Maternal thyroid function in the first half of pregnancy and neurodevelopmental outcomes in early adolescence in the Amsterdam Born Children and their Development (ABCD) cohort

Maternal thyroid hormone levels in pregnancy have been implicated to play a role in brain development, but few observational studies have examined their relationship with neurodevelopmental outcomes beyond early childhood. We investigated associations between maternal thyroid function during the first 20 weeks of pregnancy and neurodevelopmental outcomes in 1824 children aged 10-13 years from the Amsterdam Born Children and their Development (ABCD) cohort. Outcomes included neurocognition (non-verbal intelligence [Raven's Progressive Matrices], executive working memory [SOPT]), behavioural organisation (behaviour regulation and metacognition [BRIEF], and internalizing behaviour and risk-seeking [SURPS]), and emotional, social, and behavioural problems (mother-, teacher-, and self-reported SDQ internalizing and externalizing problems). We fitted linear and quadratic multivariable regression models, as well as restricted cubic splines with three knots for the 10th, 50th and 90th percentiles, choosing the best model to assess associations across the continuous range of thyroid-stimulating hormone (TSH) and free thyroxine (FT4) on the outcomes, both in pregnancies without overt thyroid disease and in the full cohort. Secondary analyses examined potential threshold effects (10th and 90th percentiles of TSH and FT4), and impact of clinical thyroid dysfunction based on cohort-specific reference ranges, anti-TPO positivity, and sex differences. We found a small but significant positive linear association between maternal log-transformed TSH in pregnancies free of overt thyroid disease and non-verbal intelligence in girls (estimate: 0.05, 95 % CI: 0.01 to 0.09, p = 0.02; SMD: 0.015), but not in boys, after correction for multiple testing. No other neurodevelopmental outcomes were associated with maternal thyroid function. These findings suggest that maternal thyroid function in early pregnancy, in the absence of overt thyroid disease, shows no consistent associations with child neurodevelopmental outcomes in adolescence, apart from a small association with non-verbal intelligence in girls that may not be clinically relevant.