Abstract
Background: Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent; this is of concern as observational studies have shown negative associations with child neurodevelopment. Though neither the benefits nor the safety of iodine supplementation in pregnancy in areas of mild-to-moderate deficiency are well researched, such supplementation is increasingly being recommended by health authorities in a number of countries. Objective: By reviewing the most recent published data on the effects of iodine supplementation in mildly-to-moderately deficient pregnant women on maternal and infant thyroid function and child cognition, we aimed to determine whether the evidence was sufficient to support such recommendations in these areas. Design: A systematic review of randomised controlled trials (RCTs), non-RCT interventions and observational studies was conducted. To identify relevant papers we searched the PubMed and Embase databases. We defined mild-to-moderate iodine deficiency as a baseline, median, urinary iodine-concentration (UIC) of 50-149 µg/L. Eligible studies were included in meta-analyses. Results: In total, 37 publications were included – ten RCTs, four non-RCT interventions and 23 observational studies. Most studies showed no effect of iodine supplementation on maternal or infant thyroid-stimulating hormone and free-thyroxine. Most RCTs found that supplementation reduced maternal thyroglobulin and in three RCTs, it prevented or diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed child neurodevelopment; only one was adequately-powered. Meta-analyses of two RCTs showed no effect on child cognitive [mean difference (MD) (95%CI): -0.18 (-1.22, 0.87)], language [MD (95%CI): 1.28 (-0.28, 2.83)] or motor scores [MD (95%CI): 0.28 (-1.10, 1.66)]. 4 Conclusions: There is insufficient good-quality evidence to support current recommendations for iodine supplementation in pregnancy in areas of mild-to-moderate deficiency. Well designed RCTs with child cognitive outcomes are needed in areas of moderate deficiency (median UIC<100 µg/L). The maternal intra-thyroidal iodine stores should be considered in future trials by including appropriate measures of pre-conceptional iodine intake.