Lee Yi-Feng, Wu Meng-Che, Huang Yen-Chu, Huang Jing-Yang, Wei James Cheng-Chung
Division of Neonatology, Children's Medical Center, Taichung Veterans General Hospital, Taichung, Taiwan.
School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
Front Pediatr. 2025 Mar 4;13:1440366. doi: 10.3389/fped.2025.1440366. eCollection 2025.
Currently, tics and Tourette's disorder are burdensome neurological disorders that manifest in vocal and motor tics with onset during childhood. Previous studies have demonstrated that maternal autoimmune diseases may cause several neurodevelopmental disorders in offspring via maternal immune activation. However, the association between them has never been thoroughly researched. Thus, in this study, we aimed to explore whether maternal autoimmune diseases are associated with the risk of tics and Tourette's disorder in offspring in a real-world nationwide population-based cohort study.
We analyzed offspring with or without autoimmune disease exposure between 2009 and 2016 from national population databases in Taiwan. Multivariate analysis, multiple Cox regression analyses, and stratified analyses were conducted in the study.
In total, 76,411 offspring with autoimmune disease exposure and 1,211,936 offspring without maternal autoimmune disease exposure were selected and analyzed in this study. The incidence of childhood tics and Tourette's disorder was 2.35 [95% confidence interval (CI) 2.23-4.86] and 1.89 (95% CI 1.86-1.92) per 10,000 person-months in children exposed to maternal autoimmune disease and non-exposed children, respectively. The children whose mothers had an autoimmune disease had a 1.26-fold risk of tics and Tourette's disorder compared to children whose mothers did not have an autoimmune disease [crude hazard ratio: 1.26; 95% CI, 1.20-1.34, adjusted hazard ratio (aHR): 1.22; 95% CI, 1.15-1.29]. Offspring of mothers with rheumatoid arthritis (aHR: 1.46, 95% CI, 1.07-1.97), system lupus erythematosus (aHR: 1.57, 95% CI, 1.18-2.09), Sjogren's syndrome (aHR: 1.28, 95% CI, 1.09-1.50), ankylosing spondylitis (aHR: 1.49, 95% CI, 1.07-2.09), Graves' disease (aHR: 1.26, 95% CI, 1.15-1.37), Hashimoto's thyroiditis (aHR: 1.59, 95% CI, 1.29-1.98), and type I diabetes (aHR: 1.68, 95% CI, 1.13-2.50) had a significantly higher risk of developing tics and Tourette's disorder. Aside from maternal autoimmune diseases, mothers with urinary tract infections, diabetes mellitus, hyperlipidemia, anemia, a sleep disorder, endometriosis, and depression were also associated with childhood tics and Tourette's disorder.
Maternal autoimmune diseases appeared to be associated with tics and Tourette's disorder in offspring, especially in mothers with the abovementioned diseases. Further research is warranted to investigate the possible pathogenetic mechanisms of these associations.
目前，抽动症和妥瑞氏症是令人负担沉重的神经系统疾病，表现为发声和运动抽动，起病于儿童期。既往研究表明，母体自身免疫性疾病可能通过母体免疫激活导致子代出现多种神经发育障碍。然而，它们之间的关联从未得到充分研究。因此，在本项基于全国人群的队列研究中，我们旨在探讨母体自身免疫性疾病是否与子代患抽动症和妥瑞氏症的风险相关。
我们分析了2009年至2016年间来自台湾全国人口数据库的有或无自身免疫性疾病暴露的子代。研究中进行了多变量分析、多重Cox回归分析和分层分析。
本研究共纳入并分析了76411名有自身免疫性疾病暴露的子代和1211936名无母体自身免疫性疾病暴露的子代。有母体自身免疫性疾病暴露的儿童和无暴露儿童的儿童期抽动症和妥瑞氏症发病率分别为每10000人月2.35[95%置信区间（CI）2.23 - 4.86]和1.89（95%CI 1.86 - 1.92）。母亲患有自身免疫性疾病的儿童患抽动症和妥瑞氏症的风险是母亲未患自身免疫性疾病儿童的1.26倍[粗危险比：1.26；95%CI，1.20 - 1.34，调整后危险比（aHR）：1.22；95%CI，1.15 - 1.29]。患有类风湿关节炎（aHR：1.46，95%CI，1.07 - 1.97）、系统性红斑狼疮（aHR：1.57，95%CI，1.18 - 2.09）、干燥综合征（aHR：1.28，95%CI，1.09 - 1.50）、强直性脊柱炎（aHR：1.49，95%CI，1.07 - 2.09）、格雷夫斯病（aHR：1.26，95%CI，1.15 - 1.37）、桥本甲状腺炎（aHR：1.59，95%CI，1.29 - 1.98）和I型糖尿病（aHR：1.68，95%CI，1.13 - 2.50）的母亲的子代患抽动症和妥瑞氏症的风险显著更高。除母体自身免疫性疾病外，患有尿路感染、糖尿病、高脂血症、贫血、睡眠障碍、子宫内膜异位症和抑郁症的母亲也与儿童期抽动症和妥瑞氏症有关。
母体自身免疫性疾病似乎与子代的抽动症和妥瑞氏症有关，尤其是患有上述疾病的母亲。有必要进一步研究这些关联的可能致病机制。
