A new study has found that persistent thyroid hormone imbalance across pregnancy is associated with an increased risk of autism spectrum disorder (ASD) in children. The findings, published in The Journal of Clinical Endocrinology & Metabolism, are based on data from more than 51,000 births.
Researchers reported that autism was more common among children whose mothers experienced thyroid hormone imbalance in multiple trimesters. The longer the dysfunction persisted, the higher the risk.
“We found that adequately treated chronic thyroid dysfunction was not associated with increased autism risk in offspring, but ongoing imbalance across multiple trimesters was,” said Idan Menashe, PhD, of Ben-Gurion University of the Negev. “These findings underscore the need for routine monitoring and timely adjustment of therapy.”
Study Design And Thyroid Classification
The retrospective cohort study examined the relationship between maternal thyroid dysfunction and ASD risk. Participants were members of Clalit Health Services from 2011 to 2017, with follow-up through January 2021.
Researchers drew on sociodemographic and medical data from health records and linked these to prenatal and perinatal information from the medical center where the study was conducted. ASD diagnoses were obtained from the Azrieli National Center for Autism and Neurodevelopment Research.
Thyroid dysfunction was categorized as chronic, gestational, or both. Diagnoses were based on ICD-9 codes and trimester-specific measurements of TSH and early-pregnancy free T4 levels. These measures also allowed investigators to distinguish between gestational hypothyroidism and hyperthyroidism.
Highest Autism Risk Seen In Combined Thyroid Dysfunction
Of the 51,296 women included, 4,409 had abnormal thyroid function: 1,161 had chronic hypothyroidism, 1,600 had gestational hypothyroidism, and 1,054 had both. Smaller numbers had chronic or gestational hyperthyroidism.
Children were diagnosed with ASD at a median age of 4.6 years. A significantly higher cumulative incidence of ASD was observed in children born to mothers with both chronic and gestational thyroid dysfunction, compared with those whose mothers had normal thyroid function.
No significant risk increase was seen in children of mothers with only chronic or only gestational dysfunction. The adjusted hazard ratio (aHR) was 1.33 for these groups combined. In contrast, the aHR for ASD among children of mothers with both types of thyroid dysfunction was 2.68—more than double the risk.
Women with both chronic and gestational hypothyroidism also showed an increased risk (aHR 2.61), whereas chronic-only and gestational-only hypothyroidism did not produce significant associations.
Risk Increases With Each Affected Trimester
ASD risk rose steadily with the number of trimesters affected by thyroid dysfunction, increasing between 28% and 39% per trimester. A single trimester of dysfunction was linked to an aHR of 1.69, two trimesters to 2.39, and all three to 3.25. For women with both chronic and gestational hypothyroidism, the aHRs were:
- 1.35 for dysfunction in one trimester
- 2.04 for two trimesters
- 2.87 for all three trimesters
The authors concluded that maternal thyroid hormone levels during pregnancy are linked to offspring ASD risk, although chronic hypothyroidism alone did not show an association.
“While causal conclusions are premature, these results support recommendations for routine monitoring of thyroid hormone levels during pregnancy and prompt treatment to maintain normal thyroid function,” the researchers wrote.
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