Prior iodine exposure and impact on thyroid function during controlled ovarian hyperstimulation: A prospective study.

AIMS: Iodine supplements are recommended for women planning pregnancy, but their impact on thyroid function during controlled ovarian hyperstimulation (COH) and into pregnancy is unknown. The aim of this study was to assess the impact of iodine supplementation on thyroid function during COH. METHODS: One-hundred and six euthyroid women (thyroid stimulating hormone (TSH) 0.4-2.5 mIU/L) planning their first COH cycle were subdivided according to iodine supplementation (nil, <6 months, ≥6 months) and compared to levothyroxine (LT4)-treated controls. Serial TSH, free thyroxine, free triiodothyronine and thyroglobulin (Tg) levels were recorded at four time points: (i) baseline, (ii) day 7 ovarian stimulation, (iii) ovulation trigger and (iv) two weeks post oocyte retrieval. Oocyte numbers, fertilisation rates and pregnancy outcome were recorded. RESULTS: TSH increased during COH for those women taking iodine supplements for ≥6 months (P = 0.025). One quarter recorded a TSH level >2.5 mIU/L before embryo transfer. A similar increase in TSH was demonstrated by LT4-dependent controls (P = 0.024) but not the remaining subgroups. Tg levels did not change during COH in any group but decreased significantly post oocyte retrieval if nil iodine (P < 0.0001) or supplemented for ≥6 months (P < 0.005). Iodine supplementation did not influence oocyte count, fertilisation or implantation rates. Women taking iodine for <6 months were four times more likely to achieve a live birth than women taking iodine for longer. CONCLUSIONS: Women taking iodine supplements for ≥6 months are less able to adapt to the thyroidal demands of COH, with responses comparable to LT4-dependent patients.

Optimal Assessment and Quantification of Iodine Nutrition in Pregnancy and Lactation: Laboratory and Clinical Methods, Controversies and Future Directions.

Iodine intake must be boosted during pregnancy to meet the demands for increased production and placental transfer of thyroid hormone essential for optimal foetal development. Failure to meet this challenge results in irreversible brain damage, manifested in severity from neurological cretinism to minor or subtle deficits of intelligence and behavioural disorders. Attention is now being focused on explaining observational studies of an association between insufficient iodine intake during pregnancy and mild degrees of intellectual impairment in the offspring and confirming a cause and effect relationship with impaired maternal thyroid function. The current qualitative categorisation of iodine deficiency into mild, moderate and severe by the measurement of the median urinary iodine concentration (MUIC) in a population of school-age children, as a proxy measure of dietary iodine intake, is inappropriate for defining the degree or severity of gestational iodine deficiency and needs to be replaced. This review examines progress in analytical techniques for the measurement of urinary iodine concentration and the application of this technology to epidemiological studies of iodine deficiency with a focus on gestational iodine deficiency. We recommend that more precise definitions and measurements of gestational iodine deficiency, beyond a spot UIC, need to be developed. We review the evidence for hypothyroxinaemia as the cause of intrauterine foetal brain damage in gestational iodine deficiency and discuss the many unanswered questions, from which we propose that further clinical studies need to be designed to address the pathogenesis of neurodevelopmental impairments in the foetus and infant. Agreement on the testing instruments and standardization of processes and procedures for Intelligence Quotient (IQ) and psychomotor tests needs to be reached by investigators, so that valid comparisons can be made among studies of gestational iodine deficiency and neurocognitive outcomes. Finally, the timing, safety and the efficacy of prophylactic iodine supplementation for pregnant and lactating women needs to be established and confirmation that excess intake of iodine during pregnancy is to be avoided.

The impact of mandatory iodine fortification and supplementation on pregnant and lactating women in Australia.

