Iodine Supplementation Before, During and After Pregnancy

Abstract

This narrative review reports on the currently insufficient intake of iodine and the iodine status of pregnant and breastfeeding women in Germany, Europe, and worldwide, as well as presenting the associated risks, particularly for children’s neurocognitive and psychomotor development. The responsibility of public health bodies to introduce appropriate measures which will ensure adequate iodine intake for all population groups and to monitor their implementation, especially during pregnancy and lactation which are particularly critical periods for the unborn child and the breastfed infant, is emphasized. Based on recent studies, the current national recommendations for iodine supplementation are reviewed, and the benefits and drawbacks of necessary measures to improve iodine intake for pregnant and breastfeeding women and their children are discussed. The most important iodine prophylaxis method – even during pregnancy and lactation – remains universal salt iodization. If this approach to improve widespread iodine intake is not feasible, the AKJ recommends that especially women of reproductive age should take continuous iodine supplements, starting at least three months prior to conception and continuing throughout pregnancy and breastfeeding.

Keywords

iodine prophylaxis - women of childbearing age - pregnancy - breastfeeding - infants

Introduction

The iodine intake of the population in Germany has decreased in recent years [1] [2]. According to the criteria of the WHO a slight iodine deficiency is again present in the general population in Germany [3]. Although the damaging effects of severe iodine deficiency are generally known, the benefits of correcting mild to moderate iodine deficiency in pregnant women are not clear as randomized controlled studies on this issue are lacking [4] [5]. Observational data are increasingly indicating that good iodine intake during pregnancy may offer significant health and economic benefits [6].

The aim of this narrative review is to present the benefits and potential drawbacks of iodine supplementation before, during and after pregnancy for the iodine intake of pregnant women, breastfeeding women, and their infants. The current implementation of different recommendations on iodine supplementation is additionally discussed.

Method

A selective search of the literature was carried out in PubMed, Google Scholar and the Cochrane Library and relevant articles were additionally considered.

Background

Iodine intake and iodine status of the general population and of pregnant women in Germany and Europe

Iodine (I) is an essential micronutrient which is needed for the synthesis of the thyroid hormones triiodothyronine (T3) and thyroxine (T4). Iodine deficiency remains an important health concern for pregnant women and infants worldwide [7] [8]. Several recent studies have reported insufficient iodine intake and iodine deficiency in pregnant and breastfeeding women in many countries [9] [10] [11] [12] [13] [14] [15] [16] [17].

Despite global efforts to overcome iodine deficiency, especially by using iodine enrichment programs, current epidemiological studies show that in Germany the iodine intake of around 30 percent of adults, 48 percent of women of reproductive age, and 44 percent of children and adolescents is below the median requirement ([18] [19], s. also references in Tab. 1 in [20]). This also applies to more than 70 % of 29 European countries [21]. The reason for this is that most women of reproductive age live in European countries where salt iodization is voluntary. Because of this, the mean iodine concentration in urine (UIC) in these countries is under 100 μg /l [3] [23] [24]. A median UIC value of > 150 μg /l, which has been proposed by the WHO as an indicator of sufficient iodine intake for pregnant women, has only been measured in a few EU countries with mandatory universal salt iodization (USI) programs [20] [23].

However, sufficient iodine intake materially depends on the level of iodization of the iodized salt. International studies show that only mandatory universal salt iodization with 25 mg iodine/kg salt will – if implemented universally – ensure adequate iodine intake of the total population. Vulnerable groups such as women of reproductive age, pregnant and breastfeeding women, and breastfed infants could benefit from this ([Fig. 1], [25]).

Fig. 1 Impact of universal salt iodization (USI) on iodine status of the population (data from [25]). Values with different letters differ significantly (p < 0.05). UIC: urine iodine concentration.

Sufficient iodine intake over the entire lifespan ensures that sufficient iodine stores are available in times of increased physiological need. The risk of excessive iodine intake from salt is minimal if the salt is iodized in the recommended amounts which are adapted to current salt intake and if closely monitored salt quality assurance measures are used to ensure compliance with the salt standard [22] [25] [26].

Incorporation in statutory regulations and food enrichment

In Germany there is no legal requirement to iodize table salt. The use of iodized salt is voluntary. The amount of iodine which can be added to salt is regulated by law. It is currently between 15 and 25 milligrams per kilogram (mg/kg). The percentage of iodized table salt used in households of around 70–80 % has been stable since the 2000s. However, iodized table salt and iodized pickling salt as a percentage of all bulk sales of salt is < 30 % and therefore significantly lower. The lower use of iodized salt in the food industry and changed eating habits have contributed to the decrease in iodine intake since the 2000s [19] [22].

It was considered whether increasing the legal maximum amount of iodine in table salt from 25 to 30 mg/kg would reduce the risk of insufficient iodine intake without simultaneously exceeding the tolerable daily upper intake level (UL). But merely increasing the iodine content in tablet salt by 5 mg/kg without increasing the amount of iodized salt used in the production of industrial and artisanal foods is not useful [24].

Thyroid function in pregnancy

As thyroid hormones (THs) play an essential role in the CNS development of the embryo and fetus [27], the current knowledge about the iodine status of infants and young children raises fundamental questions about the long-term consequences. Pregnant women and their fetuses react very sensitively to iodine deficiency, which is why monitoring iodine status during these stages in life must be prioritized [28] [29]. In the first trimester of pregnancy the development of the fetal brain is highly dependent on maternal thyroid hormones. From the 12th–14th week of gestation, the fetus is able to generate thyroid hormones itself; the fetus is then very dependent on iodide, which is transported through the placenta, and is no longer as dependent on maternal T4 of which lower amounts reach the fetus across the placenta from week 12 on. Iodine intake and storage by the placenta depend on maternal iodine intake; the total storage capacity of the placenta of between 18 and 100 μg iodine can play an important role for fetal iodine status [28] [30] [31] [32].

Effects of mild iodine deficiency and maternal hypothyroxinemia on prenatal brain development

Iodine deficiency increases the risk of isolated maternal hypothyroxinemia (IMH) in healthy pregnant women (without clinical symptoms or underlying thyroid pathologies) and may result in a maternal inability to transfer sufficient thyroxine (T4) to the embryo. This can lead to impaired neurological development with poorer fine-motor abilities, behavioral disorders, and a lower intelligence quotient [19]. IMH is primarily the result of mildly or moderately inadequate iodine intake. When iodine intake is inadequate, the intrathyroidal iodine stores (normally 5 to 20 mg) are exhausted in pregnancy because of the elevated T4 requirements of the mother and unborn child. This then changes the ratio of T4 to T3 in thyroid secretions, with a relative rise of T3 as the amount of available iodine is insufficient for T4 synthesis. Women who are unable to increase their T4 production at the start of pregnancy because they are already iodine deficient represent a population whose children are at risk of cognitive and motor disabilities and behavioral disorders [19]. Estimates have shown that up to 50 % of neonates in Europe may be threatened by iodine deficiency [33].

Measures to improve the iodine intake of the general population including women of reproductive age are urgently required [20] [22]. Reports of low iodine excretion levels in the urine (UIC) of pregnant women have prompted public health authorities in several European countries to recommend taking iodine preparations prior to conception, during pregnancy, and during lactation, although the recommendations in the different European countries vary and information for many countries is lacking [22].

Status of national recommendations for action on iodine supplementation

[Table 1] shows some national and international reference values and tolerable intake amounts of iodine for women, pregnant women, breastfeeding women, and infants [26] [38] [39] [40] [41]. The differences between countries and international associations reflect the limited scientific data and different methodologies.

Table 1 Reference values and tolerable total iodine intake for women, pregnant women, breastfeeding women, and infants.

