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儿童时期首次接触抗生素与神经发育结局。

Age at first exposure to antibiotics and neurodevelopmental outcomes in childhood.

机构信息

Department of Psychological Medicine, Faculty of Medical and Health Sciences, University of Auckland, Building 507, 22-30 Park Avenue, Grafton, Auckland, 1023, New Zealand.

School of Psychology, Faculty of Science, University of Auckland, Auckland, New Zealand.

出版信息

Psychopharmacology (Berl). 2023 May;240(5):1143-1150. doi: 10.1007/s00213-023-06351-5. Epub 2023 Mar 17.

Abstract

RATIONALE

Viral illnesses in children are common and are frequently treated with antibiotic medication. Antibiotics reduce the diversity and composition of the gut microbiota, leading to poor developmental outcomes.

OBJECTIVES

To investigate the relationship between age at first exposure to antibiotics and cognitive and behavioural development at 4.5 years while controlling for multiple confounders, including otitis media.

METHODS

Study participants were 5589 children enrolled in the broadly generalisable Growing Up in New Zealand cohort study, with antibiotic exposure data, maternal antenatal information, and age 4.5-year behaviour and cognitive outcome data. Children were categorised as first exposed to antibiotics according to the following mutually exclusive ages: 0-2 months; 3-5 months; 6-8 months; 9-11 months; 12-54 months or not exposed by 54 months. Developmental outcome measures included the Strengths and Difficulties Questionnaire, Luria hand clap task, and the Peabody Picture Vocabulary Test-III.

RESULTS

In univariate analysis, there was an evident dose-response relationship where earlier exposure to antibiotics in the first year of life was associated with behavioural difficulties, lower executive function scores, and lower receptive language ability. After adjusting for confounders, pairwise comparisons showed that first antibiotic exposure between birth and 3 months or between 6 and 9 months was associated with lower receptive vocabulary. Antibiotic exposure at any age prior to 12 months was associated with increases in behavioural difficulties scores at 4.5 years.

CONCLUSIONS

Following adjustment for socioeconomic factors and otitis media, there is evidence that antibiotic exposure during potentially sensitive windows of development is associated with receptive language and behaviour later in childhood.

摘要

背景

儿童常见病毒性疾病,常采用抗生素治疗。抗生素会减少肠道微生物多样性和组成,导致发育不良。

目的

研究首次接触抗生素的年龄与控制中耳炎等多种混杂因素后 4.5 岁时认知和行为发育的关系。

方法

研究对象为参加新西兰广泛代表性的“成长中的新西兰”队列研究的 5589 名儿童,他们有抗生素暴露数据、母亲产前信息和 4.5 岁时的行为和认知结果数据。根据以下互斥的年龄分组将儿童分为首次接触抗生素:0-2 个月;3-5 个月;6-8 个月;9-11 个月;12-54 个月或 54 个月前未接触抗生素。发育结果测量包括长处和困难问卷、Luria 手拍手任务和 Peabody 图片词汇测试-III。

结果

在单变量分析中,早期接触抗生素与行为困难、执行功能评分降低和接受性语言能力降低之间存在明显的剂量反应关系。在调整混杂因素后,两两比较显示,生命头 3 个月或 6-9 个月之间首次接触抗生素与接受性词汇量较低有关。12 个月前任何年龄的抗生素暴露均与 4.5 岁时行为困难评分增加有关。

结论

在调整社会经济因素和中耳炎后,有证据表明,在发育的潜在敏感时期接触抗生素与儿童后期的接受性语言和行为有关。

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本文引用的文献

2
Antibiotics as Major Disruptors of Gut Microbiota.抗生素作为肠道微生物群的主要干扰因素。
Front Cell Infect Microbiol. 2020 Nov 24;10:572912. doi: 10.3389/fcimb.2020.572912. eCollection 2020.
8
Gut microbiota composition is associated with temperament traits in infants.肠道微生物组成与婴儿的气质特征有关。
Brain Behav Immun. 2019 Aug;80:849-858. doi: 10.1016/j.bbi.2019.05.035. Epub 2019 May 24.
10
Early life colonization of the human gut: microbes matter everywhere.人类肠道的早期定植:微生物无处不在。
Curr Opin Microbiol. 2018 Aug;44:70-78. doi: 10.1016/j.mib.2018.06.003. Epub 2018 Aug 4.

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