Iodine status of Queensland children and the associations with diet and thyroid function

Iodine deficiency is often referred to the leading cause of preventable mental impairment in the world (1), although excessive consumption of iodine can have detrimental effects also (38). This essential micronutrient is fundamental in the intricate production of thyroid hormones which regulate metabolic processes, protein synthesis and somatic growth (1). Across the lifespan the body requires a constant small amount of dietary iodine, with the most critical period of iodine nutrition occurring from conception to the third year of life (1). The iodine status of Australian children is variable across the country (11, 86, 111), with some regions deficient whilst others border on excessive (11). In order to counteract iodine deficiency amongst school aged children in some regions of Australian (11), Food Standards Australia and New Zealand (FSANZ) introduced the mandatory use of iodised salt in bread manufacturing from 2009 (12). With undesired consequences observed amongst other iodine sufficient populations exposed to iodine prophylaxis programs (5, 35), it remains unknown whether the approach to reduce iodine deficiency in Australia will be detrimental to children residing in the iodine replete regions (2, 8). This thesis explores the influences of iodine nutrition (including iodine fortification) on children residing in a preciously iodine replete region of south east Queensland. Also, one of few Australian study’s to evaluate the relationship between iodine status, dietary intake and thyroid analytes in paediatric cohorts. The overall aim of this thesis is to report the iodine status of Queensland children after the introduction of iodine fortification to Australian bread products. It focuses on school aged children aged 8-10 years so that the results can be compared with surveys conducted prior to iodine fortification, and also includes young children age 2-3 years, as this age group were identified as being the most vulnerable to changes in dietary iodine exposure (10). Chapters 1, 2 and 3 of this thesis discuss the background and history of iodine status globally and within Australia, followed by the objectives and methods implemented by this study. Chapter 4 examines the challenges in assessing iodine status. With the populations’ median urinary iodine concentration (UIC) being the recommended determinant of iodine status (1), this paper discusses the challenges of categorising iodine status and the distribution of iodine status within a population using one spot urine sample. A total of 4 spot UIC samples from 51 young children and 30 school aged children were analysed and adjusted for inter and intra variability typically observed when evaluating urinary iodine. The results show that the coefficient of variance (CV) of UIC for children aged 2-3 years were reduced by 35.6%, 36.5% and 39.7% when two, three and four samples were included in the adjustment respectively. Similarly, the CV of UIC for children aged 8-10 years was reduced by 24.7%, 30.7% and 34.7%. The paper concludes that using an adjusted UIC from multiple UIC samples reduces the large coefficient of variation typically observed between individuals and within individuals to provide a more accurate reflection on iodine status within the distribution of the cohort. It also confirms that the timing of urine collection is an important consideration when assessing iodine status. Dietary sources of iodine and their impact on UIC amongst school aged children are explored in chapter 5. The adjusted median UIC for this age groups was determined to be 143.8ug/L (IQR 119.5-209.6ug/L). This paper reports that bread (r=.37, p=0.02) is the only statistically significant contributor of dietary iodine impacting UIC with 14% of variation in UIC explained by bread consumption. This is an important finding as whilst other surveys (119) suggest that the UIC of Queensland children has increased since the implementation of iodine fortification this paper provides the only data to report a direct association between bread intake and iodine status. Chapter 6 reports the impact of iodine fortification on children aged 2-3 years, a cohort identified as being at risk of attaining excessive iodine status post iodine fortification (10). This paper reports that the percentage of UIC samples above the upper level for dietary iodine was almost double than expected. The adjusted median UIC was reported to be 223. 3μg/L. With no validated criterion to assess UIC available for this age group, a crude dietary intake was calculated from the UIC based on an estimated urine output (80). The estimated median dietary iodine intake was 124.8ug/day (SD 47.0) with 9.8% of samples above the upper level of 200ug for dietary iodine for children within this age group. This status was not associated with iodine fortification in bread or any other foods. The chapter highlights the limitations of interpreting iodine status using the current WHO criterion for this particular age group. The paper concludes with emphasises that a universal criterion for children aged 2-3years using UIC as a marker of iodine nutrition is warranted. The influence of discretionary use of iodised salt, supplement use and drinking water iodine concentration on UIC has not been previously explored in Australian children. The paper presented in chapter 7 shows a significant positive association between the use of iodised salt on any occasion and the iodine status of children exposed to it. Iodised salt was consumed by 76.4% of 2-3 year olds and 66.6% of 8-10 year olds on any occasion. Independent t-tests revealed significant differences in UIC between those children receiving iodised salt and those who did not (2-3 year olds p=0.029; 8-10 year olds p=0.041). Approximately 14% of children consumed iodine supplements. Independent t-tests showed a significant mean difference in UIC (p=0.013) between children who consumed iodine supplements and those who did not in only 8-10 year olds. No significant correlations between DWIC and UIC were detected. These data have never been described elsewhere in Australia and provides a valuable contribution to reports compiled by the World Health Organisation. The paper concludes that other environmental factors, in addition to iodine concentration of drinking water, may have an impact on the inconsistent iodine status’ observed across the country. The important role of iodine in thyroid hormone production is discussed in chapter 8. As this part of the study was an additional option for participants, only Twenty-seven children (eleven 2-3 year old and sixteen 8-10 year olds) provide blood samples. The paper reports no associations between thyroid analytes and iodine status in either age group, although it does reveal that 1 in 5 children had some form of abnormality in their thyroid analytes. No children had fT4, fT3 or Tg levels outside the reference ranges. Seven children had one or more thyroid analytes outside the references ranges of TSH or TPOAb. Five children had a TSH (mean 2.7mU/L) above the recommended reference, all of whom had normal fT4 (mean 15.0pmol/L) and fT3s (mean 5.9pmol/L) and only one child with corresponding TPOAbs of 75U/mL. A difference of 23.5ug/L (p= 0.021) in Tg levels was observed between the two age groups. Familial history was only a predictor for TSH for both age groups combined (β0.19, p=0.016, 95%CI 0.03-0.34). The paper concludes that the use of adult reference ranges and varying interpretations of laboratory results may cause some children with subclinical thyroid anomalies to remain undiagnosed. Finally, chapter 9 amalgamates the thesis by discussing the findings and limitations of the overall research project. The thesis concludes that the discretionary use of iodised salt has greatest influence on the iodine status of Queensland children. Dietary contributors of iodine vary according to age and thus the impact of the mandatory introduction of iodine in bread varies also.