Perinatal risk factors in Tourette’s and chronic tic disorders: a total population sibling comparison study

• Published in: Molecular psychiatry Vol. 23; no. 5; pp. 1189 - 1197
• Main Authors: Brander, G, Rydell, M, Kuja-Halkola, R, Fernández de la Cruz, L, Lichtenstein, P, Serlachius, E, Rück, C, Almqvist, C, D'Onofrio, B M, Larsson, H, Mataix-Cols, D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Nature Publishing Group
• Subjects: 631/378; 692/699/476; Attention deficit hyperactivity disorder; Behavioral Sciences; Biological Psychology; Cesarean section; Developmental neurology; Epigenetic inheritance; Fetuses; Health aspects; Health risk assessment; Hyperactivity; Medicine; Medicine & Public Health; Neurologi; Neurology; Neurosciences; Original; original-article; Pharmacotherapy; Population studies; Pregnancy; Premature birth; Prenatal influences; Psychiatric research; Psychiatry; Risk factors; Siblings; Smoking; Statistical analysis; Tourette syndrome
• ISSN: 1359-4184; 1476-5578; 1476-5578
• DOI: 10.1038/mp.2017.31

Adverse perinatal events may increase the risk of Tourette’s and chronic tic disorders (TD/CTD), but previous studies have been unable to control for unmeasured environmental and genetic confounding. We aimed to prospectively investigate potential perinatal risk factors for TD/CTD, taking unmeasured factors shared between full siblings into account. A population-based birth cohort, consisting of all singletons born in Sweden in 1973–2003, was followed until December 2013. A total of 3 026 861 individuals were identified, 5597 of which had a registered TD/CTD diagnosis. We then studied differentially exposed full siblings from 947 942 families; of these, 3563 families included siblings that were discordant for TD/CTD. Perinatal data were collected from the Medical Birth Register and TD/CTD diagnoses were collected from the National Patient Register, using a previously validated algorithm. In the fully adjusted models, impaired fetal growth, preterm birth, breech presentation and cesarean section were associated with a higher risk of TD/CTD, largely independent from shared family confounders and measured covariates. Maternal smoking during pregnancy was associated with risk of TD/CTD in a dose–response manner but the association was no longer statistically significant in the sibling comparison models or after the exclusion of comorbid attention-deficit/hyperactivity disorder. A dose–response relationship between the number of adverse perinatal events and increased risk for TD/CTD was also observed, with hazard ratios ranging from 1.41 (95% confidence interval (CI): 1.33–1.50) for one event to 2.42 (95% CI: 1.65–3.53) for five or more events. These results pave the way for future gene by environment interaction and epigenetic studies in TD/CTD.