Relationship between mild iodine deficiency in pregnant women and thyroid function: A meta-analysis

BackgroundPregnant women are among the key groups in iodine nutrition evaluation. The purpose of the present study was to summarize the evidence supporting the relationship between mild iodine deficiency (UIC: 100–150 μg/L) in pregnant women and levels of thyroid function tests.MethodsThis review follows the guidelines for systematic reviews (PRISMA 2020). Three electronic databases (PubMed, Medline, and Embase) were searched for relevant publications in English on the association between mild iodine deficiency in pregnant women and thyroid function. Articles published in Chinese were searched in China’s electronic databases (CNKI, WanFang, CBM, and WeiPu). Pooled effects were presented as standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs) using fixed or random effect models, respectively. This meta-analysis was registered at www.crd.york.ac.uk/prospero as CRD42019128120.ResultsWe summarized the results from 7 articles with 8261 participants. The overall pooled results showed that the levels of FT₃, FT4, and abnormal TgAb (the antibody levels exceeded the upper limit of the reference range) were significantly increased in pregnant women with mild iodine deficiency compared to pregnant women with adequate iodine status (FT₃: SMD=0.854, 95% CI: 0.188, 1.520; FT₄: SMD=0.550, 95% CI: 0.050, 1.051; TgAb: OR=1.292, 95% CI: 1.095; 1.524). Subgroup analysis was carried out on the sample size, ethnicity, country, and gestation of FT₃, FT_4, and TSH, but no plausible factor was found. Egger’s tests indicated no publication bias.The increase in FT₃ and FT_4, as well as TgAb levels, in pregnant women is associated with mild iodine deficiency.ConclusionMild iodine deficiency is associated with an increase in FT_3,FT₄ and TgAb levels in pregnant women. Mild iodine deficiency may increase the risk of thyroid dysfunction in pregnant women.     

Development of thyroid dysfunction among women with excessive iodine intake – A 3-year follow-up

ObjectivesThyroid dysfunction can be a result of excessive iodine intake, which may have adverse health consequences, particularly for women in fertile age. In 2010, we conducted a cross-sectional study among lactating women with excessive iodine intake in the Saharawi refugee camps in Algeria and found a high prevalence of thyroid dysfunction. Three years later, we conducted a follow-up study to monitor the iodine situation and explore whether thyroid dysfunction still was highly prevalent when the women no longer were post-partum. None of the women were treated for hyper- or hypothyroidism between baseline and follow-up.MethodsIn 2013, we were able to recapture 78 of the 111 women from the baseline. Thyroid hormones and antibodies were measured in serum and thyroid size was assessed by palpation. Urinary iodine concentration (UIC) and drinking water iodine concentration were measured.ResultsThe overall prevalence of thyroid dysfunction and/or positive antibodies was 34.3% and was not significantly changed from baseline. Of the non-pregnant women we reexamined, 17 had hypo- or hyperthyroidism in 2010; among these, 12 women still had abnormal thyroid function at follow-up. In addition, we found 9 new cases with marginally abnormal thyroid function. Women with thyroid dysfunction and/or positive antibodies had significantly higher BMI and thyroglobulin than women with normal thyroid function. We also found that women with high breast milk iodine concentration (BMIC) at baseline had more thyroid dysfunction at follow-up than the women with lower BMIC at baseline.ConclusionsAt follow-up, the prevalence of thyroid dysfunction was still high and had not changed during the 3 years between studies and from a postpartum period. The women still had a high iodine intake indicated by high UIC. Breast milk iodine concentration from baseline predicted thyroid dysfunction at follow-up.     

Contribution of milk to iodine intake in France

A survey based on 838, samples of milk obtained from 537 dairies covering 70 of 95 districts in France was organized to assess iodine content of milk and its contribution to total intake. Iodine levels were significantly higher in winter than in summer. Very low iodine contents (<25 μg I/kg) were found in the eastern part of the country (the Vosges, Jura, and the Alpes) and the Massif Central. During milk processing, much of the iodine is lost in the whey. The other significant sources of dietary iodine are fish and eggs. Iodized salt is sold only to households and not to industry. Even if about 20% of the iodine is lost over the first 3 mo, salt remains the main source for this trace element. It is concluded that, if iodized salt is not provided systematically for both domestic and agro-industrial use, then milk may be the most important source of iodine. This key role may explain seasonal and geographical variations in the frequencies of goiter in France.     

