Patterns and Determinants of Micronutrient Dietary Biomarkers and Their Associations with Dietary Intakes in Young Children.

BACKGROUND: Circulating dietary biomarkers are not direct proxies for intake, as the biomarkers reflect not only food and supplement consumption but also nutrient absorption, metabolism, and tissue distribution. Therefore, along with nutrient intake, several other upstream factors can impact dietary biomarker concentrations, including demographic, medical history, and genetic factors. OBJECTIVES: The aim of this study was to explore the dietary and nondietary determinants of circulating levels of vitamins A, C, D, and E among children aged 6 mo-4 y. METHODS: Plasma retinol, ß-carotene, ascorbic acid, 25(OH)D, α-tocopherol, and γ-tocopherol were measured in 2887 samples from 1490 children enrolled in The Environmental Determinants of Diabetes in the Young study. Dietary intake was assessed with 3-d food records. Associations of genetic and environmental factors with biomarker concentrations were examined using multivariable linear regression models with random intercepts. RESULTS: All biomarkers except retinol were positively associated with intake of the same nutrient. Inverse associations were identified between recent gastrointestinal infection and ß-carotene, ascorbic acid, and α-tocopherol, whereas recent respiratory infection was associated inversely with plasma retinol. Several genetic determinants of biomarker status were identified, validating previously reported findings. For some genetic and environmental exposures, we found evidence of statistical interaction with same-nutrient intake, indicating that the association between intake and biomarker concentration is dependent on the level or status of these other exposures. For example, the association between ß-carotene intake and concentration is weaker among children with a recent respiratory infection. CONCLUSIONS: Our findings suggest that nondietary exposures including childhood infections can alter micronutrient metabolism. This summary of micronutrient determinants will facilitate improved design of future analyses exploring the role of diet in childhood chronic disease etiology through a better understanding of relevant potential confounders and mediators of the diet-outcome relationships.

Iodine status of breastfed infants and their mothers' breast milk iodine concentration.

Iodine is an essential nutrient for growth and development during infancy. Data on iodine status of exclusively (EBF) and partially breastfed (PBF) infants as well as breast milk iodine concentration (BMIC) are scarce. We aimed to assess (a) infant iodine nutrition at the age of 5.5 months by measuring urinary iodine concentration (UIC) in EBF (n = 32) and PBF (n = 28) infants and (b) mothers' breast milk iodine concentration (n = 57). Sixty mother-infant pairs from three primary health care centres in Reykjavik and vicinities provided urine and breast milk samples for iodine analysis and information on mothers' habitual diet. The mother-infant pairs were participants of the IceAge2 study, which focuses on factors contributing to infant growth and development, including body composition and breast-milk energy content. The median (25th-75th percentiles) UIC was 152 (79-239) µg/L, with no significant difference between EBF and PBF infants. The estimated median iodine intake ranged from 52 to 86 µg/day, based on urinary data (assuming an average urine volume of 300-500 ml/day and UIC from the present study). The median (25th-75th percentiles) BMIC was 84 (48-114) µg/L. It is difficult to conclude whether iodine status is adequate in the present study, as no ranges for median UIC reflecting optimal iodine nutrition exist for infants. However, the results add important information to the relatively sparse literature on UIC, BMIC, and iodine intake of breastfed infants.

Validation of a Spectrophotometric Method for Urinary Iodine Determination on Microplate Based on Sandell-Kolthoff Reaction.

OBJECTIVE: Iodine is an essential part of the thyroid hormones thyroxine and triiodothyronine. Therefore, it is essential to monitor iodine supply in a population. The biochemical marker for assessing and controlling iodine is urinary iodine concentration (UIC). MATERIALS AND METHODS: This cross-sectional study included 180 pregnant women and 308 women of reproductive age. Urine specimens from 185 of the 488 volunteers were used. The urine specimens were measured using 2 methods: (1) ammonium persulfate digestion (APD), followed by the Sandell-Kolthoff (S-K) reaction modified on microplate for spectrophotometric detection; and (2) the reference method, inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The regression equation between the methods was ICP-MS method = 1.137*(APD S-K)-5.57. A Passing-Bablok regression showed no deviation from linearity (P = .17). A Bland-Altman plot showed a negative mean bias of -2.7%. CONCLUSION: The APD S-K reaction modified on microplate for spectrophotometric detection of UIC can be implemented into routine work. Its results are comparable to those of laboratories worldwide and to ICP-MS.

