ContextAlthough the consequences of severe iodine deficiency are beyond doubt, the effects of mild to moderate iodine deficiency in pregnancy on child neurodevelopment are less well established.ObjectiveTo study the association between maternal iodine status during pregnancy and child IQ and identify vulnerable time windows of exposure to suboptimal iodine availability.DesignMeta-analysis of individual participant data from three prospective population-based birth cohorts: Generation R (Netherlands), INMA (Spain), and ALSPAC (United Kingdom); pregnant women were enrolled between 2002 and 2006, 2003 and 2008, and 1990 and 1992, respectively.SettingGeneral community.Participants6180 mother-child pairs with measures of urinary iodine and creatinine concentrations in pregnancy and child IQ. Exclusion criteria were multiple pregnancies, fertility treatment, medication affecting the thyroid, and preexisting thyroid disease.Main Outcome MeasureChild nonverbal and verbal IQ assessed at 1.5 to 8 years of age.ResultsThere was a positive curvilinear association of urinary iodine/creatinine ratio (UI/Creat) with mean verbal IQ only. UI/Creat <150 µg/g was not associated with lower nonverbal IQ (−0.6 point; 95% CI: −1.7 to 0.4 points; P = 0.246) or lower verbal IQ (−0.6 point; 95% CI: −1.3 to 0.1 points; P = 0.082). Stratified analyses showed that the association of UI/Creat with verbal IQ was only present up to 14 weeks of gestation.ConclusionsFetal brain development is vulnerable to mild to moderate iodine deficiency, particularly in the first trimester. Our results show that potential randomized controlled trials investigating the effect of iodine supplementation in women with mild to moderate iodine deficiency on child neurodevelopment should begin supplementation not later than the first trimester.

Background Mild-to-moderate iodine deficiency, particularly in pregnancy, is prevalent; this is of concern because observational studies have shown negative associations with child neurodevelopment. Although 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. Objectives 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 recommendations in these areas. Methods A systematic review of randomized controlled trials (RCTs), non-RCT interventions, and observational studies was conducted. To identify relevant articles, 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—10 RCTs, 4 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 3 RCTs, it prevented or diminished the increase in maternal thyroid volume during pregnancy. Three RCTs addressed child neurodevelopment; only 1 was adequately powered. Meta-analyses of 2 RCTs showed no effect on child cognitive [mean difference (MD): −0.18; 95% CI: −1.22, 0.87], language (MD: 1.28; 95% CI: −0.28, 2.83), or motor scores (MD: 0.28; 95% CI: −1.10, 1.66). 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 pregnant women who are moderately deficient (median UIC &lt; 100 µg/L). Maternal intrathyroidal iodine stores should be considered in future trials by including appropriate measures of preconceptional iodine intake. This review was registered at www.crd.york.ac.uk/prospero as CRD42018100277.

Low maternal FT4 was consistently associated with a lower IQ across the cohorts. Further studies are needed to replicate the findings of autistic traits and investigate the potential modifying role of maternal iodine status. FT4 seems a reliable marker of fetal thyroid state in early pregnancy, regardless of the type of immunoassay.

Milk is the main source of iodine in the United Kingdom (UK), however, the consumption and popularity of plant-based milk-alternative drinks is increasing. Consumers may be at risk of iodine deficiency as, unless fortified, milk alternatives have a low iodine concentration. We therefore aimed to compare the iodine intake and status of milk-alternative consumers to that of cows’-milk consumers. We used data from the UK National Diet and Nutrition Survey from Years 7-9 (2014-2017; before a few manufacturers fortified their milk-alternative drinks with iodine). Data from four-day food diaries were used to identify consumers of milk-alternative drinks and cows’ milk, along with the estimation of their iodine intake (µg/day) (available for n=3976 adults and children ≥ 1.5 years). Iodine status was based on urinary iodine concentration (UIC, µg/L) from spot-urine samples (available for n=2845 adults and children ≥ 4 years). Milk-alternative drinks were consumed by 4.6% (n=185; n=88 consumed these drinks exclusively). Iodine intake was significantly lower in exclusive consumers of milk-alternatives than cows’-milk consumers (94 vs 129 µg/day; P<0.001). Exclusive consumers of milk-alternatives also had a lower median-UIC than cows’-milk consumers (79 vs 132 µg/L; P<0.001) and were classified as iodine-deficient by the WHO criterion (median-UIC < 100 µg/L) whereas cows’-milk consumers were iodine-sufficient. These data show that consumers of unfortified milk-alternative drinks are at risk of iodine deficiency. As a greater number of people consume milk-alternative drinks, it is important that these products are fortified appropriately to provide a similar iodine content to that of cows’ milk.

Acknowledgements EUthyroid project: This project has received funding from the European Union´s Horizon 2020 research and innovation programme under grant agreement No 634453. ALSPAC: We are extremely grateful to all the families who took part in this study, the midwives for their help in recruiting them, and the whole ALSPAC team, which includes interviewers, computer and laboratory technicians, clerical workers, research scientists, volunteers, managers, receptionists and nurses. The UK Medical Research Council and Wellcome (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This publication is the work of the authors and Dr Bath will serve as a guarantor for the contents of this paper. ALSPAC data collection is funded from a wide range of sources, a comprehensive list of which is available on the ALSPAC website (http://www.bristol.ac.uk/alspac/external/documents/grant-acknowledgements.pdf). The existing iodine measurements in ALSPAC were funded from (i) the NUTRIMENTHE project, which received a research grant from the European Community's 7th Framework Programme (FP7/2008-2013) under grant agreement 212652; and (ii) a Ph.D. studentship that was funded by Wassen International and the Waterloo Foundation (2009-2012). We would like to thank Dr Pauline Emmett for helping with the dietary analysis of the ALSPAC food frequency questionnaire.