Iodine status in Danish pregnant and breastfeeding women including studies of some challenges in urinary iodine status evaluation

Denmark was previously iodine deficient with regional differences. Moderate iodine deficiency appeared in West Denmark and mild iodine deficiency in East Denmark and also Danish pregnant and breastfeeding women suffered from iodine deficiency. The Danish mandatory iodine fortification of salt was introduced in the year 2000 and has increased iodine intake in the Danish population. However, median urinary iodine concentration in the general population and in pregnant and breastfeeding women is still below the level recommended, corresponding to mild iodine deficiency. Certain characteristics may challenge the evaluation of urinary iodine status in pregnancy and during breastfeeding. This review also addresses methodological challenges related to spot urine sampling conditions and the use of iodine supplement and discusses the use of non-pregnant population groups as a proxy for iodine intake in pregnant women.     

Iodine status of Turkish pregnant women and their offspring: A national cross-sectional survey

BackgroundThis national cross-sectional survey aimed to assess the iodine status in pregnant women and their offspring, and also to demonstrate regional differences by measuring urinary iodine concentration (UIC). For each woman and her newborn a questionnaire was prepared with basic facts as age, parity number or birth weight and additional information regarding thyroid diseases, use of iodized salt in the household, extra iodine supplementation during pregnancy, education level and wage income.MethodsThe target population represented 1444 pregnant women who gave birth between January 1 st, 2018 and 2019, and their offspring. Iodine deficiency for pregnant women and their offspring were defined as urine iodine level <150 μg/L and <100 μg/L, respectively. Results are given as median (25th–75th percentile).ResultsThe median UIC in the group of pregnant woman was 94 (52–153) μg/L. Within the sample of 1444 pregnant women, UIC indicative of mild iodine deficiency (100−149 μg/L) was present in 21 % (n = 306), moderate deficiency (50−99 μg/L) in 30 % (n = 430), and severe deficiency (<50 μg/L) in 23 % (n = 337). This study showed a prevalence of 74 % of iodine deficiency in Turkish pregnant woman. The median UIC in the group of offspring was 96 (41−191) μg/L. Within the new-borns, UIC indicative of mild iodine deficiency (50−99 μg/L) was present in 22 % (n = 323), moderate deficiency (20−49 μg/L) in 15 % (n = 222), and severe deficiency (<20 μg/L) in 13 % (n = 192). This survey showed a prevalence of 51 % of iodine deficiency in Turkish new-borns. Pregnant women with lower socioeconomic and education level, lower access to household iodized salt, lower rates of exposure to povidone-iodine containing skin disinfectant, higher parity and higher iodine deficiency had higher rates of iodine deficiency in their offspring. Regional differences were observed both in mothers and their offspring concerning their iodine status.ConclusionsOur findings suggest that iodine deficiency is still an important public health problem in Turkey. More drastic measures should be taken to decrease these important iodine deficiencies, both in pregnant women and in their offspring.     

Urinary iodine and thyroid function in a population of healthy pregnant women in the North of Spain

BackgroundIodine is an essential trace element for the synthesis of thyroid hormones, which are keys in maternal metabolism during pregnancy as well as in neurological development during fetal and postnatal life. This was a prospective study on iodine status and thyroid function in women during pregnancy in the Basque country to assess whether there was any relationship among maternal urinary iodine, maternal thyroid function and thyrotropin (TSH) in newborns, and to explore any difference in women experiencing miscarriages.MethodsWe analyzed TSH, free T₄ (FT₄), free T₃ (FT₃), thyroid peroxidase antibody (TPO-Ab) titers in serum and urinary iodine concentrations (UIC) in 2104 women in the first trimester of pregnancy and in 1322 of them in their second trimester. We obtained neonatal TSH levels in 1868 cases.ResultsIn the first (T1) and second trimesters (T2), the median UICs were 88.5 μg/L and 140 μg/L, respectively. No relationship was found between UIC and FT₄, or maternal and neonatal TSH. In T1 and T2, 9.7% and 7.5% of women were TPO-Ab positive, respectively. The total miscarriage rate was 10%. The percentage of miscarriages in healthy women was 8.9%, lower than in women with overt hypothyroidism (21.2%; p < 0.001) and than in women with subclinical hypothyroidism (15.6%; p < 0.025). The miscarriage rate was not higher in TPO-Ab-positive women.ConclusionsIn this study most women had iodine deficiency during pregnancy. Neonatal TSH is not correlated with maternal UIC during pregnancy. Pregnant women with hypothyroidism have a higher rate of miscarriages.     

