BACKGROUND: Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain. METHODS: The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models. RESULTS: A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, -0.7; 95% CI, -0.93 to -0.47; P < 0.0001) and language/cognition (estimate, -0.34; 95% CI, -0.52 to -0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure. CONCLUSIONS: These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.
BACKGROUND: Animal studies demonstrate general anesthetic (GA) toxicity in the developing brain. Clinical reports raise concern, but the risk of GA exposure to neurodevelopment in children remains uncertain. METHODS: The authors undertook a retrospective matched cohort study comparing children less than 4 yr of age exposed to GA to those with no GA exposure. The authors used the Early Development Instrument (EDI), a 104-component questionnaire, encompassing five developmental domains, completed in kindergarten as the outcome measure. Mixed-effect logistic regression models generated EDI estimates for single versus multiple GA exposure and compared both single and multiple exposures by the age of 0 to 2 or 2 to 4 yr. Known sociodemographic and physical confounders were incorporated as covariates in the models. RESULTS: A total of 18,056 children were studied: 3,850 exposed to a single GA and 620 exposed to two or more GA, who were matched to 13,586 nonexposed children. In children less than 2 yr of age, there was no independent association between single or multiple GA exposure and EDI results. Paradoxically, single exposure between 2 and 4 yr of age was associated with deficits, most significant for communication/general knowledge (estimate, -0.7; 95% CI, -0.93 to -0.47; P < 0.0001) and language/cognition (estimate, -0.34; 95% CI, -0.52 to -0.16; P < 0.0001) domains. Multiple GA exposure at the age of 2 to 4 yr did not confer greater risk than single GA exposure. CONCLUSIONS: These findings refute the assumption that the earlier the GA exposure in children, the greater the likelihood of long-term neurocognitive risk. The authors cannot confirm an association between multiple GA exposure and increased risk of neurocognitive impairment, increasing the probability of confounding to explain the results.
Authors: James D O'Leary; Magdalena Janus; Eric Duku; Duminda N Wijeysundera; Teresa To; Ping Li; Jason T Maynes; David Faraoni; Mark W Crawford Journal: JAMA Pediatr Date: 2019-01-01 Impact factor: 16.193
Authors: Michael J Zaccariello; Ryan D Frank; Minji Lee; Alexandra C Kirsch; Darrell R Schroeder; Andrew C Hanson; Phillip J Schulte; Robert T Wilder; Juraj Sprung; Slavica K Katusic; Randall P Flick; David O Warner Journal: Br J Anaesth Date: 2019-05 Impact factor: 9.166
Authors: Yu Shi; Danqing Hu; Erin L Rodgers; Slavica K Katusic; Stephen J Gleich; Andrew C Hanson; Darrell R Schroeder; Randall P Flick; David O Warner Journal: Paediatr Anaesth Date: 2018-03-13 Impact factor: 2.556
Authors: Devan Darby Bartels; Mary Ellen McCann; Andrew J Davidson; David M Polaner; Elizabeth L Whitlock; Brian T Bateman Journal: Paediatr Anaesth Date: 2018-05-02 Impact factor: 2.556
Authors: Caleb Ing; Ming Sun; Mark Olfson; Charles J DiMaggio; Lena S Sun; Melanie M Wall; Guohua Li Journal: Anesth Analg Date: 2017-12 Impact factor: 5.108