Maternal Iodine Supplementation Research Articles

An update: maternal iodine supplementation, thyroid function tests, and child neurodevelopmental outcomes.

The impact of maternal iodine supplementation (MIS) during pregnancy on thyroid function and child neurodevelopmental outcomes in areas of mild-to-moderate iodine deficiency (MMID) remains unclear. Despite growing success of salt iodization programs, a 2022 meta-analysis found that 53% of pregnant patients worldwide continue to have insufficient iodine intake during pregnancy. A 2021 randomized controlled trial (RCT) found that MIS in women with mild iodine deficiency led to iodine sufficiency and positive effects on maternal thyroglobulin. A 2021 cohort study of MIS initiated prior to pregnancy was associated with lower thyroid-stimulating hormone (TSH), higher FT3, and FT4. Other cohort studies, however, found that neither salt iodization nor MIS were adequate to meet pregnancy iodine needs. Data have been mixed regarding maternal iodine status and pregnancy outcomes in patients of MMID. Meta-analyses have not shown any clear benefit on infant neurocognitive outcomes with MIS of MMID patients. A 2023 meta-analysis found that the prevalence of excess iodine intake in pregnancy was 52%. MMID continues to exist during pregnancy. Salt iodization alone may be insufficient to ensure adequate iodine status during pregnancy. There is an absence of high-quality data to support routine MIS in areas of MMID. However, patients with specialized diets (vegan, nondairy, no seafood, noniodized salt, and so on) may be at risk for inadequate iodine status in pregnancy. Excess iodine intake can be detrimental to the fetus and should be avoided during pregnancy.

A systematic review and meta-analysis on the associations of maternal iodine status and supplementation with thyroid function during postpartum

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Maternal Iodine Supplementation During Lactation May Improve Child's Cognitive Development at 3 Years of Age in a Mild-to-Moderately Iodine-Deficient Population

Maternal Iodine Supplementation During Lactation May Improve Child's Cognitive Development at 3 Years of Age in a Mild-to-Moderately Iodine-Deficient Population

Does maternal iodine supplementation during the lactation have a positive impact on neurodevelopment of children? Three-year follow up of a randomized controlled trial.

The aim of this study was to examine, for the first time, the neurodevelopmental outcomes in children whose mothers received different doses of iodine supplements during lactation. We conducted a follow-up study on children whose mothers participated in a randomized clinical trial to receive placebo, 150µg/day or 300µg/day of iodine until 12months postpartum. Child neurocognitive development was assessed at 36months of age using the Bayley Scales of Infant and Toddler Development Third Edition. Linear mixed-model analysis was preformed to assess iodine supplement dose effects on child cognitive, language, and motor functions. A total of 122 children provided neurodevelopmental data as follows: 300µg/d iodine group: 45; 150µg/d iodine group: 35; and placebo group: 42. Cognitive scores were higher in children whose mothers received 150µg iodine/d compared to children whose mothers received placebo [102.8 (SD 13.2) vs. 99.2 (SD 10.5); β = 4.43, P = 0.032]. However, supplementation with 150µg iodine/d had no effect on language or motor development. No significant differences were observed in cognitive, language, or motor functions between children whose mothers received 300µg iodine/d and those whose mothers received 150µg iodine/d or placebo. Maternal iodine supplementation with 150µg/d during lactation may have a beneficial effect on child cognitive development; however, we found no evidence of either improved or delayed neurodevelopmental outcomes in children whose mothers received iodine supplements at doses higher than recommended. Further randomized controlled trials with larger sample sizes are needed to confirm these results. IRCT201303164794N8; registration date: 2013-05-20.

Lithium from breast-milk inhibits thyroid iodine uptake and hormone production, which are remedied by maternal iodine supplementation.

