Alan S Brown1, Heljä-Marja Surcel2, Susanna Hinkka-Yli-Salomäki3, Keely Cheslack-Postava4, Yuanyuan Bao5, Andre Sourander6. 1. 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. 2. National Institute for Health and Welfare, Oulu, Finland. 3. Department of Child Psychiatry, Faculty of Medicine, University of Turku, Turku, Finland. 4. Department of Epidemiology, Columbia University Mailman School of Public Health, 722 West 168th Street, New York, NY 10032, United States. 5. 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. 6. 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.
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. METHOD: 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.
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. METHOD: 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.
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