title: Prenatal Nicotine Exposure and Risk of Schizophrenia Among Offspring in a National Birth Cohort.
abstract: Cigarette smoking during pregnancy is a major public health problem leading to adverse health outcomes and neurodevelopmental abnormalities among offspring. Its prevalence in the United States and Europe is 12%-25%. This study examined the relationship between prenatal nicotine exposure (cotinine level) in archived maternal sera and schizophrenia in offspring from a national birth cohort.
  
  
  
  The authors conducted a population-based nested case-control study of all live births in Finland from 1983 to 1998. Cases of schizophrenia in offspring (N=977) were identified from a national registry and matched 1:1 to controls on date of birth, sex, and residence. Maternal serum cotinine levels were prospectively measured, using quantitative immunoassay, from early- to mid-gestation serum specimens archived in a national biobank.
  
  
  
  A higher maternal cotinine level, measured as a continuous variable, was associated with an increased odds of schizophrenia (odds ratio=3.41, 95% confidence interval, 1.86-6.24). Categorically defined heavy maternal nicotine exposure was related to a 38% increased odds of schizophrenia. These findings were not accounted for by maternal age, maternal or parental psychiatric disorders, socioeconomic status, and other covariates. There was no clear evidence that weight for gestational age mediated the associations.
  
  
  
  To the authors' knowledge, this is the first study of the relationship between a maternal smoking biomarker and schizophrenia. It provides the most definitive evidence to date that smoking during pregnancy is associated with schizophrenia. If replicated, these findings suggest that preventing smoking during pregnancy may decrease the incidence of schizophrenia.
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Solja
authors.initials: S
authors.lastname: Niemelä
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Andre
authors.initials: A
authors.lastname: Sourander
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Heljä-Marja
authors.initials: HM
authors.lastname: Surcel
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Susanna
authors.initials: S
authors.lastname: Hinkka-Yli-Salomäki
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Ian W
authors.initials: IW
authors.lastname: McKeague
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Keely
authors.initials: K
authors.lastname: Cheslack-Postava
authors.affiliation: From the Research Unit of Clinical Neuroscience, University of Oulu, Oulu, Finland, and the Department of Psychiatry, Lapland Hospital District, Rovaniemi, Finland; the Department of Child Psychiatry, Faculty of Medicine, University of Turku, and Turku University Hospital, Turku, Finland; the National Institute for Health and Welfare, Oulu, Finland; the Department of Psychiatry, College of Physicians and Surgeons of Columbia University, and New York State Psychiatric Institute, New York; and the Departments of Biostatistics and Epidemiology, Columbia University Mailman School of Public Health, New York.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Brown
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D015331:Cohort Studies; D003367:Cotinine / Q000097:blood; D005260:Female; D005387:Finland; D006801:Humans; D009538:Nicotine / Q000009:adverse effects* / Q000493:pharmacokinetics; D016017:Odds Ratio; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D012042:Registries; D012307:Risk Factors; D012559:Schizophrenia / Q000097:blood / Q000139:chemically induced*; D012907:Smoking / Q000009:adverse effects* / Q000097:blood; D013223:Statistics as Topic; D014029:Tobacco Use Disorder / Q000150:complications*; D055815:Young Adult
chemical_list: D009538:Nicotine; D003367:Cotinine