Lithium is especially taken as a maintenance medication for Bipolar Disorder. In women with bipolar disorder, lithium is often effective during postpartum period, but breast-feeding for medicated mothers is controversial because of harmful effects for her child. At present, the biological mechanisms of lithium are not well-understood, affecting its usage and overall health implications. We developed a rat lithium and breast-feeding model at human therapeutic levels to study the effects of lithium exposure through breast-milk on pups' thyroid function. Novel laser analytical spectroscopy, along with traditional blood and immunohistochemical tests, were applied to further investigate the mechanisms behind the thyroid dysfunction. Maternal iodine supplementation was evaluated as a therapeutic method to address the pups' thyroid dysfunction. Pups exposed to lithium via breastmilk, even with the dam on a sub-therapeutic level, experienced weight gain, reduced blood thyroxine (T4 ), and elevated blood urea nitrogen, indicating effects on thyroid and kidney function. We show that lithium inhibited iodine uptake by thyroid follicles, initiating a mechanism that reduced iodination of tyrosine, thyroglobulin cleavage, and thyroid hormone production. Importantly, infant thyroid function can be significantly improved by administering supplementary iodine to the medicated dam's diet during breast-feeding. These results elucidate the mechanisms of lithium in thyroid function, provide valuable information on use postpartum, and suggest a clinically applicable remedy to side-effects. The results are particularly important for patients (and their infants) who respond well to lithium and need, or choose, to breast-feed.

Iodine Supplementation in Mildly Iodine-Deficient Pregnant Women Does Not Improve Maternal Thyroid Function or Child Development: A Secondary Analysis of a Randomized Controlled Trial.

Background: Iodine deficiency during pregnancy may be associated with lower offspring IQ, but there are few data on the safety and efficacy of maternal iodine supplementation on child development. In a previously reported multi-center randomized trial conducted in Thailand and India, we assessed the effect of iodine supplementation in mildly iodine-deficient pregnant women on offspring development. In this secondary analysis of that trial, we report data only from the Thai pregnant women in the study, who were more iodine deficient at entry.Methods: Pregnant women in Bangkok, Thailand, were randomized to receive daily 200 μg oral iodine or placebo until delivery. We assessed thyroid size and thyroid function during pregnancy and cognitive and motor development at ages 1, 2, and 5.7 years. The trial was registered at www.clinicaltrials.gov/NCT00791466.Findings: Women (n = 514) entered the trial between November 2008 and March 2011 at a mean ± SD gestational age of 11 ± 2.8 weeks; their median (IQR) UIC was 112 (75, 170) μg/L. Mean compliance with supplementation was 88%. We assessed 397 mothers in the 3rd trimester, 231 infants at age 2 y, and 157 children at mean age 5.7 y. During pregnancy, there was a slightly greater decrease in free and total thyroxine concentrations in the iodine group (p < 0.05). At age 2 years, the iodine group had borderline lower scores for combined fine and gross motor function (p = 0.05), but there were no other significant differences in development. At 5.7 years, there were no significant group differences in child development.Conclusion: Daily iodine supplementation in mildly iodine deficient pregnant women was associated with small negative effects on maternal thyroxine concentrations, but did not affect child development. The safety and efficacy of iodine supplementation in mildly-iodine deficient pregnant women needs to be evaluated further in large randomized controlled trials.

Iodine supplementation of lactating women and assessment of infant visual information processing and maternal and infant thyroid function: A randomized trial.

Iodine deficiency is one of the major causes of brain damage in childhood. However, iodine supplementation during early pregnancy and lactation can prevent the ill effects of iodine deficiency. This study evaluated maternal and infant thyroid function and infant visual information processing (VIP) in the context of maternal iodine supplementation. A community-based, randomized, supplementation trial was conducted. Mother infant dyads (n = 106) were enrolled within the first 10 days after delivery to participate in this study. Mothers were randomly assigned either to receive a potassium iodide capsule (225 μg iodine) daily for 26 weeks or iodized salt weekly for 26 weeks. Maternal thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), thyroglobulin (Tg), urinary iodine concentration (UIC), breast milk iodine concentration (BMIC) and infant T4, TSH, UIC and VIP were measured as outcome variables. At baseline, neither mothers nor infants in the two groups were significantly different in any of the biomarkers or anthropometric measurements. Maternal TSH and goiter prevalence significantly decreased following iodine supplementation. The percentage of infants who preferentially remembered the familiar face was 26% in the capsule and 51% in the I-salt groups. Infant sex, length for age Z score, BMIC, maternal education and household food security were strong predictors of novelty quotient. In conclusion supplementation daily for six months with an iodine capsule or the use of appropriately iodized salt for an equivalent time was sufficient to reduce goiter and TSH in lactating women. Higher BMIC and LAZ as well as better household food security, maternal education, and male sex predicted higher novelty quotient scores in the VIP paradigm.

