TSH Mediated the Effect of Iodized Salt on Child Cognition in a Randomized Clinical Trial

Objectives: This study examines the hormonal mediators of the effect of iodized salt in pregnancy on child cognition. Methods: Sixty districts across 6 zones in the Amhara region of Ethiopia were randomly allocated to a control or intervention arm of early market access to iodized salt. Twenty-two villages per arm were randomly selected for this sub-study. A total of 1220 pregnant women who conceived after the intervention began were enrolled and assessed for their iodine and iron status. Data were collected once on the household socio-demographic status and iodized salt use, and maternal urinary iodine during pregnancy. Then, infants’ diet, urinary iodine level, cognitive development (Bayley III), serum hormonal levels, iron status, and inflammation markers were measured between 2 and 13 months of age. Results: The median maternal urinary iodine concentration was adequate and significantly higher in the intervention mothers than that of the controls (163 vs 121 µg/L, P < .0001). Intervention children compared to the control children had lower thyroid-stimulating hormone (TSH) (mean: 2.4 ± 1.0 µIU/mL vs 2.7 ± 1.0 µIU/mL, effect size = 0.18, P < .01) and thyroglobulin (Tg) (41.6 ± 1.0 ng/mL vs 45.1 ± 1.0 ng/mL, effect size = 0.14, P < .05). There was an interaction between the intervention and iron stores such that cognition was higher with iron (effect size = 0.28, 100 vs 94 IQ points). TSH was a partial mediator (12%) of the effect of the intervention on child cognition (Sobel z-score = 2.1 ± 0.06, P < .05). Conclusion: TSH partially mediated the effect of the iodized salt intervention on child cognition.