Oxidative stress may be involved in the progression of hypothyroidism in patients with Hashimoto thyroiditis (HT). Vitamin C is a well-known powerful antioxidant. To our knowledge, whether vitamin C intake relates to hypothyroidism in patients with HT remains unclear. In this cross-sectional study based on the National Health and Nutrition Examination Survey, 2007–2012, we aimed to explore the relationship between total vitamin C intake and hypothyroidism in patients with HT, using multivariate logistic regression models and restricted cubic spline analyses. Our results showed a significant negative linear association between total vitamin C intake (log10-transformed data) and hypothyroidism in HT. Compared with those with the lowest quartile of total vitamin C intake (log10-transformed), participants with the highest quartile were at lower odds of having hypothyroidism (adjusted OR 0·40, 95 % CI: 0·18, 0·88, Ptrend = 0·027). This association was consistent in subgroups stratified by sex (Pfor interaction = 0·084) and age (≥ 60 years and < 60 years, Pfor interaction = 0·330). This study revealed that total vitamin C intake was inversely associated with hypothyroidism among individuals with HT, indicating that higher vitamin C intakes (4·57–1258·9 mg/d) may be associated with a lower likelihood of hypothyroidism among HT participants.

Salivary iodine concentrations (SIC) and urinary iodine concentrations are correlated. This study aimed to verify the use of SIC as a biomarker for estimating iodine intake in pregnant and lactating women and to diagnose abnormal thyroid function. A cross-sectional study was conducted in northern Xinjiang, China. Participants provided venous blood, random urine, saliva and milk samples. A total of 607 pregnant and 171 lactating women volunteered to participate in the study. The average daily iodine intake was calculated for each participant. Pregnant women were divided according to trimester. The median daily iodine intake was 436·41 μg/d in the first trimester, 425·83 μg/d in the second trimester and 430·56 μg/d in the third trimester. The average daily iodine intake in lactating women was 416·16 μg/d. Different indicators were used to diagnose excessive iodine intake (> 500 μg/d). Among pregnant women, SIC had an AUC of 0·62 (P < 0·01), sensitivity of 51·75 % and specificity of 65 %. Among lactating women, SIC had an AUC of 0·63 (P = 0·03), sensitivity of 43·52 % and specificity of 85 %. SIC was an effective biomarker for diagnosing abnormal thyroid function (P = 0·03). In conclusion, this study demonstrated that SIC is a reliable biomarker for evaluating both iodine nutrition status and abnormal thyroid function in pregnant and lactating women.

Depression has been associated with subclinical hypothyroidism and altered hypothalamic-pituitary-thyroid axis functioning. Adequate iodine nutrition is essential for healthy thyroid functioning. We therefore determined associations of iodine and thyroid status with paediatric major depressive disorder (pMDD) among Swiss adolescents and explored whether associations are sex-specific and mediated by stress. We conducted a matched case–control study in 95 adolescents with diagnosed pMDD and 95 healthy controls. We assessed depression severity using the Children’s Depression Rating Scale-Revised and stress using the perceived stress scale (PSS) and measuring hair cortisol levels. We determined iodine status by measuring urinary iodine concentrations (UIC) and thyroid status by thyroid-stimulating hormone (TSH) and free thyroxine (FT4) in serum. Median (IQR) UIC did not differ between cases (121 (87, 174) µg/l) and controls (114 (66, 183) μg/l, P = 0·3). Median TSH and FT4 were lower in cases than controls (TSH: 1·36 (0·91, 2·00) mlU/l v. 1·50 (1·18, 2·06) mlU/l, P = 0·039; FT4: 14·7 (12·9, 16·9) pmol/l v. 15·7 (14·3, 17·2) pmol/l, P = 0·004). The prevalence of hypothyroxinaemia (normal TSH; low FT4) was higher among female cases than controls (21 % v. 4%, P = 0·006). PSS scores were higher while hair cortisol was lower in cases than controls (PSS: 25 (20, 28) v. 11 (7, 15), P < 0·001; cortisol: 2·50 (1·34, 3·57) pg/mg v. 3·23 (1·79, 4·43) pg/mg, P = 0·044). After adjusting for confounders, the associations of TSH and hair cortisol with pMDD were no longer significant. Furthermore, TSH and FT4 were not associated with PSS scores and hair cortisol levels. Summarising, iodine nutrition was adequate for adolescents with and without pMDD. However, FT4 concentrations were lower in those with pMDD, and 1 in 5 female adolescents with pMDD were hypothyroxinaemic.

