What do we know about iodine supplementation in pregnancy

Despite major progress over the last four decades, iodine deficiency remains the leading preventable cause of mental retardation. It has been estimated that 20% of the 2 billion individuals worldwide currently at risk for iodine deficiency disorders reside in Europe (1). The study of Velasco et al. (2), published in this issue of JCEM, demonstrated that infants of Spanish mothers who had received oral 300 g potassium iodide (KI) supplements daily during pregnancy and lactation had higher Bayley Psychomotor Development scores at 3–18 months of age than infants whose mothers did not receive iodine supplements. A strength of the study was the authors’ ability to collect trimester-specific urinary iodine concentrations (UIC) and thyroid function data, cord blood thyroid function studies, infant UIC, breast milk iodine concentrations, and infant neurocognitive data in a majority of the treatment group; this was a heroic feat. The major limitation of the study is the fact that it was not rigorously controlled. Apparently this was not by choice. The authors note that “the Ethics Committee . . . did not authorize the inclusion of a control group without treatment.” The authors selected a group of 61 untreated women to serve as controls. Because they were enrolled in the eighth month of pregnancy, thyroid function and urinary iodine measurements were not obtained in these women before the third trimester. Another 31 untreated women who experienced miscarriage at wk 8–12 were recruited to provide only UIC. Although there was no difference between treated and untreated groups in infant birth weights, Apgar scores, maternal age, frequency of prematurity, frequency and duration of breastfeeding, or parental education, neurodevelopment is an extremely complex process, and there are many potential confounders that could have contributed to the apparent difference in infant development between the study groups. Was the decision of the Ethics Committee appropriate? It would clearly be unethical to withhold iodine supplementation from pregnant women known to be severely iodine deficient. A blinded, placebo-controlled clinical trial begun in the 1960s in Papua, New Guinea, demonstrated that preconception supplementation of severely iodine-deficient women (median UIC 20 g/liter) with iodinated oil eliminated the risk for cretinism and improved offspring cognitive function and survival (3). These findings have subsequently been replicated in many regions of the world (4). A meta-analysis of Chinese studies suggests that iodine supplementation in severely iodinedeficient regions may increase the average child IQ by 12.5 points (5). The women in the Velasco study, however, were moderately but not severely iodine deficient at baseline. Although sample sizes were small, in the two untreated control groups, the median UIC were 69 and 88 g/liter—both below the optimal range of 150–249 g/liter as defined by the World Health Organization (6), and similar to the UIC of 84 g/liter previously reported for third-trimester pregnant women from Andalusia (7). What is known about the effects of iodine supplementation in pregnant women with this moderate degree of iodine deficiency? Seven previous controlled trials of iodine supplementation in moderately iodine-deficient pregnant European women have been published, although doses and timing of iodine supplementation varied, and only one previous trial examined effects on offspring development.