Different tissue responses for iodine and iodide in rat thyroid and mammary glands

This research describes the effects of short-term elemental iodine (I₂) and iodide (I⁻) replacement on thyroid glands and mammary glands of iodine-deficient (ID) Sprague-Dawley female rats. Iodine deficiency causes atypical tissue and physiologic changes in both glands. Tissue histopathology and the endocrine metabolic parameters, such as serum TT₄, tissue and body weights, and vaginal smears, are compared. A moderate reduction in thyroid size from the ID control (IDC) was noted with both I⁻ and I₂, whereas serum total thyroxine approached the normal control with both I⁻ and I₂, but was lower in IDC. Thyroid gland IDC hyperplasia was reduced modestly with I₂, but eliminated with I⁻. Lobular hyperplasia of the mammary glands decreased with I₂ and increased with I⁻ when compared with the IDC; extraductal secretions remained the same as IDC with I₂, but increased with I⁻; and periductal fibrosis was markedly reduced with I₂, but remained severe with I⁻. Thus, orally administered I₂ or I⁻ in trace doses with similar iodine availability caused different histopathological and endocrine patterns in thyroid and mammary glands of ID rats. The significance of this is that replacement therapy with various forms of iodine are tissue-specific.     

Effect of dietary iodine on thyroid hormones and energy blood metabolites in lactating goats

Aim of this work was to evaluate if long-term dietary supplementation of potassium iodide (KI) to dairy goats can influence metabolic and hormonal parameters. Thirty Sarda crossbred dairy goats were divided into three groups, which were orally administered 0 (control group; CON), 0.45 (low iodine group; LI) or 0.90 (high iodine group; HI) mg of KI/day, respectively. The daily dose of KI (76.5% of iodine) was administered as salt dissolved in water for 8 weeks. Plasma contents of nonesterified fatty acids (NEFA), urea, glucose, insulin, free triiodothyronine (FT₃) and thyroxine (FT₄) were determined weekly. Iodine supplementation increased significantly the FT₃ hormone (P = 0.007) and FT₃/FT₄ ratio (P = 0.001) and tended to influence the FT₄ hormone (P = 0.059). An iodine level × week of sampling interaction for NEFA (P = 0.013) evidenced a temporary concentration increase in supplemented groups. The ‘Revised Quantitative Insulin Sensitivity Check Index’ increased with KI supplementation (P ⩽ 0.01). Blood urea nitrogen (BUN) and insulin were lowered (P ⩽ 0.01) by iodine supplementation (groups LI and HI; P ⩽ 0.01). The glucose concentration evidenced an iodine level × week of sampling interaction (P = 0.025) due to an unexpected and temporary increase of its concentration in the CON group. Glucose concentration was decreased by KI supplementation only in LI group (P < 0.05). In conclusion, the daily supplementation of low doses of KI can improve insulin sensitivity and decrease BUN in dairy goats.     