	DGE/ÖGEa		SGEb Switzerland	EFSAc		WHOd		NAMe
Age and stage	EAR	RNI	AI	AI	UL	RNI	Intake amount above which no additional health benefit is expected	EAR	RDA	Ul
	µg/day
a DGE/ÖGE [38]; b SGE [39]; c EFSA [40]; d WHO [26]; e NAM [41] * In addition to a balanced diet which includes iodized table salt, pregnant women should take a daily supplement of 100 µg (up to 150 µg) iodine. ** During pregnancy women should take a supplement of 100 µg/day in addition to eating a balanced diet with iodized salt. § Infants exclusively fed with pureed foods prepared at home should be given a supplement of about 50 µg iodine/day [38]. AI (Adequate Intake): The appropriate adequate intake is a dietary recommendation issued when there is not enough data to calculate the average requirement (AR). It corresponds to the estimated DGE/ÖGE reference values for nutritional intakes. EAR (Estimated Average Requirement) is a measure used for nutritional recommendations. It is the estimated average daily nutrient intake level which meets the nutritional requirements of 50 percent of a healthy population or is sufficient to ensure that 50 percent of a healthy population will not be nutrient-deficient. The EAR is two standard deviations below the recommended daily allowance (RDA). RNI (Reference Nutrient Intake)/RDA (Recommended Daily Allowances [RDAs]): The amount of a nutrient which is sufficient to cover the requirements of 97.5 % of a population (calculated from the EAR + 2 SD). It corresponds to the recommended intake levels for DGE/ÖGE nutrient reference values. UL (Tolerable Upper Intake Level): The tolerable upper intake level is the maximum daily amount of a nutrient from all sources and supplements that is unlikely to cause adverse health effects in almost all individuals in the general population.
Women	95	150	150	150	600	150	> 500	95	150	900 (14–18 years) 1100 (≥ 19 years)
Pregnant women	160	230*	250	200	600	200		160	220
Breastfeeding women	167	260**	250	200	600	250	> 500	209	290	900 (14–18 years) 1100 (≥ 19 years)
0–4 months	72	80	50	–	200	90 (< 2 years)	> 180 (< 2 years)	110		Data are insufficient to determine levels
4–12 months		80§	90	90 (from the 7th month)	200			130

The need for many micronutrients only increases significantly at the end of the first trimester of pregnancy, while a higher intake of folic acid, iodine and iron is already recommended from or prior to conception compared to non-pregnant women [42]. It is difficult for pregnant and breastfeeding women in Germany to achieve the recommended intake of 230 µg or 260 µg iodine per day through their diet alone [38]. Even using iodized salt at home will not provide sufficient iodine (s. Info box 1). The risk of iodine deficiency can be estimated by evaluating the individual’s dietary history of iodine intake. The evaluation should include questions about the individual’s use of iodized salt and foods which contain iodine such as milk and marine fish and whether the individual takes iodine tablets or iodine-rich preparations made from kelp/seaweed [36].

There are currently no generally accepted biomarkers to assess the iodine status of individuals. Recommendations are therefore based on epidemiological studies of iodine excretion in the general population [34].

According to the national recommendations for action, in addition to eating a balanced diet (which should include iodized salt, dairy products, saltwater fish) pregnant and breastfeeding women should take daily iodine supplements (s. Info box 1). Daily supplementation with 100 (to 150) µg iodine is recommended during pregnancy and 100 µg is recommended during lactation [38] [35] [43]. This corresponds to the lower to middle range of 100–200 µg per day given in the Mutterschafts-Richtlinien (Mu-RL, German Maternity Policy Guidelines) which are considered safe [37].

Importance of Supplementation Prior to Conception

It is important that women of reproductive age take sufficient iodine to maximize thyroid iodine stores [45]. Scientific knowledge about the absolute daily amount of iodine after which iodine stores begin to decrease and thyroid dysfunction occurs is limited ([46], s. [Fig. 2]). To achieve an iodine balance in adults living in iodine-rich regions, the daily iodine turnover in the thyroid must be about 60–95 μg. Iodine can accumulate in thyroid cells and is stored in the follicles of the thyroid where it attaches to thyroglobulin (Tg) [47] [48]. Because of its strong association with existing iodine stories in euthyroid individuals, the determination of Tg levels is a sensitive indicator of iodine deficiency, especially in pregnant women with a UIC of < 100 μg/l [48] [49] [50] [51] [52] [53]. The thyroid’s iodine reserves may be utilized in times of low iodine intake. In adults, the mean amount of stored iodine in the thyroid is about 5–20 mg; however, there are significant differences between individuals which depend on prior iodine intake [54]. Short-term deficits in iodine intake can be offset by intrathyroidal iodine stores and increased fractional clearance of circulating iodine [56] [57]. However, if iodine intake is chronically low, the iodine reserves in the thyroid will be gradually used up. A release of Tg is triggered by increased secretion of TSH in the pituitary gland and increased synthesis and release of T3. One indication of a less efficient utilization of available iodine reserves is a lower relative secretion of T4 as a ratio of T4/T3 which leads to a relative increase in thyroid T3 secretion in reaction to the lower iodine intake [57]. Hypertrophy and hyperplasia of the thyroid tissue result in higher formation of Tg. This is why Tg serum concentrations are typically elevated in individuals with an iodine-poor diet [46]. Women who become pregnant without thyroid iodine reserves may be iodine-deficient throughout the entire pregnancy even if they began taking iodine preparations in early pregnancy [52]. This suggests that iodine deficiency in women of reproductive age should be rectified prior to pregnancy to avoid persistent iodine deficiency. Creating a sufficiently high iodine status is a step-by-step process which can take between several months and two years [58] [59]. In regions with mild iodine deficiency, delaying the additional iodine intake in pregnant women at the start of pregnancy by 6–10 weeks increases the risk of permanent changes to the gross and fine motor skills and the social development of their offspring [60]. If iodine supplementation of 100–150 μg per day is only started after conception, it may be too late to counter the adverse impacts on the child’s neurocognitive and psychomotor development which especially occur in the first trimester of pregnancy and are associated with long-term inadequate iodine intake. It is especially important to emphasize this as many pregnancies are unplanned, many women are not aware that they are in the early stages of pregnancy, and very few of them are familiar with the recommendations on iodine supplementation prior to conception. Young women who are vegan or vegetarian have an especially high risk of iodine deficiency if they do not take iodine supplements [61]. This can be explained by the fact that 37 % of our daily iodine intake is through dairy products and up to 21 % from meat and cold cuts [62] [63] [64]. Additional risk factors for iodine deficiency are smoking, the use of non-iodized salt, and/or the consumption of foods which contain goitrogenic substances, for example, certain cruciferous vegetables, a soy-rich or sorghum-rich diet, and different types of nuts such as walnuts and peanuts [46] [64] [65]. The omnipresent exposure to endocrine disruptors is an additional threat to the thyroid hormone system which can reinforce the negative effects of iodine deficiency in pregnant women on the neurocognitive and psychomotor development of their offspring [20].

Fig. 2 Simplified model of thyroid stores (data from [46]). A simplified model of human iodine and thyroid status for various stages (from left to right) of iodine intake is shown here: sufficient iodine intake, low iodine intake without thyroid dysfunction and finally, very low iodine intake with hypothyroidism. S. text for further explanations.

Results of Supplementation Before, During and After Pregnancy

A randomized controlled study carried out in Guatemala, India and Pakistan investigated the effects of daily iodine supplements in women prior to conception in resource-poor environments with populations with marginal iodine intake and limited iodine availability despite national salt iodization programs [66]. Maternal iodine status was better after the end of the first trimester and the prevalence of inadequate iodine excretion levels (iodine/creatinine < 150 μg/g) was lower in women who had started taking sufficient iodine-containing dietary supplements at least three months prior to conception compared to women without dietary supplements.

At two of three screening sites, more than one third of women who had received dietary supplements prior to conception had elevated iodine excretion levels (I/Cr in urine of ≥ 250 μg/g) without any side effects. The iodine status of pregnant women at the end of the first trimester but not in the third trimester of pregnancy showed a positive association with birth height and head circumference [66].

Although there has been a great improvement in iodine intake levels in Guatemala, India and Pakistan following universal salt iodization programs, these results still indicate that the provision of iodine to women of reproductive age is suboptimal. The reported consumption of iodized salt in households in Pakistan is only 60–80 % compared to Guatemala or India (> 80 % for both) as coverage with iodized salt is partially inadequate [66]. More than 90 % of households would need to use iodized salt and the median UIC would have to be > 100 µg/l to ensure that no iodine supplements will be required [26]. It has also been reported that the population in Pakistan has lower mean iodine concentrations in urine compared to Guatemala or India. This study is further evidence showing that supplementation initiated several months prior to conception has a greater impact than supplementation which is only initiated after the first trimester of pregnancy [66].

Serum Tg levels are considered a biomarker for iodine status. Tg data from Hungary confirm that women of reproductive age who live in iodine-poor regions should start with iodine supplementation before becoming pregnant to maintain optimal iodine intake during pregnancy ([67], [Fig. 3]). In contrast to urine iodine concentrations, serum Tg concentrations in the 16th week of gestation reflect both the iodine status prior to pregnancy and in the first trimester of pregnancy, which covers the critical phase of fetal brain development [67].

Fig. 3 The effect of duration of intake of ≥ 150 μg/day of iodine-containing pregnancy supplements on: a concentrations of thyroid-stimulating hormone (TSH), b urine iodine concentration (UIC), c creatinine-normalized UIC (UIC/Cr), and d serum thyroglobulin concentration (Tg) (data from [67]). Pregnancy starters: o no supplements; + women who started iodine supplementation once they knew they were pregnant; § Pre-pregnancy starters: women who started iodine supplementation at least 4 weeks prior to pregnancy. Median, interquartile range and 5–95 % areas are shown. Results of post-hoc Kruskal-Wallis H-tests: # p = 0.020; * p < 0.005; ** p < 0.001

Another study from Italy investigated the effects of taking an iodine supplement of 225 µg per day during pregnancy on iodine status, Tg levels, and thyroid function parameters in a randomized, placebo-controlled study carried out in a region with low to moderate iodine deficiency [68]. The data suggest that Tg could be a good marker for iodine intake in the middle to late trimesters of pregnancy, and the better correlation in the third trimester would indicate that it especially reflects long-term iodine intake and not recent intake. The level of iodine supplementation was found not to have no harmful effects on the pregnancy and had no appreciable harmful effects on thyroid function [68].