BACKGROUND AND OBJECTIVES: In Australia, two public health measures were introduced between 2009 and 2010 to reduce iodine deficiency. However there has been a shortage of information regarding their effectiveness and the ongoing prevalence of iodine deficiency in Australia. The primary aim of this study was to assess the extent to which these public health measures have reduced rates of iodine deficiency among pregnant and lactating women. METHODS AND STUDY DESIGN: A review was conducted to identify all studies published since January 2010 that quantitatively measured the iodine status of pregnant and/or lactating women in Australia. RESULTS: We found 25 publications, of which seven were included in this review after our exclusion criteria were applied. Of the seven included publications, three demonstrated the pregnant and lactating women in their studies to be iodine replete (median urinary iodine concentrations (MUIC) greater than 150 µg/L, or a breast milk iodine concentration (BMIC) of greater than 100 µg/L). The remaining four publications found MUIC of pregnant and lactating women to be below the 150 µg/L threshold, in the mild-to-moderate iodine deficiency category. Only two studies, documented iodine sufficiency among pregnant and lactating women in the absence of iodine supplementation. CONCLUSIONS: Many pregnant and lactating women in Australia remain at least mildly iodine deficient. Antenatal iodine supplementation was the factor most consistently associated with an adequate iodine status. Larger, more representative studies or sentinel studies with a National coordination are needed to understand the differences in iodine status that exist across the country.

Iodine status of Indigenous and non-Indigenous young adults in the Top End, before and after mandatory fortification.

OBJECTIVE: To assess the median urine iodine concentration (UIC) of young adults in the Top End of Northern Territory, before and after fortification of bread with iodised salt became mandatory. DESIGN, SETTING: Analysis of cross-sectional data from two longitudinal studies, the Aboriginal Birth Cohort and the non-Indigenous Top End Cohort, pre- (Indigenous participants: 2006-2007; non-Indigenous participants: 2007-2009) and post-fortification (2013-15). PARTICIPANTS: Indigenous and non-Indigenous Australian young adults (mean age: pre-fortification, 17.9 years (standard deviation [SD], 1.20 years); post-fortification, 24.9 years (SD, 1.34 years). MAIN OUTCOME MEASURE: Median UIC (spot urine samples analysed by a reference laboratory), by Indigenous status, remoteness of residence, and sex. RESULTS: Among the 368 participants assessed both pre- and post-fortification, the median UIC increased from 58 µg/L (interquartile range [IQR], 35-83 µg/L) pre-fortification to 101 µg/L (IQR, 66-163 µg/L) post-fortification (P < 0.001). Urban Indigenous (median IUC, 127 µg/L; IQR, 94-203 µg/L) and non-Indigenous adults (117 µg/L; IQR, 65-160 µg/L) were both iodine-replete post-fortification. The median UIC of remote Indigenous residents increased from 53 µg/L (IQR, 28-75 µg/L) to 94 µg/L (IQR, 63-152 µg/L; p < 0.001); that is, still mildly iodine-deficient. The pre-fortification median UIC for 22 pregnant women was 48 µg/L (IQR, 36-67 µg/L), the post-fortification median UIC for 24 pregnant women 93 µg/L (IQR, 62-171 µg/L); both values were considerably lower than the recommended minimum of 150 µg/L for pregnant women. CONCLUSIONS: The median UIC of young NT adults increased following mandatory fortification of bread with iodised salt. The median UIC of pregnant Indigenous women in remote locations, however, remains low, and targeted interventions are needed to ensure healthy fetal development.

Salt intake and iodine status of women in Samoa.

The objective of this study was to determine iodine nutrition status and whether iodine status differs across salt intake levels among a sample of women aged 18-45 years living in Samoa. A cross-sectional survey was completed and 24-hr urine samples were collected and assessed for iodine (n=152) and salt excretion (n=119). The median urinary iodine concentration (UIC) among the women was 88 µg/L (Interquartile range (IQR)=54-121 µg/L). 62% of the women had a UIC <100 µg/L. The crude estimated mean 24-hr urinary salt excretion was 6.6 (standard deviation 3.2) g/day. More than two-thirds (66%) of the women exceeded the World Health Organization recommended maximum level of 5 g/day. No association was found between median UIC and salt excretion (81 µg/L iodine where urinary salt excretion >=5 g/day versus 76 µg/L where urinary salt excretion <5 g/day; p=0.4). Iodine nutrition appears to be insufficient in this population and may be indicative of iodine deficiency disorders in Samoan women. A collaborative approach in monitoring iodine status and salt intake will strengthen both programs and greatly inform the level of iodine fortification required to ensure optimal iodine intake as population salt reduction programs take effect.

