Neonatal thyroid‐stimulating hormone and association with attention‐deficit/hyperactivity disorder

Abstract

Background Normal brain development is dependent on maternal, fetal and neonatal thyroid function. Measuring neonatal thyroid‐stimulating hormone (TSH) 48‐72 hours after birth screens for congenital hypothyroidism, allowing early treatment to avoid serious impairment. However, even within sub‐clinical ranges, disrupted thyroid homeostasis during brain development has been linked to adverse neurodevelopmental outcomes, including attention‐deficit/hyperactivity disorder (ADHD). Objectives To estimate the association between neonatal TSH below threshold for potential congenital hypothyroidism and subsequent ADHD diagnosis using a population‐based birth cohort. Methods Children with a diagnosis of ADHD in the Norwegian Mother, Father and Child Cohort Study (MoBa) were identified through linkage with the Norwegian Patient Registry using ICD‐10 codes for hyperkinetic disorders. The study included 405 ADHD cases and 1,092 controls (born 2003‐2008) with available neonatal TSH concentrations below 10 mU/L (cut‐off for potential congenital hypothyroidism) measured in dried blood spots sampled 48‐72 hours after birth. Results In multivariable, quintile models the relationship appeared to follow a U‐shaped pattern with elevated odds ratios (OR) at lower and higher TSH levels. Among children with TSH in the lowest quintile, odds of ADHD was approximately 1.5‐fold higher than children in the middle quintile (OR 1.60, 95% CI 1.09, 2.34), which was driven by substantially elevated risk among girls, with no association among boys (Pinteraction = 0.02; girls OR 3.10, 95% CI 1.53, 6.30; boys OR 1.16, 95% CI 0.73, 1.84). Conclusions ADHD risk appeared to be elevated among newborns with low TSH levels (i.e. with hyperthyroid status), and this association was mainly found among girls. Because our findings are suggestive of increased risk at very low TSH concentrations, where analytical accuracy is low, future studies should employ highly sensitive assays capable of accurate quantitation at very low concentrations. Also, larger studies are needed to investigate these associations at higher neonatal TSH concentrations where data are more widely distributed.

The association between thyroid function biomarkers and attention deficit hyperactivity disorder

“…Overall, our results support the notion that lower serum TSH may be related to a higher risk for ADHD in children but not adolescents. These findings agree with recent work by Villanger et al who reported that ADHD risk appeared to be elevated among newborns with low TSH levels after analyzing TSH concentrations below 10 mIU/L in 405 ADHD cases and 1092 controls 37 .…”

Impact of lowering TSH cut-off on neonatal screening for congenital hypothyroidism in Minas Gerais, Brazil

“…It is important, also, to consider that excessive treatment in CH patients seems to be associated to unfavorable cognitive outcomes. There are reports of an increase in cases of attention deficit hyperactivity disorder and even a decrease in intelligence quotient related to excessive treatment [46][47][48]. There is yet no consensus on this subject, more research is needed.…”

Impact of Lowering TSH Cut-Off on Neonatal Screening for Congenital Hypothyroidism in Minas Gerais, Brazil

“…On the other hand, excessive treatment in CH patients appears to be linked to unfavorable cognitive outcomes [ 46 , 47 , 48 ]. There is still no consensus on this matter; further research is needed.…”