Earlier studies in iodine-deficient regions showed that the Tg levels of pregnant women were higher than those of a non-pregnant control group of women and this was the result of increased thyroid stimulation to maintain euthyroidism while no increase in Tg levels was recorded for normal iodine availability [69] [70]. Several studies have also identified a correlation between Tg and UIC during pregnancy in regions with iodine deficiency [52] [71] [72] while such a correlation is lost under other circumstances, both in iodine-rich and iodine-poor scenarios [69] [71].

The iodine abundance of thyroid stores before pregnancy plays an important role as it can be a possible source of iodine even in cases with suboptimal iodine intake during pregnancy [71]. The higher mean Tg levels in the placebo group point to overstimulation of the thyroid, which is reflected by the higher increase in Tg levels under the conditions of lower iodine intake [68].

Overall, the results of observational studies suggest that improving iodine intake (either through universal utilization of iodized salt or with nutritional supplements) prior to pregnancy is associated with lower TSH, higher fT4, lower Tg levels, and a lower thyroid volume [60] [73] compared to studies in which nutritional supplements or iodized salt only began to be utilized during pregnancy [74] [75].

Results of a meta-analysis of three prospective population-based birth cohorts show that the development of the fetal brain is especially susceptible to low to moderate iodine deficiency in the first trimester of pregnancy. Prospective randomized controlled studies which investigated the effect of iodine supplementation in women with mild to moderate iodine deficiency on the development of their offspring confirm that supplementation must be started in the first trimester of pregnancy at the latest [75].

In contrast, three further meta-analyses which evaluated the results of interventional studies were unable to provide clear conclusions about the benefit of iodine supplementation for pregnant women in areas with mild-to-moderate iodine deficiency [76]. Although the findings of the meta-analyses suggest that iodine status during pregnancy plays a role in the health of mother and child, the results of meta-analyses of interventional studies continue to be controversial. Several factors, including the level of iodine deficiency and pool studies carried out in areas with different levels of iodine intake, could explain the lack of benefits reported in meta-analyses of interventional studies. More high-quality randomized controlled studies which include information about iodine intake before starting supplementation and report on the timing, dosages and iodine supplementation regimen will be necessary to clarify this issue [76].

Carrying out such studies can be difficult, especially in regions where recommendations on iodine supplementation during pregnancy are already available. Studies which would more clearly define the safe upper limits of iodine intake for pregnant women, develop new biomarkers to assess iodine status [77], and determine how to best assess the neurocognitive and psychomotor developmental impact of iodine deficiency in pregnancy and lactation are also needed [78] [79].

The optimal iodine intake prior to conception has some similarities to the optimal folic acid intake prior to conception, which also requires time to replenish stores and metabolize folic acid and only plays a protective role in the first trimester of pregnancy [80] [81]. It is this problem of timing that helps to explain the lack of proof for the benefit of initiating iodine supplementation in pregnancy [82] [83] [84] [85]. Excessive iodine intake in the first trimester of pregnancy may lead to transient inhibition of thyroid hormone production and/or release [73] [86], which could result in potential impairment of the developing fetus [74] [87]. As the ability of the fetus to completely escape the acute Wolff-Chaikoff effect only matures fully in the 36th week of gestation, it is also possible that the fetus becomes selectively hypothyroid when faced with an excessive iodine load, even when the mother remains euthyroid [88] [89]. Most reported cases can be traced back to medications, supplements, or the consumption of kelp [85]. The tolerable upper intake level of 600 µg iodine per day for pregnant women must not be exceeded over the longer term and the overall iodine intake from all sources of nutrition must be taken into account (see [Table 1]). Greater importance should also be attached to ensuring that women have an adequate iodine intake before becoming pregnant [86]. The ideal solution would be to already create intrathyroidal iodine stores in all women of reproductive age to achieve euthyroidism in pregnant and lactating women. This was achieved in women who received 150 μg iodine/day in addition to already using iodized salt prior to conception [91] [92].

General salt iodization versus supplementation for lactating women?

The WHO has noted that general iodization of salt is currently the most effective method to ensure sufficient iodine intake by the entire population [23] [25]. Iodine deficiency in a population is defined using the median urine iodine concentration (mUIC). The WHO guidelines currently recommend a cut-off of 100 μg/l. However, the recommended cut-off for lactating women is 150 µg/l [26] [93]. In countries or regions where less than 90 % of households consume iodized salt, lactating women should receive a daily iodine supplement to ensure that their iodine intake reaches the recommended nutrient intake (RNI) of 250 μg iodine/day [26]. Iodine requirements are high when breastfeeding as iodine is transferred to the infant through breast milk but is also required for maternal thyroid function. The expression of sodium iodide symporter (NIS, a transport protein) in breast tissue increases in late pregnancy and during lactation [94].

The reference values for iodine for lactating women and infants vary (s. [Table 1]). The WHO, the United Nations Children’s Fund (UNICEF), und the Iodine Global Network (IGN) recommend an iodine concentration of 100 μg/l in the urine of mother and child to ensure sufficient iodine intake [93]. Iodine concentrations between 150–180 μg/l (range 100–300 μg/l) have been proposed for breast milk to ensure sufficient iodine intake by mother and child [95]. In iodine-deficient areas, concentrations may decrease to 9–32 μg/l [96]. However, there are no national or international guidelines on iodine concentrations in breast milk [95] [97]. Because the iodine intake of lactating mothers is inadequate, many countries and institutions recommend daily supplementation with 150 μg iodine during lactation [28] [33] [98] [99]. Even mild iodine deficiency in infancy can have a negative impact on brain development [100]. To ensure regular neonatal thyroid function and adequate neurological development in breastfed infants it is important to be aware of the increased iodine requirements of women when breastfeeding, irrespective of whether their diet is vegetarian or omnivorous [101]. In this situation, as long as attempts to improve salt iodization programs continue, the addition of a nutritional supplement or the use of iodine-enriched baby food may be needed for infants between the ages of seven and 24 months ([93] [102], s. Info box 2).

Iodine Intake of Pregnant and Lactating Women and Breastfed Babies

Many countries have universal salt iodization programs which require all table salt and animal fodder to be enriched with iodine. This generally ensures that the iodine intake of school children and adults is sufficient [62]. But in some countries, the iodine intake of lactating women is still inadequate. A systematic review of the available data on the iodine intake status of breastfeeding mothers living in countries with mandatory or voluntary iodization programs and/or iodine supplementation between 1964 and 2013 [103] found that in some countries with mandatory iodine enrichment programs, the UIC values of lactating women were < 100 µg/l, for example, in India, Australia and Slovakia, whereas in countries such as Chile, Iran and Nigeria the median or mean UIC was > 100 µg/l. In countries with voluntary iodization including Switzerland, Ireland, and Germany, the median UIC value of almost all lactating women was less than 100 µg/l. Although salt iodization continues to be the most feasible and affordable approach to control iodine deficiency in pregnant and breastfeeding mothers, the UIC values of breastfeeding mothers in most countries with voluntary iodine enrichment programs and even in some regions with mandatory iodine enrichment still indicate a level of iodine deficiency. While implementing and maintaining universal salt iodization is still the best strategy for ensuring that pregnant and breastfeeding mothers have sufficient iodine, it is not the only means to achieve optimal iodine intake. While the median UIC is an index for the success or failure of iodine enrichment programs, it may be affected by different factors, including insufficient monitoring of the salt iodization program, inadequate state support, changes in the iodine content in foods, infrequent use of iodized salt in households, increased use of non-iodized salt in commercial food products and insufficient amounts of iodine in salt. As long as the optimal conditions for sufficient iodine intake by pregnant and breastfeeding women are not assured, prenatal iodine supplementation with 150 µg per day is justified [103].

In a later meta-analysis of the iodine content in breast milk (BMIC) and the iodine excretion of their babies (s-UIC) using relevant studies published between 1986 and 2016, Nazeri et al. (2018) [104] found that there was no significant difference in the mean iodine content of mature breast milk between countries with sufficient iodine intake and countries with iodine deficiency (71.5 μg/l [CI 51.0 to 92.0 μg/l] or 28.0 μg/l [CI − 13.8 to 69.9 μg/l]). In both cases, the mean BMIC was below the 100–200 µg/l which Andersson and Braegger [97] considered to be sufficient. Of the 21 studies in countries with sufficient iodine intake, six countries (Chile, China, Iran, Slovakia, Switzerland, and USA) had a mean BMIC of less than 100 µg/l.

