Charles J. DiMaggio; Lena S. Y. Sun; Guohua Li
(See Anesthesia and Analgesia. 2011 Nov; 113(5): 1143-51)
Background: 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% confidence interval [CI]: 1.4, 1.8). The risk increased from 1.1 (95% CI: 0.8, 1.4) for 1 operation to 2.9 (94% CI: 2.5, 3.1) for 2 operations and 4.0 (95% CI: 3.5, 4.5) for ≥3 operations. The relative 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.
Charles J. DiMaggio; Lena S. Y. Sun; Athina Kakavouli; Mary W. Byrne; Guohua Li
(See Journal of Neurosurgical Anesthesiology. 2009; 21(4):286-291.)
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.