Iodine deficiency, pregnancy, and autoimmunity

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Iodine deficiency is still a serious concern, especially for pregnant women in North America, as reported in a review just published in the journal Thyroid. Despite global improvements since 1990, iodine sufficiency has actually been declining in US adults. As the authors state, the consequences can be severe:

"Dietary iodine intake is required for the production of thyroid hormone. Consequences of iodine deficiency include goiter, intellectual impairments, growth retardation, neonatal hypothyroidism, and increased pregnancy loss and infant mortality. Thyroid hormone is particularly crucial for fetal and infant neurodevelopment in utero and in early life, and insufficient iodine during pregnancy and infancy results in neurological and psychological deficits in children...Iodine deficiency remains the leading cause of preventable mental retardation worldwide. In adults, mild-to-moderate iodine deficiency increases the incidence of hyperthyroidism due to toxic goiter."

The authors defined population iodine sufficiency as a median urinary iodine concentrations of 100–299 μg/L in school-aged children and equal to or more than 150 μg/L in pregnant women, with these serious implications for pregnant women and their children in the US:

"Based on National Health and Nutrition Examination Surveys (NHANES), the median UIC in U.S. adults decreased by >50% between the early 1970s and the late 1990s. Of particular concern, the prevalence of UICs <50 μg/L among women of childbearing age increased by almost fourfold, from 4% to 15%, over this period. The most recent NHANES survey (2009–2010) demonstrated that the overall U.S. population remains iodine-sufficient, with a median UIC of 144 μg/L among individuals aged six years and older. However, aggregate NHANES data from 2001 to 2006 showed that U.S. pregnant women sampled were only marginally iodine-sufficient (median UIC, 153 μg/L) and the most recent NHANES data from 2007 to 2010 demonstrated that the median UIC among pregnant U.S. women had dropped to <150 μg/L, indicating mild iodine deficiency."

Considering possible causes for this growing insufficiency they note...

"Reductions in U.S. dietary iodine over the last several decades have been variously ascribed to a possible reduction in the iodine content of dairy products, the removal of iodate dough conditioners in commercially produced bread, new recommendations for reduced salt intake for blood-pressure control, and the increasing use of noniodized salt by the food industry."

Processed food producers in the US typically do not use iodized salt. Iodate dough conditioners have been largely replaced by bromate which competes with iodine (as does fluoride). Iodizing salt is the tried and true method for preventing iodine deficiency in the general population, but considering the shortfall lead author Dr. Elizabeth Pearce commented for Medscape:"That leaves public-health recommendations for groups at risk and the recommendation for women who are pregnant, planning a pregnancy, or breast-feeding is to take an iodine-containing supplement of 150 µg of iodine daily in the form of potassium iodide."But the authors note caution must be taken when supplementing iodine:

"Following exposure to high iodine levels, the synthesis of thyroid hormone is normally inhibited via the acute Wolff–Chaikoff effect. If excessive iodine exposure persists, the thyroid is able to “escape” from the acute Wolff–Chaikoff effect within a few days...Conversely, individuals with subtle defects in thyroid hormone synthesis, such as those with Hashimoto's thyroiditis, may be unable to escape from the acute Wolff–Chaikoff effect, and can develop iodine-induced hypothyroidism. In addition, even small increases in population iodine intake are associated with an increased prevalence of thyroid autoimmunity."

Bear in mind that by far the most common form of hypothyroid in developed countries is Hashimoto's thyroiditis (autoimmune thyroiditis). The authors conclude:

"Although substantial progress has been made over the last several decades, iodine deficiency remains a significant public health problem worldwide, including in developed nations. The ongoing monitoring of the population iodine status remains crucially important, and particular attention may need to be paid to monitoring the status of vulnerable populations. There is also a need for ongoing monitoring of iodized salt and other dietary iodine sources in order to prevent excess as well as insufficient iodine nutrition. Finally, it will be essential to coordinate interventions designed to reduce population sodium intake with salt iodization programs in order to maintain adequate levels of iodine nutrition as salt intake declines."