A prospective cohort study which investigated the iodine status of mothers and their babies in Australia after the introduction of mandatory iodine enrichment found that the iodine status of both mothers and their babies was adequate [105]. The authors also found that mothers with insufficient iodine excretion (UIC < 100 μg/l) were very likely to also have lower iodine concentrations in their breast milk (BMIC < 100 μg/l) and their infants had a higher risk of iodine deficiency. Although the median UIC of breastfed infants whose mothers had a BMIC of < 100 μg/l was considered sufficient, these infants had a six times higher risk of UIC of < 100 μg/l compared to breastfed infants whose mothers had a BMIC of ≥ 100 μg/l. This indicates that the iodine intake of breastfed infants may be suboptimal if BMIC is < 100 μg/l. These results emphasize the importance of achieving and maintaining a sufficient iodine status during lactation to ensure that the iodine intake of the breastfed infant is adequate [105].

The effectiveness of iodine substitution during pregnancy is well documented for severe iodine deficiency but has not been properly documented for populations with mild to moderate iodine deficiency [106] [107]. Antenatal iodine substitution may be beneficial for the neonate during the first few days after birth [108] [109] [110] but the effect is likely to be transient as BMIC depends on the current maternal iodine intake. The maternal iodine stores may be quickly exhausted if the iodine intake from food during the lactation period is limited and a daily supply of iodine is not maintained. Current data on populations with mild to moderate iodine intake show that prenatal iodine intake which ends with childbirth does not ensure adequate maternal iodine status postpartum [109] [111].

Observational studies of breastfeeding women found a higher BMIC among women who took iodine preparations compared to those who did not [10] [112] [113] [114]. Very few prospective studies have investigated the impact of iodine substitution after childbirth [115].

We found four studies of lactating women with iodine deficiency [110] [116] [117] [118]. Mulrine et al. [116] carried out a small randomized controlled study on iodine substitution where breastfeeding women with mild to moderate iodine deficiency in New Zealand received 75 µg/day, 150 µg/day, or placebo for six months. The BMIC remained low throughout the entire study and was between 24 and 70 µg/l. No overall effect from the treatment time was reported. Compared to the placebo group, the BMIC of women who received 75 µg/day or 150/µg day was slightly higher but they did not observe a dose-response relationship. The mUIC of the infants remained low in all groups. Starting in the 17th to 18th week of gestation and continuing until twelve months after childbirth, Pedersen et al. [110] administered 200 μg iodine per day to 54 women compared to a control group. Five days after delivery, the BMIC and the UIC of the infants born to mothers who received iodine were higher than in the control group which had not received iodine supplements, although they were still low in both groups. Mothers who received iodine-containing supplements had higher UIC and Tg levels in the postpartum period compared to mothers who did not receive iodine-containing supplements, while the levels of TSH, T4, T3 and free T4 remained unchanged. Another small prospective study in which daily doses of 50 μg or 200 μg iodine were administered during pregnancy and up to six months after delivery to women with mild iodine deficiency was carried out in Italy [117]. Iodine excretion measured in the urine of pregnant women was 74 μg/g creatinine on admission to the study and increased to 123 μg/g creatinine by six months after delivery in the group which received 50 μg/day and to 156 μg/g creatinine in the group which received 200 μg/day. But the study did not have a control group and did not measure BMIC. No differences with regard to maternal thyroid volume or serum concentrations of Tg, TSH, free T4 or free T3 were observed between groups. Another larger study investigated the daily intake of lipid-based nutrient supplements (LNS) with or without 250 μg iodine during pregnancy and lactation in women with moderate iodine deficiency in Bangladesh [118]. The geometric mean of the UIC of pregnant women on admission to the study (13th week of gestation) was low at just 50 μg/l and decreased further in both groups by the 36th week of gestation and six months after childbirth, without there being a difference between groups. The effectiveness of iodine supplementation in the postpartum phase is difficult to evaluate in this study as it did not measure BMIC or infant UIC.

In summary, iodine supplementation during lactation probably improves BMIC in iodine-deficient populations but the evidence from randomized controlled studies is weak and the optimal dose is still unknown. While the few available studies on daily iodine supplementation show a certain limited efficacy, their methodology means that they do not provide meaningful results [104] [110] [116] [117] [120] [121]. Some studies lacked a control group [117] [120] or the iodine content of breast milk was not recorded [117] [118] or investigations were carried out in mothers with sufficient iodine intake [119] [120]. Only one study measured the thyroid function of infants [120] and none of the controlled studies investigated the long-term health benefits of iodine intake in infants. Guidelines on postnatal iodine intake in iodine-deficient population groups are therefore still awaiting well-designed efficacy studies which measure BMIC, iodine status, and the thyroid function of infants and follow up their psychomotor development over the longer term. The available data do not support targeted iodine substitution for lactating mothers living in areas covered by functioning salt iodization programs [97].

The individual iodine status of a specific population is normally used as a measure to assess iodine deficiency. The preferred measure is the mean urine iodine concentration (mUIC) which can also be used for infants even though threshold values for appropriate iodine intake have not yet been determined. However, the mUIC is not always a reliable indicator of the iodine status of breastfeeding women because of the different distribution of iodine between breast milk and urine. It is therefore important to determine both BMIC and mUIC [123].

The available date on the iodine status of infants in their first year of life is currently still limited. Based on measurement of the median urine iodine concentrations of infants (UIC), two recent studies from Germany showed that sufficient iodine intake in the first year of life is possible with iodine supplementation during pregnancy and lactation, even if recent studies found mild iodine deficiency in adults [124] [125].

A recent Norwegian cohort study of 113 infants at the age of three, six and eleven months by Næss and colleagues [126] investigated the iodine status of the infants in the context of breastfeeding status, thyroid function, and maternal iodine intake ([Fig. 4]). The UIC of infants and mothers, maternal iodine intake, iodine concentrations in breast milk (BMIC), breastfeeding status, and infant thyroid hormone levels were measured. The median UIC of infants at the age of three months was 82 µg/l, which is below the WHO threshold of 100 µg/l. Later, the infant UIC was sufficient (median: 110 µg/l at the age of six and eleven months). The UIC of infants showed a positive association with maternal UIC (β = 0.33, 95 % CI [0.12–0.54]), maternal iodine intake (β = 0.30, 95 % CI [0.18–0.42]) and BMIC (β = 0.46, 95 % CI [0.13–0.79]). Breastfed infants had lower median UIC levels at the age of three months (76 vs. 190 µg/l) and six months (105 vs. 315 µg/l) than infants who received formula, as formula is enriched with iodine. Neither UIC nor BMIC showed an association with thyroid function disorders in infants. This means that in infants, thyroid hormone production was maintained despite mild iodine deficiency. However, such a moderately deficient iodine status which does not reduce thyroid hormone concentrations in infants may still impair infant development as was shown in another study (randomized, controlled) of school-age children [127].

Fig. 4 Box plot of iodine concentrations in the urine of infants (UIC) at the age of three, six and eleven months according to breastfeeding category (data from [126]). The boxes show the upper (75th percentile) and lower (25th percentile) quartiles and the thick black line represents the median (50th percentile). The T-bars are 1.5 times the length of the box (interquartile range). The solid circles are outliers, defined as a value which is > 1.5 times the length of the box. The stars are extreme outliers, defined as a value which is > 3.0 times the length of the box.

The data show that breastfed infants in Norway are at risk of inadequate iodine intake in the first few months of their life. The iodine requirements of infants who are not breastfed are sufficiently covered by the mandatory enrichment of formula with iodine while the addition of iodine to infant solid food products is merely optional and depends very much on the manufacturer. It is therefore extremely important that the iodine status of breastfeeding women is sufficient throughout the entire lactation period [126].

Compliance with Recommendations on Nutritional Supplementation Before, During and After Pregnancy

Almost two thirds of all pregnant women in Germany do not take enough folic acid or iodine prior to conception. This especially applies to women who have a low socioeconomic and educational status, are very young, did not plan their pregnancy, do not speak German and/or have a different nationality [128]. As many pregnancies are unplanned and many women do not know they are pregnant until far into the first trimester of pregnancy, it is important that women of reproductive age take sufficient iodine prior to conception to ensure that the embryo develops normally in early pregnancy [129].

Many pregnant women demonstrate knowledge gaps with regard to their folic acid and iodine requirements: consequently, women often reach for the recommended supplements too late or not at all.

A prospective survey of 962 mother-child pairs in a cross-sectional part of the SUSE-II study (2017–2019) on compliance with the recommendations for nutritional supplementation in the context of pregnancy confirmed that the overwhelming majority of mothers did not adhere to the recommendations. Only 36.2 % took folic acid and 31.9 % took iodine during the recommended time periods, and only 15.2 % adhered to the recommendations for both nutritional supplements [130] [131]. The most important predictors for adherence to recommendations for both nutrients were lifestyle characteristics and diet-related intentions such as prior experience with breastfeeding and intention to breast feed; common sociodemographic characteristics were not predictors. The results of this study show informational and compliance deficits with regard to the supplementation of women of reproductive age in Germany. The actual prevalence of mothers who take supplements in accordance with recommendations is clearly insufficient [131].

