PANDA (Pediatric Anesthesia & NeuroDevelopment Assessment) Study

Cognition - Other Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00881764
• Other study ID #: AAAC8756
• Secondary ID: R34HD060741HHSF2
• Status: Completed
• Start date: May 2009
• Est. completion date: January 2016

Study information

• Verified date: February 2023
• Source: Columbia University
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 369
• Est. completion date: January 2016
• Est. primary completion date: April 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 8 Years to 15 Years

Eligibility

Inclusion Criteria:

Exposed cohort:

1. Subjects who had inguinal hernia surgery before 36 months of age

2. Ages 8 yr, 0 mo to 15 yr, 0 mo

3. Gestation age greater or equal to 36 weeks

4. Categorized as ASA I or ASA II

5. English speaking

6. Biologically related to the unexposed sibling

Unexposed cohort:

1. Sibling within 36 months of age of the exposed cohort

2. Never had surgery or exposure to anesthesia prior to 36 months of age

3. Ages 8 yr, 0 mo to 15 yr, 0 mo

4. Gestation age greater or equal to 36 weeks

5. Categorized as ASA I or ASA II

5. English speaking 6. Biologically related to the exposed sibling

Exclusion criteria:

Exposed cohort:

1. Gestational age less than 36 weeks at birth

2. No exposure to surgery or anesthesia prior to 36 months of age

3. Surgery/Anesthesia other than index hernia repair prior to 36 months of age

4. Not categorized as ASA I or ASA II

5. Not ages 8 yr, 0 mo to 15 yr, 0 mo

6. Not English speaking

7. Not biologically related to the unexposed sibling

Unexposed cohort:

1. Gestational age under 36 weeks at birth

2. Any exposure to surgery or anesthesia prior to 36 months of age

3. Not categorized as ASA I or ASA II

4. Not ages 8 yr, 0 mo to 15 yr, 0 mo

5. Not English speaking

6. Not biologically related to the unexposed sibling

Related Conditions & MeSH terms

• Cognition - Other

Intervention

Procedure:
• Inguinal hernia surgery
Non-experimental procedure
• General anesthesia
Non-experimental procedure/treatment

Locations

Country	Name	City	State
United States	Children's Hospital Boston	Boston	Massachusetts
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	Columbia University, 622 W. 168th St.	New York	New York
United States	The Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Columbia University	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Office of Acquisitions and Grants Services (OAGS)

Country where clinical trial is conducted

United States, 

References & Publications (11)

Anand KJ, Soriano SG. Anesthetic agents and the immature brain: are these toxic or therapeutic? Anesthesiology. 2004 Aug;101(2):527-30. doi: 10.1097/00000542-200408000-00033. No abstract available. — View Citation

Anand KJ. Anesthetic neurotoxicity in newborns: should we change clinical practice? Anesthesiology. 2007 Jul;107(1):2-4. doi: 10.1097/01.anes.0000268484.05444.35. No abstract available. — View Citation

Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vockler J, Dikranian K, Tenkova TI, Stefovska V, Turski L, Olney JW. Blockade of NMDA receptors and apoptotic neurodegeneration in the developing brain. Science. 1999 Jan 1;283(5398):70-4. doi: 10.1126/science.283.5398.70. — View Citation

Jevtovic-Todorovic V, Hartman RE, Izumi Y, Benshoff ND, Dikranian K, Zorumski CF, Olney JW, Wozniak DF. Early exposure to common anesthetic agents causes widespread neurodegeneration in the developing rat brain and persistent learning deficits. J Neurosci. 2003 Feb 1;23(3):876-82. doi: 10.1523/JNEUROSCI.23-03-00876.2003. — View Citation

Jevtovic-Todorovic V. General anesthetics and the developing brain: friends or foes? J Neurosurg Anesthesiol. 2005 Oct;17(4):204-6. doi: 10.1097/01.ana.0000178111.26972.16. No abstract available. — View Citation

Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesth Analg. 2007 Mar;104(3):509-20. doi: 10.1213/01.ane.0000255729.96438.b0. — View Citation

Olney at al. FDA symposium. 2002:12:488-498

Olney JW, Young C, Wozniak DF, Jevtovic-Todorovic V, Ikonomidou C. Do pediatric drugs cause developing neurons to commit suicide? Trends Pharmacol Sci. 2004 Mar;25(3):135-9. doi: 10.1016/j.tips.2004.01.002. No abstract available. — View Citation

Slikker et al. FDA science 2005 Forum

Slikker W Jr, Zou X, Hotchkiss CE, Divine RL, Sadovova N, Twaddle NC, Doerge DR, Scallet AC, Patterson TA, Hanig JP, Paule MG, Wang C. Ketamine-induced neuronal cell death in the perinatal rhesus monkey. Toxicol Sci. 2007 Jul;98(1):145-58. doi: 10.1093/toxsci/kfm084. Epub 2007 Apr 10. — View Citation

Walden M, Carrier CT. Sleeping beauties: the impact of sedation on neonatal development. J Obstet Gynecol Neonatal Nurs. 2003 May-Jun;32(3):393-401. doi: 10.1177/0884217503253454. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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