Association between maternal thyroid dysfunction and neurodevelopmental disorders in offspring: a population-based...

Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) are both common neurodevelopmental disorders (NDDs), but their association between maternal thyroid dysfunction and NDDs in offspring remains equivocal. This study aimed to evaluate the association between maternal thyroid dysfunction, related medications, and neurodevelopmental disorders in offspring. This population-based retrospective birth cohort study included children born between 2004 and 2020, with surveillance continuing through 2021. Maternal thyroid dysfunction during pregnancy was identified by any outpatient or inpatient diagnosis of hyperthyroidism or hypothyroidism. Medications for hyperthyroidism during pregnancy, including propylthiouracil (PTU) and methimazole (MMI), as well as levothyroxine for hypothyroidism, were also examined. Associations between maternal thyroid dysfunction with medication use and child NDDs were modeled using Cox proportional hazards regression. The study cohort consisted of 3,175,328 live-born children. Among them, 39,294 (1.2%) were born to mothers with hyperthyroidism, and 14,630 (0.5%) had mothers with hypothyroidism. A higher risk of ADHD was noted in children whose mothers had thyroid dysfunction, whether they had hyperthyroidism (adjusted HR, 1.19; 95% CI,1.14-1.24) or hypothyroidism (adjusted HR,1.28; 95% CI,1.19-1.37), and a similarly increased risk of ASD was observed in association with maternal hyperthyroidism (adjusted HR, 1.14; 95% CI, 1.03-1.27) or hypothyroidism (adjusted HR, 1.34; 95% CI, 1.19-1.51). For medications in treating hyperthyroidism during pregnancy, continuous propylthiouracil (PTU) use was associated with a lower risk of ADHD (adjusted HR, 0.91; 95% CI, 0.83-0.99) or ASD (adjusted HR, 0.80; 95% CI, 0.67-0.96). This study identified the association between maternal thyroid dysfunction during pregnancy and offspring ADHD. Moreover, we observed that continuous use of PTU for treating maternal hyperthyroidism during pregnancy may be associated with a reduced risk of childhood ADHD.