The cluster-randomized interventional study “Gesund leben in der Schwangerschaft (Living healthily in pregnancy, GeliS)” was also unable to significantly improve the supplementation behavior of women before and after pregnancy:

• Prior to conception 31.3 % of women in the intervention group (IG) and 31.4 % of women in the control group (CG) took folic acid supplements.

• Prenatally, around half of the women took folic acid (IG: 54.1 %; CG: 52.0 %) or iodine (IG: 50.2 %; CG: 48.2 %) supplements. There were no statistically significant differences in supplementation behavior between groups, either before inclusion in the study or during the intervention [132].

An online survey was carried out in Germany to rectify the lack of data about dietary supplements taken by breastfeeding mothers, focusing on iodine, docosahexaenoic acid (DHA) and vitamin B₁₂ [132]. The study participants (n = 2054) were asked to state whether they had specific preferred eating habits (omnivorous, vegetarian, vegan) and whether they used nutritional supplements. More than half of the participants reported that they had at least taken nutritional supplements when they were breastfeeding. Vegans were most likely to take nutritional supplements (98.02 %), followed by vegetarians (84.87 %) and omnivores (67.33 %) (p < 0.001). But more than one third of mothers did not report taking any iodine supplements, irrespective of their eating habits [133].

Although all breastfeeding women in Germany are recommended to take iodine supplements and this recommendation has even been included in official pregnancy and puerperium guidelines [37], there has been very little improvement in supplementation rates since 2009 [134]. One possible explanation is the limited knowledge about supplementation recommendations. Only about 40 % of the participants reported that they were familiar with the recommendations on supplementation in “Gesunder Start ins Leben – Netzwerk Junge Familie” (A healthy start to life – the young family network). Vegans stated most often that they knew about supplementation, followed by vegetarians and omnivores [132].

The general state of knowledge and adherence to supplementation recommendations covering the time prior to conception, during pregnancy and when breastfeeding needs to be improved by expanding educational activities. Although the most important healthcare providers can play an important role, more studies are required to develop strategies to increase the acceptance of recommendations [131] [133] [135].

Ideally, sufficient iodine intake can be achieved through effective universal salt iodization programs. Targeted supplementation programs are more expensive than universal salt iodization, cannot be initiated prior to conception in cases of unplanned pregnancy, and may be particularly difficult to implement in resource-poor regions with no strong system of antenatal care [107] [136]. The improvements in cognitive development resulting from sufficient iodine intake and the positive impact on future earnings suggest that there could be potential global economic benefit amounting to almost 33 billion dollars [137]. Salt iodization programs are attractive for national governments as the health and economic consequences of iodine deficiency are serious and can be averted economically and sustainably with universal salt iodization [138] [139] [140].

Conclusions

Because the iodine status of non-pregnant and pregnant women, children, and adolescents in Germany and in most European countries is inadequate, urgent measures to improve the iodine intake of the population and monitor the iodine status of vulnerable population groups are needed. Universal salt iodization in accordance with the recommendations of the WHO should be prioritized to ensure that the iodine intake of the population is adequate.

As long as this is not possible, the opinion of the AKJ is that especially young women of reproductive age should be recommended to already start taking iodine preparations at least three months prior to conception and take them continuously throughout pregnancy and while breastfeeding.

It is necessary to improve adherence by increasing the level of information targeting women of reproductive age, at the latest during pregnancy, to protect the unborn child. Health insurance companies should be asked to cover the costs of this sustainable preventive health measure as it was found that individual procurement was often an obstacle.

Practical Conclusions

• Iodine intake in Germany and Europe, particularly of many pregnant and breastfeeding women, is inadequate and this poses significant risks for the neurocognitive and psychomotor development of their children.

• It is recommended that women of reproductive age take iodine preparations, starting at least three months prior to conception and continuing throughout the entire pregnancy and during lactation.

• There is a significant discrepancy between the recommendations on iodine supplementation and the actual iodine intake of pregnant women.

• Only the universal use of iodized salt, including its inclusion in processed foods, will ensure a sufficient iodine intake across all population groups in all stages of life.

Contributorsʼ Statement

R.G. carried out the literature search and drafted the manuscript. K.-P. L., B.L. and F.T. contributed to the contents and revised the manuscript. All of the authors reviewed and approved the final draft of the manuscript.

Conflict of Interest

The authors declare that they have no conflict of interest.

Acknowledgement

The authors would like to thank Sabrina Schaftner and Daniel Schwind from the Iodine Deficiency Working Group (Arbeitskreis Jodmangel e.V.) for their excellent support during virtual editorial revision meetings.

