PROJECT SUMMARY Mild-to-moderate iodine deficiency (ID) remains widespread worldwide among pregnant and lactating women who have higher dietary requirements than the general population. Iodine is required for the synthesis of thyroid hormone, which is essential for human brain development, particularly visual attention, fine motor development, language and memory. The benefits of iodine supplementation for severe ID during pregnancy and in childhood have been established. However, the effects of iodine supplementation in settings with mild- to-moderate ID and during lactation remain unclear. Furthermore, few trials to date have examined the effects of iodine supplementation in pregnancy or lactation on iodine-specific neural functions. In response to NICHD NOSI (NOT-HD-19-039), we present a unique opportunity to build upon an ongoing, randomized controlled trial (RCT) to address the consequences of iodine deficiency on fetal and infant neurodevelopment in a population of mild-to-moderate iodine deficiency in rural Ethiopia. In the funded parent pregnancy trial, women in early pregnancy are randomized to receive a package of strengthened nutrition support (including monthly supply of iodized salt) and/or a package of infection control. The funded parent pregnancy trial will determine the effect of the interventions on infant birth outcomes. With support from this award, we propose to add a lactation intervention utilizing an efficient 2x2 factorial design and randomize women after delivery to receive a) an intensive iodized salt intervention, including provision of a monthly supply of high-quality, adequately iodized salt and counseling regarding appropriate storage and use, or b) standard care, until 6 months post- partum. Our overall goal is to examine the effects of iodine in pregnancy and lactation on infant brain function, as well as maternal and infant iodine status and thyroid function. The specific aims of this project are to: (1) determine the effects of an intensive salt intervention in pregnancy and lactation on infant visual evoked potentials (primary outcome), as well as visual attention, motor function, and head circumference at 6 months of age; (2) determine the effect of the iodized salt intervention on maternal breast milk iodine concentration, as well as infant iodine status and thyroid function; and (3) examine interactions between iron and iodine on thyroid function in pregnancy and lactation. Globally, salt iodization is the primary intervention strategy for iodine delivery. To our knowledge, this trial will be the first rigorous, adequately powered RCT of high-fidelity iodized salt provision along the continuum of pregnancy and lactation in a setting of mild-moderate iodine deficiency. These discoveries will improve our understanding of the role of iodine in early human brain development in order to develop effective targeted intervention strategies to improve iodine status and neurodevelopmental outcomes in children worldwid...