Direct iodine supplementation of infants versus supplementation of their breastfeeding mothers: a double-blind, randomised, placebo-controlled trial.

BACKGROUND Iodine deficiency in infants can damage the developing brain and increase mortality. Present recommendations state that oral iodised oil should be given to breastfeeding mothers to correct iodine deficiency in infancy when iodised salt is not available, and that direct supplementation should be given to infants who are not being breastfed or receiving iodine-fortified complimentary foods. However, there is little evidence for these recommendations. We aimed to assess the safety and efficacy of direct versus indirect supplementation of the infant. METHODS We did this double blind, randomised, placebo-controlled trial in Morocco. Healthy breastfeeding mothers and their term newborn babies (aged ≤8 weeks) were block randomised by clinic day to receive either: one dose of 400 mg iodine to the mother and placebo to the infant (indirect infant supplementation), or one dose of about 100 mg iodine to the infant and placebo to the mother (direct infant supplementation). Randomisation was masked to participants and investigators. Coprimary outcomes were: maternal and infant urinary iodine concentrations, breastmilk iodine concentration, maternal and infant thyroid-stimulating hormone (TSH) concentrations, maternal and infant thyroxine (T4) concentrations, and infant growth. These outcomes were measured at baseline, and when infants were aged about 3 months, 6 months, and 9 months, and the two groups were compared using mixed effects models. This study is registered with ClinicalTrials.gov, number NCT01126125. FINDINGS We recruited 241 mother-infant pairs between Feb 25, and Aug 10, 2010, and completed data collection by Aug 6, 2011. At baseline, median urinary iodine concentration was 35 μg/L (IQR 29-40) in mothers and 73 μg/L (29-237) in infants, suggesting iodine deficiency. During the study, maternal urinary iodine concentration (p=0.011), breastmilk iodine concentration (p<0.0001), and infant urinary iodine concentration (p=0.042) were higher in the indirect infant supplementation group than in the direct supplementation group. Maternal TSH (p=0.276) and T4 (p=0.074) concentrations did not differ between the groups over the course of the study, nor did infant TSH (p=0.597) and T4 (p=0.184) concentrations, but the number of infants with thyroid hypofunction was lower (p=0.023) in the indirect supplementation group than the direct supplementation group. The infant groups did not differ in anthropomorphic measures, except that length-for-age Z score was slightly greater in the direct infant supplementation group (p=0.032). At 3 months and 6 months of age, median infant urinary iodine concentration in the indirect infant supplementation group was sufficient (>100 μg/L), whereas infant urinary iodine concentration was sufficient only at 6 months in the direct supplementation group. There were no serious adverse events in either group. INTERPRETATION In regions of moderate-to-severe iodine deficiency without effective salt iodisation, lactating women who receive one dose of 400 mg iodine as oral iodised oil soon after delivery can provide adequate iodine to their infants through breastmilk for at least 6 months, enabling the infants to achieve euthyroidism. Direct supplementation is less effective in improving infant iodine status. FUNDING ETH Zurich, Switzerland; the Medicor Foundation, Vaduz, Lichtenstein.