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BACKGROUND: Over the past decade, the safety of anesthetic agents in children has been questioned after the discovery that immature animals exposed to anesthesia display apoptotic neurodegeneration and long-term cognitive deficiencies. We examined the association between exposure to anesthesia in children under age 3 and outcomes in language, cognitive function, motor skills, and behavior at age 10. METHODS: We performed an analysis of the Western Australian Pregnancy Cohort (Raine) Study, which includes 2868 children born from 1989 to 1992. Of 2608 children assessed, 321 were exposed to anesthesia before age 3, and 2287 were unexposed. RESULTS: On average, exposed children had lower scores than their unexposed peers in receptive and expressive language (Clinical Evaluation of Language Fundamentals: Receptive [CELF-R] and Expressive [CELF-E]) and cognition (Colored Progressive Matrices [CPM]). After adjustment for demographic characteristics, exposure to anesthesia was associated with increased risk of disability in language (CELF-R: adjusted risk ratio [aRR], 1.87; 95% confidence interval [CI], 1.20–2.93, CELF-E: aRR, 1.72; 95% CI, 1.12–2.64), and cognition (CPM: aRR, 1.69; 95% CI, 1.13–2.53). An increased aRR for disability in language and cognition persisted even with a single exposure to anesthesia (CELF-R aRR, 2.41; 95% CI, 1.40–4.17, and CPM aRR, 1.73; 95% CI, 1.04–2.88). CONCLUSIONS: Our results indicate that the association between anesthesia and neuropsychological outcome may be confined to specific domains. Children in our cohort exposed to anesthesia before age 3 had a higher relative risk of language and abstract reasoning deficits at age 10 than unexposed children.

Recent animal studies have shown that commonly used anesthetic agents may have serious neurotoxic effects on the developing brain. The purpose of this study was to assess the association between surgery for hernia repair and the risk of behavioral and developmental disorders in young children. We performed a retrospective cohort analysis of children who were enrollees of the New York State Medicaid program. Our analysis involved following a birth cohort of 383 children who underwent inguinal hernia repair during the first three years of life, and a sample of 5050 children frequency-matched on age with no history of hernia-repair before age 3. After controlling for age, gender, and complicating birth-related conditions such as low birth weight, children who underwent hernia repair under three years of age were more than twice as likely as children in the comparison group to be subsequently diagnosed with a developmental or behavioral disorder (adjusted HR 2.3, 95% CI 1.3, 4.1). Our findings add to recent evidence of the potential association of surgery and its concurrent exposure to anesthetic agents with neurotoxicity and underscore the need for more rigorous clinical research on the long-term effects of surgery and anesthesia in children.

Introduction In vitro and in vivo studies of anesthetics have demonstrated serious neurotoxic effects on the developing brain. However the clinical relevance of these findings to children undergoing anesthesia remains unclear. Using data from a sibling birth cohort, we assessed the association between exposure to anesthesia in the setting of surgery in patients younger than 3 years and the risk of developmental and behavioral disorders. Methods We constructed a retrospective cohort of 10,450 siblings who were born between 1999 and 2005 and who were enrolled in the New York State Medicaid program. The exposed group was 304 children without a history of developmental or behavioral disorders who underwent surgery when they were younger than 3 years. The unexposed group was 10,146 children who did not receive any surgical procedures when they were younger than 3 years. Exposed children were entered into analysis at the date of surgery. Unexposed children were entered into analysis at age 10 months (the mean age at which exposed children underwent surgery). Both exposed and unexposed children were followed until diagnosis with a developmental or behavioral disorder, loss to follow-up, or the end of 2005. The association of exposure to anesthesia with subsequent developmental and behavioral disorders was assessed with both proportional hazards modeling, and pair-matched analysis. Results The incidence of developmental and behavioral disorders was 128.2 diagnoses per 1000 person-years for the exposed cohort and 56.3 diagnoses per 1000 person-years for the unexposed cohort. With adjustment for sex and history of birth-related medical complications, and clustering by sibling status, the estimated hazard ratio of developmental or behavioral disorders associated with any exposure to anesthesia when they were younger than 3 years was 1.6 (95% CI 1.4, 1.8). The risk increased from 1.1 (95% CI 0.8, 1.4) for one surgery to 2.9 (94% CI 2.5, 3.1) for two surgeries and 4.0 (95% CI 3.5, 4.5) for three or more surgeries. The risk in a matched analysis of 138 sibling pairs was 0.9 (95% CI 0.6, 1.4) Conclusion The risk of being subsequently diagnosed with developmental and behavioral disorders in children who were enrolled in a state Medicaid program and who had surgery when they were younger than 3 years was 60% greater than that of a similar group of siblings who did not undergo surgery. More tightly matched pairwise analyses indicate that the extent to which the excess risk is causally attributable to anesthesia or mediated by unmeasured factors remains to be determined.

The estimated number of deaths attributable to social factors in the United States is comparable to the number attributed to pathophysiological and behavioral causes. These findings argue for a broader public health conceptualization of the causes of mortality and an expansive policy approach that considers how social factors can be addressed to improve the health of populations.