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Increased Risk of Tics in Children Infected with Enterovirus

A Nationwide Population-Based Study

Lin, Jiun-Nong MD, PhD*,†; Lin, Cheng-Li MSc‡,§; Yen, Hung-Rong MD, PhD; Yang, Chi-Hui PhD; Lai, Chung-Hsu MD, PhD*,†; Lin, Hsi-Hsun MD, PhD*,†; Kao, Chia-Hung MD**,††,‡‡

Journal of Developmental & Behavioral Pediatrics: May 2017 - Volume 38 - Issue 4 - p 276–282
doi: 10.1097/DBP.0000000000000435
Original Articles

Objective: Both tics and enterovirus (EV) infections are common in children. The association between EV infections and tics has been seldom evaluated. The aim of this study was to evaluate the risk of diagnosed tics after EV infections in children.

Methods: A nationwide retrospective cohort study was conducted to determine the risk of tics after EV infections by analyzing data from the National Health Insurance Research Database in Taiwan. Children aged < 18 years with EV infection during 2000 to 2007 were enrolled. For comparison, non-EV–infected children were randomly selected and matched with EV-infected children at a 1:1 ratio according to sex, age, urbanization level, parental occupation, and the year of EV infection. All patients were followed up until the diagnosis of tics, death, loss to follow-up, withdrawal from the insurance system, or December 31, 2008.

Results: A total of 282,321 EV-infected and 282,317 non-EV–infected children were included in this study. The mean age was 2.39 years in both cohorts. The overall incidences of tics were 9.12 and 6.21 per 10,000 person-years in the EV-infected and non-EV–infected cohorts, respectively. Children with EV infection were significantly associated with an increased risk of tics compared with those without EV infection (adjusted hazard ratio, 1.38; 95% confidence interval, 1.27–1.5). Multivariable analyses showed that boys, children living in urbanized areas, children whose parents had white-collar jobs, and children with allergic rhinitis or bronchial asthma exhibited a significantly increased risk of tics.

Conclusion: This study revealed an increased risk of tics after EV infection in children.

*Division of Infectious Diseases, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan;

School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan;

Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan;

§College of Medicine, China Medical University, Taichung, Taiwan;

Research Center for Traditional Chinese Medicine, China Medical University & Hospital, Taichung, Taiwan;

Department of Biological Science and Technology, Meiho University, Pingtung, Taiwan;

**Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan;

††Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan;

‡‡Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan.

Address for reprints: Chia-Hung Kao, MD, Graduate Institute of Clinical Medical Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Rd, Taichung 404, Taiwan; e-mail:

Supported in part by Taiwan Ministry of Health and Welfare Clinical Trial and Research Center of Excellence (MOHW 106-TDU-B-212-113004), China Medical University Hospital, Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10501010037), NRPB Stroke Clinical Trial Consortium (MOST 105-2325-B-039-003), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.

Disclosure: The authors declare no conflict of interest.

All authors have contributed substantially to, and are in agreement with the content of, the manuscript: Conception/Design: J.-N. Lin, C.-H. Kao; Provision of study materials: C.-H. Kao; Collection and/or assembly of data: all authors; Data analysis and interpretation: all authors; Manuscript preparation: all authors; Final approval of manuscript: all authors. The guarantor of the paper, taking responsibility for the integrity of the work as a whole, from inception to published article: C.-H. Kao.

Received October , 2016

Accepted February , 2017

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