Iodine is a trace element required to produce the thyroid hormones, which are critical for development, growth and metabolism. To ensure appropriate population iodine nutrition, convenient and accurate methods of monitoring are necessary. Current methods for determining iodine status either involve a significant participant burden or are subject to considerable intra-individual variation. The continuous secretion of iodide in saliva potentially permits its use as a convenient, non-invasive assessment of status in populations. To assess its likely effectiveness, we reviewed studies analysing the association between salivary iodide concentration (SIC) and dietary iodine intake, urinary iodide concentration (UIC) and/or 24-h urinary iodide excretion (UIE). Eight studies conducted in different countries met the inclusion criteria, including data for 921 subjects: 702 healthy participants and 219 with health conditions. SIC correlated positively with UIC and/or UIE in four studies, with the strength of relationship ranging from r = 0·19 to r = 0·90 depending on sampling protocol, age, and if salivary values were corrected for protein concentration. Additionally, SIC positively correlated with dietary intake, being strongest when saliva was collected after dinner. SIC varied with external factors, including thyroid function, use of some medications, smoking and overall health status. Evidence provided here supports the use of SIC as a viable, low-burden method for determining iodine status in populations. However, small sample sizes and high variability indicates the need for more extensive analyses across age groups, ethnicities, disease states and dietary groups to clarify the relative accuracy and reliability in each case and standardise procedure.

Iodine and thyroid hormones (TH) transport in the placenta are essential for fetal growth and development, but there is little research focus on the human placenta. The research aimed to investigate iodine and TH transport mechanisms in the human placenta. The placenta was collected from sixty healthy pregnant women. Urinary iodine concentration (UIC), serum iodine concentration (SIC), placenta iodine storage (PIS) and the concentration of serum and placenta TH were examined. Five pregnant women were selected as insufficient intake (II), adequate intake (AI) and above requirements intake (ARI) groups. Localisation/expression of placental sodium/iodide symporter (NIS) and Pendrin were also studied. Results showed that PIS positively correlated with the UIC (R = 0·58, P < 0·001) and SIC (R = 0·55, P < 0·001), and PIS was higher in the ARI group than that in the AI group (P = 0·017). NIS in the ARI group was higher than that in the AI group on the maternal side of the placenta (P < 0·05). NIS in the II group was higher than that in the AI group on the fetal side (P < 0·05). In the II group, NIS on the fetal side was higher than on the maternal side (P < 0·05). Pendrin was higher in the II group than in the AI group on the maternal side (P < 0·05). Free triiodothyronine (r = 0·44, P = 0·0067) and thyroid-stimulating hormone (r = 0·75, P < 0·001) between maternal and fetal side is positively correlated. This study suggests that maternal iodine intake changes the expression of NIS and Pendrin, thereby affecting PIS. Serum TH levels were not correlated with placental TH levels.

Alzheimer's disease and vascular dementia are the two most common types of dementia. It becomes difficult to distinguish between the two, especially when there are no specific genetic causes or vascular changes apparent. The aim of this review was to identify specific biomarkers supporting the diagnosis of vascular dementia by conducting a literature search for systematic reviews and observational studies. We found seven studies meeting our inclusion/exclusion criteria, and from these we identified four specific biomarkers supporting the diagnosis of vascular dementia: high levels of thyroid-stimulating hormone, lipoprotein(a), homocysteine and N-terminal prosomatostatin. However, the studies were small and a well-conducted study with larger populations is recommended to strengthen the evidence base.

