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

Prog Neuropsychopharmacol Biol Psychiatry. 2015 Mar 3:57:86-92. doi: 10.1016/j.pnpbp.2014.10.010. Epub 2014 Oct 29.


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.

Keywords: Autism; Autoantibody; Autoimmune; Birth cohort; Epidemiology; Thyroid.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Autistic Disorder / blood
  • Autistic Disorder / immunology*
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Biomarkers / blood
  • Case-Control Studies
  • Child
  • Cohort Studies
  • Female
  • Finland / epidemiology
  • Humans
  • Pregnancy
  • Prevalence
  • Registries*
  • Risk Factors
  • Thyroid Hormones / blood
  • Young Adult


  • Autoantibodies
  • Biomarkers
  • Thyroid Hormones
  • thyroid microsomal antibodies