Infant Anesthesia Exposure and Neuro-outcome

• Quality of life [ Time Frame: one day ] [ Designated as safety issue: No ]
• Behavioral function [ Time Frame: one day ] [ Designated as safety issue: No ]
• Emotional function [ Time Frame: one day ] [ Designated as safety issue: No ]
• Neurological function [ Time Frame: one day ] [ Designated as safety issue: No ]
• Family function [ Time Frame: one day ] [ Designated as safety issue: No ]

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.

Specific Aim: To compare neurocognitive functions in sibling pairs: one of whom had exposure to general anesthesia during surgery before 36 months of age (exposed cohort group) and who will be ages 8 yr, 0 mo to 15 yr, 0 mo at the time of the study, and the other who never had any exposure to anesthesia or surgery less than 36 months of age (unexposed cohort group), who will be ages 8 yr, 0 mo to 15 yr, 0 mo at the time of the study . Sibling pairs will be within 36 months of age from one another.

According to the National Hospital Discharge Survey, around 2.5 million children have surgical procedures requiring anesthesia each year in the US. The exposure to general anesthesia for children is much greater as many children receive general anesthesia for non-surgical procedures. Furthermore, there is an increased use of pediatric imaging studies requiring the use of sedation and anesthesia. The number of children having anesthesia is likely to grow substantially in the future. Given the extent of this growing pediatric exposure to anesthetics, it is disturbing that 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. Our goal is to determine whether the use of anesthetic agents in infants and children have long term adverse effects on neurocognitive development.

The study will be a multi-center study based at Columbia University with the following participating centers: Boston Children's (Harvard University), Chicago Children's Memorial (Northwestern University), Children's Hospital of Philadelphia (University of Pennsylvania), Cincinnati Children's Hospital (University of Cincinnati College of Medicine), University of Pittsburgh Children's Hospital, University of Michigan Children's Hospital, 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.

• Exposed Cohort
  Children who had surgery 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.
• Unexposed Cohort
  Children who are siblings of the exposed children 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.

• Ikonomidou C, Bosch F, Miksa M, Bittigau P, Vöckler 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.
• Anand KJ, Soriano SG. Anesthetic agents and the immature brain: are these toxic or therapeutic? Anesthesiology. 2004 Aug;101(2):527-30. Review. No abstract available.
• Anand KJ. Anesthetic neurotoxicity in newborns: should we change clinical practice? Anesthesiology. 2007 Jul;107(1):2-4. No abstract available.
• 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. Review. No abstract available.
• 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. Review.
• Mellon RD, Simone AF, Rappaport BA. Use of anesthetic agents in neonates and young children. Anesth Analg. 2007 Mar;104(3):509-20. Review.

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

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

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

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

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Office of Acquisitions and Grants Services (OAGS)