Association between Exposure of Young Children to Procedures Requiring General Anesthesia and Learning and Behavioral Outcomes in a Population-based Birth Cohort

Abstract

Background: Exposure of young animals to general anesthesia causes neurodegeneration and lasting behavioral abnormalities; whether these findings translate to children remains unclear. This study used a population-based birth cohort to test the hypothesis that multiple, but not single, exposures to procedures requiring general anesthesia before age 3 yr are associated with adverse neurodevelopmental outcomes.

Methods: A retrospective study cohort was assembled from children born in Olmsted County, Minnesota, from 1996 to 2000 (inclusive). Propensity matching selected children exposed and not exposed to general anesthesia before age 3 yr. Outcomes ascertained via medical and school records included learning disabilities, attention-deficit/hyperactivity disorder, and group-administered ability and achievement tests. Analysis methods included proportional hazard regression models and mixed linear models.

Results: For the 116 multiply exposed, 457 singly exposed, and 463 unexposed children analyzed, multiple, but not single, exposures were associated with an increased frequency of both learning disabilities and attention-deficit/hyperactivity disorder (hazard ratio for learning disabilities = 2.17 [95% CI, 1.32 to 3.59], unexposed as reference). Multiple exposures were associated with decreases in both cognitive ability and academic achievement. Single exposures were associated with modest decreases in reading and language achievement but not cognitive ability.

Conclusions: These findings in children anesthetized with modern techniques largely confirm those found in an older birth cohort and provide additional evidence that children with multiple exposures are more likely to develop adverse outcomes related to learning and attention. Although a robust association was observed, these data do not determine whether anesthesia per se is causal.

Figure 1

Age of LD (Panel A) or ADHD (Panel B) diagnosis for children not exposed, singly exposed, or multiply exposed. Bands indicate 95% confidence intervals (CI). Cumulative incidence at age 18 estimated by Kaplan Meier analysis with 95% CI are also indicated for each exposure category. Also shown on the x-axis are the numbers of children at risk (i.e., not censored) at ages 4, 8, 12 and 16 years for each analysis, given emigration, death, last available follow-up in medical and/or school records, and end of study (at which time the youngest children were 14 years of age).

Figure 1

Age of LD (Panel A) or ADHD (Panel B) diagnosis for children not exposed, singly exposed, or multiply exposed. Bands indicate 95% confidence intervals (CI). Cumulative incidence at age 18 estimated by Kaplan Meier analysis with 95% CI are also indicated for each exposure category. Also shown on the x-axis are the numbers of children at risk (i.e., not censored) at ages 4, 8, 12 and 16 years for each analysis, given emigration, death, last available follow-up in medical and/or school records, and end of study (at which time the youngest children were 14 years of age).