NCT00881764

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
369

participants targeted

Target at P75+ for all trials

Timeline
Completed

Started May 2009

Longer than P75 for all trials

Geographic Reach
1 country

4 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 14, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

April 15, 2009

Completed
16 days until next milestone

Study Start

First participant enrolled

May 1, 2009

Completed
5.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2015

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2016

Completed
Last Updated

February 17, 2023

Status Verified

February 1, 2023

Enrollment Period

5.9 years

First QC Date

April 14, 2009

Last Update Submit

February 16, 2023

Conditions

Cognition - Other

Keywords

AnesthesiaNew YorkColumbiaChildrenNeurodevelopmentChild developmentPediatric

Outcome Measures

Primary Outcomes (1)

  • 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 Outcomes (12)

  • Change in domain-specific function related to visual memory and learning

    Varies; when the participant is 8-15 years of age

  • Change in domain-specific function related to verbal memory and learning

    Varies; when the participant is 8-15 years of age

  • Change in domain-specific function related to receptive language

    Varies; when the participant is 8-15 years of age

  • Change in domain-specific function related to expressive language

    Varies; when the participant is 8-15 years of age

  • Change in domain-specific function related to working memory

    Varies; when the participant is 8-15 years of age

  • +7 more secondary outcomes

Study Arms (2)

Exposed Cohort

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 surgeryProcedure: General anesthesia

Unexposed Cohort

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.

Interventions

Inguinal hernia surgeryPROCEDURE

Non-experimental procedure

Exposed Cohort
General anesthesiaPROCEDURE

Non-experimental procedure/treatment

Exposed Cohort

Eligibility Criteria

Age8 Years - 15 Years
Sexall
Healthy VolunteersYes
Age GroupsChild (0-17)
Sampling MethodNon-Probability Sample
Study Population

The study will be a multi-center study based at Columbia University with the following participating centers: Boston Children's (Harvard University), Children's Hospital of Philadelphia (University of Pennsylvania), Monroe Carell Children's Hospital (Vanderbilt University), and Morgan Stanley Children's Hospital of New York (Columbia University). Children exposed to anesthesia prior to 36 months must be ages 8 yr, 0 mo to 15 yr, 0 mo and have a sibling with no history of surgery or anesthesia prior to 36 months of age.

You may qualify if:

  • 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
  • \. English speaking 6. Biologically related to the exposed sibling

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (4)

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

Columbia University, 622 W. 168th St.

New York, New York, 10032, United States

Location

The Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232, United States

Location

Related Publications (11)

  • 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.

    PMID: 9872743BACKGROUND

  • 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.

    PMID: 15277935BACKGROUND

  • 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.

    PMID: 17585205BACKGROUND

  • 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.

    PMID: 15019268BACKGROUND

  • 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.

    PMID: 12774882BACKGROUND

  • 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.

    PMID: 17312200BACKGROUND

  • 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.

    PMID: 12574416BACKGROUND

  • Slikker et al. FDA science 2005 Forum

    BACKGROUND

  • 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.

    PMID: 17426105BACKGROUND

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

    BACKGROUND

  • 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.

    PMID: 16184065BACKGROUND

MeSH Terms

Interventions

Anesthesia, General

Intervention Hierarchy (Ancestors)

AnesthesiaAnesthesia and Analgesia

Study Officials

  • Lena S Sun, MD

    Columbia University

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
OTHER
Time Perspective
OTHER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Emanuel M. Papper Professor of Anesthesiology and Professor of Pediatrics

Study Record Dates

First Submitted

April 14, 2009

First Posted

April 15, 2009

Study Start

May 1, 2009

Primary Completion

April 1, 2015

Study Completion

January 1, 2016

Last Updated

February 17, 2023

Record last verified: 2023-02

Locations

US(4)