BACKGROUND Children with asthma are at risk of depression and anxiety and growing evidence suggest they may also be at risk of attention deficit hyperreactivity disorder (ADHD) and autism spectrum disorder (ASD). Here, we conducted a systematic review with meta-analysis of studies investigating association between asthma and ADHD or ASD in children. METHODS A comprehensive search using PubMed, EMBASE and Cochrane Library databases was completed in March 2019. Observational human studies published in English, clinic-based or population-based with a healthy comparator group, evaluating asthma-ADHD or asthma-ASD overlap in children 18 years or younger using categorical diagnoses (yes/no) were considered for inclusion. Random effects meta-analysis models were used to analyse data. The Newcastle Ottawa tool was used to evaluate risk of bias. RESULTS A total of 25 asthma-ADHD studies were included of which 17 showed significant positive associations and one a negative association: 17/25 studies were population-based, 19/25 were cross-sectional or cohort studies and 7/25 had a low risk of bias. We performed a meta-analysis of 23 of the studies, which showed a significant association between asthma and ADHD: odds ratio (OR) 1.52 (1.42-1.63), p<0.001, I2=60%. All studies were adjusted for age and sex and a large proportion, i.e. 19/23 were further adjusted for relevant confounders. Seventeen asthma-ASD studies were included, whereof 7 showed a positive association and 3 a negative association 8/17 were population-based with a cross-sectional study design and 4/17 had a low risk of bias. We performed a meta-analysis of 14 of the studies did not show a significant association between asthma and ASD: OR 1.12 (0.93-1.34), p=0.24, I2=89%. All studies were adjusted for age and sex and 10/14 were further adjusted for relevant confounders. CONCLUSIONS This systematic review with meta-analyses show a significant overlap between asthma and ADHD, but not between asthma and ASD in children. Clinicians taking care of children with asthma or ADHD should be aware of such association to aid an early diagnosis and treatment of such comorbidity.

中文翻译：

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儿童哮喘与注意力缺陷多动或自闭症谱系障碍之间的关联：荟萃分析的系统评价

背景 患有哮喘的儿童有患抑郁症和焦虑症的风险，越来越多的证据表明他们也可能有患注意力缺陷多动障碍 (ADHD) 和自闭症谱系障碍 (ASD) 的风险。在这里，我们对调查儿童哮喘与 ADHD 或 ASD 之间关联的研究进行了系统回顾和荟萃分析。方法 使用 PubMed、EMBASE 和 Cochrane 图书馆数据库的全面搜索已于 2019 年 3 月完成。以英语发表的基于临床或基于人群的观察性人体研究与健康对照组一起评估了 18 岁儿童的哮喘-ADHD 或哮喘-ASD 重叠年龄或以下使用分类诊断（是/否）被考虑纳入。随机效应荟萃分析模型用于分析数据。Newcastle Ottawa 工具用于评估偏倚风险。结果 共纳入 25 项哮喘-ADHD 研究，其中 17 项显示显着的正相关，1 项为负相关：17/25 的研究是基于人群的，19/25 是横断面或队列研究，7/25 的低偏见的风险。我们对 23 项研究进行了荟萃分析，结果显示哮喘与 ADHD 之间存在显着关联：优势比 (OR) 1.52 (1.42-1.63)，p<0.001，I2=60%。所有研究都针对年龄和性别进行了调整，其中很大一部分（即 19/23）针对相关混杂因素进行了进一步调整。纳入 17 项哮喘-ASD 研究，其中 7 项呈正相关，3 项呈负相关 8/17 是基于人群的横断面研究设计，4/17 的偏倚风险较低。我们对 14 项研究进行了荟萃分析，未显示哮喘与 ASD 之间存在显着关联：OR 1.12 (0.93-1.34)，p=0.24，I2=89%。所有研究都针对年龄和性别进行了调整，10/14 进一步针对相关混杂因素进行了调整。结论 本系统评价和荟萃分析显示哮喘和 ADHD 之间存在显着重叠，但儿童哮喘和 ASD 之间没有重叠。照顾患有哮喘或多动症的儿童的临床医生应该意识到这种关联，以帮助早期诊断和治疗这种合并症。