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母亲和儿童早期接触抗生素与自闭症和注意缺陷多动障碍风险的关系:一项瑞典基于人群的队列研究。

Maternal and Early-Life Exposure to Antibiotics and the Risk of Autism and Attention-Deficit Hyperactivity Disorder in Childhood: a Swedish Population-Based Cohort Study.

机构信息

Interuniversity Institute for Biostatistics and statistical Bioinformatics (I-BIOSTAT), Data Science Institute, Hasselt University, Diepenbeek, Belgium.

Department of Mathematics and ICT, College of Business Education (CBE), Dar es Salaam, Tanzania.

出版信息

Drug Saf. 2023 May;46(5):467-478. doi: 10.1007/s40264-023-01297-1. Epub 2023 Apr 23.

Abstract

INTRODUCTION

Antibiotics represent the most common type of medication used during pregnancy and infancy. Antibiotics have been proposed as a possible factor in changes in microbiota composition, which may play a role in the aetiology of autism and attention deficit/hyperactivity disorder (ADHD). Our aim was to investigate the association between maternal and early-life antibiotic use and autism and ADHD in childhood.

METHODS

This Swedish nation-wide population-based cohort study included all first live singleton births (N = 483,459) between January 2006 and December 2016. The association of dispensed antibiotics with autism and ADHD in children aged ≤ 11 years was estimated by applying multivariable logistic regression and generalised estimating equations models.

RESULTS

Of the mothers, 25.9% (n = 125,106) were dispensed ≥1 antibiotic during the exposure period (from 3 months pre-conception to delivery), and 41.6% (n = 201,040) of the children received ≥ 1 antibiotic in early life (aged ≤ 2 years). Penicillin was the most prescribed antibiotic class (17.9% of mothers, 38.2% of children). Maternal antibiotic use was associated with an increased risk of autism [odds ratio (OR) = 1.16, 95% confidence interval (CI) 1.09-1.23] and ADHD (OR = 1.29, 95% CI 1.21-1.36) in childhood. Early-life exposure to antibiotics showed an even stronger association [autism (OR = 1.46, 95% CI 1.38-1.55); ADHD (OR = 1.90, 95% CI 1.80-2.00)]. Both maternal and childhood-exposure sub-analyses suggested a dose-response relationship.

CONCLUSION

Maternal and early-life antibiotic use was associated with an increased risk of autism and ADHD in childhood. However, differences were noted by exposure period and antibiotic classes.

摘要

介绍

抗生素是孕期和婴儿期最常用的药物类型。抗生素被认为是微生物群落组成变化的一个可能因素,而这种变化可能在自闭症和注意缺陷多动障碍(ADHD)的发病机制中发挥作用。我们的目的是研究母亲和婴儿期抗生素使用与儿童自闭症和 ADHD 的关系。

方法

这项瑞典全国性基于人群的队列研究纳入了 2006 年 1 月至 2016 年 12 月期间所有首次活产的单胎妊娠(N=483459)。通过应用多变量逻辑回归和广义估计方程模型,估计了母亲和婴儿期(≤11 岁)使用抗生素与儿童自闭症和 ADHD 的相关性。

结果

母亲中,有 25.9%(n=125106)在暴露期(受孕前 3 个月至分娩期间)使用了≥1 种抗生素,有 41.6%(n=201040)的儿童在婴儿期(≤2 岁)使用了≥1 种抗生素。青霉素是最常用的抗生素类别(母亲中占 17.9%,儿童中占 38.2%)。母亲使用抗生素与儿童自闭症(比值比[OR] = 1.16,95%置信区间[CI] 1.09-1.23)和 ADHD(OR=1.29,95% CI 1.21-1.36)的风险增加相关。婴儿期接触抗生素的相关性更强(自闭症[OR=1.46,95% CI 1.38-1.55];ADHD[OR=1.90,95% CI 1.80-2.00])。母亲和儿童暴露亚分析均提示存在剂量-反应关系。

结论

母亲和婴儿期抗生素使用与儿童自闭症和 ADHD 的风险增加有关。然而,暴露期和抗生素类别不同,差异也不同。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5efa/10164008/c9545a564b08/40264_2023_1297_Fig1_HTML.jpg

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