title: Perinatal risk factors in Tourette's and chronic tic disorders: a total population sibling comparison study.
abstract: 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.
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Brander
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: M
authors.initials: M
authors.lastname: Rydell
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: R
authors.initials: R
authors.lastname: Kuja-Halkola
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: L
authors.initials: L
authors.lastname: Fernández de la Cruz
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Lichtenstein
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.|Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
authors.forename: E
authors.initials: E
authors.lastname: Serlachius
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.|Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Rück
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Almqvist
authors.affiliation: Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN, USA.
authors.forename: B M
authors.initials: BM
authors.lastname: D'Onofrio
authors.affiliation: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.|Department of Medical Sciences, Örebro University, Örebro, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Larsson
authors.affiliation: Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, Stockholm, Sweden.|Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Mataix-Cols
mesh_terms: D000293:Adolescent; D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D015897:Comorbidity; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018743:Perinatal Care; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology; D011446:Prospective Studies; D012307:Risk Factors; D035781:Siblings; D012907:Smoking / Q000453:epidemiology; D013548:Sweden / Q000453:epidemiology; D013981:Tic Disorders / Q000235:genetics* / Q000378:metabolism; D005879:Tourette Syndrome / Q000235:genetics* / Q000378:metabolism