Incidence of thyroid diseases in Zhejiang Province,China, after 15 years of salt iodization

Thyroid diseases(TD) can be induced by either deficient or excessive iodine intake. Universal Salt Iodization(USI) program has been implemented in China since 1995, to prevent iodine deficiency disorders (IDD). To evaluate the current conditions of TD and the role of USI, a multi-stage stratified random sampling scheme was used to perform a cross-sectional survey on the incidence of TD among participants in 6600 households in Zhejiang Province, a coastal area in China. Iodine nutrition status of the population was assessed by dietary iodine intake recall and urinary iodine concentration (UIC) of the participants, and TD were diagnosed by thyroid ultrasonography for 15122 participants and for 5873 participants by serum criteria for thyroid function(fT3, fT4, TSH, TRAb, TgAb, TPOAb; see Introduction for abbreviations). The median UIC of the surveyed population was 163 μg iodine/L. From the participants 23.2% had UIC < 100 μg/L which is moderately iodine-deficient according to WHO classification. Diffuse goiter was present in 2.3% of the population and thyroid nodule in 20.9%. The incidence of hyperthyroidism, subclinical hyperthyroidism, hypothyroidism, subclinical hypothyroidism, Graves’ disease and chronic lymphocytic thyroiditis was 0.5%, 0.6%, 0.6%, 7.8%, 0.2% and 0.3%, respectively. The proportion of several TD for participants with non-iodized salt intake was higher than that for participants with iodized salt intake.     

Selenium, zinc, and copper concentrations in the blood and milk of lactating women

The aim of the study was to determine Se, Zn, and Cu concentrations in blood plasma and milk of lactating women from central Poland who were in different stages of lactation and to investigate the relationship between the content of trace elements in mothers’ blood and concentrations of microelements in their milk. Se and Zn concentrations in blood plasma of mothers were the lowest and Cu was the highest on the first 4 d of lactation (colostrum, n=43) and were found to be 34.9±11.8 μg/L, 0.51±0.13 mg/L, and 1.70±0.55 mg/L, respectively. The highest plasma level of Se and Zn and the lowest content of Cu could be observed between d 10 and 30 of lactation (mature milk, n=41), and were found to be 54.3±14.6 μg/L for Se (p<0.001), 0.76±0.20 mg/L for Zn (p<0.001), and 1.03±0.30 mg/L (p<0.001) for Cu. The results of Se, Zn, and Cu determination in breast milk samples demonstrate a pattern of decline in their concentration with advancing stages of lactation. We found out that Se, Zn, and Cu concentrations were the highest in colostrum (n=43) and amounted to 24.8±10.1 μg/L, 8.2±2.8 mg/L, and 0.45±0.11 mg/L, respectively. The content of all determined microelements declined significantly during the time of lactation. Statistically significant linear correlation was found between concentrations of Zn in blood plasma and milk in the first stage of lactation. Weak but statistically significant linear correlations were also found between plasma Se content in plasma and in transitional and mature milk of breast-feeding women.     

Urinary iodine and sodium concentration and thyroid status in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

ObjectivesTo evaluate urinary iodine concentration (UIC) in civil servants aged 35-74 years of the Brazilian Study of Adults Health (ELSA-Brasil) to analyze its relationship with sociodemographic, clinical risk factors, lifestyle, urinary Na and thyroid status.DesignCross-sectional study in six Brazilian cities.MethodsThis analysis included 792 participants with information about urinary iodine concentration (UIC). Thyroid status was defined by serum levels of TSH/FT4 and the current use of antithyroid drugs for treatment of overt hyperthyroidism or levothyroxine to treat overt hypothyroidism. The determination of UIC was carried out with an inductively coupled plasma mass spectrometer (ICP-MS) and was expressed as median with Interquartile Range (IQR).ResultsIn 792 participants, thereof 52% women, mean age was 51.9 (9.0) years. The median UIC was 219 (IQR, 166-291) for all persons studied, thereof 211 (IQR, 157-276) for women and 231 (IQR, 178-304) for men. According to the WHO classification, for all persons studied, 60% had more than adequate iodine-supply (UIC ≥200 μg/L), 37% were adequately supplied (UIC 100-199 μg/L) and <3% had a deficient iodine status (<100 μg/L). In the 35-44-year age strata, which includes women of childbearing age, 23.2% of women presented less than 150 μg/L of UIC. No differences in UIC were detected according to thyroid status. (P = 0.39) The correlation between Ur-Na and UIC showed a Spearman coefficient of 0.52 (P < 0.0001) and it was also found an association of Ur-Na with UIC: Beta of 1.76 (95% Confidence Interval (95% CI): 1.01 to 2.51. The urinary Na concentration showed a synergy with the UIC, that means medians of 57, 72, 107 and 141 mmol Na/L urine (P < 0.001) in the groups with the four UIC classes according to the WHO grading mentioned above. The very low Na content in the persons exhibiting <100 μg/L UIC seems to reflect also a higher urine volume due to the frequent use of diuretics. The strong relationship between the urinary Na concentration and the UIC points to a dependence of the UIC on the individual consumption of iodized salt, which should be more considered in future studies. The strong relationship between the urinary Na concentration and the UIC points to a dependence of the UIC on the individual consumption of iodized salt, which should be more considered in future studies.ConclusionsEuthyroid persons were dominating by more than four fifths and no significant association was found between UIC and thyroid status. Although most of the persons studied present more than adequate iodine intake it was observed that nearly a quarter of women in childbearing age are iodine deficient.     

