Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort.
Early childhood exposure to anesthesia and risk of developmental and behavioral disorders in a sibling birth cohort.
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DOI：
10.1213/ane.0b013e3182147f42
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发表时间：
2011-11
影响因子：
5.7
通讯作者：
Li G
中科院分区：
文献类型：
--
作者：
DiMaggio C;Sun LS;Li G
体外和体内的研究表明，麻醉剂对发育中的大脑有严重的神经毒性作用。然而，这些发现与接受麻醉的儿童的临床相关性仍不清楚。使用来自同胞出生队列的数据，我们评估了3岁以下患者在手术环境中暴露于麻醉剂与发育和行为障碍风险之间的关系。我们建立了一个回顾性队列，包括10,450名出生于1999年至2005年之间的兄弟姐妹，他们参加了纽约州医疗补助计划。暴露组是304名没有发育或行为障碍史的儿童，他们在3岁以下时接受了手术。未暴露组为10，146名3岁以下未接受任何手术的儿童。暴露儿童在手术当天进入分析。未暴露儿童在10个月大时（暴露儿童接受手术的平均年龄）进入分析。对暴露和未暴露的儿童进行随访，直至诊断为发育或行为障碍、失访或2005年底。暴露于麻醉与随后的发育和行为障碍的关联进行了评估与比例风险建模，配对分析。暴露队列中发育和行为障碍的发生率为128.2例诊断/1000人-年，未暴露队列为56.3例诊断/1000人-年。校正性别和出生相关医学并发症史，并按兄弟姐妹状态聚类，3岁以下儿童与任何麻醉暴露相关的发育或行为障碍的估计风险比为1.6（95% CI 1.4，1.8）。风险从1次手术的1.1（95% CI 0.8，1.4）增加到2次手术的2.9（94% CI 2.5，3.1）和3次或更多次手术的4.0（95% CI 3.5，4.5）。在138对兄弟姐妹的匹配分析中，风险为0.9（95%CI 0.6，1.4），在参加国家医疗补助计划并在3岁以下接受手术的儿童中，随后被诊断为发育和行为障碍的风险比未接受手术的类似兄弟姐妹组高60%。更紧密匹配的成对分析表明，在何种程度上的过度风险是因果关系归因于麻醉或介导的不可测量的因素仍有待确定。
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. 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. 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) 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.