A paper just published in the prestigious medical journal The Lancet documented the serious effects of even mild iodine deficiency during pregnancy. The authors state:

"As a component of thyroid hormones, iodine is essential for fetal brain development. Although the UK has long been considered iodine replete, increasing evidence suggests that it might now be mildly iodine deficient. We assessed whether mild iodine deficiency during early pregnancy was associated with an adverse effect on child cognitive development."

They examined data for measured urinary iodine concentration for 1040 first-trimester pregnant women andlater the intelligence quotient (IQ) in their children at age 8 years and reading ability at 9 years of age. To define iodine deficiency they used the WHO criteria of 150 μg/g in pregnancy. Their data revealed a growing public health problem:

"The group was classified as having mild-to-moderate iodine deficiency on the basis of a median urinary iodine concentration of 91·1 μg/L. After adjustment for confounders, children of women with an iodine-to-creatinine ratio of less than 150 μg/g were more likely to have scores in the lowest quartile for verbal IQ, reading accuracy, and reading comprehension than were those of mothers with ratios of 150 μg/g or more. When the less than 150 μg/g group was subdivided, scores worsened ongoing from 150 μg/g or more, to 50—150 μg/g, to less than 50 μg/g."

For the authors, this is an issue that demands attention:

"Our results show the importance of adequate iodine status during early gestation and emphasise the risk that iodine deficiency can pose to the developing infant, even in a country classified as only mildly iodine deficient. Iodine deficiency in pregnant women in the UK should be treated as an important public health issue that needs attention."

How do we go about testing for iodine deficiency when a single spot collection is only accurate for large populations studies and doesn't reliably apply to the individual and ten spot collections are cumbersome? According to the National Institute of Health Office of Dietary Supplements:

"Iodine status is typically assessed using urinary iodine measurements. Urinary iodine reflects dietary iodine intake directly because people excrete more than 90% of dietary iodine in the urine. Spot urine iodine measurements are a useful indicator of iodine status within populations. However, 24-hour urinary iodine or multiple spot urine measurements are more accurate for individuals."

Both 10 spot collections and one 24-hour collection are acceptable even though a study published in The Journal of Nutrition found a bit less intra-individual variation (CV) with the 24-hour collection:

"In a prospective, longitudinal, 15-mo study, healthy Swiss women (n = 22) aged 52–77 y collected repeated 24-h urine samples (total n = 341) and corresponding fasting, second-void, morning spot urine samples (n = 177). From the UIC in spot samples, 24-h urinary iodine excretion (UIE) was extrapolated based on the age- and sex-adjusted iodine:creatinine ratio. Measured UIE in 24-h samples, estimated 24-h UIE, and UIC in spot samples were (geometric mean ± SD) 103 ± 28 μg/24 h, 86 ± 33 μg/24 h, and 68 ± 28 μg/L, respectively, with no seasonal differences. Intra-individual variation (mean CV) was comparable for measured UIE (32%) and estimated UIE (33%). The CV tended to be higher for the spot UIC (38%) than for the estimated 24-h UIE (33%)."

The issue of how to test for iodine deficiency was examined in a study published in the American Journal of Clinical Nutrition in which the authors showed that the spot check ofurinary iodine concentration (UIC) could be confounded by hydration status, but that a 24-hour collection was not. They investigated how well each tracked the effect of iodine supplementation:

"Urine osmolality (Uosm) and 24-h urinary excretion rates of iodine (24-h UI), sodium, creatinine, and total urine volume (24-h Uvol) were measured in 1046 specimens that were collected at repeated intervals from 1996 to 2003 in a sample of 358 German children aged 6–12 y. Energy intake and food consumption were calculated from 3-d weighed dietary records that were collected in parallel to the urine samples."

It was only the 24-hour collection which matched the 'real world' changes:

"During the 4-y period from 1996 to 1999, the median 24-h UI increased from 87 to 93 μg I/d, whereas urinary iodine concentration (UIC), Uosm, and 24-h Uvol did not change significantly. Thereafter (from 2000 to 2003), UIC stagnated and Uosm decreased, whereas 24-h Uvol and 24-h UI increased. The final median 24-h UI reached 120 μg I/d. Milk, fish, egg, and meat intakes and 24-h sodium excretion were all significant predictors of IS, with an almost doubled contribution from milk intake during the second 4-y period."

