Maternal Thyroid Anomalies and Risk of Attention Deficit Hyperactivity Disorder in Progeny

Abstract

Background. The fetus is dependent on adequate maternal supply of thyroid hormones, which have important neurodevelopmental roles. Impaired thyroid function was linked with exposure to several environmental toxicants, and these thyroid-related effects may be a mechanism through which environmental toxicants affect neurodevelopment. Extreme maternal thyroid dyshomeostasis causes adverse neurodevelopmental effects, but impacts of subtler thyroid disruption remain unclear. We evaluated the risk of Attention Deficit Hyperactivity Disorder (ADHD) in children of mothers with thyroid anomalies, and the relation between gestational maternal thyroid hormone levels and child ADHD risk. Methods. The study included 445,477 singletons born in 1999-2012 in a large Israeli health fund, with data on ADHD diagnoses retrieved through 2019. Maternal thyroid conditions were ascertained through ICD-9 codes with subsequent validation through review of drug dispensing and laboratory data. ADHD cases were identified through ICD-9 codes, with additional information on dispensing of stimulants and nonstimulants medications. Analyses were performed using Cox proportional hazard and additive Poisson regression models employing a robust variance estimator. Results. Children of mothers who experienced hypothyroidism had a higher ADHD risk compared to children of mothers without thyroid conditions (HR=1.11, 95% C.I:1.07-1.15), with more robust results in the subgroup of ADHD children who also received pharmaceutical ADHD treatments. Hyperthyroidism results were less consistent. Results were materially unchanged when restricting to mothers gestationally treated with levothyroxine. Analysis of maternal gestational thyrotropin and free-thyroxine levels did not show consistent associations with ADHD risk. Conclusions. Maternal hypothyroidism was associated with increased child ADHD risk, but seemingly not due to direct effects of thyroid hormones. Instead, factors that influence maternal thyroid function may have etiologic roles in ADHD through pathways independent of maternal gestational thyroid hormones, and thus be unaffected by medication treatment. Environmental factors known to disrupt thyroid function should be examined for possible involvement in ADHD etiology.