@article {5866, title = {Association of Perinatal Risk Factors With Obsessive-Compulsive Disorder: A Population-Based Birth Cohort, Sibling Control Study}, journal = {JAMA PsychiatryJAMA PsychiatryJAMA Psychiatry}, volume = {73}, number = {11}, year = {2016}, note = {2168-6238
Brander, Gustaf
Rydell, Mina
Kuja-Halkola, Ralf
Fernandez de la Cruz, Lorena
Lichtenstein, Paul
Serlachius, Eva
Ruck, Christian
Almqvist, Catarina
D{\textquoteright}Onofrio, Brian M
Larsson, Henrik
Mataix-Cols, David
Journal Article
United States
JAMA Psychiatry. 2016 Nov 1;73(11):1135-1144. doi: 10.1001/jamapsychiatry.2016.2095.}, month = {Nov 1}, pages = {1135-1144}, edition = {2016/11/03}, abstract = {Importance: Perinatal complications may increase the risk of obsessive-compulsive disorder (OCD). Previous reports were based on small, retrospective, specialist clinic-based studies that were unable to rigorously control for unmeasured environmental and genetic confounding. Objective: To prospectively investigate a wide range of potential perinatal risk factors for OCD, controlling for unmeasured factors shared between siblings in the analyses. Design, Setting, and Participants: This population-based birth cohort study included all 2421284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1403651 families in the cohort, differentially exposed siblings from the 743885 families with siblings were evaluated; of these, 11592 families included clusters of full siblings that were discordant for OCD. Analysis of the data was conducted from January, 26, 2015, to September, 5, 2016. Exposures: Perinatal data were collected from the Swedish Medical Birth Register and included maternal smoking during pregnancy, labor presentation, obstetric delivery, gestational age (for preterm birth), birth weight, birth weight in relation to gestational age, 5-minute Apgar score, and head circumference. Main Outcomes and Measures: Previously validated OCD codes (International Statistical Classification of Diseases and Health Related Problems, Tenth Revision, code F42) in the Swedish National Patient Register. Results: Of 2421284 individuals included in the cohort, 17305 persons were diagnosed with OCD. Of these, 7111 were men (41.1\%). The mean (SD) age of individuals at first diagnosis of OCD was 23.4 (6.5) years. An increased risk for OCD remained after controlling for shared familial confounders and measured covariates (including sex, year of birth, maternal and paternal age at birth, and parity), for smoking 10 or more cigarettes per day during pregnancy (hazard ratio [HR], 1.27; 95\% CI, 1.02-1.58), breech presentation (HR, 1.35; 95\% CI, 1.06-1.71), delivery by cesarean section (HR, 1.17; 95\% CI, 1.01-1.34), preterm birth (HR, 1.24; 95\% CI, 1.07-1.43), birth weight 1501 to 2500 g (HR, 1.30; 95\% CI, 1.05-1.62) and 2501 to 3500 g (HR, 1.08; 95\% CI, 1.01-1.16), being large for gestational age (HR, 1.23; 95\% CI, 1.05-1.45), and Apgar distress scores at 5 minutes (HR, 1.50; 95\% CI, 1.07-2.09). Gestational age and birth weight followed inverse dose-response associations, whereby an increasingly higher risk for OCD was noted in children with a shorter gestational age and lower birth weight. We also observed a dose-response association between the number of perinatal events and increased OCD risk, with HRs ranging from 1.11 (95\% CI, 1.07-1.15) for 1 event to 1.51 (95\% CI, 1.18-1.94) for 5 or more events. Conclusions and Relevance: A range of perinatal risk factors is associated with a higher risk for OCD independent of shared familial confounders, suggesting that perinatal risk factors may be in the causal pathway to OCD.}, keywords = {*Perinatal Care, *Prenatal Exposure Delayed Effects, Adolescent, Adult, Apgar Score, Birth Weight, Breech Presentation, Case-Control Studies, Cesarean Section, Cohort Studies, Epigenesis, Genetic, Female, Gene-Environment Interaction, Gestational Age, Humans, Infant, Low Birth Weight, Infant, Newborn, Infant, Premature, Diseases/epidemiology/genetics, Male, Obsessive-Compulsive Disorder/*epidemiology/*etiology/genetics, Pregnancy, Retrospective Studies, Risk Factors, Siblings, Sweden, Tobacco Smoke Pollution/adverse effects, Young Adult}, isbn = {2168-622x}, doi = {10.1001/jamapsychiatry.2016.2095}, author = {Brander, G. and Rydell, M. and Kuja-Halkola, R. and Fernandez de la Cruz, L. and Lichtenstein, P. and Serlachius, E. and Ruck, C. and Almqvist, C. and D{\textquoteright}Onofrio, B. M. and Larsson, H. and Mataix-Cols, D.} }