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Original Investigation
November 2016

Association of Perinatal Risk Factors With Obsessive-Compulsive DisorderA Population-Based Birth Cohort, Sibling Control Study

Author Affiliations
  • 1Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
  • 2Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
  • 3Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
  • 4Astrid Lindgren Children’s Hospital, Karolinska University Hospital, Stockholm, Sweden
  • 5Department of Psychological and Brain Sciences, Indiana University, Bloomington
  • 6Department of Medical Sciences, Örebro University, Örebro, Sweden
JAMA Psychiatry. 2016;73(11):1135-1144. doi:10.1001/jamapsychiatry.2016.2095
Key Points

Question  Do adverse perinatal events increase the risk for obsessive-compulsive disorder (OCD)?

Findings  In a population-based birth cohort study of 2.4 million children in Sweden, maternal smoking during pregnancy, breech presentation, delivery by cesarean section, preterm birth, low birth weight, being large for gestational age, and Apgar distress scores were associated with a higher risk of developing OCD, independently of shared familial confounders. A dose-response association was identified for a number of perinatal events, with a higher risk for OCD noted in individuals with a greater number of events.

Meaning  The findings of this study are important for the understanding of the cause of OCD and will inform future studies on gene by environment interaction and epigenetics.


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 2 421 284 children from singleton births in Sweden from January 1, 1973, to December 31, 1996, who were followed up through December 31, 2013. From the 1 403 651 families in the cohort, differentially exposed siblings from the 743 885 families with siblings were evaluated; of these, 11 592 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 2 421 284 individuals included in the cohort, 17 305 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.