PANDA (Pediatric Anesthesia & NeuroDevelopment Assessment) Study

Study Overview
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Brief Summary
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The purpose of this study is to determine whether the use of anesthetic agents in infants and children have long term adverse effects on neurocognitive development. According to the National Hospital Discharge Survey, around 2.5 million children have surgical procedures requiring anesthesia each year in the US. Recent animal studies have suggested that the exposure of the immature organism to a variety of commonly used anesthetic agents may lead to neurobehavioral functional deficits in vivo and to neuronal apoptosis in vitro. While the relevance of these findings on children exposed to anesthetics remains to be determined, it is clearly critically important to public health that this issue is resolved quickly and clearly. Hypothesis: Exposure to anesthetic agents within the first three years of life will not significantly impair cognitive functions at ages 8 yr, 0 mo to 15 yr, 0 mo.

Detailed Description
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The purpose of our study is to compare neurocognitive functions in sibling pairs: one of whom had exposure to anesthesia during surgery before 36 months of age (exposed sibling cohorts) and who would be from ages 8yr, 0 mo to15 yr, 0 mo at the time of the study; and the other who never had anesthesia or surgery less than 36 months of age, is from ages 8yr, 0mo to 15 yr, 0 mo at the time of the study, and is within 36 months of age range from the exposed sibling(unexposed sibling cohort). Neuropsychological assessments are administered to the sibling cohorts prospectively and parents of the siblings will complete parental interviews/questionnaires. We assess individually neurocognitive, behavioral and emotional function for both exposed and unexposed siblings. Family function will also be evaluated. We will also obtain complete medical history for each participant, including significant perinatal events and social history. We also review medical records when appropriate. All testing are performed during a one day site visit.

Official Title
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Anesthesia Exposure and Neurodevelopment in Infants and Children: Pediatric Anesthesia & NeuroDevelopment (PANDA) Study

Conditions
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Cognition - Other

Intervention / Treatment
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* Procedure: Inguinal hernia surgery
* Procedure: General anesthesia


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Exposed cohort: Subjects who had inguinal hernia surgery before 36 months of age Ages 8 yr, 0 mo to 15 yr, 0 mo Gestation age greater or equal to 36 weeks Categorized as ASA I or ASA II English speaking Biologically related to the unexposed sibling Unexposed cohort: Sibling within 36 months of age of the exposed cohort Never had surgery or exposure to anesthesia prior to 36 months of age Ages 8 yr, 0 mo to 15 yr, 0 mo Gestation age greater or equal to 36 weeks Categorized as ASA I or ASA II 5. English speaking 6. Biologically related to the exposed sibling Exclusion criteria: Exposed cohort: Gestational age less than 36 weeks at birth No exposure to surgery or anesthesia prior to 36 months of age Surgery/Anesthesia other than index hernia repair prior to 36 months of age Not categorized as ASA I or ASA II Not ages 8 yr, 0 mo to 15 yr, 0 mo Not English speaking Not biologically related to the unexposed sibling Unexposed cohort: Gestational age under 36 weeks at birth Any exposure to surgery or anesthesia prior to 36 months of age Not categorized as ASA I or ASA II Not ages 8 yr, 0 mo to 15 yr, 0 mo Not English speaking Not biologically related to the unexposed sibling

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Exposed Cohort<br>Children who had inguinal hernia surgery and general anesthesia before 36 months of age (n=500). These children should be ages 8 yr, 0 mo to 15 yr, 0 mo at the time of the study period. | Procedure: Inguinal hernia surgery<br>* Non-experimental procedure<br>Procedure: General anesthesia<br>* Non-experimental procedure/treatment<br>|
| Unexposed Cohort<br>Children who are siblings of the exposed children (inguinal hernia surgery and general anesthesia) and differ in age from the exposed children by less than 36 months and have no history of surgery or exposure to volatile and intravenous anesthetics or sedatives including barbiturates, benzodiazepines and chloral hydrate less than 36 months of age. These children should also be ages 8 yr, 0 mo to 15 yr, 0 mo at the time of the study period. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in neurocognitive function | Global cognitive function: verbal, performance and full IQ assessed by Wechsler Abbreviated Scale of Intelligence (WASI). These are one unit of measure for IQ. | Varies; when the participant is 8-15 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in domain-specific function related to visual memory and learning | NEPSY II (A Developmental Neuropsychological Assessment) assesses visual memory learning | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to verbal memory and learning | California Verbal Learning Test-Children (CVLT-C) assesses verbal memory and learning. | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to receptive language | NEPSY II (A Developmental Neuropsychological Assessment) is used to assess receptive language and speeded naming. | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to expressive language | WASI is used to assess expressive language and verbal reasoning | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to working memory | Weschler Intelligence Scale for Children (WISC-IV) is used to assess working memory, attention and executive function. | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to all executive function components | Behavior Rating In Executive Function (BRIEF) is used to assess all components of executive function. | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to selective attention and impulsivity | Continuous Performance Test-II (CPT-II) is used to assess sustained and selective attention as well as impulsivity. | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to cognitive flexibility aspects of executive function | Delis-Kaplan Executive Function System (DKEFS) is used to assess cognitive flexibility. | Varies; when the participant is 8-15 years of age | 
| Change in domain-specific function related to motor and processing speed | Grooved pegboard and Weschler Intelligence Scale for Children (WISC-IV) are used to assess motor and processing speed | Varies; when the participant is 8-15 years of age | 
| Changes in behavior | Childhood Behavior Check List (CBCL) assesses emotionally reactive, anxious/depressed, somatic complaints, withdrawn, attention problems and aggressive behavior. | Varies; when the participant is 8-15 years of age | 
| Changes in adaptive behavior | Adaptive behavior is assessed using Adaptive Behavior Assessment Systems II (ABAS-II), which measures overall adaptive behavior and skills. | Varies; when the participant is 8-15 years of age | 
| Changes in parental relationships | Parent Relationship Questionnaire (PRQ) is used to explore parents' perspectives on parent-child relationship. | Varies; when the participant is 8-15 years of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Anesthesia, New York, Columbia, Children, Neurodevelopment, Child development, Pediatric