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Association of Tics and Tourette's Disorder in Offspring with Maternal Autoimmune Diseases: Real-World Evidence in Taiwan
30 Pages Posted: 29 Aug 2023
More...Abstract
Background: Nowadays, tics and Tourette’s disorder is a burdensome neurologic disorder that manifests in vocal and motor tics with onset during childhood. Earlier studies have demonstrated that maternal autoimmune disease may cause several neurodevelopmental disorders in offspring via maternal immune activation. However, the clinical impact of maternal autoimmune disease on tics and Tourette’s disorder in offspring has never been thoroughly researched. Thus, in this study we aimed to explore whether maternal autoimmune disease influenced the risk of developing tics and Tourette’s disorder in offspring in a real-world nationwide population-based cohort study.
Methods: We analyzed 76411 offspring with maternal autoimmune disease and 1211936 individuals without maternal autoimmune disease between 2009 and 2016 from databases, including the National Health Insurance program, birth certificate applications, cause of death data, and Maternal and Child Health Database, regulated by the Health and Welfare Data Science Center (HWDC) in Taiwan. The following variables were selected as covariates for the multivariate analysis: birth year, children's sex, birth weight, gestational age, mode of delivery, presence of congenital defects, level of urbanization, insurance coverage, prenatal maternal and paternal comorbidities, and medication exposure during pregnancy. To assess the adjusted hazard ratio (aHR) of tics and Tourette's disorder, we conducted multiple Cox regression analyses. Additionally, we performed stratified analyses to observe the HRs within different subgroups.
Results: In the 2009-2016 birth cohort, the incidence of childhood tics and Tourette's disorder was 2.35 (95% 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 results of multivariable Cox regression analysis showed that the children whose mothers had autoimmune disease had a 1.26-fold risk of tics and Tourette’s disorder compared to children whose mothers did not have autoimmune disease (crude hazard ratio: 1.26; 95% CI, 1.20-1.34, aHR: 1.22; 95% CI, 1.15-1.29). As for the subgroup analyses, children in the maternal autoimmune disease group had a higher likelihood of tics and Tourette’s disorder irrespective of the child’s sex, gestational age, and maternal age. Based on the stratified analysis, offspring with maternal 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.
Conclusion: Maternal autoimmune diseases appeared to be associated with tics and Tourette’s disorder in offspring, especially in mothers with rheumatoid arthritis, system lupus erythematosus, Sjogren’s syndrome, ankylosing spondylitis, Graves’ disease, Hashimoto’s thyroiditis, or type I diabetes. Further research is warranted to investigate the possible pathogenetic mechanisms of these associations.
Funding: The authors have not declared a specific grant for this study from any funding agency in the public, commercial, or not-for-profit sectors.
Declaration of Interest: There was no conflict of interest in this study.
Ethical Approval: This study was approved by the Institutional Review Board of Chung Shan Medical University Hospital (Approval number CS2-21006) in Taiwan. The requirement for written consent from study subjects was waived by the Institutional Review Board, as the LHID consists of de-identified secondary data.
Keywords: Maternal Autoimmune Diseases, Maternal Immune Activation, Tics and Tourette's Disorder, Maternal and Child Health Database, Taiwan NHIRD
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