Maternal Hypothyroxinemia in Early Pregnancy Predicts Reduced Performance in Reaction Time Tests in 5-to 6-Year-Old Offspring

Context: Overt hypothyroidism in pregnant women is associated with poorer neurodevelopment in their children. Findings from studies investigating the effect of less severe impairments in the maternal thyroid function on cognitive functioning in offspring are difficult to interpret for a number of reasons, including lack of objective cognitive tests, preschool age at assessment, and small sample sizes. Objective: We aimed to assess the effect of the maternal thyroid status in early pregnancy on their offspring's cognitive performance at 5 to 6 years of age. Design and Participants: This was a prospective study that included the data of 1765 healthy 5- to 6-year-old children from the Amsterdam Born Children and their Development study. Maternal serum free T4 and TSH were obtained at a median gestational age of 90 (interquartile range, 83 to 100) days. Main Outcome Measures: Cognitive performance was tested using a computerized assessment program that measured response speed, response speed stability, visuomotor skills, response selection, and response inhibition. Results: Maternal hypothyroxinemia (ie, maternal free T4 in the lowest 10% of distribution) was associated with a 41.3 (95% confidence interval, 20.3-62.4) ms slower response speed in a simple reaction time task. In this test, it was also associated with a decreased stability in response speed. The relations found persisted after adjustment for family background and perinatal conditions. The effect of hypothyroxinemia on these outcomes was dependent on its interaction with TSH level. Conclusions: Lower maternal free T4 concentration at the end of the first trimester predicted slower response speed and decreased stability in response speed in offspring at 5 to 6 years of age. (J Clin Endocrinol Metab 98: 1417-1426, 2013)