity and late abnormal neurobehavioral functions as adults. Results from clinical studies have all been analyzed using existing data sets, and these studies produced inconsistent results. To provide more definitive evidence to address the clinical relevance of anesthetic neurotoxicity in children, an interdisciplinary team of investigators designed and developed the Pediatric Anesthesia NeuroDevelopment Assessment (PANDA) project. We present pilot study results in 28 sibling pairs recruited and tested at the Columbia University Medical Center (CUMC) and Children's Hospital of Boston (CHB) for the PANDA project. METHODS: The PANDA project uses an ambidirectional cohort design. We performed prospective neuropsychological assessment in 28 exposed-unexposed sibling pairs from 6 to 11 years of age. The exposed siblings were ASA 1 or 2 and had received a single episode of anesthesia for inguinal hernia repair before the age of 36 months and the unexposed siblings had no anesthesia before the age of 36 months. All the sibling pairs were English speaking and were 36 weeks of gestational age or older. Each sibling pair underwent a direct testing using the Wechsler Abbreviated Scale of Intelligence (WASI) and the NEuroPSYchological Assessment, second edition (NEPSY II), and the parents completed questionnaires related to behavior using CBCL and Conners rating. Data are presented as means±SD. We conducted descriptive analyses of the demographic data. We compared both the exposed and the unexposed sibling groups on WASI and NEPSY II, and total and T scores from CBCL and Conners rating were analyzed as continuous data using the paired t test between the two groups. A P<0.05 was considered significant. RESULTS: After the Institutional Review Board approval for the study at both CUMC and CHB, the full PANDA study protocol was implemented to perform a pilot feasibility study. Our success rate was 96.7% in obtaining detailed medical and anesthesia records in our historical cohort. The scores for verbal IQ (exposed=106.1±16.3, unexposed=109.2±17.9), performance IQ (exposed=109.1±16.0, unexposed=113.9±15.9), and full IQ (exposed=108.2±14.0, unexposed=112.8±16.8) were comparable between the siblings. There were no differences between the two groups in T scores for any of the NEPSY II subdomains, CBCL, or Conners rating. An abstraction protocol with web-based electronic data capture forms also was developed in conjunction with the International Center for Health Outcomes and Innovation Research (InCHOIR). CONCLUSIONS: The pilot study provided useful information for feasibility to recruit the sample size and to obtain relevant clinical data. For the final study protocol, both the neuropsychological battery and the age range for testing were revised. Our results confirmed the feasibility of our study approach and yielded pilot data from neuropsychological testing.