Iodine Status and Association With Gut Health: A Multi-Site Birth Cohort Study in Eight Low- and Middle-Income Countries

Abstract Objectives (To 1) describe trends of iodine status among infants from 6–24 mos old and (2) assess associations between iodine status, intestinal permeability, and inflammation from 6–15 mos old. Methods Data from 1565 children enrolled in the MAL-ED birth cohort were included in these analyses from eight sites (Dhaka, Bangladesh (BGD); Fortaleza, Brazil (BRF); Vellore, India (INV); Bhaktapur, Nepal (NEB); Loreto, Peru (PEL); Naushero Feroze, Pakistan (PKN); Venda, South Africa (SAV); and Haydom, Tanzania (TZH)) from enrolment (≤17 d old) to 24 mos old. Urinary iodine concentration (UIC) was measured at 6, 15, and 24 mos of age using the Sandell-Kolthoff technique. Gut inflammation and permeability were assessed via fecal neopterin (NEO), myeloperoxidase (MPO) and alpha-1-anti-trypsin (AAT) concentrations (monthly in first year and quarterly in second) and the lactulose-mannitol (LM) test (3, 6, 9, 15 mos). The mean of fecal biomarkers available up to 94 days (interquartile range: 92–120) preceding the iodine quantification were used. LM values used were contemporary to the iodine sampling (6 and 15 mos). Frequency of household use of iodized salt (I-salt) was recorded. A multinomial regression analysis was used to assess classified UIC (deficiency or excess). Results I-salt was used in four sites (BGD, BRF, NEB and PEL), but used by fewer than 20% of families in the others. At 6 mos, all sites had adequate (≥100 mg/L) to excess (≥371 mg/L) median UIC. INV had the lowest median UIC (204 μg/L [95%:171–238]) and NEB had the highest (893 μg/L [95%:762–1026]). Between 6–24 mos, five sites displayed a significant decline in the infant's median UIC (BRF, BGD and SAV sites were constant). An increase of NEO concentration and LM ratio by + 1 sd were found to reduce the odds of high UIC by 0.87 [95%:0.78–0.96] and 0.88 [95%:0.79–0.98] respectively. Conclusions Excess UIC was predominant at 6 mos and tended to normalize at 24 mos. Aspects of gut inflammation and increased permeability appear to be protective against high UIC in children aged 6–15 mos. Programs addressing iodine-related health should consider the use and appropriate formulation of I-salt and the role of gut permeability in vulnerable individuals. Funding Sources The MAL-ED study was supported by the Bill & Melinda Gates Foundation, with grants to the Foundation for the NIH and NIH/FIC.