Neuropsychological and Behavioral Outcomes after Exposure of Young Children to Procedures Requiring General Anesthesia: The Mayo Anesthesia Safety in Kids (MASK) Study

Abstract

Background: Few studies of how exposure of children to anesthesia may affect neurodevelopment employ comprehensive neuropsychological assessments. This study tested the hypothesis that exposure to multiple, but not single, procedures requiring anesthesia before age 3 yr is associated with adverse neurodevelopmental outcomes.

Methods: Unexposed, singly exposed, and multiply exposed children born in Olmsted County, Minnesota, from 1994 to 2007 were sampled using a propensity-guided approach and underwent neuropsychological testing at ages 8 to 12 or 15 to 20 yr. The primary outcome was the Full-Scale intelligence quotient standard score of the Wechsler Abbreviated Scale of Intelligence. Secondary outcomes included individual domains from a comprehensive neuropsychological assessment and parent reports.

Results: In total, 997 children completed testing (411, 380, and 206 unexposed, singly exposed, and multiply exposed, respectively). The primary outcome of intelligence quotient did not differ significantly according to exposure status; multiply exposed and singly exposed children scoring 1.3 points (95% CI, -3.8 to 1.2; P = 0.32) and 0.5 points (95% CI, -2.8 to 1.9; P = 0.70) lower than unexposed children, respectively. For secondary outcomes, processing speed and fine motor abilities were decreased in multiply but not singly exposed children; other domains did not differ. The parents of multiply exposed children reported increased problems related to executive function, behavior, and reading.

Conclusions: Anesthesia exposure before age 3 yr was not associated with deficits in the primary outcome of general intelligence. Although secondary outcomes must be interpreted cautiously, they suggest the hypothesis that multiple, but not single, exposures are associated with a pattern of changes in specific neuropsychological domains that is associated with behavioral and learning difficulties.

Figure 1

Flow diagram of subject recruitment. Of the 27,213 children identified by the Minnesota Department of Health as being born in to mothers residing in Olmsted County from 1994-2007, the following were excluded from being potentially eligible for recruitment: 34 who could not be matched to a Rochester Epidemiology Project record, 3,455 who did not provide authorization to use their medical records for research, 2,784 who were not resident in Olmsted County until age 3, 161 who were deceased at the start of recruitment, and 1,483 who lived more than 25 miles from Rochester, MN at the start of recruitment. From the remaining 19,296, a total of 3,926 were sampled using propensity scores as described in the methods for possible recruitment. The original intention was to sample all multiply-exposed children, but recruitment goals were met before all were invited. Of those sampled, 820 were not invited for the reasons indicated. Regarding conditions precluding testing, among all exposure categories, 10 children (0.2% of those sampled) were excluded because of severe intellectual disability, 37 (0.9%) because of autism, 7 (0.2%) because of spastic cerebral palsy, and 59 (1.5%) because of limited English proficiency. Fourteen children responded directly to television advertisements directed towards the multiply-exposed without receiving invitations (one child who was singly-exposed was originally thought to be multiply-exposed but actually had a procedure without general anesthesia). A total of 998 children were enrolled rather than the planned 1000 due to a clerical error that duplicated two children in the recruitment log.

Figure 2

Standardized differences between the factors used in the propensity scoring for the primary analysis before (red circles) and after (blue diamonds) inverse probability treatment weighting. WASI, Wechsler Abbreviated Scale of Intelligence; IQ, intelligence quotient; ADG, aggregated diagnostic groups; exp., exposed. For both mother's and father's education (the two factors with the largest differences after weighting in multiply-exposed subjects), the residual differences from the weighted estimates are in the direction of the unexposed group having parents who are slightly less educated than the exposed groups. Therefore, if lower parental education is associated with worse outcomes, any residual confounding should bias results toward the null.