• References/Literatur

• 1 Thamm R, Hey I, Liesenkötter K-P. et al. Jodversorgung von Kindern und Jugendlichen in Deutschland – Querschnittsergebnisse aus KiGGS Welle 2 und Trends. Pädiatrische Praxis 2023; 100: 18-28
• 2 Johner S, Remer T, Thamm M. Kapitel 1.3 Versorgungssituation der deutschen Bevölkerung mit ausgewählten Nährstoffen anhand der Ergebnisse der Studie zur Gesundheit Erwachsener in Deutschland (DEGS), 1.3.6 Jod. In: 13. Ernährungsbericht 2016. Bonn: Deutsche Gesellschaft für Ernährung; 2016: 59-64 Accessed September 03, 2025 at: https://www.dge.de/fileadmin/dok/wissenschaft/ernaehrungsberichte/13eb/13-DGE-Ernährungsbericht.pdf
• 3 Ittermann T, Albrecht D, Arohonka P. et al. Standardized map of iodine status in Europe. Thyroid 2020; 30: 1346-1354
• 4 Monaghan AM, Mulhern MS, McSorley EM. et al. Associations between maternal urinary iodine assessment, dietary iodine intakes and neurodevelopmental outcomes in the child: A systematic review. Thyroid Res 2021; 14: 14
• 5 Zimmermann MB. Iodine supplements form idly iodine-deficient pregnant women: are they worthwhile?. Am J Clin Nutr 2020; 112: 247-248
• 6 Monahan M, Boelaert K, Jolly K. et al. Costs and benefits of iodine supplementation for pregnant women in a mildly to moderately iodine-deficient population: A modelling analysis. Lancet Diabetes Endocrinol 2015; 3: 715-722
• 7 Patriota ES, Lima IC, Nilson EA. et al. Prevalence of insufficient iodine intake in pregnancy worldwide: a systematic review and meta-analysis. Eur J Clin Nutr 2022; 76: 703-715
• 8 Biban BG, Lichiardopol C. Iodine deficiency, still a global problem?. Curr Health Sci J 2017; 43: 103
• 9 Aarsland TE, Solvik BS, Bakken KS. et al. Iodine nutrition in children≤ 2 years of age in Norway. J Nutr 2023; 153: 3237-3246
• 10 Jin Y, Coad J, Skeaff SA. et al. Iodine status of postpartum women and their infants aged 3, 6 and 12 months: Mother and Infant Nutrition Investigation (MINI). Br J Nutr 2022; 127: 570-579
• 11 Aakre I, Morseth MS, Dahl L. et al. Iodine status during pregnancy and at 6 weeks, 6, 12 and 18 months post-partum. Matern Child Nutr 2021; 17: e13050
• 12 Adalsteinsdottir S, Tryggvadottir EA, Hrolfsdottir L. et al. Insufficient iodine status in pregnant women as a consequence of dietary changes. Food Nutr Res 2020; 64
• 13 Groufh-Jacobsen S, Mosand LM, Oma I. et al. Mild to moderate iodine deficiency and inadequate iodine intake in lactating women in the inland area of Norway. Nutrients 2020; 12: 630
• 14 Stoutjesdijk E, Schaafsma A, Dijck-Brouwer DA. et al. Iodine status during pregnancy and lactation: a pilot study in the Netherlands. Neth J Med 2018; 76: 210-217
• 15 Kirkegaard-Klitbo DM, Perslev K, Andersen SL. et al. Iodine deficiency in pregnancy is prevalent in vulnerable groups in Denmark. Dan Med J 2016; 63: A5286
• 16 Lindorfer H, Krebs M, Kautzky-Willer A. et al. Iodine deficiency in pregnant women in Austria. Eur J Clin Nutr 2015; 69: 349-354
• 17 Bath SC, Walter A, Taylor A. et al. Iodine deficiency in pregnant women living in the South East of the UK: the influence of diet and nutritional supplements on iodine status. Br J Nutr 2014; 111: 1622-1631
• 18 Hey I, Thamm M, Thamm R. Monitoring der Jodversorgung bei Kindern und Jugendlichen. Studie zur Gesundheit von Kindern und Jugendlichen in Deutschland (KiGGS Welle 2). Berlin: Robert Koch-Institut; 2019
• 19 Remer T, Hua YF, Esche J. et al. The DONALD study as a longitudinal sensor of nutritional developments: iodine and salt intake over more than 30 years in German children. Eur J Nutr 2022; 61: 2143-2151
• 20 Grossklaus R, Liesenkötter K, Doubek K. et al. Key Messages of the Iodine Deficiency Working Group (AKJ): Maternal Hypothyroxinemia Due to Iodine Deficiency and Endocrine Disruptors as Risks for Child Neurocognitive Development. Geburtshilfe Frauenheilkd 2025; 85: 796-809
• 21 Grossklaus R, Liesenkötter KP, Doubek K. et al. Iodine Deficiency, Maternal Hypothyroxinemia and Endocrine Disrupters Affecting Fetal Brain Development: A Scoping Review. Nutrients 2023; 15: 2249
• 22 Bissinger K, Herrmann R, Jordan I. Salt iodisation of processed foods in Germany: evidence, processors’ perceptions and implications for public health. Br Food J 2022; 124: 718-731
• 23 WHO. Prevention and control of iodine deficiency in the WHO European Region: adapting to changes in diet and lifestyle. Copenhagen: WHO Regional Office for Europe; 2024. Licence: CC BY-NC-SA 3.0 IGO
• 24 Bundesinstitut für Risikobewertung (BfR). Rückläufige Jodzufuhr in der Bevölkerung: Modellszenarien zur Verbesserung der Jodaufnahme. Stellungnahme Nr. 005/2021 des BfR vom 9. Februar 2021. Berlin: Bundesinstitut für Risikobewertung (BfR); 2021.
• 25 Dold S, Zimmermann MB, Jukic T. et al. Universal salt iodization provides sufficient dietary iodine to achieve adequate iodine nutrition during the first 1000 days: a cross-sectional multicenter study. J Nutr 2018; 148: 587-598
• 26 Andersson M, de Benoist B, Delange F. WHO Secretariat. et al. Prevention and control of iodine deficiency in pregnant and lactating women and in children less than 2-years-old: conclusions and recommendations of the Technical Consultation. Public Health Nutr 2007; 10: 1606-1611
• 27 Velasco I, Bath SC, Rayman MP. Iodine as essential nutrient during the first 1000 days of life. Nutrients 2018; 10: 290
• 28 Moog NK, Entringer S, Heim C. et al. Influence of maternal thyroid hormones during gestation on fetal brain development. Neuroscience 2017; 342: 68-100
• 29 Zimmermann MB. Iodine deficiency in pregnancy and the effects of maternal iodine supplementation on the offspring: a review. Am J Clin Nutr 2009; 89: 668S-672S
• 30 Zoeller RT, Rovet J. Timing of thyroid hormone action in the developing brain: clinical observations and experimental findings. J Neuroendocrinol 2004; 16: 809-818
• 31 Bernal J, Nunez J. Thyroid hormones and brain development. Eur J Endocrinol 1995; 133: 390-398
• 32 Burns R, O’Herlihy C, Smyth PP. The placenta as a compensatory iodine storage organ. Thyroid 2011; 21: 541-546
• 33 Volzke H, Erlund I, Grunert I. et al. The Krakow Declaration on Iodine: Tasks and Responsibilities for Prevention Programs Targeting Iodine Deficiency Disorders. Eur Thyroid J 2018; 7: 201-204
• 34 Rodriguez-Diaz E, Pearce EN. Iodine status and supplementation before, during, and after pregnancy. Best Pract Res Clin Endocrinol Metab 2020; 34: 101430
• 35 Koletzko B, Cremer M, Flothkötter M. et al. Diet and Lifestyle Before and During Pregnancy – Practical Recommendations of the Germany-wide Healthy Start – Young Family Network. Geburtshilfe Frauenheilkd 2018; 78: 1262-1282
• 36 BfR: Bundesinstitut für Risikobewertung. Merkblatt „Jod, Folat/Folsäure und Schwangerschaft – Ratschläge für die ärztliche Beratung“. 2022 Accessed November 14, 2025 at: https://www.bfr.bund.de/cm/350/jod-folat-folsaeure-und-schwangerschaft.pdf
• 37 Gemeinsamer Bundesausschuss. Richtlinien des Gemeinsamen Bundesausschusses über die ärztliche Betreuung während der Schwangerschaft und nach der Entbindung (Mutterschafts-Richtlinie/MU-RL) in der Fassung vom 21. September 2023 veröffentlicht im Bundesanzeiger (BAnz AT 14.12.2023 B6) zuletzt geändert am 28. September 2023 veröffentlicht im Bundesanzeiger AT 18.12.2023 B2 in Kraft getreten am 19. Dezember 2023. Accessed November 14, 2025 at: https://www.g-ba.de/downloads/62-492-3335/Mu-RL_2023-09-28_iK-2023-12-19.pdf
• 38 Deutsche Gesellschaft für Ernährung, Österreichische Gesellschaft für Ernährung. Referenzwerte für die Nährstoffzufuhr. 3. Bonn: Deutsche Gesellschaft für Ernährung, Österreichische Gesellschaft für Ernährung; 2025
• 39 Schweizerische Gesellschaft für Ernährung (SGE). Schweizer Referenzwerte für die Nährstoffzufuhr 2022. Accessed November 14, 2025 at: https://www.sge-ssn.ch/grundlagen/lebensmittel-und-naehrstoffe/naehrstoffempfehlungen/
• 40 EFSA Panel on Dietetic Products Nutrition and Allergies (NDA). Scientific opinion on dietary reference values for iodine. EFSA J 2014; 12: 3660
• 41 NAM – US National Academy of Medicine, former Institute of Medicine (IOM). Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academies Press; 2001
• 42 Koletzko B, Godfrey KM, Poston L. et al. Nutrition during pregnancy, lactation and early childhood and its implications for maternal and long-term child health: the early nutrition project recommendations. Ann Nutr Metab 2019; 74: 93-106
• 43 Abou-Dakn M, Abu-Omar K, Alaze-Hagemann F. et al. Ernährung und Bewegung von Säuglingen und stillenden Frauen 2024. Monatsschr Kinderheilkd 2025; 173 (Suppl. 1) 69-93
• 44 Bundesinstitut für Risikobewertung. Gesundheitliche Risiken durch zu hohen Jodgehalt in getrockneten Algen (aktualisierte Stellungnahme Nr. 026/2007 des BfR). Accessed November 14, 2025 at: http://www.bfr.bund.de/cm/343/gesundheitliche_risiken_durch_zu_hohen_jodgehalt_in_getrockneten_algen.pdf
• 45 Robinson SM, Crozier SR, Miles EA. et al. Preconception maternal iodine status is positively associated with IQ but not with measures of executive function in childhood. J Nutr 2018; 148: 959-966
• 46 Rohner F, Zimmermann M, Jooste P. et al. Biomarkers of nutrition for development–iodine review. J Nutr 2014; 144: 1322S-1342S
• 47 Ravera S, Reyna-Neyra A, Ferrandino G. et al. The sodium/iodide symporter (NIS): molecular physiology and preclinical and clinical applications. Annu Rev Physiol 2017; 79: 261-289
• 48 Citterio CE, Targovnik HM, Arvan P. The role of thyroglobulin in thyroid hormonogenesis. Nat Rev Endocrinol 2019; 15: 323-338
• 49 Mullan K, McMullan P, Kayes L. et al. Thyroglobulin levels among iodine deficient pregnant women living in Northern Ireland. Eur J Clin Nutr 2022; 76: 1542-1547
• 50 Nazeri P, Shab-Bidar S, Pearce EN. et al. Thyroglobulin Concentration and Maternal Iodine Status During Pregnancy: A Systematic Review and Meta-Analysis. Thyroid 2020; 30: 767-779
• 51 Bilek R, Dvořáková M, Grimmichova T. et al. Iodine, thyroglobulin and thyroid gland. Physiol Res 2020; 69 (Suppl. 2) S225
• 52 Moreno-Reyes R, Glinoer D, Van Oyen H. et al. High prevalence of thyroid disorders in pregnant women in a mildly iodine-deficient country: a population-based study. J Clin Endocrinol Metab 2013; 98: 3694-3701
• 53 Zimmermann MB, Aeberli I, Andersson M. et al. Thyroglobulin is a sensitive measure of both deficient and excess iodine intakes in children and indicates no adverse effects on thyroid function in the UIC range of 100–299 µg/L: a UNICEF/ICCIDD study group report. J Clin Endocrinol Metab 2013; 98: 1271-1280
• 54 Zimmermann MB. Iodine and the Iodine Deficiency Disorders. In: Marriott B, Birt D, Stalling V, Yates A. , ed. Present Knowledge in Nutrition. London: Academic Press; 2020: 429-441
• 55 Chung HR. Iodine and thyroid function. Ann Pediatr Endocrinol Metab 2014; 19: 8-12
• 56 Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet 2008; 372: 1251-1262
• 57 Delange F, Camus M, Ermans AM. Circulating thyroid hormones in endemic goiter. J Clin Endocrinol Metab 1972; 34: 891-895
• 58 Ma ZF, Venn BJ, Manning PJ. et al. Iodine supplementation of mildly iodine-deficient adults lowers thyroglobulin: a randomized controlled trial. J Clin Endocrinol Metab 2016; 101: 1737-1744
• 59 Zimmermann MB, Hess SY, Adou P. et al. Thyroid size and goiter prevalence after introduction of iodized salt: a 5-y prospective study in schoolchildren in Côte d’Ivoire. Am J Clin Nutr 2003; 77: 663-667
• 60 Berbel P, Mestre JL, Santamaría A. et al. Delayed neurobehavioral development in children born to pregnant women with mild hypothyroxinemia during the first month of gestation: the importance of early iodine supplementation. Thyroid 2009; 19: 511-519
• 61 Eveleigh ER, Coneyworth L, Welham SJ. Systematic review and meta-analysis of iodine nutrition in modern vegan and vegetarian diets. Br J Nutr 2023; 130: 1580-1594
• 62 Großklaus R, Jahreis G. Universelle Salzjodierung für Mensch und Tier. Ernährungs-Umschau 2004; 51: 138-143
• 63 Hildebrand T. Validität der Abschätzung der Jod- und Selenzufuhr anhand eines Food-Frequency-Tables und der Versorgung mit diesen beiden Spurenelementen ermittelt durch die Jodurie und Plasmaselenwerte bei omnivoren, lacto- vegetarisch und vegan sich ernährenden Personen. Eine epidemiologische klinische Querschnittstudie. Dissertation zur Erlangung des akademischen Grades Doctor medicinae (Dr. med.) vorgelegt der Medizinischen Fakultät der LMU München. 2014 Accessed November 14, 2025 at: https://edoc.ub.uni-muenchen.de/17661/1/Hildbrand_Thomas.pdf?utm_source=chatgpt.com
• 64 CDC, Center of Desease Control. Breastfeeding special circumstances. 2024 Accessed November 14, 2025 at: https://www.cdc.gov/breastfeeding-special-circumstances/hcp/diet-micronutrients/iodine.html
• 65 Bielenberg J. Kropfbildende Naturstoffe. Erfahrungsheilkunde 2020; 69: 320-326
• 66 Young AE, Kemp JF, Uhlson C. et al. Improved first trimester maternal iodine status with preconception supplementation: The Women First Trial. Matern Child Nutr 2021; 17: e13204
• 67 Katko M, Gazso AA, Hircsu I. et al. Thyroglobulin level at week 16 of pregnancy is superior to urinary iodine concentration in revealing preconceptual and first trimester iodine supply. Matern Child Nutr 2018; 14: e12470
• 68 Censi S, Watutantrige-Fernando S, Groccia G. et al. The Effects of Iodine Supplementation in Pregnancy on Iodine Status, Thyroglobulin Levels and Thyroid Function Parameters: Results from a Randomized Controlled Clinical Trial in a Mild-to-Moderate Iodine Deficiency Area. Nutrients 2019; 11: 2639
• 69 Raverot V, Bournaud C, Sassolas G. et al. Pregnant French women living in the Lyon area are iodine deficient and have elevated serum thyroglobulin concentrations. Thyroid 2012; 22: 522-528
• 70 Mitchell ML, Klein RZ, Sargent JD. et al. Iodine sufficiency and measurements of thyroid function in maternal hypothyroidism. Clin Endocrinol (Oxf) 2003; 58: 612-616
• 71 Stinca S, Andersson M, Weibel S. et al. Dried blood spot thyroglobulin as a biomarker of iodine status in pregnant women. J Clin Endocrinol Metab 2017; 102: 23-32
• 72 Eltom A, Elnagar B, Elbagir M. et al. Thyroglobulin in serum as an indicator of iodine status during pregnancy. Scand J Clin Lab Invest 2000; 60: 1-7
• 73 Moleti M, Di Bella B, Giorgianni G. et al. Maternal thyroid function in different conditions of iodine nutrition in pregnant women exposed to mild-moderate iodine deficiency: an observational study. Clin Endocrinol (Oxf) 2011; 74: 762-768
• 74 Bath SC. The effect of iodine deficiency during pregnancy on child development. Proc Nutr Soc 2019; 78: 150-160
• 75 Levie D, Korevaar TI, Bath SC. et al. Association of maternal iodine status with child IQ: a meta-analysis of individual participant data. J Clin Endocrinol Metab 2019; 104: 5957-5967
• 76 Croce L, Chiovato L, Tonacchera M. et al. Iodine status and supplementation in pregnancy: an overview of the evidence provided by meta-analyses. Rev Endocr Metab Disord 2023; 24: 241-250
• 77 Pearce EN, Caldwell KL. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status. Am J Clin Nutr 2016; 104 (Suppl. 3) 898S-901S
• 78 Bell MA, Ross AP, Goodman G. Assessing infant cognitive development after prenatal iodine supplementation. Am J Clin Nutr 2016; 104 (Suppl. 3) 928S-934S
• 79 Bauer PJ, Dugan JA. Suggested use of sensitive measures of memory to detect functional effects of maternal iodine supplementation on hippocampal development. Am J Clin Nutr 2016; 104 (Suppl. 3) 935S-940S
• 80 De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC. et al. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2015; (12) CD007950
• 81 de Benoist B. Conclusions of a WHO Technical Consultation on folate and vitamin B12 deficiencies. Food Nutr Bull 2008; 29 (Suppl. 2) S238-S244
• 82 Abel MH, Brandlistuen RE, Caspersen IH. et al. Language delay and poorer school performance in children of mothers with inadequate iodine intake in pregnancy: results from follow-up at 8 years in the Norwegian Mother and Child Cohort Study. Eur J Nutr 2019; 58: 3047-3058
• 83 Abel MH, Caspersen IH, Meltzer HM. et al. Suboptimal maternal iodine intake is associated with impaired child neurodevelopment at 3 years of age in the Norwegian mother and child cohort study. J Nutr 2017; 147: 1314-1324
• 84 Markhus MW, Dahl L, Moe V. et al. Maternal iodine status is associated with offspring language skills in infancy and toddlerhood. Nutrients 2018; 10: 1270
• 85 Bath S. Iodine supplementation in pregnancy in mildly deficient regions. Lancet Diabetes Endocrinol 2017; 5: 840-841
• 86 Abel MH, Korevaar TI, Erlund I. et al. Iodine intake is associated with thyroid function in mild to moderately iodine deficient pregnant women. Thyroid 2018; 28: 1359-1371
• 87 Zimmermann MB. Iodine deficiency. Endocr Rev 2009; 30: 376-408
• 88 Chittimoju SB, Pearce EN. Iodine deficiency and supplementation in pregnancy. Clin Obstet Gynecol 2019; 62: 330-338
• 89 Leung AM, Braverman LE. Consequences of excess iodine. Nat Rev Endocrinol 2014; 10: 136-142
• 90 Farebrother J, Zimmermann MB, Andersson M. Excess iodine intake: sources, assessment, and effects on thyroid function. Ann N Y Acad Sci 2019; 1446: 44-65
• 91 Lazarus J, Brown RS, Daumerie C. et al. 2014 European thyroid association guidelines for the management of subclinical hypothyroidism in pregnancy and in children. Eur Thyroid J 2014; 3: 76-94
• 92 Berbel P, Obregon MJ, Bernal J. et al. Iodine supplementation during pregnancy: a public health challenge. Trends Endocrinol Metab 2007; 18: 338-343
• 93 World Health Organization, UNICEF, ICCIDD. Assessment of Iodine Deficiency Disorders and Monitoring their Elimination. Geneva: WHO; 2007
• 94 Cho JY, Léveillé R, Kao R. et al. Hormonal regulation of radioiodide uptake activity and Na+/I− symporter expression in mammary glands. J Clin Endocrinol Metab 2000; 85: 2936-2943
• 95 Fisher W, Wang J, George NI. et al. Dietary Iodine Sufficiency and Moderate Insufficiency in the Lactating Mother and Nursing Infant: A Computational Perspective. PLoS One 2016; 11: e0149300
• 96 Dorea JG. Iodine nutrition and breasst feeding. J Trace Elem Med Biol 2002; 16: 207-220
• 97 Andersson M, Braegger CP. The role of iodine for thyroid function in lactating women and infants. Endocr Rev 2022; 43: 469-506
• 98 Alexander EK, Pearce EN, Brent GA. et al. 2017 Guidelines of the American Thyroid Association for the Diagnosis and Management of Thyroid Disease During Pregnancy and the Postpartum. Thyroid 2017; 27: 315-389
• 99 National Health and Medical Research Council (NHMRC). Iodine supplementation for pregnant and breastfeeding women. NHMRC public statement, January 2010. Accessed July 29, 2025 at: https://www.nhmrc.gov.au/about-us/publications/iodine-supplementation-pregnant-and-breastfeeding-women%23
• 100 Remer T, Johner SA, Gärtner R. et al. Jodmangel im Säuglingsalter ein Risiko für die kognitive Entwicklung. Dtsch Med Wochenschr 2010; 135: 1551-1556
• 101 Azizi F, Smyth P. Breastfeeding and maternal and infant iodine nutrition. Clin Endocrinol (Oxf) 2009; 70: 803-809
• 102 Alexy U, Drossard C, Remer T. et al. Iodine intake in the youngest: impact of commercial complementary food. Eur J Clin Nutr 2009; 63: 1368-1370
• 103 Nazeri P, Mirmiran P, Shiva N. et al. Iodine nutrition status in lactating mothers residing in countries with mandatory and voluntary iodine fortification programs: an updated systematic review. Thyroid 2015; 25: 611-620
• 104 Nazeri P, Kabir A, Dalili H. et al. Breast-milk iodine concentrations and iodine levels of infants according to the iodine status of the country of residence: a systematic review and meta-analysis. Thyroid 2018; 28: 124-138
• 105 Huynh D, Condo D, Gibson R. et al. Iodine status of postpartum women and their infants in Australia after the introduction of mandatory iodine fortification. Br J Nutr 2017; 117: 1656-1662
• 106 Dineva M, Fishpool H, Rayman MP. et al. Systematic review and meta-analysis of the effects of iodine supplementation on thyroid function and child neurodevelopment in mildly-to-moderately iodine-deficient pregnant women. Am J Clin Nutr 2020; 112: 389-412
• 107 Pearce EN. Iodine supplementation during pregnancy. Commentary. World Health Organization, e-Library of Evidence for Nutrition Actions (eLENA), WHO. 2017 Accessed September 05, 2024 at: https://www.who.int/tools/elena/commentary/iodine-pregnancy
• 108 Ittermann T, Völzke H, Krey A. et al. Median urinary iodine concentration reflected sufficient iodine supply in neonates from Northeast Germany in 2005–2006. Eur J Nutr 2019; 58: 1815-1820
• 109 Eriksen KG, Andersson M, Hunziker S. et al. Effects of an iodine-containing prenatal multiple micronutrient on maternal and infant iodine status and thyroid function: a randomized trial in The Gambia. Thyroid 2020; 30: 1355-1365
• 110 Pedersen KM, Laurberg P, Iversen E. et al. Amelioration of some pregnancy-associated variations in thyroid function by iodine supplementation. J Clin Endocrinol Metab 1993; 77: 1078-1083
• 111 Gowachirapant S, Jaiswal N, Melse-Boonstra A. et al. Effect of iodine supplementation in pregnant women on child neurodevelopment: a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2017; 5: 853-863
• 112 Jin Y, Coad J, Zhou SJ. et al. Use of iodine supplements by breastfeeding mothers is associated with better maternal and infant iodine status. Biol Trace Elem Res 2021; 199: 2893-2903
• 113 Kirk AB, Kroll M, Dyke JV. et al. Perchlorate, iodine supplements, iodized salt and breast milk iodine content. Sci Total Environ 2012; 420: 73-78
• 114 Jorgensen A, O’Leary P, James I. et al. Assessment of breast milk iodine concentrations in lactating women in Western Australia. Nutrients 2016; 8: 699
• 115 Harding KB, Peña-Rosas JP, Webster AC. et al. Iodine supplementation for women during the preconception, pregnancy and postpartum period. Cochrane Database Syst Rev 2017; (03) CD011761
• 116 Mulrine HM, Skeaff SA, Ferguson EL. et al. Breast-milk iodine concentration declines over the first 6 mo postpartum in iodine-deficient women. Am J Clin Nutr 2010; 92: 849-856
• 117 Antonangeli L, Maccherini D, Cavaliere R. et al. Comparison of two different doses of iodide in the prevention of gestational goiter in marginal iodine deficiency: a longitudinal study. Eur J Endocrinol 2002; 147: 29-34
• 118 Mridha MK, Matias SL, Paul RR. et al. Daily consumption of lipid-based nutrient supplements containing 250 μg iodine does not increase urinary iodine concentrations in pregnant and postpartum women in Bangladesh. J Nutr 2017; 147: 1586-1592
• 119 Nazeri P, Tahmasebinejad Z, Mehrabi Y. et al. Lactating mothers and infants residing in an area with an effective salt iodization program have no need for iodine supplements: results from a double-blind, placebo-controlled, randomized controlled trial. Thyroid 2018; 28: 1547-1558
• 120 Gebreegziabher T, Stoecker BJ. Comparison of two sources of iodine delivery on breast milk iodine and maternal and infant urinary iodine concentrations in southern Ethiopia: A randomized trial. Food Sci Nutr 2017; 5: 921-928
• 121 Chierici R, Saccomandi D, Vigi V. Dietary supplements for the lactating mother: influence on the trace element content of milk. Acta Paediatr Suppl 1999; 88: 7-13
• 122 Gebreegziabher T, Woltamo T, Thomas DG. et al. Iodine supplementation of lactating women and assessment of infant visual information processing and maternal and infant thyroid function: A randomized trial. PLoS One 2019; 14: e0223348
• 123 Brough L. Improving iodine status in lactating women: What works?. Curr Nutr Rep 2022; 11: 592-599
• 124 Ittermann T, Völzke H, Krey A. et al. Median urinary iodine concentration reflected sufficient iodine supply in neonates from Northeast Germany in 2005–2006. Eur J Nutr 2019; 58: 1815-1820
• 125 Wallborn T, Vogel M, Kneuer A. et al. Spot urine iodine levels below the WHO recommendation are not related to impaired thyroid function in healthy children and adolescents. Eur J Nutr 2021; 60: 493-502
• 126 Næss S, Aakre I, Strand TA. et al. Infant iodine status and associations with maternal iodine nutrition, breast-feeding status and thyroid function. Br J Nutr 2023; 129: 854-863
• 127 Gordon RC, Rose MC, Skeaff SA. et al. Iodine supplementation improves cognition in mildly iodine-deficient children. Am J Clin Nutr 2009; 90: 1264-1271
• 128 Birkenberger A, Henrich W, Chen F. Folsäure-Einnahme bei Berliner Frauen in Abhängigkeit vom sozioökonomischen Status. Z Geburtshilfe Neonatol 2019; 223: 213-220
• 129 Hynes KL, Seal JA, Otahal P. et al. Women Remain at Risk of Iodine Deficiency during Pregnancy: The Importance of Iodine Supplementation before Conception and Throughout Gestation. Nutrients 2019; 11: 172
• 130 Kersting M, Hochkamp N, Burak C. Deutsche Gesellschaft für Ernährung. et al. Studie zur Erhebung von Daten zum Stillen und zur Säuglingsernährung in Deutschland – SuSe II. In: 14. DGE-Ernährungsbericht. Vorveröffentlichung Kapitel 3. Bonn: DGE; 2020: V1-V34
• 131 Doru B, Hockamp N, Sievers E. et al. Adherence to recommendations for nutrient supplementation related to pregnancy in Germany. Food Sci Nutr 2023; 11: 5236-5247
• 132 Geyer K, Günther J, Hoffmann J. et al. Dietary Supplementation Before, During and After Pregnancy: Results of the Cluster-Randomized GeliS Study. Geburtshilfe Frauenheilkd 2022; 82: 736-746
• 133 Delgas F, Bitsch L, König LM. et al. Dietary supplement use among lactating mothers following different dietary patterns – an online survey. Matern Health Neonatol Perinatol 2024; 10: 3
• 134 Röhl S, Schücking B. Jodversorgung bei Schwangeren und Stillenden. Ernährungsumschau 2011; 58: 596-601
• 135 Malek L, Umberger W, Makrides M. et al. Poor adherence to folic acid and iodine supplement recommendations in preconception and pregnancy: a cross-sectional analysis. Aust N Z J Public Health 2016; 40: 424-429
• 136 Untoro J, Timmer A, Schultink W. The challenges of iodine supplementation: a public health programme perspective. Best Pract Res Clin Endocrinol Metab 2010; 24: 89-99
• 137 Gorstein JL, Bagriansky J, Pearce EN. et al. Estimating the health and economic benefits of universal salt iodization programs to correct iodine deficiency disorders. Thyroid 2020; 30: 1802-1809
• 138 Zimmermann MB. The remarkable impact of iodisation programmes on global public health. Proc Nutr Soc 2023; 82: 113-119
• 139 Schaffner M, Rochau U, Mühlberger N. et al. The economic impact of prevention, monitoring and treatment strategies for iodine deficiency disorders in Germany. Endocr Connect 2021; 10: 1-12
• 140 Engle PL, Black MM, Behrman JR. et al. Strategies to avoid the loss of developmental potential in more than 200 million children in the developing world. Lancet 2007; 369: 229-242

Publication History

Received: 15 May 2025

Accepted after revision: 02 November 2025

Article published online:
11 December 2025