Dr.med. 6, 7. and North Texas Veterans Affairs Medical Center, Dallas, Texas, USA; 6 Department

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1 1 Seasonal iodine deficiency in n school children Ilze Konrade, Dr.med. 1,2, Maija Dambrova, Dr.pharm. 1,3, Marina Makrecka, M.Sc. 1,3, Lolita Neimane, M.Sc. 1, Ieva Strele, Dr.med. 1, Edgars Liepinsh, Dr.pharm. 3, Aivars Lejnieks, Dr.med. 1,2, Parsla Vevere, MD 4, Ugis Gruntmanis, MD 5, & Valdis Pīrāgs, Dr.med. 6, 7 1 Riga Stradins University, Riga, ; 2 Department of Medicine, Riga East Clinical University Hospital, Riga, ; 3 n Institute of Organic Synthesis, Riga, ; 4 Clinic of Medical Genetics, Children s University Hospital, Riga, ; 5 Department of Medicine, University of Texas, Southwestern Medical Center and North Texas Veterans Affairs Medical Center, Dallas, Texas, USA; 6 Department of Medicine, University of, Riga, ; 7 Pauls Stradins Clinical University Hospital, Riga,. Ilze Konrade, Riga Stradins University, Riga, drkonrade@inbox.lv Dr.med. Riga East Clinical University Hospital, Department of Medicine, Riga, Maija Dambrova, n Institute of Organic md@biomed.lu.lv Dr.pharm. Synthesis, Riga, Riga Stradins University, Riga, 1

2 Page 2 of 10 2 Marina Makrecka, n Institute of Organic makrecka@biomed.lu.lv M.Sc. Synthesis, Riga, Riga Stradins University, Riga, Lolita Neimane, Riga Stradins University, Riga, lolita.neimane@inbox.lv M.Sc. Ieva Strele, Dr.med. Riga Stradins University, Riga, ievastrele@inbox.lv Edgars Liepinsh, n Institute of Organic ledgars@biomed.lu.lv Dr.pharm. Synthesis, Riga, Aivars Lejnieks, Dr.med. Riga Stradins University, Riga, Riga East Clinical University lejnieks@latnet.lv Hospital, Department of Medicine, Riga, Parsla Vevere, MD Children s University Hospital, labbiochem@bkus.lv Clinic of Medical Genetics, Riga, Ugis Gruntmanis, University of Texas, Southwestern ugis.gruntmanis@utsouthwestern.edu MD Medical Center and North Texas Veterans Affairs Medical Center, Department of Medicine, Dallas, Texas, United States Valdis Pīrāgs, Dr.med. University of, Department of Medicine, Riga, Pauls Stradins Clinical University Hospital, Riga, pirags@latnet.lv Running title: Seasonal iodine deficiency Key words: Iodine deficiency, urinary iodine, neonatal thyrotropin, season, 2

3 3 Dear Editor: In the year 2000, a nation-wide survey to determine the iodine status in found that the median urinary iodine level was 59 µg/l (1). The n Neonatal Thyrotropin (TSH) Registry data from 2000 showed that TSH levels of >5 miu/l were found in 16.5% of newborns (2). Both studies support the hypothesis that is a mild iodine-deficient region. Despite these findings, introduction of a mandatory salt iodization program in was rejected, and instead, voluntary iodine fortification of foods was promoted. Notably, the nation-wide survey in 2000 was conducted only during spring (1). To determine if there are seasonal variations in iodine intake in, we performed a 10-year follow-up cross-sectional school-based cluster survey that included 915 children aged 9 12 from 46 randomly selected schools in all regions of. Urine samples were collected in October 2010 and April We also analyzed n Neonatal TSH Registry data for 31,274 newborns, collected between 2009 and We found that the median creatinine-standardized urinary iodine (UIC) concentration was (IQR ) μg/g. The median UIC was significantly lower in the spring samples (78.3 μg/g Cr) than in the autumn samples (129.7 μg/g Cr). In the spring we found UIC values below 100 μg/g in 63% of schoolchildren and UIC values below 50 μg/g in 28.2% of schoolchildren (see Supplementary Data Figure S1). Seasonal fluctuations in the UIC have also been reported in other mild iodine-deficient regions (3). The data from the n Neonatal TSH Registry also confirmed the seasonal differences in TSH levels (see Supplementary Data Figure S2). The prevalence of TSH levels >5 miu/l was 8.7% in ; TSH levels >5 miu/l are indicative of mild iodine deficiency. In accordance with the iodine concentrations in the urine 3

4 Page 4 of 10 4 samples, the prevalence of TSH level >5 miu/l in April was markedly higher than in September (8.3% vs. 4.1%, p < 0.001). Despite the observed seasonal pattern, the prevalence of elevated neonatal TSH levels, as well as the lower limit of the 95% CI of the estimate, exceeded 3% even in September. In countries having no mandatory salt iodination program, foods such as milk and bread are primary sources of iodine due to the use of iodine-containing compounds in agriculture and to the use of iodized salt in food preparation (4). Therefore, it could be hypothesized that the observed changes in the n iodine status are due to decreased food-related iodine intake during the winter months. According to the n Food Center data, less than 1% of all edible salt was iodized in 1999 (1). The self-reported prevalence of consumption of regular iodized salt among n schoolchildren in the present study was 10.2%, but there was no significant association between UIC and the consumption of iodized salt. The increased intake of iodized salt could account for some of the improvement in the iodine status. In conclusion, in the absence of a mandatory salt iodization program, there is a persisting mild iodine deficiency among n schoolchildren, particularly during the spring season. The results of our study provide evidence that iodine deficiency studies should be performed during different seasons to account for the seasonality of iodine status. Acknowledgments This study was supported by the n Association of Endocrinology, n State Research Program BIOMEDICINE and O. Veide Scholarship Fund. 4

5 5 The authors thank A. Kuzjukevich ( Diamedica ) for providing the data from the n Newborn TSH screening laboratory. Disclosure Statement The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported. * Corresponding author: Ilze Konrade Address: Department of Endocrinology, Riga East Clinical University Hospital, Hipokrata 2, Riga LV1038, Phone Fax: drkonrade@inbox.lv 5

6 Page 6 of 10 6 References 1. Selga G, Sauka M, Gerasimov G 2000 Status of Iodine Deficiency in Reconsidered: Results of Nation-wide Survey of 587 Schoolchildren in the Year IDD Newsletter 16: Gyurjyan RH, Lugovska R, Vevere P, van der Haar F 2006 Newborn thyrotropin screening confirms iodine deficiency in. Eur J Clin Nutr 60: Moreno-Reyes R, Carpentier YA, Macours P, Gulbis B, Corvilain B, Glinoer D, Goldman S 2011 Seasons but not ethnicity influence urinary iodine concentrations in Belgian adults. Eur J Nutr 50: Zimmermann MB 2009 Iodine deficiency. Endocr Rev 30:

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8 Proportion of participants, % Page 8 of 10 8 Supplementary Data 60 Autumn 50 Spring < Urinary iodine concentration, μg/g Cr SUPPLEMENTARY FIG. S1. Interseasonal changes of iodine excretion frequency distribution in n schoolchildren (autumn n=504, spring n=411). Data are presented as percentage of participants (95%CI). 8

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10 Jan Feb Mar Apr May Jun Jul Aug Sep Oct Nov Dec Proportion of participants, % Page 10 of SUPPLEMENTARY FIG. S2. Percentage of neonatal TSH above 5 miu/l by month of birth (combined data from 2009 and 2010, n=31,274). Data are presented as percentage of participants (95%CI). 10