Adequacy of Iodine Status and Associations with Gut Health: A Prospective Cohort Study among Infants in 8 Low- and Middle-Income Countries

MAL-ED Network Investigators

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Background: Environmental enteric dysfunction increases the likelihood of micronutrient deficiencies among infants, but few studies have assessed the potential impact of gut health on urinary iodine concentration (UIC) among this vulnerable group. Objectives: We describe the trends of iodine status among infants from 6 to 24 mo old and examine the associations between intestinal permeability, inflammation, and UIC from 6 to 15 mo of age. Methods: Data from 1557 children enrolled in this birth cohort study conducted in 8 sites were included in these analyses. UIC was measured at 6, 15, and 24 mo of age by using the Sandell-Kolthoff technique. Gut inflammation and permeability were assessed using the concentrations of fecal neopterin (NEO), myeloperoxidase (MPO) and alpha-1–antitrypsin (AAT), and lactulose–mannitol ratio (LM). A multinomial regression analysis was used to assess the classified UIC (deficiency or excess). Linear mixed regression was used to test the effect of interactions among biomarkers on logUIC. Results: All studied populations had adequate (≥100 μg/L) to excess (≥371 μg/L) median UIC at 6 mo. Between 6 and 24 mo, 5 sites displayed a significant decline in the infant's median UIC. However, median UIC remained within the optimal range. An increase of NEO and MPO concentrations by +1 unit in ln scale reduced the risk of low UIC by 0.87 (95% CI: 0.78–0.97) and 0.86 (95% CI: 0.77–0.95), respectively. AAT moderated the association between NEO and UIC (P < 0.0001). The shape of this association appears to be asymmetric and in a reverse J-shape, with a higher UIC observed at both lower NEO and AAT concentrations. Conclusions: Excess UIC was frequent at 6 mo and tended to normalize at 24 mo. Aspects of gut inflammation and increased permeability appear to reduce the prevalence of low UIC in children aged 6 to 15 mo. Programs addressing iodine-related health should consider the role of gut permeability in vulnerable individuals.

Original languageEnglish (US)
Pages (from-to)828-838
Number of pages11
JournalJournal of Nutrition
Issue number3
StatePublished - Mar 2023


  • gut inflammation
  • gut permeability
  • infant
  • iodine excess
  • urinary iodine

ASJC Scopus subject areas

  • Nutrition and Dietetics
  • Medicine (miscellaneous)


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