Hundreds of thousands of children in the United States are exposed to anesthesia for surgical procedures each year, making the safety of anesthetic agents a pressing concern. In the past few years, the discovery of apoptotic neurodegeneration in immature animals after exposure to anesthesia has raised questions about whether similar adverse effects occur in the developing brains of children. The results from recent clinical studies show a 1.6 to 2-fold increase in cognitive disability associated with early anesthetic exposure. While neurotoxic susceptibility to anesthetic agents in the animal model has been well defined based on neurodevelopmental age, similar data from clinical studies is lacking. Despite this lack of information, clinicians and parents have begun delaying elective procedures in children with little guidance regarding how long to delay and if anesthetics should be avoided in all young children. This proposal addresses these gaps in knowledge by looking specifically at the association between the age of exposure and neuropsychological disorder, as well as vulnerability in latent class subgroups of children using a large US sample. Using Medicaid Analytic eXtract (MAX) files, we will construct a longitudinal retrospective multi-state cohort of children enrolled in Medicaid from 1999 to 2009 (11 years). We will assess children who underwent five specific International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9) coded procedure types requiring anesthesia and commonly performed in otherwise healthy children: inguinal hernia repair, pyloromyotomy, appendectomy, tonsillectomy and adenoidectomy, and circumcisions outside the perinatal period. We hypothesize that the risk of neuropsychological disorder varies by age of initial exposure, with increased risk seen in children exposed at earlier ages. We expect this association to also be reflected in the incidence of psychotropic medication prescription fills. Based on preliminary data from an alternate birth cohort, we additionally hypothesize that while some subgroups of children may be affected by anesthesia exposure, others will not be affected.
In Aim 1, we will identify the critical period of exposure associated with ICD-9 coded behavioral and developmental delay by assessing children with initial exposure to specific surgical procedures from birth until 4 years of age in stratified 6-month intervals.
In Aim 2 we will assess the increased risk of National Drug Code (NDC) coded psychotropic medication use in children exposed to anesthesia and test for differences in the incidence of classes of medications including stimulants and antipsychotics.
In Aim 3 we will identify latent class subgroups of children with ICD-9 coded disability and NDC coded psychotropic medication use. At the conclusion of these studies we will have expanded the knowledge of the age related association between anesthesia exposure and neuropsychological disability, helped identify vulnerable groups of children, and generated data for researchers to direct prospective studies and clinicians to advise concerned parents.
Each year hundreds of thousands of children are exposed to anesthesia in the United States for surgical and diagnostic procedures, while mounting evidence points to an increased risk of long-term cognitive disability in children exposed to anesthetic agents at an early age. Our preliminary data indicates that subgroups of children may be particularly vulnerable and that susceptibility may vary by age of initial exposure. In this proposal we will construct a longitudinal retrospective multi-state cohort of children enrolled in the Medicaid program from 1999 to 2009 to determine the critical age of exposure to anesthesia, the association between exposure and psychotropic medication use, and to identify potentially vulnerable groups of children.