Maternal hypothyroxinaemia in early pregnancy and school performance in 5-year-old offspring

Objective: Overt hypothyroidism in pregnant women is associated with a lower intelligence quotient in their children. More recently, subtle decreases in maternal thyroid function have also been associated with neurodevelopmental impairment in offspring. We tested the effect of hypothyroxinaemia during early pregnancy on school performance. Design: This was a longitudinal study that included the data of 1196 mother-child pairs from the Amsterdam Born Children and Their Development study. Methods: Maternal serum free thyroxine (T-4) and TSH were obtained at a median gestational age of 12.9 (interquartile range: 11.9-14.3) weeks. School performance was assessed at age 5 years and based on scores obtained in arithmetic and language tests from the national monitoring and evaluation system. Poor school performance was defined as a test result <25th percentile and subnormal school performance as a result <50th percentile of the norm population. To estimate the impact of possible non-response bias, we conducted inverse-probability weighted analyses. Results: Maternal hypothyroxinaemia (i.e., a maternal free T4 in the lowest 10% of distribution) was associated with a 1.61 (95% CI: 1.05-2.47) -fold increased odds of subnormal arithmetic performance after adjustment for confounders (P=0.03). However, the odds ratio dropped to 1.48 (95% CI: 0.94-2.32) after inverse-probability weighting (P=0.09). No such relations were found with TSH. Conclusions: Maternal hypothyroxinaemia at the end of the first trimester was associated with reduced performance in an arithmetic test, but not in a language test, in 5-year-old offspring. However, our results should be interpreted carefully because of possible non-response bias.