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既往麻醉暴露与自闭症谱系障碍(ASD):一项基于波多黎各人群的同胞队列研究。

Previous Exposure to Anesthesia and Autism Spectrum Disorder (ASD): A Puerto Rican Population-Based Sibling Cohort Study.

作者信息

Creagh O, Torres H, Rivera K, Morales-Franqui M, Altieri-Acevedo G, Warner D

出版信息

Bol Asoc Med P R. 2016;108(2):73-80.

Abstract

BACKGROUND

Autism Spectrum Disorder (ASD) is characterized by impaired social interaction and communication, and by restricted and repetitive behavior, that begins usually before a child is three years old.(1) Researchers have shown that prevalence rates in the U.S. may be as high as 1 in 68.(52) A number of studies have examined the effects of early exposure to anesthesia on brain development and subsequent impairment in neurocognitive function; yet, little is known about the possible effects of anesthetic agents on social-behavioral functioning. The association between exposure to anesthesia either in uterus, during the first years of life, or later and development of Autistic Spectrum Disorder (ASD) or its severity was determined in a retrospective population based cohort study.

OBJECTIVES

Identify if children who had previous exposure to anesthesia either in uterus, first years of life during their developing brain years, or later, are at risk of developing ASD and its severe form of the disease.

METHODS

Data was obtained from structured interviews administered to a sample of 515 parents/guardians distributed in two groups: ASD = 262 children diagnosed with this condition and Non-ASD: 253 children (siblings of ASD group) without diagnosis (95% confidence interval) that freely decided to participate and agreed to a consent form. Variables studied include: demographics, diagnosis and severity of ASD, exposure to anesthesia, method of childbirth, and age of exposure Children less than 2 years of age were considered into have developing brain period. Data was analyzed using Chi-square or Fisher exact test.

RESULTS

In contrast to non-ASD group, most of the children within ASD group were male, 76% (p=0.0001). With regards to methods of childbirth, 64% of the ASD population were vaginal delivery (VD; Non-anesthesia exposure group) and 36% cesarean delivery (CD) compared to non-autistic population with 71% VD and 29% CD, which demonstrates no statistical difference between both groups (p=0.1113). Out of the 36% of ASD population that underwent CD, 7% were performed using general anesthesia and 93% regional anesthesia, while the 29% of the CD of non-ASD, 5% were performed using general anesthesia and 95% regional anesthesia. This reveals no statistical significance (p=0.7569) with the development of ASD and the type of anesthesia used when comparing ASD with non-ASD patients. In view of severity of autism, in VD, 56% of ASD population had mild form of the disorder, 34% moderate, and 10% severe; while CD had a 54% mild form of the disorder, 33% moderate, and 13% severe. This shows no statistical association (p=0.8069) when comparing exposure to anesthesia in uterus to subsequent severe form of ASD. Of the 262 ASD patients, 99 had exposure to anesthetics before their diagnosis, while in Non-ASD population, 110 had exposure to anesthesia, demonstrating no statistically significant association between both groups (p=0.2091). Out of 99 ASD patients exposed to anesthesia prior to their diagnosis, 72 were exposed before age 2. When compared to the 110 Non-ASD patients exposed to anesthesia, 86 had exposure during this developing brain period, which indicates no statistically significant association (p=0.4207). In addition, most of the ASD children exposed to anesthesia during developing brain were diagnosed with mild degree of the disorder when compared to ASD children without any previous exposure to anesthesia (p=0.9700) during the same period. When the exposure occurred after age 2, ASD children developed mild form of the disorder as compared with ASD children without any previous exposure to anesthesia (p=0.1699) in that period.

CONCLUSIONS

Children under early exposure to anesthesia in uterus, first 2 years of life, or later are not more likely to develop neither ASD nor severe form of the disorder.

摘要

背景

自闭症谱系障碍(ASD)的特征是社交互动和沟通受损,以及存在局限的重复行为,通常在儿童三岁前发病。(1)研究人员表明,美国的患病率可能高达1/68。(52)许多研究探讨了早期接触麻醉对大脑发育以及随后神经认知功能损害的影响;然而,关于麻醉剂对社会行为功能的可能影响却知之甚少。在一项基于回顾性人群的队列研究中,确定了子宫内、生命最初几年或之后接触麻醉与自闭症谱系障碍(ASD)的发生或其严重程度之间的关联。

目的

确定先前在子宫内、大脑发育的最初几年或之后接触过麻醉的儿童是否有患ASD及其严重形式的风险。

方法

数据来自对515名父母/监护人进行的结构化访谈,这些父母/监护人分为两组:ASD组 = 262名被诊断患有该疾病的儿童,非ASD组:253名儿童(ASD组儿童的兄弟姐妹)未被诊断(95%置信区间),他们自愿决定参与并签署了同意书。研究的变量包括:人口统计学特征、ASD的诊断和严重程度、麻醉暴露情况、分娩方式以及暴露年龄。小于2岁的儿童被视为处于大脑发育阶段。数据采用卡方检验或Fisher精确检验进行分析。

结果

与非ASD组相比,ASD组中的大多数儿童为男性,占76%(p = 0.0001)。关于分娩方式,ASD人群中有64%为阴道分娩(VD;非麻醉暴露组),36%为剖宫产(CD),而非自闭症人群中VD占71%,CD占29%,两组之间无统计学差异(p = 0.1113)。在接受剖宫产的36%的ASD人群中,7%采用全身麻醉,93%采用区域麻醉,而在非ASD组的29%的剖宫产中,5%采用全身麻醉,95%采用区域麻醉。这表明在比较ASD患者与非ASD患者时,ASD的发生与所使用的麻醉类型之间无统计学意义(p = 0.7569)。鉴于自闭症的严重程度,在阴道分娩中,56%的ASD人群患有轻度疾病,34%为中度,10%为重度;而剖宫产中轻度疾病占54%,中度占33%,重度占13%。这表明在比较子宫内接触麻醉与随后ASD的严重形式时无统计学关联(p = 0.8069)。在262名ASD患者中,99名在诊断前接触过麻醉剂,而在非ASD人群中,110名接触过麻醉,两组之间无统计学显著关联(p = 0.2091)。在99名诊断前接触过麻醉的ASD患者中,72名在2岁前接触过。与110名接触过麻醉的非ASD患者相比,86名在这个大脑发育阶段接触过,这表明无统计学显著关联(p = 0.4207)。此外,与同期未接触过任何麻醉的ASD儿童相比,大多数在大脑发育期间接触过麻醉的ASD儿童被诊断为轻度疾病(p = 0.9700)。当接触发生在2岁之后时,与该时期未接触过任何麻醉的ASD儿童相比,ASD儿童患轻度疾病(p = 0.1699)。

结论

在子宫内、生命的前两年或之后早期接触麻醉的儿童患ASD及其严重形式的可能性并不更高。

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