Neurodevelopmental Outcomes after Multiple General Anesthetic Exposures before 5 Years of Age: A Cohort Study

Background: The general anaesthesia or awake-regional anaesthesia in infancy (GAS) trial demonstrated evidence that most neurodevelopmental outcomes at 2 and 5 yr of age in infants who received a single general anesthetic for elective inguinal herniorrhaphy were clinically equivalent when compared to infants who did not receive general anesthesia. More than 20% of the children in the trial had at least one subsequent anesthetic exposure after their initial surgery. Using the GAS database, this study aimed to address whether multiple (two or more) general anesthetic exposures compared to one or no general anesthetic exposure in early childhood were associated with worse neurodevelopmental outcomes at 5 yr. Methods: Children with multiple general anesthetic exposures and children with one or no general anesthetic exposure were identified from the GAS database. The primary outcome was the full-scale intelligence quotient on the Wechsler Preschool and Primary Scale of Intelligence (third edition) at 5 yr of age. Secondary outcomes included neurocognitive tests addressing all major developmental domains and caregiver-reported questionnaires assessing emotional and behavioral problems. Results: Complete assessment was available from a total of 90 children in the multiple general anesthetic group and 141 children in the no or one general anesthetic group. Compared with children with a single or no general anesthetic exposure, multiply exposed children scored on average almost 6 points lower (mean, −5.8; 95% CI, −10.2 to −1.4; P = 0.011) in the Wechsler Preschool and Primary Scale of Intelligence full-scale intelligence quotient. They also demonstrated lower verbal and performance IQ scores and more emotional, behavioral, and executive function difficulties. However, significant residual confounding cannot be excluded from the results due to the observational nature of this study. Conclusions: Multiple general anesthetic exposures before 5 yr of age were associated with reduced performance in general intelligence score and some domains of neurodevelopmental assessments. The clinical significance of this study’s results must be cautiously interpreted in light of several sources of limitations including small sample size and unadjusted residual confounding. This study illustrates the limitations of trial data sets that may not be fit for the purpose for the secondary analysis.