Iodine consumption and cognitive performance: Confirmation of adequate consumption.

Iodine, a dynamic nutrient present in thyroid hormones, is responsible for regulating thyroid function, supporting a healthy metabolism, and aiding growth and development. Iodine is also essential for brain development during specific time windows influencing neurogenesis, neuronal and glial cell differentiation, myelination, neuronal migration, and synaptogenesis. About 1.5 billion people in 130 countries live in areas at risk of iron deficiencies (IDs). Reduced mental ability due to IDs occurs in almost 300 million people. Ensuring the consumption of minimum recommended daily allowances of iodine remains challenging. The effects of ID disorders range from high mortality of fetuses and children to inhibited mental development (cretinism). Poor socioeconomic development and impaired school performance are also notable. Currently, ID disorders are the single greatest contributor to preventable brain damage in fetuses and infants and arrested psychomotor development in children. Iodized salt may help fulfill iodine requirements. Increases in food salt iodization programs can help overcome ID disorders. Dietary plans can be well adjusted to incorporate iodinated foods. Maternal iodine supplementation for offspring requires adequate attention. Fruits, vegetables, bread, eggs, legumes (beans and peas), nuts, seeds, seafood, lean meats and poultry, and soy products provide small quantities of iodine. Nutrient‐dense foods containing essential vitamins and minerals such as iodine may confer positive effects. To some extent, fortified foods and daily dietary supplements can be provided for different nutrients including iodine; otherwise, iodine may be consumed in less than the recommended amounts. This review focuses on aspects of adequate iodine consumption to avoid cognitive impairments.

Maternal iodine supplementation improves motor coordination in offspring by modulating the mGluR1 signaling pathway in mild iodine deficiency-induced hypothyroxinemia rats

Iodine is an essential component for thyroid hormone synthesis. Epidemiological investigations have demonstrated that maternal mild iodine deficiency (ID)-induced hypothyroxinemia can affect intellectual and behavioral function in offspring. There is no definitive evidence demonstrating the effects of maternal iodine supplementation on neurobehavioral function in regional areas with mild ID. Thus, we aimed to clarify the effects of maternal mild ID and iodine supplementation on motor coordination in offspring and illuminate the underlying molecular mechanisms. Animal models of maternal mild ID and iodine supplementation were generated by providing Wistar rats an iodine-deficient diet and deionized water supplemented with potassium iodide during pregnancy and lactation. We found that mild ID-induced hypothyroxinemia led to a shorter latent time before falling down from the rotarod, a longer time to traverse the balance beam and poorer wire grip of the forelimbs, which imply motor coordination dysfunction. However, these impairments in the offspring were improved by iodine supplementation during pregnancy and lactation. We further observed that the ultrastructure and dendritic tree morphology of cerebellar Purkinje cells were altered in mild ID-induced hypothyroxinemia but that these changes could be reversed by iodine supplementation. Maternal mild ID and iodine supplementation also affected expression of the mGluR1 signaling pathway in offspring. Together, iodine supplementation during pregnancy and lactation can improve motor coordination in offspring by modulating the mGluR1 signaling pathway in mild ID-induced hypothyroxinemia rats.

Consequences of iodine deficiency and excess in pregnant women: an overview of current knowns and unknowns ,

