title: Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort.
abstract: OBJECTIVE
  Autoimmune disruption may contribute to risk for autism; however, since previous studies relied upon clinical diagnoses, exposure misclassification and recall bias are limitations. Thyroid peroxidase antibody (TPO-Ab) is an autoantibody involved in autoimmune thyroiditis. We aimed to test the a priori hypothesis that positivity to maternal serum TPO-Ab (TPO-Ab+) (defined as >156 IU/ml) during pregnancy is related to childhood autism.
  
  
  METHODS
  The study was based on a nested case-control design of the Finnish Prenatal Study of Autism (FiPS-A), a national birth cohort that includes prospectively drawn archived maternal serum specimens from virtually the entire pregnant population of Finland beginning in 1983. Cases of childhood autism (ICD-10F84.0) born from 1987 to 2005 were ascertained by performing linkages between national birth and inpatient/outpatient registries. All diagnosed cases in Finland over the birth years, and comparison subjects without ASD or severe/profound intellectual disability were matched 1:1 on date of birth, sex, birthplace, and residence in Finland. Maternal serum specimens were assayed in 967 matched case-control pairs for TPO-Ab by a chemiluminescent microparticle immunoassay blind to case/control status. Data were analyzed by conditional logistic regression for matched sets.
  
  
  RESULTS
  The prevalence of maternal TPO-Ab+ was significantly increased in pregnancies giving rise to autism cases (6.15%) compared to controls (3.54%). The odds of autism were increased by nearly 80% among offspring of mothers who were TPO-Ab+ during pregnancy (OR=1.78, 95% CI=1.16-2.75, p=0.009), compared to mothers negative for this autoantibody. There was also a significant relationship between maternal TPO-Ab defined as a continuous variable and odds of autism (OR=1.09, 95% CI=1.01, 1.17, p=0.02). Measures of maternal thyroid hormones did not differ between groups.
  
  
  CONCLUSIONS
  These findings provide the first biomarker-based evidence that a class of known maternal autoimmune disorders is related to autism in offspring.
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States; Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168th Street, New York, NY 10032, United States. Electronic address: asb11@columbia.edu.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Brown
authors.affiliation: National Institute for Health and Welfare, Oulu, Finland.
authors.forename: Heljä-Marja
authors.initials: HM
authors.lastname: Surcel
authors.affiliation: Department of Child Psychiatry, Faculty of Medicine, University of Turku, Turku, Finland.
authors.forename: Susanna
authors.initials: S
authors.lastname: Hinkka-Yli-Salomäki
authors.affiliation: Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168th Street, New York, NY 10032, United States.
authors.forename: Keely
authors.initials: K
authors.lastname: Cheslack-Postava
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Psychiatry, College of Physicians and Surgeons of Columbia University, New York State Psychiatric Institute, 1051 Riverside Drive, New York, NY 10032, United States; Department of Child Psychiatry, Faculty of Medicine, University of Turku, Turku, Finland; Department of Child Psychiatry, Turku University Hospital, Turku, Finland.
authors.forename: Andre
authors.initials: A
authors.lastname: Sourander
mesh_terms: D000328:Adult; D001321:Autistic Disorder / Q000097:blood / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood / Q000276:immunology*; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D015331:Cohort Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D006801:Humans; D011247:Pregnancy; D015995:Prevalence; D012042:Registries; D012307:Risk Factors; D013963:Thyroid Hormones / Q000097:blood; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D013963:Thyroid Hormones; C056626:thyroid microsomal antibodies
keywords: Autism; Autoantibody; Autoimmune; Birth cohort; Epidemiology; Thyroid