Related Experiment Video
Updated: May 26, 2026
Generation of a Mouse Spontaneous Autoimmune Thyroiditis Model
Published on: March 17, 2023
Maternal thyroid autoimmunity during pregnancy and the risk of attention deficit/hyperactivity problems in children:
Akhgar Ghassabian1, Jacoba J Bongers-Schokking, Yolanda B de Rijke
1The Generation R Study Group, Erasmus University Medical Center, Rotterdam, The Netherlands.
Insights
Elevated maternal thyroid peroxidase antibodies (TPOAbs) during pregnancy are linked to increased externalizing problems, particularly attention deficit/hyperactivity, in children. This association is partially mediated by maternal thyroid-stimulating hormone (TSH) levels.
Area of Science:
- Reproductive Endocrinology
- Developmental Psychology
- Pediatric Neurology
Background:
- Maternal thyroid dysfunction and autoimmunity during pregnancy are linked to adverse offspring developmental outcomes.
- Thyroid peroxidase antibodies (TPOAbs) are a common marker of autoimmune thyroid disease.
Purpose of the Study:
- To investigate the association between elevated maternal TPOAbs in early pregnancy and cognitive/behavioral outcomes in preschool children.
- To explore the mediating role of maternal thyroid parameters, such as TSH, in this association.
Main Methods:
- A population-based cohort study of 3139 mother-child pairs (Generation R Study).
- Maternal thyroid parameters (TSH, free Thyroxine, TPOAbs) measured at 13.5 weeks gestation.
- Child cognitive function assessed at 2.5 years; child behavior assessed at 3 years using validated questionnaires.
Main Results:
- Elevated maternal TPOAbs did not predict child cognitive functioning.
- Maternal TPOAbs were associated with increased risk of externalizing problems (OR=1.64) and specifically attention deficit/hyperactivity problems (OR=1.77) in children.
- The association between TPOAbs and externalizing problems remained significant after adjusting for maternal TSH (OR=1.56).
Conclusions:
- Elevated maternal TPOAbs in pregnancy are associated with increased risk of problem behavior, particularly ADHD, in children.
- The effect of TPOAbs on child behavior is only partially mediated by maternal TSH levels.
- Findings suggest a potential mechanism for ADHD and highlight the need for further research on monitoring and early detection in at-risk populations.
Background:
Maternal thyroid status and autoimmunity during pregnancy have been associated with impaired development of the offspring in animal and human studies. Our objective was to examine whether elevated titers of maternal thyroid peroxidase antibodies (TPOAbs) in early pregnancy increased the risk of cognitive impairment and problem behavior in preschool children. Second, we aimed at exploring to what extent any effect on child behavior was mediated by maternal thyroid parameters during pregnancy.
Methods:
In the Generation R Study, a population-based cohort of 3139 children and their mothers, we measured maternal thyroid parameters (thyrotropin [TSH], free Thyroxine, and TPOAbs) at 13.5±1.8 weeks of gestation. Children's verbal and nonverbal cognitive functioning was measured at 2.5 years using the Language Development Survey and the Parent Report of Children Abilities. At 3 years, children's behavior was assessed using the Child Behavior Checklist.
Results:
Elevated titers of TPOAbs during pregnancy did not predict the verbal and nonverbal cognitive functioning of the children. However, elevated titers of TPOAbs in mothers were associated with externalizing problems in children (odds ratio [OR]=1.64, 95% confidence interval [CI]: 1.17-2.29, p=0.004). In particular, children of TPOAb-positive mothers were at a higher risk of attention deficit/hyperactivity problems (OR=1.77, 95% CI: 1.15-2.72, p=0.01). To explore whether the effect of maternal TPOAbs on child problem behavior was mediated by maternal thyroid parameters, we added maternal TSH to the model. After correcting for TSH, the effect of TPOAbs on externalizing problems was attenuated slightly but remained significant (OR=1.56, 95% CI: 1.14, 2.14, p=0.005).
Conclusions:
Our findings imply that the elevated titers of TPOAbs during pregnancy impact children's risk of problem behavior, in particular, attention deficit/hyperactivity. The observed effect is only partially explained by maternal TSH levels. These findings may point to a specific mechanism of Attention Deficit/Hyperactivity Disorder in children. Nevertheless, we can only speculate about public health implication of the study, as there is no specific treatment for TPOAb-positive pregnant women with normal thyroid function. Further investigation is needed to explore whether TPOAb-positive pregnant women and their children can benefit from close monitoring and early detection of developmental delay in populations at risk.
Related Concept Videos
01:30Attention-Deficit/Hyperactivity Disorder
Diagnostic Criteria and Symptoms
To diagnose ADHD, symptoms must manifest before age 12 and be evident across multiple settings.
01:28Graves' Disease I: Introduction
01:24Graves Disease II: Pathophysiology
01:25Hyperthyroidism I: Introduction
01:27Hyperthyroidism II: Pathophysiology
01:20Synthesis and Regulation of Thyroid Hormones
Upon reaching the thyroid gland, TSH stimulates the follicular cells' active uptake of iodide ions from the blood. The ions diffuse to the apical surface of the cells and are oxidized to iodine. The iodine is then...