Adequate iodine nutrition during infancy is required for normal thyroid function and, subsequently, brain development. However, data on infant iodine status in the first year of life are scarce. This study aimed to describe infant iodine status and further explore its associations with maternal iodine nutrition, breast-feeding status and thyroid function. In this cohort study, 113 infants were followed up at ages 3, 6 and 11 months in Norway. Infant and maternal urinary iodine concentration (UIC), maternal iodine intake, breast milk iodine concentration (BMIC), breast-feeding status and infant thyroid function tests were measured. The median infant UIC was 82 µg/l at the age of 3 months and below the WHO cut-off of 100 µg/l. Infant UIC was adequate later in infancy (median 110 µg/l at ages 6 and 11 months). Infant UIC was associated positively with maternal UIC (β = 0·33, 95 % CI (0·12, 0·54)), maternal iodine intake (β = 0·30, 95 % CI (0·18, 0·42)) and BMIC (β = 0·46, 95 % CI (0·13, 0·79)). Breastfed infants had lower median UIC compared with formula-fed infants at ages 3 months (76 v. 190 µg/l) and 6 months (105 v. 315 µg/l). Neither infant UIC nor BMIC were associated with infant thyroid function tests. In conclusion, breastfed infants in Norway are at risk of insufficient iodine intake during the first months of life. Maternal iodine nutrition is important for providing sufficient iodine intake in infants, and awareness of promoting adequate iodine nutrition for lactating women should be prioritised.

Autoimmune thyroiditis (AIT) has a complex aetiology and the susceptibility to it is determined by a combination of genetic and environmental factors, although these are not yet fully understood. The present research aimed to explore the DNA methylation patterns in whole blood of extrinsic apoptotic signalling pathway-related genes in AIT among areas with different iodine levels. We selected the iodine-fortification areas, iodine-adequate areas and water-based iodine-excess areas from Shandong Province of China as survey sites. Totally, 176 AIT cases and 176 controls were included. MethylTargetTM and QT-PCR technology were used to detect candidate genes’ DNA methylation levels and mRNA expression levels, respectively. We found that death associated protein kinase 1 (DAPK1) DNA methylation levels in AIT cases (especially in female) were significantly higher than controls (t = 2·7715, P = 0·0059; t = 2·4638, P = 0·0143 in female). There were differences in DAPK1 (t = 2·5384, P = 0·0121), TNF superfamily member 8 (t = 2·1667, P = 0·0334) and TNF-α-induced protein 8 (TNFAIP8) (t = 2·5672, P = 0·0121) genes methylation between cases and controls with different water iodine levels. The mRNA expression of DAPK1 (t = 4·329, P < 0·001) and TNFAIP8 (t = 3·775, P < 0·001) in the cases was increased. We identified the differences in the DNA methylation status of the extrinsic apoptotic signalling pathway-related genes between AIT and controls and in different iodine levels areas. The results were verified at the mRNA level. The environmental iodine may affect DNA methylation to some extent.

Reducing sedentary behaviour (SB) and increasing physical activity (PA) by sitting less and standing/walking more is advised to prevent chronic diseases. However, the mechanisms underlying this recommendation are not well established, especially in individuals with obesity living in low-income regions. The present study evaluated whether there are associations between PA indicators (PAI – standing time, walking time and the number of steps/d) and SB indicators (SBI – sitting/lying down time) with the hormonal profile and resting energy expenditure (REE) of adult women living in a low-income region. This is a cross-sectional study. We collected data on hormones (insulin resistance, leptin and thyroid axis), body composition (tetrapolar bioimpedance), REE (indirect calorimetry), and PAI and SBI (triaxial accelerometers, ActivPAL). Multivariable linear models adjusting for age and fat-free mass were performed. Fifty-eight women (mean age of 31 years and BMI of 33 kg/m2) were included. The mean sitting/lying down time and standing time were 16·08 and 5·52 h/d, respectively. Sitting/lying down time showed a direct association with free thyroxine (FT4) (β = 0·56 ng/dl; 95 % CI = −1·10, −0·02). Standing time showed a direct association with FT4 (β = 0·75 ng/dl; 95 % CI = 0·01; 1·48) and inverse association with free triiodothyronine (β = −2·83 pg/ml 95 % CI = −5·56, −0·10). There were no associations between PAI and SBI with the REE, insulin resistance, leptin and thyroid-stimulating hormone. Thus, decreased SB is associated with thyroid hormones levels but not with REE, insulin resistance or leptin in women with obesity living in low-income regions.

