Neurodevelopmental Outcomes After Multiple General Anaesthetic Exposure Before Five Years Of Age – A Cohort Study

Background The GAS trial demonstrated evidence that most neurodevelopmental outcomes at 2 years and 5 years of age in infants who received a single general anaesthetic (GA) for elective inguinal herniorrhaphy were clinically equivalent when compared to infants who did not receive GA. More than 20% of the children in the trial had at least one subsequent anaesthetic exposure after their initial surgery. Using the GAS database, this study aimed to address whether multiple (2 or more) GA exposures compared to one or no GA exposure in early childhood were associated with worse neurodevelopmental outcomes at 5 years. Methods Children with multiple GA exposures and children with one or no GA exposure were identified from the GAS database. The primary outcome was the full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence third edition (WPPSI-III) at 5 years of age. Secondary outcomes included neurocognitive tests addressing all major developmental domains and caregiver-reported questionnaires assessing emotional and behavioural problems. Results Complete assessment was available from a total of 90 children in the multiple GA group and 141 children in the 0 or 1 GA group. Compared with children with a single or no GA 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 WPPSI-III FSIQ. They also demonstrated lower verbal and performance IQ scores and more emotional, behavioural, and executive function difficulties. However, significant residual confounding cannot be excluded from the results due to the observational nature of this study. Conclusions Multiple GA exposure before 5 years of age was associated with reduced performance in general intelligence score and some domains of neurodevelopmental assessments. The clinical significance of our 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.