Severe iodine deficiency during development results in maternal and fetal hypothyroidism and associated serious adverse health effects, including cretinism and growth retardation. Universal salt iodization is the first-line strategy for the elimination of severe iodine deficiency. Iodine supplementation is recommended for vulnerable groups in severely iodine-deficient regions where salt iodization is infeasible or insufficient. A recent clinical trial has informed best practices for iodine supplementation of severely iodine-deficient lactating mothers. Because of successful programs of universal salt iodization in formerly severely iodine-deficient regions around the world, public health concern has shifted toward mild to moderate iodine deficiency, which remains prevalent in many regions, especially among pregnant women. Observational studies have shown associations between both mild maternal iodine deficiency and mild maternal thyroid hypofunction and decreased child cognition. Iodine supplementation has been shown to improve indexes of maternal thyroid function, even in marginally iodine-deficient areas. However, no data are yet available from randomized controlled trials in regions of mild to moderate iodine insufficiency on the relation between maternal iodine supplementation and neurobehavioral development in the offspring; thus, the long-term benefits and safety of such supplementation are uncertain. Although it is clear that excessive iodine intake can cause alterations in thyroid function in susceptible individuals, safe upper limits for iodine intake in pregnancy have not been well defined. Well-designed, prospective, randomized controlled trials that examine the effects of iodine supplementation on maternal thyroid function and infant neurobehavioral development in mildly to moderately iodine-deficient pregnant women are urgently needed. In addition, clinical data on the effects of iodine excess in pregnant and lactating women are needed to inform current recommendations for safe upper limits on chronic iodine ingestion in general and on iodine supplementation in particular.

Research needs for assessing iodine intake, iodine status, and the effects of maternal iodine supplementation

The Office of Dietary Supplements of the NIH convened 3 workshops on iodine nutrition in Rockville, Maryland, in 2014. The purpose of the current article is to summarize and briefly discuss a list of research and resource needs developed with the input of workshop participants. This list is composed of the basic, clinical, translational, and population studies required for characterizing the benefits and risks of iodine supplementation, along with related data, analyses, evaluations, methods development, and supporting activities. Ancillary studies designed to use the participant, biological sample, and data resources of ongoing and completed studies (including those not originally concerned with iodine) may provide an efficient, cost-effective means to address some of these research and resource needs. In the United States, the foremost question is whether neurobehavioral development in the offspring of mildly to moderately iodine-deficient women is improved by maternal iodine supplementation during pregnancy. It is important to identify the benefits and risks of iodine supplementation in all population subgroups so that supplementation can be targeted, if necessary, to avoid increasing the risk of thyroid dysfunction and related adverse health effects in those with high iodine intakes. Ultimately, there will be a need for well-designed trials and other studies to assess the impact of maternal supplementation on neurodevelopmental outcomes in the offspring. However, 2 basic information gaps loom ahead of such a study: the development of robust, valid, and convenient biomarkers of individual iodine status and the identification of infant and toddler neurobehavioral development endpoints that are sensitive to mild maternal iodine deficiency during pregnancy and its reversal by supplementation.

Assessing infant cognitive development after prenatal iodine supplementation

Little information is available on infant behavioral development outcomes of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Studies performed to date, all of which relied on global developmental assessments, have yielded inconsistent findings with regard to psychomotor development, negative findings with regard to mental development, and no information as to the development of specific cognitive functions. Our review of these studies leads us to suspect that the use of global developmental assessments might partially explain the negative and inconsistent findings. To identify cognitive processes that might be sensitive to prenatal iodine supplementation, we examined the timing of thyroid hormone action on specific brain systems. The development of infant visual attention is sensitive to thyroid hormone during the early prenatal period, when the fetus is entirely dependent on maternal thyroid hormone. For this reason, infant visual attention has the potential to be a sensitive measure of infant outcomes in prenatal iodine supplementation studies. We suggest the assessment of infant visual attention, with follow-up examination of childhood executive functions, as a means of capturing the effects of maternal iodine deficiency and prenatal iodine supplementation on specific cognitive processes. In particular, we propose comparison of infant performance on global developmental tests and specialized tests of visual attention in pilot trials of prenatal iodine supplementation in regions of mild to moderate iodine deficiency. Only by comparing the 2 types of tests side by side will it be possible to establish whether the use of a sensitive measure of infant visual attention will increase the reliability of such supplementation studies. Recognizing that exposure misclassification may also provide a partial explanation for the inconsistent neurodevelopmental outcomes in previous studies, we suggest that urinary iodine concentration or creatinine-corrected iodine excretion be monitored regularly in such trials throughout the prenatal period.