Maternal thyroid hormones facilitate optimal foetal neurodevelopment; however, the exact role of the thyroid hormones on specific cognitive outcomes is unknown. The present study aimed to investigate associations between maternal thyroid function and neurodevelopmental outcomes in the Seychelles Child Development Study (SCDS) Nutrition 2 cohort (n 1328). Maternal free thyroid hormones (fT3, fT4 and fTSH) were assessed at 28 weeks’ gestation with a range of child cognitive outcomes analysed at 20 months. Dietary iodine intake was analysed for a subset of women through a Food Frequency Questionnaire. Linear regression analysis was used to test associations between serum concentrations of maternal thyroid hormones and child neurodevelopment outcomes. Thyroid hormones were analysed as continuous data and categorised as quintiles. 95% of mothers had optimal thyroid function based on fTSH concentrations. Overall, the present study shows that maternal thyroid function is not associated with neurodevelopmental outcomes in this high fish-eating population. However, a positive association, using quintiles for fT3, was reported for the Mental Developmental Index, between Q3 v. Q4 (β 0⋅073; P 0⋅043) and for Q3 v. Q5 (β value 0⋅086; P 0⋅018). To conclude, mothers in our cohort, who largely have optimal thyroid function and iodine intakes, appear able to regulate thyroid function throughout pregnancy to meet neurodevelopmental needs. However, it is possible that minor imbalances of fT3, as indicated from our secondary analysis, may impact offspring neurodevelopment. Further investigation of the relationship between maternal thyroid function and infant neurodevelopment is warranted, particularly in populations with different dietary patterns and thereby iodine intakes.

Iodine is an important element in thyroid hormone biosynthesis. Thyroid function is regulated by the hypothalamic–pituitary–thyroid axis. Excessive iodine leads to elevated thyroid-stimulating hormone (TSH) levels, but the mechanism is not yet clear. Type 2 deiodinase (Dio2) is a Se-containing protease that plays a vital role in thyroid function. The purpose of this study was to explore the role of hypothalamus Dio2 in regulating TSH increase caused by excessive iodine and to determine the effects of iodine excess on thyrotropin-releasing hormone (TRH) levels. Male Wistar rats were randomised into five groups and administered different iodine dosages (folds of physiological dose): normal iodine, 3-fold iodine, 6-fold iodine, 10-fold iodine and 50-fold iodine. Rats were euthanised at 4, 8, 12 or 24 weeks after iodine administration. Serum TRH, TSH, total thyroxine (TT4) and total triiodothyronine (TT3) were determined. Hypothalamus tissues were frozen and sectioned to evaluate the expression of Dio2, Dio2 activity and monocarboxylate transporter 8 (MCT8). Prolonged high iodine intake significantly increased TSH expression (P < 0·05) but did not affect TT3 and TT4 levels. Prolonged high iodine intake decreased serum TRH levels in the hypothalamus (P < 0·05). Dio2 expression and activity in the hypothalamus exhibited an increasing trend compared at each time point with increasing iodine intake (P < 0·05). Hypothalamic MCT8 expression was increased in rats with prolonged high iodine intake (P < 0·05). These results indicate that iodine excess affects the levels of Dio2, TRH and MCT8 in the hypothalamus.

The study aimed to assess the associations between newborn thyroid-stimulating hormone (TSH) concentration, a marker of iodine nutrition in early life, and childhood neurodevelopment and growth using data collected from two pregnancy studies, one in a borderline iodine-deficient setting (DHA to Optimize Mother Infant Outcome (DOMInO) Study) and one in an iodine-sufficient setting (Pregnancy Iodine and Neurodevelopment in Kids (PINK) Study). TSH data were obtained from routine newborn screening. Neurodevelopment was assessed at 18 months using the Bayley Scales of Infant and Toddler Development, third edition (Bayley-III). Weight, height and head circumference were measured at 18 months. In total, 1467 children were included in the analysis. Comparing the highest with the lowest TSH quartile, the mean differences (MD) in the Bayley-III scores ranged from −2·0 (95 % CI −4·7, 0·7) to −2·2 (95 % CI −5·8, 1·3) points in DOMInO and 1·0 (95 % CI −1·6, 3·6) to 2·0 (95 % CI −0·4, 4·4) points in PINK in the cognitive, language and motor scales; the MD in the anthropometric z scores ranged from −0·01 (95 % CI −0·5, 0·5) to −0·5 (95 % CI −0·9, −0·1) in both studies. A 1 mIU/l increase in TSH was associated with −0·3 (95 % CI −0·9, 0·2) point and 0·2 (95 % CI −0·3, 0·7) point changes in the mean cognitive score in the DOMInO and PINK, respectively. A null association between TSH and growth was also observed in both studies. Longitudinal studies that utilise newborn TSH data and examine neurodevelopmental outcomes at later ages are warranted, as neurodevelopmental assessments in older children are more predictive of later achievement.

