Maternal thyroid autoantibody and elevated risk of autism in a national birth cohort

• Published in: Progress in neuro-psychopharmacology & biological psychiatry 2015-03, Vol.57, p.86-92
• Main Authors: Brown, Alan S., Surcel, Heljä-Marja, Hinkka-Yli-Salomäki, Susanna, Cheslack-Postava, Keely, Bao, Yuanyuan, Sourander, Andre
• Format: Article
• Language: English
• Subjects: Adult; Autism; Autistic Disorder - blood; Autistic Disorder - immunology; Autoantibodies - blood; Autoantibodies - immunology; Autoantibody; Autoimmune; Biomarkers - blood; Birth cohort; Case-Control Studies; Child; Cohort Studies; Epidemiology; Female; Finland - epidemiology; Humans; Pregnancy; Prevalence; Registries; Risk Factors; Thyroid; Thyroid Hormones - blood; Young Adult
• ISSN: 0278-5846; 1878-4216
• DOI: 10.1016/j.pnpbp.2014.10.010

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 >156IU/ml) during pregnancy is related to childhood autism. 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. 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. These findings provide the first biomarker-based evidence that a class of known maternal autoimmune disorders is related to autism in offspring. •Odds of autism were raised after prenatal thyroid peroxidase antibody exposure.•The finding was observed in a large national birth cohort.•There were no associations between maternal hypothyroidism and autism.•This is the first biomarker-based prenatal autoimmune association with autism.•Further prospective studies are needed to confirm this finding.