Associations Between Serum Fatty Acids and Immunological Markers in Children Developing Islet Autoimmunity-The TRIGR Nested Case-Control Study.

Aims: Altered immune functions as well as fatty acid intake and status have been associated with the development of type 1 diabetes. We aimed to study the relationship between fatty acids and immunological markers in young children with increased genetic risk for type 1 diabetes in order to define putative mechanisms related to development of islet autoimmunity. Methods: Serum samples for fatty acid and immunological marker measurements were obtained in the Trial to Reduce IDDM in the Genetically at Risk (TRIGR) ancillary study (Divia) from children born between 2002 and 2007 in 15 countries. Case children (n = 95) were defined as having repeated positivity for at least two out of four diabetes-associated autoantibodies. For each case child, control children were selected matched for country and date of birth (n = 173). Serum fatty acids and immunological markers were measured from cord serum and at the age of 6 and 12 months. Spearman correlation coefficients were calculated between fatty acids and immunological markers. Results: Correlations between circulating fatty acids and immunological markers were different in case children who developed islet autoimmunity than in control children already at birth continuing across the first year of life. In case children, saturated fatty acids (SFAs) showed stronger correlations with immunological markers, while in controls, polyunsaturated fatty acids (PUFAs) showed stronger correlations. Conclusions: In cases, SFAs were associated with several immunological markers (CXCL10, IL-6, IL-9, IL-17, and CM-CSF) previously linked to the type 1 diabetes disease process. Findings indicate that fatty acids could have immunomodulatory potential in the early phase of the disease development, although causality between fatty acids and the immunological pathways remains to be explored. Trial registry number: NCT00179777.

Insufficient iodine status in pregnant women as a consequence of dietary changes.

BACKGROUND: Historically, Iceland has been an iodine-sufficient nation due to notably high fish and milk consumption. Recent data suggest that the intake of these important dietary sources of iodine has decreased considerably. OBJECTIVE: To evaluate the iodine status of pregnant women in Iceland and to determine dietary factors associated with risk for deficiency. METHODS: Subjects were women (n = 983; 73% of the eligible sample) attending their first ultrasound appointment in gestational weeks 11-14 in the period October 2017-March 2018. Spot urine samples were collected for assessment of urinary iodine concentration (UIC) and creatinine. The ratio of iodine to creatinine (I/Cr) was calculated. Median UIC was compared with the optimal range of 150-249 µg/L defined by the World Health Organization (WHO). Diet was assessed using a semiquantitative food frequency questionnaire (FFQ), which provided information on main dietary sources of iodine in the population studied (dairy and fish). RESULTS: The median UIC (95% confidence interval (CI)) and I/Cr of the study population was 89 µg/L (42, 141) and 100 (94, 108) µg/g, respectively. UIC increased with higher frequency of dairy intake, ranging from median UIC of 55 (35, 79) µg/L for women consuming dairy products <1 time per week to 124 (98, 151) µg/L in the group consuming dairy >2 times per day (P for trend <0.001). A small group of women reporting complete avoidance of fish (n = 18) had UIC of 50 (21, 123) µg/L and significantly lower I/Cr compared with those who did not report avoidance of fish (58 (34, 134) µg/g vs. 100 (94, 108) µg/g, P = 0.041). Women taking supplements containing iodine (n = 34, 3.5%) had significantly higher UIC compared with those who did not take supplements (141 (77, 263) µg/L vs. 87 (82, 94), P = 0.037). CONCLUSION: For the first time, insufficient iodine status is being observed in an Icelandic population. There is an urgent need for a public health action aiming at improving iodine status of women of childbearing age in Iceland.