Suggested use of sensitive measures of memory to detect functional effects of maternal iodine supplementation on hippocampal development ,

Maternal hypothyroxinemia secondary to iodine deficiency may have neurodevelopmental effects on the specific neurocognitive domain of memory. Associated disruption of thyroid hormone–dependent protein synthesis in the hippocampus has the potential to result in compromised development of the structure with consequential impairments in memory function. Despite links between maternal iodine deficiency during gestation and lactation and abnormal hippocampal development in rat fetuses and pups, there has been little research on the specific function of memory in human infants and young children born to iodine-deficient mothers. Several candidate measures have proven to be sensitive to the effects of gestational iron deficiency on memory function in infants and young children, including habituation and dishabituation, imitation-based tasks, and event-related potentials. Such measures could be used to test the effects of maternal iodine supplementation on the specific neurocognitive domain of memory in infants and young children. Furthermore, progress in understanding the effects of maternal iodine supplementation on neurocognitive development could be accelerated by the development of a nonhuman primate model to complement the rodent model.

Assessing iodine intake, iodine status, and the effects of maternal iodine supplementation: introduction to articles arising from 3 workshops held by the NIH Office of Dietary Supplements

The NIH Office of Dietary Supplements (ODS) convened 3 workshops on iodine nutrition in 2014, each held in Rockville, Maryland. These workshops were part of the ongoing ODS Iodine Initiative, begun in 2011 in response to concerns that US pregnant women may be at risk of iodine deficiency and that a high fraction of prenatal dietary supplements do not contain the recommended amounts of iodine. The primary purpose of the workshops was to consider the data and resources necessary to evaluate the clinical and public health benefits and risks of maternal iodine supplementation in the United States. The first workshop focused on the assessment of iodine intake, the second focused on the assessment of iodine status, and the third focused on the design and interpretation of clinical trials of maternal iodine supplementation. Here we provide the background of the ODS Iodine Initiative, summarize the 3 workshops held in 2014, and introduce the articles that arose from the workshops and are published in this supplement issue.

Supplement—Assessing Iodine Intake, Iodine Status, and the Effects of Maternal Iodine Supplementation

Supplement—Assessing Iodine Intake, Iodine Status, and the Effects of Maternal Iodine Supplementation

Effect of maternal iodine supplementation on thyroid function and birth outcome in goiter endemic areas

Objective:The study was undertaken to examine the clinical and endocrine parameters of thyroid in a total of 460 pregnant women belonging to non-goiter areas (group 1; n = 156) and endemic areas without (group 2; n = 154) and with iodine supplementation (group 3; n = 150), and their respective newborns.Methods:Women of group 3 with visible goiter were administered two capsules of iodized oil orally each containing 200 mg of iodine, from weeks 6--8 of pregnancy. Blood samples were obtained from all groups during each trimester, at parturition (umbilical cord blood) and after delivery. Serum triiodothyronine (T3), thyroxine (T4) and thyroid stimulating hormone (TSH) levels were measured by specific enzyme immunoassays.Results:In group 2, serum T4 concentrations were low while T3 and TSH levels were high which showed hypothyroidism in the women of endemic areas. Goiter size decreased in most of the subjects who received a single dose of iodized oil and resulted in increase in serum concentrations of thyroid hormones; whereas, TSH levels decreased. Iodine supplementation also resulted in raised T4 and low TSH levels in the cord blood of neonates. During the course of study, two abortions, three still births and one cretin were reported in group 2; none was reported in group 3; and one still birth was reported in group 1.Conclusions:The oral administration of a single dose of iodized oil is capable of correcting iodine deficiency both clinically and endocrinologically in mothers and neonates. Iodine supplementation has the potential to positively impact the birth weight of newborns.