Iodine Intake and Thyroid Function in Pregnant Women in a Private Clinical Practice in Northwestern Sydney before Mandatory Fortification of Bread with Iodised Salt.

Aim. The primary objective of the study was to assess the iodine nutritional status, and its effect on thyroid function, of pregnant women in a private obstetrical practice in Sydney. Methods. It was a cross-sectional study undertaken between November 2007 and March 2009. Blood samples were taken from 367 women at their first antenatal visit between 7 and 11 weeks gestation for measurement of thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels and spot urine samples for urinary iodine excretion were taken at the same time as blood collection. Results. The median urinary iodine concentration (UIC) for all women was 81 µg/l (interquartile range 41-169 µg/l). 71.9% of the women exhibited a UIC of <150 µg/l. 26% of the women had a UIC <50 µg/l, and 12% had a UIC <20 µg/l. The only detectable influences on UIC were daily milk intake and pregnancy supplements. There was no statistically significant association between UIC and thyroid function and no evidence for an effect of iodine intake on thyroid function. Conclusions. There is a high prevalence of mild to moderate iodine deficiency in women in Western Sydney but no evidence for a significant adverse effect on thyroid function. The 6.5% prevalence of subclinical hypothyroidism is unlikely to be due to iodine deficiency.

Management of thyroid dysfunction during pregnancy and postpartum: an Endocrine Society clinical practice guideline.

OBJECTIVE: The aim was to update the guidelines for the management of thyroid dysfunction during pregnancy and postpartum published previously in 2007. A summary of changes between the 2007 and 2012 version is identified in the Supplemental Data (published on The Endocrine Society's Journals Online web site at http://jcem.endojournals.org). EVIDENCE: This evidence-based guideline was developed according to the U.S. Preventive Service Task Force, grading items level A, B, C, D, or I, on the basis of the strength of evidence and magnitude of net benefit (benefits minus harms) as well as the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to describe both the strength of recommendations and the quality of evidence. CONSENSUS PROCESS: The guideline was developed through a series of e-mails, conference calls, and one face-to-face meeting. An initial draft was prepared by the Task Force, with the help of a medical writer, and reviewed and commented on by members of The Endocrine Society, Asia and Oceania Thyroid Association, and the Latin American Thyroid Society. A second draft was reviewed and approved by The Endocrine Society Council. At each stage of review, the Task Force received written comments and incorporated substantive changes. CONCLUSIONS: Practice guidelines are presented for diagnosis and treatment of patients with thyroid-related medical issues just before and during pregnancy and in the postpartum interval. These include evidence-based approaches to assessing the cause of the condition, treating it, and managing hypothyroidism, hyperthyroidism, gestational hyperthyroidism, thyroid autoimmunity, thyroid tumors, iodine nutrition, postpartum thyroiditis, and screening for thyroid disease. Indications and side effects of therapeutic agents used in treatment are also presented.

Estimating the iodine supplementation level to recommend for pregnant and breastfeeding women in Australia.

OBJECTIVE: To identify a level of iodine supplementation to recommend for pregnant and breastfeeding women in Australia. DESIGN, SETTING AND PARTICIPANTS: Dietary modelling indicated that mandatory fortification of bread with iodine by replacing salt with iodised salt would still leave a gap in iodine intakes in pregnant and breastfeeding women in Australia. Iodine shortfall was estimated by two separate methods: (i) analysis of data from published studies reporting mean urinary iodine concentrations in populations of Australian women who were pregnant or had given birth in the past 6 months; and (ii) modelling based on the postmandatory fortification iodine intake estimates calculated by Food Standards Australia New Zealand using food consumption reported by women aged 19-44 years who participated in the 1995 National Nutrition Survey. MAIN OUTCOME MEASURE: Estimated level of daily supplementation required to provide sufficient iodine to result in a low proportion of pregnant and breastfeeding women having inadequate iodine intakes. RESULTS: Estimations from both data sources indicate that a supplement of 100-150 µg/day would increase iodine intakes to a suitable extent in pregnant and breastfeeding women in Australia. CONCLUSIONS: The final level of supplementation we recommend should be based on these calculations and other factors. There will be population subgroups for whom our general recommendation is not appropriate.

