Background: While current research suggests that genetic factors confer the greatest risk for the development of tic disorders, studies of environmental factors are relatively few, with a lack of consistent risk factors across studies. Our aim is to analyze the association of tic disorders with exposure to prenatal and perinatal morbidity. Methods: This was a nested case-control study design. Cases and controls were selected and identified from a mainstream, school-based sample. The diagnosis of tic disorders was assigned by a movement disorder neurologist using 'Diagnostic and statistical manual of mental disorders, 4th edition, text revision' criteria, and neuropsychiatric comorbidities were screened using the Spanish computerized version of the Diagnostic Interview Schedule for Children Predictive Scale. Information regarding the exposure to pre-perinatal risk factors was collected by a retrospective review of the birth certificates. Logistic regression analyses were then performed to test the association of tic disorders with pre-perinatal risk factors. Results: Out of 407 participants, complete pre-perinatal data were available in 153 children (64 with tics and 89 without tics). After adjusting for family history of tics, neonatal respiratory distress syndrome, body mass index, prenatal infection, and coexisting comorbid neuropsychiatric disturbances, tic disorders were associated with prenatal exposure to tobacco (odds ratio [OR]53.07, 95% confidence interval [CI] 1.24-7.60, p50.007), and cesarean section (OR55.78, 95% CI 1.60-20.91, p50.01). Discussion: This nested case-control study of children with tic disorders demonstrates higher adjusted odds for tics in children with exposure to cesarean delivery and maternal smoking. Longitudinal, population-based samples are required to confirm these results.

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