Context: Thyroglobulin (Tg) could be a sensitive biomarker of iodine nutrition in pregnant women (PW). A dried blood spot (DBS) assay would simplify collection and transport in field studies. Objectives: Our aims were to (1) establish and test a reference range for DBS-Tg in PW; (2) determine whether co-measurement of Tg antibodies (Abs) is necessary to define population iodine status. Design, Setting, and Participants: Standardized cross-sectional studies of 3870 PW from 11 countries. For the DBS-Tg reference range, we included TgAb-negative PW (n = 599) from 3 countries with sufficient iodine intake. Main Outcome Measures: We measured the urinary iodine concentration and DBS thyroidstimulating hormone, total thyroxin, Tg, and TgAb. Results: In the reference population, the median DBS-Tg was 9.2 g/L (95% confidence interval, 8.7 to 9.8 g/L) and was not significantly different among trimesters. The reference range was 0.3 to 43.5 g/L. Over a range of iodine intake, the Tg concentrations were U-shaped. Within countries, the median DBS-Tg and the presence of elevated DBS-Tg did not differ significantly between all PW and PW who were TgAb-negative. Conclusions: A median DBS-Tg of 10 g/L with <3% of values 44 g/L indicated population iodine sufficiency. Concurrent measurement of TgAb did not appear necessary to assess the population iodine status.
Objective: To compare the iodine status of pregnant women and their children who were sharing all meals in Bangalore, India. Design: A cross-sectional study evaluating demographic characteristics, household salt iodine concentration and salt usage patterns, urinary iodine concentrations (UIC) in women and children, and maternal thyroid volume (ultrasound). Setting: Antenatal clinic of an urban tertiary-care hospital, which serves a low-income population. Subjects: Healthy pregnant women in all trimesters, aged 18-35 years, who had healthy children aged 3-15 years. Results: Median (range) iodine concentrations of household powdered and crystal salt were 55·9 (17·2-65·9) ppm and 18·9 (2·2-68·2) ppm, respectively. The contribution of iodine-containing supplements and multi-micronutrient powders to iodine intake in the families was negligible. Adequately iodized salt, together with small amounts of iodine in local foods, were providing adequate iodine during pregnancy: (i) the overall median (range) UIC in women was 172 (5-1024) µg/l; (ii) the median UIC was >150 µg/l in all trimesters; and (iii) thyroid size was not significantly different across trimesters. At the same time, the median (range) UIC in children was 220 (10-782) µg/l, indicating more-than-adequate iodine intake at this age. Median UIC was significantly higher in children than in their mothers (P = 0·008). Conclusions: In this selected urban population of southern India, the iodized salt programme provides adequate iodine to women throughout pregnancy, at the expense of higher iodine intake in their children. Thus we suggest that the current cut-off for median UIC in children indicating more-than-adequate intake, recommended by the WHO/UNICEF/International Council for the Control of Iodine Deficiency Disorders may, need to be reconsidered.
Key words Iodine Iodized salt Urinary iodine concentration Pregnant women Children IndiaUniversal salt iodization (USI) is a mass fortification approach that is intended to cover the iodine requirements of all individuals in the population; it is estimated that 128 countries have established iodized salt programmes (1) .As USI programmes mature in many countries, greater emphasis is being placed on ensuring that USI meets the increased needs of pregnant women because of the risk of irreversible fetal brain damage due to iodine deficiency (2,3) . Another focus of mature programmes is the need for careful monitoring to avoid not only iodine deficiency but also iodine excess (1) . Median urinary iodine concentration (UIC) in school-aged children (SAC) and household access to adequately iodized salt based on national standards are routinely used as the primary indicator of the impact of USI programmes. However, the iodine requirement of SAC is disproportionately lower than that of pregnant women, which leaves only a narrow intake range to meet the needs of pregnant women without leading to more-than-adequate intake in children according to the current UIC cut-off of 200 μg/l (4) .
The folate binding protein (FBP), also known as the folate receptor (FR), is a glycoprotein which binds the vitamin folic acid and its analogues. FBP contains multiple N-glycosilation sites, is selectively expressed in tissues and body fluids, and mediates targeted therapies in cancer and inflammatory diseases. Much remains to be understood about the structure, composition, and the tissue specificities of N-glycans bound to FBP. Here, we performed structural characterization of N-linked glycans originating from bovine and human milk FBPs. The N-linked glycans were enzymatically released from FBPs, purified, and permethylated. Native and permethylated glycans were further analyzed by matrix-assisted laser desorption/ionization (MALDI) and electrospray ionization (ESI) mass spectrometry (MS), while tandem MS (MS/MS) was used for their structural characterization. The assignment of putative glycan structures from MS and MS/MS data was achieved using Functional Glycomics glycan database and SimGlycan software, respectively. It was found that FBP from human milk contains putative structures that have composition consistent with high-mannose (Hex(5-6)HexNAc(2)) as well as hybrid and complex N-linked glycans (NeuAc(0-1)Fuc(0-3)Hex(3-6)HexNAc(3-5)). The FBP from bovine milk contains putative structures corresponding to high-mannose (Hex(4-9)HexNAc(2)) as well as hybrid and complex N-linked glycans (Hex(3-6)HexNAc(3-6)), but these glycans mostly do not contain fucose and sialic acid. Glycomic characterization of FBP provides valuable insight into the structure of this pharmacologically important glycoprotein and may have utility in tissue-selective drug targeting and as a biomarker.
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