Age at Exposure to Surgery and Anesthesia in Children and Association With Mental Disorder Diagnosis

Abstract

Background: Animals exposed to anesthetics during specific age periods of brain development experience neurotoxicity, with neurodevelopmental changes subsequently observed during adulthood. The corresponding vulnerable age in children, however, is unknown.

Methods: An observational cohort study was performed using a longitudinal dataset constructed by linking individual-level Medicaid claims from Texas and New York from 1999 to 2010. This dataset was evaluated to determine whether the timing of exposure to anesthesia ≤5 years of age for a single common procedure (pyloromyotomy, inguinal hernia, circumcision outside the perinatal period, or tonsillectomy and/or adenoidectomy) is associated with increased subsequent risk of diagnoses for any mental disorder, or specifically developmental delay (DD) such as reading and language disorders, and attention deficit hyperactivity disorder (ADHD). Exposure to anesthesia and surgery was evaluated in 11 separate age at exposure categories: ≤28 days old, >28 days and ≤6 months, >6 months and ≤1 year, and 6-month age intervals between >1 year old and ≤5 years old. For each exposed child, 5 children matched on propensity score calculated using sociodemographic and clinical covariates were selected for comparison. Cox proportional hazards models were used to measure the hazard ratio of a mental disorder diagnosis associated with exposure to surgery and anesthesia.

Results: A total of 38,493 children with a single exposure and 192,465 propensity score-matched children unexposed before 5 years of age were included in the analysis. Increased risk of mental disorder diagnosis was observed at all ages at exposure with an overall hazard ratio of 1.26 (95% confidence interval [CI], 1.22-1.30), which did not vary significantly with the timing of exposure. Analysis of DD and ADHD showed similar results, with elevated hazard ratios distributed evenly across all ages, and overall hazard ratios of 1.26 (95% CI, 1.20-1.32) for DD and 1.31 (95% CI, 1.25-1.37) for ADHD.

Conclusions: Children who undergo minor surgery requiring anesthesia under age 5 have a small but statistically significant increased risk of mental disorder diagnoses and DD and ADHD diagnoses, but the timing of the surgical procedure does not alter the elevated risks. Based on these findings, there is little support for the concept of delaying a minor procedure to reduce long-term neurodevelopmental risks of anesthesia in children. In evaluating the influence of age at exposure, the types of procedures included may need to be considered, as some procedures are associated with specific comorbid conditions and are only performed at certain ages.

Figure 1. Kaplan-Meier Analysis of Mental Disorder Diagnosis after a Single Exposure to Surgery and Anesthesia in TX and NY

For the exposed children, data in Panels A through K show the length of time after surgical procedure until diagnosis of a mental disorder. In each age at exposure category, the median age of surgery was calculated for the exposed children and applied to the unexposed children. For the unexposed children, Panels A through K show the length of time from this median age of surgery until diagnosis of a mental disorder. Panel L shows results from all age at exposure categories combined.

Figure 2. Hazard of an ICD-9 coded Mental Disorder Diagnosis after a Single Exposure to Surgery and Anesthesia in TX and NY

Hazard ratios (HR) for diagnosis of mental disorder are displayed for exposed vs. matched unexposed children. The number (n) of exposed children in each age at exposure group is also displayed. Panel A shows hazard ratios for children who had any of the four procedures of interest vs. unexposed children. Panels B, C, D, and E show hazard ratios for children who had pyloromyotomy, inguinal hernia repair, circumcision, and tonsillectomy and/or adenoidectomy respectively, compared to unexposed children.

Figure 3. Hazard of an ICD-9 coded Developmental Delay Diagnosis after a Single Exposure to Surgery and Anesthesia in TX and NY

Hazard ratios (HR) for diagnosis of a developmental delay are displayed for exposed vs. matched unexposed children. The number (n) of exposed children in each age at exposure group is also displayed. Panel A shows hazard ratios for children who had any of the four procedures of interest vs. unexposed children. Panels B, C, D, and E show hazard ratios for children who had pyloromyotomy, inguinal hernia repair, circumcision, and tonsillectomy and/or adenoidectomy respectively, compared to unexposed children.

Figure 4. Hazard of an ICD-9 coded Attention Deficit Hyperactivity Disorder Diagnosis after a Single Exposure to Surgery and Anesthesia in TX and NY

Hazard ratios (HR) for diagnosis of an attention deficit hyperactivity disorder are displayed for exposed vs. matched unexposed children. The number (n) of exposed children in each age at exposure group is also displayed. Panel A shows hazard ratios for children who had any of the four procedures of interest vs. unexposed children. Panels B, C, D, and E show hazard ratios for children who had pyloromyotomy, inguinal hernia repair, circumcision, and tonsillectomy and/or adenoidectomy respectively, compared to unexposed children.