Standardized Map of Iodine Status in Europe.

Background: Knowledge about the population's iodine status is important, because it allows adjustment of iodine supply and prevention of iodine deficiency. The validity and comparability of iodine-related population studies can be improved by standardization, which was one of the goals of the EUthyroid project. The aim of this study was to establish the first standardized map of iodine status in Europe by using standardized urinary iodine concentration (UIC) data. Materials and Methods: We established a gold-standard laboratory in Helsinki measuring UIC by inductively coupled plasma mass spectrometry. A total of 40 studies from 23 European countries provided 75 urine samples covering the whole range of concentrations. Conversion formulas for UIC derived from the gold-standard values were established by linear regression models and were used to postharmonize the studies by standardizing the UIC data of the individual studies. Results: In comparison with the EUthyroid gold-standard, mean UIC measurements were higher in 11 laboratories and lower in 10 laboratories. The mean differences ranged from -36.6% to 49.5%. Of the 40 postharmonized studies providing data for the standardization, 16 were conducted in schoolchildren, 13 in adults, and 11 in pregnant women. Median standardized UIC was <100 µg/L in 1 out of 16 (6.3%) studies in schoolchildren, while in adults 7 out of 13 (53.8%) studies had a median standardized UIC <100 µg/L. Seven out of 11 (63.6%) studies in pregnant women revealed a median UIC <150 µg/L. Conclusions: We demonstrate that iodine deficiency is still present in Europe, using standardized data from a large number of studies. Adults and pregnant women, particularly, are at risk for iodine deficiency, which calls for action. For instance, a more uniform European legislation on iodine fortification is warranted to ensure that noniodized salt is replaced by iodized salt more often. In addition, further efforts should be put on harmonizing iodine-related studies and iodine measurements to improve the validity and comparability of results.

Iodine Intake is Associated with Thyroid Function in Mild to Moderately Iodine Deficient Pregnant Women.

BACKGROUND: Studies indicate that mild to moderate iodine deficiency in pregnancy may have a long-term negative impact on child neurodevelopment. These effects are likely mediated via changes in maternal thyroid function, since iodine is essential for the production of thyroid hormones. However, the impact of iodine availability on thyroid function during pregnancy and on thyroid function reference ranges are understudied. The aim of this study was to investigate the association between iodine intake and thyroid function during pregnancy. DESIGN: In a population-based pregnancy cohort including 2910 pregnant women participating in The Norwegian Mother and Child Cohort Study, we explored cross sectional associations of maternal iodine intake measured (1) by a food frequency questionnaire and (2) as iodine concentration in a spot urine sample, with plasma thyroid hormones and antibodies. RESULTS: Biological samples were collected in mean gestational week 18.5 (standard deviation 1.3) and diet was assessed in gestational week 22. Median iodine intake from food was 121 µg/day (interquartile range 90, 160), and 40% reported use of iodine-containing supplements in pregnancy. Median urinary iodine concentration (UIC) was 59 µg/L among those who did not use supplements and 98 µg/L in the women reporting current use at the time of sampling, indicating mild to moderate iodine deficiency in both groups. Iodine intake as measured by the food frequency questionnaire was not associated with the outcome measures, while UIC was inversely associated with FT3 (p = 0.002) and FT4 (p < 0.001). Introduction of an iodine-containing supplement after gestational week 12 was associated with indications of lower thyroid hormone production (lower FT4, p = 0.027, and nonsignificantly lower FT3, p = 0.17). The 2.5th and 97.5th percentiles of TSH, FT4, and FT3 were not significantly different by groups defined by calculated iodine intake or by UIC. CONCLUSION: The results indicate that mild to moderate iodine deficiency affect thyroid function in pregnancy. However, the differences were small, suggesting that normal reference ranges can be determined based on data also from mildly iodine deficient populations, but this needs to be further studied. Introducing an iodine-containing supplement might temporarily inhibit thyroid hormone production and/or release.