Low maternal free thyroxine (FT4) early in pregnancy is associated with both reduced nonverbal and verbal IQ in the child, and there is a suggestive association between maternal hypothyroxinemia and high FT4 with an elevated risk for autistic traits, according to new findings published in the Journal of Clinical Endocrinology & Metabolism.
Previous studies have suggested an association between low maternal FT4 and poor child neurodevelopment, but the evidence remains limited for potential adverse effects of high FT4 and whether associations differ in countries with a different iodine status.
To evaluate the association of maternal thyroid function in early pregnancy with child neurodevelopment in countries with a different iodine status, investigators conducted a meta-analysis using data from individual participants. The cohort included 9036 mother-child pairs from 3 prospective population-based birth cohorts: Infancia y Medio Ambiente (INMA; Spain), Generation R (The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; United Kingdom).
There was a statistically significant nonlinear association between maternal FT4 and mean nonverbal IQ. FT4 at or below the 2.5th percentile was associated with a 3.9-point (95% CI, −5.7 to −2.3; P <.001) lower nonverbal IQ, but there was no association with high FT4. A linear association was observed between maternal FT4 and mean verbal IQ, but it was not statistically significant. FT4 at or below the 2.5th percentile also was associated with a 2.1-point (95% CI, −4.0 to −0.1; P =.039) lower verbal IQ. A continuous association between maternal FT4 with child autistic traits was not observed.
There was no continuous association of maternal Ft4 with child autistic traits. FT4 at or below the 2.5th percentile was not associated with autistic traits, whereas FT4 at or below the 5th percentile was slightly nonstatistically significant for risk for autistic traits (odds ratio, 1.5; 95% CI, 1.0-2.3; P =.080).
Hypothyroxinemia was associated with a 3.8-point (P <.001) lower nonverbal IQ and a 2.8-point (P =.007) lower verbal IQ.
“FT4 seemed a reliably marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay,” researchers wrote, adding that “[f]urther studies should replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status.”
Levie D, Korevaar TIM, Bath SC, et al. Thyroid function in early pregnancy, child IQ, and autistic Traits: a meta-analysis of individual-participant data [published online May 10, 2018]. J Clin Endocrinol Metabol. doi: 10.1210/jc.2018-00224