This study examined the contribution of long-term use of Lipiodol capsules, as a supplement to iodised salt to the control of iodine deficiency disorders among women in Xinjiang of China. A total of 1220 women across Kashgar, Aksu, Turpan and Yili Prefectures were surveyed in 2017. Lipiodol capsules were administered twice yearly in Kashgar and once yearly in Aksu and Turpan, but not in Yili. Urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody, thyroid peroxidase antibody and thyroid volume values were assessed. All the women in the four areas were in a state of non-iodine deficiency by UIC. The UIC were higher than adequate in Kashgar and Aksu (619·4 v. 278·6 μg/l). Thyroid hormone levels differed significantly in Turpan and Yili (FT3: 4·4 v. 4·6 pmol/l, FT4: 13·8 v. 14·2 pmol/l, TSH: 2·0 v. 2·7 mIU/l), but did not differ significantly in Kashgar, Aksu and Yili. The four areas did not differ significantly with regard to thyroid nodules, autoimmune thyroiditis or goitre. However, the detection rates of subclinical hypothyroidism (16·6 %) and total thyroid dysfunction (25·4 %) were higher among women in Yili. The supplementation with Lipiodol capsules had improved the iodine nutrition status of women in iodine-deficient areas of Xinjiang since 2006. To avoid negative effects of excess iodine, we suggest a gradual discontinuation of Lipiodol capsules in women with special needs based on the existing iodine nutrition level of local women.

Data on average iodine requirements for the Chinese population are limited following implementation of long-term universal salt iodisation. We explored the minimum iodine requirements of young adults in China using a balance experiment and the ‘iodine overflow’ hypothesis proposed by our team. Sixty healthy young adults were enrolled to consume a sequential experimental diet containing low, medium and high levels of iodine (about 20, 40 and 60 μg/d, respectively). Each dose was consumed for 4 d, and daily iodine intake, excretion and retention were assessed. All participants were in negative iodine balance throughout the study. Iodine intake, excretion and retention differed among the three iodine levels (P < 0·01 for all groups). The zero-iodine balance derived from a random effect model indicated a mean iodine intake of 102 μg/d, but poor correlation coefficients between observed and predicted iodine excretion (r 0·538 for μg/d data) and retention (r 0·304 for μg/d data). As iodine intake increased from medium to high, all of the increased iodine was excreted (‘overflow’) through urine and faeces by males, and 89·5 % was excreted by females. Although the high iodine level (63·4 μg/d) might be adequate in males, the corresponding level of 61·6 μg/d in females did not meet optimal requirements. Our findings indicate that a daily iodine intake of approximately half the current recommended nutrient intake (120 μg/d) may satisfy the minimum iodine requirements of young male adults in China, while a similar level is insufficient for females based on the ‘iodine overflow’ hypothesis.

The present study aimed to evaluate the status of iodine nutrition and thyroid function in adults, to understand the distribution of thyroid disease in people with autoimmune thyroid disease (AITD) in different water iodine areas and to explore the relationship between serum iodine, urine iodine and thyroid function in people with AITD. A cross-sectional survey was conducted in areas of Shandong Province with different water iodine levels, and subsequently 1225 adults were enrolled from iodine-deficient (ID), iodine-adequate (IA) and iodine-excess (IE) areas. Urinary iodine, water iodine, salt iodine, serum iodine and thyroid function were measured. According to the urine iodine concentration, the ID and IA areas were defined as iodine sufficient and the IE area as iodine excessive. Urine iodine, serum iodine, free thyroxine (FT4) and thyroid-stimulating hormone (TSH) levels were comparatively higher in the IE area. The positive rate of thyroglobulin antibody (19·1 %) and the prevalence of AITD (21·8 %) were higher in the ID areas; the prevalence of subclinical hypothyroidism was lowest in the ID areas (7·3 %) and highest in the IE area (16·3 %). Among the AITD population, urinary iodine concentration, free triiodothyronine, FT4 and TSH had a non-linear correlation with serum iodine; abnormal TSH level, serum iodine concentration > 110 µg/l and goitre were risk factors for AITD in adults, especially females. Our data collectively suggest that universal salt iodisation has improved the iodine nutritional status of the population in ID areas in China. Non-step-by-step iodine fortification may induce the transformation of thyroid autoimmune diseases from recessive-to-dominant in susceptible people. Moreover, enhanced monitoring of thyroid function in people with AITD is important.

