Faculty of Medicine and Health, Children's Hospital Westmead Clinical School, University of Sydney, Sydney, Australia.
Royal Hospital for Women, Randwick, Sydney, Australia.
JAMA Pediatr. 2021 Mar 1;175(3):e205487. doi: 10.1001/jamapediatrics.2020.5487.
Maternal autoimmune disease has been associated with increased risk of neurodevelopmental disorders in offspring, but few studies have assessed the association with attention-deficit/hyperactivity disorder (ADHD).
To examine the association between maternal autoimmune disease and ADHD within a population-based cohort and combine results in a subsequent systematic review and meta-analysis.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study was conducted of singleton children born at term gestation (37-41 weeks) in New South Wales, Australia, from July 1, 2000, to December 31, 2010, and followed up until the end of 2014; and a systematic review evaluated articles from the MEDLINE, Embase, and Web of Science databases to identify all studies published before November 20, 2019. A total of 12 610 children exposed to maternal autoimmune disease were propensity score matched (1:4) to 50 440 unexposed children, for a total cohort of 63 050. A child was considered to have ADHD if they had (1) an authorization or filled prescription for stimulant treatment for ADHD or (2) a hospital diagnosis of ADHD. Children linked to a first ADHD event before 3 years of age were excluded. Data were analyzed from January 13 to April 20, 2020.
One or more maternal autoimmune diagnoses in linked hospital admission records between July 1, 2000, and December 31, 2012. Thirty-five conditions were considered together and individually.
The main outcome was child ADHD identified from stimulant authorization or prescription data and diagnoses in linked hospital admission records. Multivariable Cox regression was used to assess the association between maternal autoimmune disease and ADHD adjusted for child sex. Pooled hazard ratios (HRs) were calculated using random-effects meta-analysis with inverse-variance weights for each exposure reported by 2 or more studies.
In the population-based cohort analysis, 831 718 singleton, term infants born to 831 718 mothers (mean [SD] age, 29.8 [5.6] years) were assessed. Of 12 767 infants (1.5%) who were linked to a maternal autoimmune diagnosis, 12 610 were propensity score matched to 50 440 control infants, for a total study cohort of 63 050 infants. In this cohort, any autoimmune disease was associated with ADHD in offspring (HR, 1.30; 95% CI 1.15-1.46), as was type 1 diabetes (HR, 2.23; 95% CI, 1.66-3.00), psoriasis (HR, 1.66; 95% CI, 1.02-2.70), and rheumatic fever or rheumatic carditis (HR, 1.75; 95% CI, 1.06-2.89). Five studies (including the present study) were included in the meta-analysis. Any autoimmune disease (2 studies: HR, 1.20; 95% CI, 1.03-1.38), type 1 diabetes (4 studies: HR, 1.53; 95% CI, 1.27-1.85), hyperthyroidism (3 studies: HR, 1.15; 95% CI, 1.06-1.26), and psoriasis (2 studies: HR, 1.31; 95% CI, 1.10-1.56) were associated with ADHD.
In this cohort study, maternal autoimmune diseases were associated with increased ADHD among children. These findings suggest possible shared genetic vulnerability between autoimmune disease and ADHD or a potential role for maternal immune activation in the expression of neurodevelopmental disorders in children. Future studies measuring disease activity, modifiers, and medication use are required to better understand the mechanisms underlying this association.
母体自身免疫性疾病与后代神经发育障碍的风险增加有关，但很少有研究评估其与注意力缺陷/多动障碍（ADHD）的关联。
在基于人群的队列中检查母体自身免疫性疾病与 ADHD 之间的关联，并在随后的系统评价和荟萃分析中合并结果。
设计、设置和参与者：对 2000 年 7 月 1 日至 2010 年 12 月 31 日在澳大利亚新南威尔士州足月（37-41 周）出生的单胎儿童进行了队列研究，并随访至 2014 年底；系统评价评估了来自 MEDLINE、Embase 和 Web of Science 数据库的所有文章，以确定截至 2019 年 11 月 20 日之前发表的所有研究。将 12767 名暴露于母体自身免疫性疾病的儿童与 50440 名未暴露的儿童进行倾向评分匹配（1:4），总计 63050 名儿童。如果儿童（1）有 ADHD 的兴奋剂治疗授权或处方，或（2）有 ADHD 的医院诊断，则认为其患有 ADHD。排除了 ADHD 事件发生在 3 岁之前的儿童。数据分析于 2020 年 1 月 13 日至 4 月 20 日进行。
在 2000 年 7 月 1 日至 2012 年 12 月 31 日期间，在关联的住院记录中存在一种或多种母体自身免疫性诊断。35 种疾病被一起考虑，并分别考虑。
主要结局是通过兴奋剂授权或处方数据以及关联的住院记录中的诊断，确定儿童 ADHD。多变量 Cox 回归用于调整儿童性别后，评估母体自身免疫性疾病与 ADHD 之间的关联。对于每个暴露于两种或两种以上研究报告的暴露，使用随机效应荟萃分析计算风险比（HR）。
在基于人群的队列分析中，评估了 831718 名出生于 831718 名母亲（平均[标准差]年龄，29.8[5.6]岁）的单胎足月婴儿。在 12767 名（1.5%）与母体自身免疫性诊断相关的婴儿中，有 12610 名婴儿与 50440 名对照婴儿进行了倾向评分匹配，总计 63050 名婴儿。在这个队列中，任何自身免疫性疾病都与后代的 ADHD 有关（HR，1.30；95%CI，1.15-1.46），1 型糖尿病（HR，2.23；95%CI，1.66-3.00），银屑病（HR，1.66；95%CI，1.02-2.70）和风湿热或风湿性心脏病（HR，1.75；95%CI，1.06-2.89）。五项研究（包括本研究）被纳入荟萃分析。任何自身免疫性疾病（2 项研究：HR，1.20；95%CI，1.03-1.38），1 型糖尿病（4 项研究：HR，1.53；95%CI，1.27-1.85），甲状腺功能亢进（3 项研究：HR，1.15；95%CI，1.06-1.26）和银屑病（2 项研究：HR，1.31；95%CI，1.10-1.56）与 ADHD 相关。
在这项队列研究中，母体自身免疫性疾病与儿童 ADHD 有关。这些发现表明，自身免疫性疾病和 ADHD 之间可能存在共同的遗传易感性，或者母体免疫激活可能在儿童神经发育障碍的表达中发挥作用。需要进一步研究疾病活动度、调节剂和药物使用情况，以更好地了解这种关联的潜在机制。
