Maternal thyroid hormone imbalance and risk of autism spectrum disorder

Maternal thyroid hormones play crucial roles in fetal neurodevelopment, with hypothyroidism and hyperthyroidism consistently being reported as potential risk factors for autism spectrum disorder (ASD) in offspring. Nevertheless, the mechanism underlying this association remains vague. In this retrospective cohort study of 51,296 singleton births in a single hospital, we examined the impact of different maternal thyroid conditions on the risk of ASD in the offspring. Chronic and gestational hyper-and hypothyroidism were determined based on ICD-9 criteria and maternal thyroid hormone levels, respectively. ASD diagnosis was determined based on DSM-5 criteria. Kaplan-Meier plots and Cox regression models were used to assess ASD risk in the offspring of women with and without thyroid conditions. A total of 4,306 (8.4%) of the mothers showed abnormal thyroid function. ASD cumulative incidence was similar in the offspring of women with normal and abnormal thyroid function (log-rank p=0.28). However, further classification of the study groups revealed an increased ASD risk in the offspring of women with both chronic and gestational thyroid dysfunction (aHR= 2.68, 95%CI=1.52-4.72). In addition, trimester-specific analysis revealed a dose effect in that the longer the period of thyroid imbalance, the higher the ASD risk, namely, for one, two or three trimesters of hypo- or hyperthyroidism, aHR= 1.69 (95%CI=1.19-2.83), aHR=2.39 (95%CI=1.24-5.78), aHR=3.25 (95%CI=1.07-7.21), respectively. Thus, the findings suggest that uncontrolled gestational thyroid dysfunction is associated with an elevated risk of ASD in offspring, underscoring the importance of routine thyroid function screening and treatment throughout pregnancy in mitigating ASD risk in offspring.