Iodine deficiency in pregnancy

Iodine is an essential micronutrient for thyroid hormone synthesis and thus is essential for the normal progression of pregnancy and for the fetus neuropsychological development. Iodine requirements increase during pregnancy for physiological changes in iodine metabolism (increased renal iodine losses, iodine transfer from maternal circulation to the fetoplacental unit and fetal iodine needs for thyroid hormone production). Therefore the iodine intake should be increased by about 50% during pregnancy and lactation and the daily dose recommended by the WHO is at least 250 µg / day corresponding to a Urinary Iodine Excretion ( UIE ) range of 150-249 µg /L. Iodine supplementation is recommended in all pregnant women , even in iodine sufficient countries or in areas where universal salt iodization has been achieved (iodized salt consumed in more than 90% of households). These measures, in fact , ensure the daily iodine intake of 150 µg / day recommended in all women of childbearing age but they are not sufficient to support the increased requirements imposed by pregnancy. Recently, even in developed countries, such as UK, USA, and Australia , moderate iodine deficiency has re-emerged as an important public health concern , likely due to a change in eating habits of the population. There are recent data that highlight how even mild degrees of iodine deficiency may adversely affect the progression of the pregnancy or the neurocognitive outcome in children. It should be emphasized that national programs of health policy must provide epidemiological surveillance measures to ensure the maintenance of iodine sufficiency over time. Because the fetal thyroid gland may be particularly sensitive to the inhibitory effect of high iodine concentrations , possible negative effects of maternal iodine supplementation during pregnancy have been hypothesized. The currently available data, however, appear to indicate a relatively low risk of these effects against the benefits derived from the adequate transfer of maternal T4 to the fetus in conditions of iodine sufficiency especially in the first trimester of gestation.

Effects of maternal iodine supplementation during pregnancy and lactation on iodine status and neonatal thyroid-stimulating hormone.

To determine the iodine status in pregnant and lactating women, as well as neonatal thyroid-stimulating hormone (TSH) concentration. Pregnant women cared at our hospital, the University Hospital in Bangkok, had routinely received 200 μg iodine tablet daily since October 2010. Urinary iodine concentrations (UICs) of 1508 pregnant and 87 lactating women and 76 offspring and breast milk iodine concentration (BMIC) (n=57) were measured. Cord serum TSH levels from hypothyroidism screening were analyzed. Median UIC levels of pregnant and lactating women were 170.6 and 138.0 μg l(-1), respectively. Median BMIC and infants' UIC at 2-month postpartum in iodine-supplemented group were higher than the respective values of non-supplemented group. Median cord serum TSH level obtained before iodine supplementation (n=8332) was higher than that obtained after supplementation (n=5181; 7.3 vs 5.2 mU l(-1)). Maternal iodine supplementation improved iodine nutrition in their breast-fed offspring. A trend toward declining in cord serum TSH values after iodine supplementation indicates improvement of iodine status during pregnancy.

Effect of iodine supplementation during pregnancy on neonatal thyroid stimulating hormone

Background Thyroid hormone is essential for neurological development, particularly in the developing brain. Iodine is the important constituent of thyroid hormone. Its requirement during pregnancy is increased. Elevated neonatal thyroid stimulating hormone (TSH) is a sensitive indicator of iodine insufficiency in pregnant women. Our previous study in the year 2000 demonstrated that median urine iodine (UI) concentration in pregnant women was 85 μg/ L, a level of which indicates mild iodine deficiency. Since October 2010, Thai national universal iodine supplementation program has been started by prescribing a 150 μgiodine tablet daily to all pregnant women throughout their gestation. We, therefore, aimed to determine the effect of maternal iodine supplementation on neonatal TSH.

Iodine Supplementation During Pregnancy and Infant Neuropsychological Development: INMA Mother and Child Cohort Study

Iodine supplementation during pregnancy is a common practice in developed countries. However, scant evidence is available regarding the safety and effectiveness of maternal iodine supplementation with regard to child neuropsychological development. We previously reported an inverse association between iodine supplementation and the psychomotor development of infants in a birth cohort from Valencia, Spain. In the present study, we assessed this association in a wider sample of mother and child pairs from 3 other regions in Spain. Neuropsychological development was assessed using the Bayley Scales of Infant Development in 1,519 infants (median age, 16 months) between 2006 and 2009. In multivariate analyses, maternal consumption of 150 μg/day or more of iodine from supplements was related to a 1.5-fold increase in the odds of a psychomotor score less than 85 (95% confidence interval: 0.8, 2.9) and to a 1.7-fold increase in the odds of a mental score less than 85 (95% confidence interval: 0.9, 3.0). Findings previously reported in the Valencia cohort were only partially verified. The results of the present study suggest that, at least in these regions, iodine supplementation does not improve infant neuropsychological development at 1 year of age. Further research is needed on the risks and benefits of supplementary iodine for both maternal thyroid function and child neurodevelopment.