Their conclusion highlights the 24-hour collection as a more dependable metric for iodine sufficiency (IS):

"Our study shows a continuous improvement of IS in a longitudinal sample of German schoolchildren. This improvement was masked when UIC was used as an IS index, especially from 2000 to 2003 because of changes in hydration status. Thus, in research-oriented studies that focus on UIC measurements, hydration status can be a relevant confounder. Longitudinal analyses of 24-h UI in cohort studies may represent an alternative hydration status–independent tool to examine trends in IS and the contribution of relevant foods to IS."

Clinical caution: There are a number of studies linking iodine supplementation to increases in autoimmune thyroiditis (Hashimoto's thyroiditis). This is understandable considering that up-regulating thyroid peroxidase, thyroglobulin and other iodine driven activity could 'wave a red flag in front of the bull' in individuals who have lost tolerance and are in the stage of silent autoimmunity. Even iodine introduced cautiously can trigger this problem as described in a paper published in Clinical Endocrinology. The authors state:

"Autoantibodies against the thyroid gland with thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) as the most common can often be demonstrated in serum."

They used these to measure the incidence of thyroid autoimmunity in the Danish population before and after their mandatory iodization of salt:

"Two identical cross-sectional population studies were performed before (Cohort 1 (C1), year 1997–1998, n = 4649, median urinary iodine 61 μg/l) and 4–5 years after (Cohort 2 (C2), year 2004–2005, n = 3570, median urinary iodine 101 μg/l) mandatory iodine fortification of salt was implemented in Denmark. Blood tests were analysed for TPO-Ab and Tg-Ab using sensitive assays."

There was a definite increase in thyroid autoimmunity:

"Antibodies were more frequent in C2 than in C1: TPO-Ab > 30 U/ml, C1 vs C2: 14·3 vs 23·8% (P < 0·001) and Tg-Ab > 20 U/ml, C1 vs C2: 13·7 vs 19·9% (P < 0·001). The C2 vs C1 effect was confirmed in multivariate regression models (C1 reference): TPO-Ab: OR (95% CI): 1·80 (1·59–2·04) and Tg-Ab: 1·49 (1·31–1·69). The increase in the frequency of thyroid antibodies was most pronounced in young women and especially observed at low concentrations of antibodies."

Clinicians considering iodine supplementation must take care to assess patients for the potential for loss of immune tolerance to thyroid, even when supplementation is undertaken with cautious amounts. The authors conclude:

"The prevalence of both TPO-Ab and Tg-Ab was higher 4–5 years after a cautious iodine fortification of salt was introduced in Denmark. The increase was most pronounced in young women and in the low concentrations of antibody. Further studies are needed to evaluate the long-term effects of increased iodine intake on thyroid autoimmunity in the population."

How much iodine should be supplemented during pregnancy and breast feeding? The authors of a paper published in JAMA last December first state:

"Dietary iodine requirements are increased during pregnancy due to increased thyroid hormone production, increased renal iodine losses, and fetal iodine requirements. Dietary requirements remain increased in lactation due to the concentration of iodine in breast milk...Adverse effects of iodine deficiency in pregnancy, when the deficiency leads to severe decreases in maternal thyroxine (T4), include include...increased pregnancy loss and infant mortality. 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 intellectual disability worldwide."

This begs the question how much postpartum depression might be contributed to by suboptimal iodine. Regarding supplementation...

"...all US women who are pregnant, lactating, or planning a pregnancy should ingest dietary supplements containing 150 µg of potassium iodide per day. The Endocrine Society has recently advocated that all daily prenatal multivitamins should contain 150 to 200 µg. The addition of 150 µg does not pose a risk, even for women who are iodine replete, because a total iodine intake of as much as 500 too 1100 µg per day is considered safe in pregnancy."

For selected food sources of iodine and other information see the National Institute of Health Office of Dietary Supplements.[wysija_form id="1"]