Screening for thyroid disease and iodine deficiency.

The high global prevalence of iodine deficiency and autoimmune thyroid disorders and the mental and physical consequences of these disorders creates a huge human and economic burden that can be prevented, in large part, by early detection and appropriate preventative or therapeutic measures. The availability of sophisticated, sensitive and accurate laboratory testing procedures provides an efficient and effective platform for the application of screening for these disorders. Measurement of urine iodine concentration (UIC) in school children or pregnant women is the recommended indicator for screening populations for iodine deficiency. The severity of the iodine deficiency is classified according to the UIC. Measurement of serum thyrotropin (TSH) as an indicator for population iodine deficiency is used only in neonates and is supplementary to UIC screening. Other indicators such as goitre rates, thyroid function and serum thyroglobulin levels are useful adjunctive but not frontline process indicators. The human and economic benefits of screening for congenital hypothyroidism by measurement of heel-prick TSH have been well documented and justify its universal application. Using this measurement for monitoring population iodine intake is recommended by the World Health Organization but further validation is required before it can be universally recommended. Subclinical thyroid dysfunction is readily detected by current highly sensitive serum TSH assays and its prevalence appears to increase with age, varies with iodine intake and ethnicity and may occur in up to 20% of older age people. Subclinical hyperthyroidism is the less common disorder and screening cannot be justified because of its low prevalence and minimal or insignificant clinical effects. The argument for screening for subclinical hypothyroidism in middle-aged and older women is stronger but lacks evidence of benefit from randomised controlled trials or cost benefit analyses of therapeutic intervention, so it cannot currently be recommended. The publication of recent Clinical Practice Guidelines for management of thyroid disease in pregnancy from the American Endocrine Society and American Thyroid Association provide persuasive arguments for early detection and treatment of overt and subclinical hypothyroidism to prevent obstetric complications and potential neurocognitive disorders in the offspring. Given the indisputable benefits of therapy, the sooner thyroid dysfunction is detected, before or as early as possible in gestation, the more likely there will be a better outcome. Because of the limitations of targeted case detection in women at risk of subclinical hypothyroidism, there has been a gradual shift in opinion to universal TSH screening of all women as soon as practicable in pregnancy. While a positive association exists between the presence of anti-thyroid antibodies and increased pregnancy loss, universal screening of all pregnant women for underlying autoimmune thyroid disease is difficult to justify until there is evidence of beneficial outcomes from randomised controlled trials. Vigorous and liberal targeted case detection remains the recommended strategy to address this problem.

Current challenges in meeting global iodine requirements.

Iodine deficiency is a global problem of immense magnitude afflicting 2 billion of the world's population. The adverse effects of iodine deficiency in humans, collectively termed iodine deficiency disorders, result from decreased thyroid hormone production and action, and vary in severity from thyroid enlargement (goiter) to severe, irreversible brain damage, termed endemic cretinism. Thyroid hormone is essential throughout life, but it is critical for normal brain development in the fetus and throughout childhood. During pregnancy, maternal thyroid hormone production must increase by 25-50% to meet maternal-fetal requirements. The principal sources of iodine in the diet include milk and dairy products, seafoods and foods with added iodized salt. Vegetables, fruits and cereals are generally poor sources of iodine because most of our soils and water supplies are deficient in iodine. The accepted solution to the problem is Universal Salt Iodization where all salt for human and animal consumption is iodized at a level of 20-40 µg/g. In principle, mandatory fortification represents the most effective public health strategy where safety and efficacy can be assured and there is a demonstrated need for the nutrient in the population. Voluntary fortification of salt and other foods has many limitations and few benefits. Iodine supplementation is a useful, but expensive, inefficient and unsustainable strategy for preventing iodine deficiency. The current worldwide push to decrease salt intake to prevent cardiovascular disease presents an entirely new challenge in addressing iodine deficiency in both developing and developed countries.

Iodine status in Melbourne adults in the early 1990s and 2007-08.

