Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (FT4) concentrations during the first 18 weeks of pregnancy with child Attention-Deficit Hyperactivity Disorder (ADHD).

Methods: 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INMA (N=1073, Spain), Generation R (N=3812, The Netherlands) and ALSPAC (N=2784, United Kingdom). Exclusion criteria were multiple pregnancies, fertility treatments, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the DSM-IV criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses.

Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither FT4 nor TSH was associated with a higher risk of ADHD [Odds ratio (OR), 95% Confidence Interval (CI): 1.1 (1.0-1.3), P=0.060 and OR 0.9, 95% CI 0.9-1.1, P=0.385, respectively] or with high symptom scores. When investigating effect modification by gestational age, a higher FT4 was associated with symptoms above the 90th percentile but only in the first trimester [for FT4 per 1SD: OR 1.2 (95% CI 1.0-1.4), P=0.027]. However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed.

Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD.