Iodine Supplementation in Pregnant Women

For adults who are not lactating or pregnant, the US Institute of Medicine, and jointly by the WHO, United Nations Children’s Fund (UNICEF) and the International Council for the Control of Iodine Deficiency Disorders (ICCIDD), recommend a daily iodine intake of 150 μg and state a tolerable upper level (the approximate threshold below which notable adverse effects are unlikely to occur in the healthy population) of 1,100 μg per day in adults 1)http://www.nature.com/ejcn/journal/v69/n2/full/ejcn2014206a.html.

For pregnant women, the U.S. Institute of Medicine’s recommended dietary allowance for iodine is 220 μg/d, higher than the 150 μg/d recommended for nonpregnant adults and adolescents. Similarly, recent World Health Organization guidelines suggest an intake of 200–300 μg/d iodine daily for pregnant women, and the Endocrine Society has recently recommended an average daily intake of 250 μg iodine daily for pregnant women. Although the World Health Organization has recommended 250 μg daily iodine supplements for pregnant women in areas with insufficient access to iodized salt, only approximately 15–30% of pregnant women in Europe currently receive iodine-containing supplements 2)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453047/.

In European countries with access to iodized salt, pregnant women and women planning a pregnancy should receive an iodine supplements containing approximately 150 μg/day 3)http://www.ncbi.nlm.nih.gov/pubmed/15220938. The American Thyroid Association has also recently recommended that North American women receive dietary supplements containing 150 μg iodine daily during pregnancy and lactation and that all prenatal vitamins contain 150 μg of iodine, recommendations that have not been adopted 4)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453047/.

Why do pregnant and breastfeeding women need more iodine intake?

Dietary iodine requirements are increased in pregnant women for several reasons. Maternal thyroid hormone production normally increases by about 50% during gestation, starting during the first trimester, due to human chorionic gonadotropin stimulation of the TSH receptor and because high estrogen levels induce an increase in the sialylation of T4-binding globulin (TBG), leading to reduced hepatic TBG clearance and increased concentrations of circulating TBG. In addition, the peripheral metabolism of thyroid hormone may be increased, especially in the second half of pregnancy, due to placental deiodination of T4 to the bioinactive reverse T3. By at least wk 10–12 of pregnancy, some maternal iodine stores are transferred to the fetus to allow for hormone production in the fetal thyroid; the amount of iodine transferred in this way is unclear. Finally, the glomerular filtration rate of iodide increases early in pregnancy, increasing renal iodide clearance and decreasing the circulating pool of plasma iodine. To compensate for renal iodine losses, there is an increased rate of uptake of iodine into the thyroid gland in pregnant women. Women with adequate iodine intake before and during pregnancy have adequate intrathyroidal iodine stores and have no difficulty adapting to the increased demand for thyroid hormone during gestation. In these women, total body iodine levels remain stable throughout pregnancy. However, in areas of even mild to moderate iodine deficiency, total body iodine stores, as reflected by urinary iodine values, decline gradually from the first to the third trimester of pregnancy. This dietary iodine deficiency results in impaired thyroid hormone synthesis. Low thyroid hormone values stimulate increased pituitary TSH production, and the increased TSH stimulates thyroid growth, which may result in maternal goiter. This was so common in some parts of Europe that it used to be assumed, mistakenly, that goiter formation was a physiological response to pregnancy. Ultimately, iodine deficiency may result in maternal thyroid failure 5)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453047/. Nowadays, 10 european countries are still characterized by mild to moderate iodine deficiency (Estonia, Latvia, Lithuania, Albania, Turkey, Hungary, Ireland, Italy, Spain, France, Belgium, and Denmark) 6)http://www.who.int/nutrition/publications/VMNIS_Iodine_deficiency_in_Europe.pdf, and even in the United States, there are concerns that a subset of women of child-bearing age may be mildly iodine deficient 7)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453047/. This is because most of the salt in the U.S. diet is from processed foods, and that salt is not iodized. As consumption of processed foods has increased, so has the level of iodine deficiency, with about one-third of pregnant women in the U.S. being deficient 8)https://www.aap.org/en-us/about-the-aap/aap-press-room/Pages/Pregnant-and-Brestfeeding-Women-May-Be-.aspx. Decreases in maternal T4 associated with even mild iodine deficiency may have adverse effects on the cognitive function of offspring, and iodine deficiency remains the leading cause of preventable mental retardation worldwide. It has recently been suggested that mild iodine deficiency may also be associated with attention-deficit and hyperactivity disorders in offspring 9)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453047/.

Whereas salt iodization programs remain essential, the addition of adequate iodine-containing prenatal multivitamins should be strongly encouraged for women from regions of even borderline iodine deficiency who are pregnant or planning to become pregnant. According to results in the Sicilian study, although long-term iodized salt use reduced the risk for maternal thyroid failure 6-fold, 6.4% of the 62 women who consistently used iodized salt for at least 2 yr before pregnancy also developed thyroid failure during pregnancy. First-trimester median urinary iodine excretion was below the World Health Organization’s optimal pregnancy range of 150–249 μg/liter 10)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2453047/.

However, iodine supplementation should be implemented to prevent a development of maternal thyroid failure during pregnancy, iodine intake must be maintained at a safe level. Both iodine deficiency and iodine excess can cause not only maternal thyroid failure but also transient congenital hypothyroidism 11)http://pediatrics.aappublications.org/content/125/Supplement_2/S54.full. Congenital hypothyroidism is thyroid hormone deficiency that affects infants at birth 12)http://www.sciencedaily.com/releases/2012/07/120726094508.htm and if left untreated, congenital hypothyroidism can lead to intellectual disability and abnormal growth. In the United States and many other countries, all newborns are tested for congenital hypothyroidism. If treatment begins in the first month after birth, infants usually develop normally 13)http://ghr.nlm.nih.gov/condition/congenital-hypothyroidism. Oral substitution of thyroxin is the standard therapy for CH. CH can manifest itself as a permanent or as a transient pathological condition. Patients with permanent CH require long-term substitution with a large dose of thyroxin. Children with transient CH show normal mental and physical development under thyroxin treatment, which can be discontinued after two or three years 14)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1390645/. There are 4 recognized causes of transient hypothyroidism: transplacental passage of TRBAbs; transplacental passage of antithyroid drugs used to treat maternal hyperthyroidism; iodine deficiency; and iodine excess 15)http://pediatrics.aappublications.org/content/125/Supplement_2/S54.full.

Newborns affected with iodine deficiency have low T4 and high TSH concentrations. On a global basis, iodine deficiency is the most common cause of transient hypothyroidism, particularly in preterm newborns. Preterm newborns are at higher risk because they have been prematurely deprived of the maternal supply of thyroid hormone, as well as iodine, which leads to inadequate accumulation of iodine in the thyroid gland compared with that of term newborns. Hypothyroidism represents a form of the broader category of iodine-deficiency disorders, which include endemic goiter, hypothyroidism, cretinism, decreased fertility rate, increased infant mortality, and intellectual disability 16)http://pediatrics.aappublications.org/content/125/Supplement_2/S54.full.

An iodine excess can be harmful to the thyroid of infants by inhibiting the process of synthesis and release of thyroid hormones (Wolff-Chaikoff effect) 17)http://www.fao.org/docrep/004/y2809e/y2809e0i.htm. Iodine passes freely from the maternal to the fetal circulation system and also can be transmitted through breast milk 18)http://pediatrics.aappublications.org/content/125/Supplement_2/S54.full. The threshold upper limit of iodine intake (the intake beyond which thyroid function is inhibited) is not easy to define because it is affected by the level of iodine intake before exposure to iodine excess. Indeed, long-standing moderate iodine deficiency is accompanied by an accelerated trapping of iodide and by a decrease in the iodine stores within the thyroid. Under these conditions, the critical ratio between iodide and total iodine within the thyroid, which is the starting point of the Wolff-Chaikoff effect, is more easily reached during iodine depletion than under normal conditions. In addition, the neonatal thyroid is particularly sensitive to the Wolff-Chaikoff effect because the immature thyroid gland is unable to reduce the uptake of iodine from the plasma to compensate for increased iodine ingestion. For these reasons transient neonatal hypothyroidism or transient hyperTSHemia after iodine overload of the mother, especially after the use of povidone iodine, has been reported more frequently in European countries such as in Belgium, France, and Germany, which have prevailing moderate iodine deficiency. Similar studies have not been conducted in the United States, where transient hypothyroidism is rarely seen perhaps because iodine intake is much higher. For example, urinary concentrations of 50 µg/dl and above in neonates, which can correspond to a Wolff-Chaikoff effect in Europe, are frequently seen in healthy neonates in North America 19)http://www.fao.org/docrep/004/y2809e/y2809e0i.htm.

Given the risks of potential iodine-induced thyroid dysfunction, the American Thyroid Association recommends against ingestion of an iodine or kelp daily supplement containing >500 μg iodine for all individuals, except for certain medical indications 20)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3976240/. In 2007, WHO Technical Consultation first recommended both a low (250 µg/day) and upper (500 µg/day) limit of iodine intake for pregnant and lactating females 21)http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4192807/.

In countries with iodine supplementation programmes, a diet generally contains enough iodine to meet Recommended Daily Allowances (RDA) for iodine intake, with common sources being iodized salt, dairy products, breads, and seafood. Because during pregnancy and lactation, women require higher amounts of iodine for the developing fetus and infant, it is recommended that pregnant and breastfeeding women take prenatal vitamin-mineral supplements containing 150 µg iodine daily in the form of potassium iodide (KI) 22)http://www.thyroid.org/ata-statement-on-the-potential-risks-of-excess-iodine-ingestion-and-exposure/ (preferably not greater), thus ensuring that daily iodine intake from all sources (iodized salt, dairy products, bread, and prenatal vitamins) meet recommended daily iodine intake which is 250 µg/day and at the same time it does not exceed upper limit of iodine which is 500 µg/day for pregnant and breastfeeding women as already mentioned.

Women who are pregnant or breastfeeding should not use kelp supplements 23)http://healthcare.utah.edu/healthlibrary/related/doc.php?type=19&id=Kelp and seaweed-based products, because of unacceptable variability in their iodine content 24)http://www.ncbi.nlm.nih.gov/pubmed/15220938. The iodine content in 17 different kelp supplements studied by one group of researchers varied from 45 µg to 57,000 µg per tablet or capsule 25)http://www.med.nyu.edu/content?ChunkIID=21786. Moreover, kelp may contain metals that are detrimental to humans. Chronic ingestion of kelps taken from areas of contaminated ocean water may increase levels of cadmium, lead, aluminum, and possibly other heavy metals 26)http://healthcare.utah.edu/healthlibrary/related/doc.php?type=19&id=Kelp. Some kelp supplements have been found to contain levels of arsenic high enough to be toxic 27)http://www.med.nyu.edu/content?ChunkIID=21786.

However, taking a multivitamins containing 150 µg is recommended for pregnant and breastfeeding women, unfortunately, only 28% (27 of 96) prescription prenatal vitamins tested by Leung, et al contained any iodine, and what is listed on the label may not reflect bioavailable iodine, especially when derived from seaweed sources rather than from potassium iodide 28)http://contemporaryobgyn.modernmedicine.com/contemporary-obgyn/RC/modernmedicine/welcome-modernmedicine/should-pregnant-women-receive-iodine-s?page=full. Prenatal supplement manufacturers should be encouraged to include adequate iodine in their products. Professional organizations should influence evolving EU legislation to ensure optimal doses for iodine in prenatal vitamin-mineral supplements 29)http://www.ncbi.nlm.nih.gov/pubmed/15220938.

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