OBJECTIVE: To investigate the iodine status of Melbourne adults in 1992-94 and 2007-08, and to assess dietary iodine intake to enable comparison with recommended Nutrient Reference Values. METHOD: A cross-sectional study utilising 24-hr urine samples collected at two time points in a random sample of the Melbourne Collaborative Cohort Study. Two hundred and fifty seven adults (128 males, 129 females) in 1992-94, with a mean age of 56 years, and 265 adults (132 males, 133 females) in 2007-08, with a mean age of 68 years, were assessed, all being Melbourne residents. Urinary iodine concentration (UIC) was determined and daily urinary iodine excretion and daily iodine intake were assessed. RESULTS: In 1992-94, the median UIC was 27 µg/L and 84% had UIC <50 µg/L. The median daily iodine intake was 51 µg/d, and 83% of participants had dietary iodine intakes below the Estimated Average Requirement of 100 µg/d. In 2007-08, the median UIC was 49 µg/L, 51% had UIC <50 µg/L and the median daily iodine intake was 98 µg/d, with 52% of intakes below the EAR. CONCLUSION: Melbourne adults were moderately iodine deficient in 1992-94, and borderline moderately deficient in 2007-08. IMPLICATIONS: While iodine status appears to have improved, it remains below an adequate level for much of the adult population of Victoria. Adequate monitoring is fundamental to assess whether the mandatory use of iodised salt in bread is effective in reducing iodine deficiency across all population groups.

Iodine status of Aboriginal teenagers in the Darwin region before mandatory iodine fortification of bread.

OBJECTIVE: To determine the iodine status of participants in the Aboriginal Birth Cohort Study who resided in the Darwin Health Region (DHR) in the "Top End" of the Northern Territory prior to the introduction of mandatory iodine fortification of bread. DESIGN, SETTING AND PARTICIPANTS: Participants in our study had been recruited at birth and were followed up at a mean age of 17.8 years. Spot urine samples were collected and assessed for iodine concentration at a reference laboratory. The median urinary iodine concentration (MUIC) of residents of the DHR was calculated and compared with international criteria for iodine status. Analyses were conducted for subgroups living in urban areas (Darwin-Palmerston) and remote communities (rural with an Aboriginal council). We collected a repeat sample in a subset of participants to explore the impact of within-person variation on the results. MAIN OUTCOME MEASURE: MUIC for residents of the DHR. RESULTS: Urine specimens were provided by 376 participants in the DHR. Overall MUIC was 58 µg/L when weighted to the 2006 Census population. Urban boys had higher values (MUIC = 77 µg/L) than urban and remote-dwelling non-pregnant girls (MUIC = 55 µg/L), but all these groups were classified as mildly iodine deficient. Remote-dwelling boys had the lowest MUIC (47 µg/L, moderate deficiency). Pregnant girls and those with infants aged less than 6 months also had insufficient iodine status. Correction for within-person variation reduced the spread of the population distribution. CONCLUSIONS: Previously, iodine deficiency was thought to occur only in the south-eastern states of Australia. This is the first report of iodine deficiency occurring in residents of the NT. It is also the first study of iodine status in a defined Indigenous population. Future follow-up will reassess iodine status in this group after the introduction of iodine fortification of bread.

Iodine deficiency in Australia: is iodine supplementation for pregnant and lactating women warranted?

Recent research has confirmed that Australian children and pregnant women are mildly iodine deficient. A considerable proportion of the pregnant population is moderately to severely iodine deficient. Even subclinical hypothyroidism in the mother, occurring as a consequence of iodine deficiency, can cause irreversible brain damage in the fetus, making it essential to avoid iodine deficiency in pregnancy. The proposal of Food Standards Australia and New Zealand (FSANZ) - Mandatory Iodine Fortification for Australia (P1003) - has been implemented. FSANZ openly admits P1003 is inadequate for covering the needs of pregnant women. Therefore, health professionals and the public must be properly informed about the limitations of this proposal. Views differ about the most effective measures to prevent iodine deficiency in Australia. We propose that women planning a pregnancy, and pregnant and lactating women should be advised to take an iodine supplement. Women with pre-existing thyroid disease should exercise caution and seek medical advice before taking a supplement.