The contribution of milk and dairy products to daily iodine intake is high but variable in many industrialised countries. Factors that affect iodine concentrations in milk and dairy products are only poorly understood. Our aim was to: (1) assess the effect of feed iodine concentration on milk iodine by supplementing five groups of five cows each with one of five dosages from 0–2 mg iodine/kg DM; (2) quantify iodine losses during manufacturing of cheese and yogurt from milk with varying iodine concentrations and assess the effect of cellar-ripening; and (3) systematically measure iodine partitioning during heat treatment and skimming of milk. Milk iodine reached a near-steady state after 3 weeks of feeding. Median milk iodine (17–302 μg/l for 0–2 mg iodine/kg DM) increased linearly with feed iodine (R2 0·96; P < 0·001). At curd separation, 75–84 % of iodine was lost in whey. Dairy iodine increased linearly with milk iodine (semi-hard cheese: R2 0·95; P < 0·001; fresh cheese and yogurt: R2 1·00; P < 0·001), and cellar-ripening had no effect. Heat treatment had no significant effect, whereas skimming increased (P < 0·001) milk iodine concentration by only 1–2 μg/l. Mean daily intake of dairy products by Swiss adults is estimated at 213 g, which would contribute 13–52 % of the adults’ RDA for iodine if cow feed is supplemented with 0·5–2 mg iodine/kg DM. Thus, modulation of feed iodine levels can help achieve desirable iodine concentrations in milk and dairy products, and thereby optimise their contribution to human iodine nutrition to avoid both deficiency and excess.

Perinatal maternal high-fat diet (HFD) increases susceptibility to obesity and fatty liver diseases in adult offspring, which can be attenuated by the potent hypolipidaemic action of fish oil (FO), an n-3 PUFA source, during adult life. Previously, we described that adolescent HFD offspring showed resistance to FO hypolipidaemic effects, although FO promoted hepatic molecular changes suggestive of reduced lipid accumulation. Here, we investigated whether this FO intervention only during the adolescence period could affect offspring metabolism in adulthood. Then, female Wistar rats received isoenergetic, standard (STD: 9 % fat) or high-fat (HFD: 28·6 % fat) diet before mating, and throughout pregnancy and lactation. After weaning, male offspring received the standard diet; and from 25 to 45 d old they received oral administration of soyabean oil or FO. At 150 d old, serum and hepatic metabolic parameters were evaluated. Maternal HFD adult offspring showed increased body weight, visceral adiposity, hyperleptinaemia and decreased hepatic pSTAT3/STAT3 ratio, suggestive of hepatic leptin resistance. FO intake only during the adolescence period reduced visceral adiposity and serum leptin, regardless of maternal diet. Maternal HFD promoted dyslipidaemia and hepatic TAG accumulation, which was correlated with reduced hepatic carnitine palmitoyl transferase-1a content, suggesting lipid oxidation impairment. FO intake did not change serum lipids; however, it restored hepatic TAG content and hepatic markers of lipid oxidation to STD offspring levels. Therefore, we concluded that FO intake exclusively during adolescence programmed STD offspring and reprogrammed HFD offspring male rats to a healthier metabolic phenotype in adult life, reducing visceral adiposity, serum leptin and hepatic TAG content in offspring adulthood.

It is well known that severe iodine deficiency during pregnancy may cause impaired brain development in the child, with effects on cognitive and motor function, hearing and speech. Whether mild-to-moderate deficiency also affects neurological development is less well known, but in the past decade a number of observational studies have been conducted to answer this question and these studies are reviewed in this article. The picture is now emerging that even mild-to-moderate iodine deficiency during pregnancy may be associated with subtle impairments in cognition and school performance, although the evidence from randomised controlled trials is still lacking. As global efforts to eradicate iodine deficiency in populations continue, it is more likely that mild-to-moderate, rather than severe, iodine deficiency will be the issue of concern in pregnancy, and therefore further research in regions of mild-to-moderate deficiency is required to strengthen the research base and to inform public-health policy.