Inference of link among diabetes,obesity, and thyroid dysfunction in data from a clinic at Saudi Arabia

The clinical link among diabetes, obesity, and thyroid dysfunction is of interest. Hence, medical records of 601 patients with diabetes, obesity, and thyroid dysfunctions at the Abha Specialist Center and Military Diabetic Endocrine Center we used in this analysis. Approximately 28% of diabetic patients had thyroid dysfunction, and 12.4% were vitamin D deficient. The patients with thyroid dysfunction had significantly elevated triglyceride levels compared to the patients without thyroid dysfunction (173.6 vs. 128. p=0.009). Vitamin D deficient obese patients were significantly younger (33.99±10.69 vs. 43.68±14.42; p<0.001) and had significantly lower levels of HbA1c (5.73±1.16 vs. 6.83±2.08; p=0.014) and lower systolic BP (120.26±11.75 vs. 124.58±13.63; p=0.049) than non-vitamin D deficient obese patients. Vitamin D deficient thyroid patients had significantly lower diastolic BP (71.4±9.9 vs. 74.9±9.7; p=0.040) and higher HbA1c (8.7±3.6 vs. 6.4±1.7; p=0.003) in comparison to non-vitamin D deficient thyroid patients. Hence, analysis of metabolic disorders in these patients will help combat complications in these cases.     

Effect of different iodide intake during pregnancy and lactation on thyroid and cardiovascular function in maternal and offspring rats

ObjectiveWe aimed to investigate the impact of different iodide intake during pregnancy and lactation on iodine concentration in urine and serum, fatty acid metabolism, thyroid and cardiovascular function in maternal and offspring rats.MethodsPregnant rats were randomly assigned to four groups: normal adult iodide intake (NAI, 7.5 μg/d), normal pregnant iodide intake (NPI, 12.5 μg/d), 5 times (5 HI, 62.5 μg/d) and 10 times higher-than-normal pregnant iodide intake (10 HI, 125 μg/d). The maternal rats were continuously administered potassium iodide until postnatal day 16 (PN16). Thyroid function was measured by enzyme-linked immunosorbent assay (ELISA). The iodine concentration in urine and serum were detected by inductively coupled plasma mass spectrometry (ICP-MS). The messenger ribonucleic acid (mRNA) expressions of Krüppel-like factor 9 (KLF9) and thioredoxin reductase 2 (Txnrd2) were measured using quantitative real-time polymerase chain reaction (RT-qPCR). Characteristic distribution of KLF9 expression and its interaction with TRβ was assessed by immunohistochemical and immunofluorescence staining. Serum fatty acids were analyzed by Liquid Chromatography-Mass Spectrometry (LC-MS). Cardiac function and blood pressure were measured by echocardiography and a non-invasive tail-cuff system.ResultsHigh iodide intake (5 HI and 10 HI) during pregnancy and lactation results in increased urinary iodine concentration (UIC), serum total iodine concentration (STIC) and serum non-protein-bound iodine concentration (SNBIC) in both maternal and offspring rats, along with significantly increased FT3 and its target gene expression of KLF9. In maternal rats of both 5 HI and 10 HI groups, systolic blood pressure (SBP) was significantly higher, the increased SBP was significantly correlated with the increased UIC (r = 0.968, p = 0.002; r = 0.844, p = 0.035), KLF9 (r = 0.935, p = 0.006; r = 0.954, p = 0.003) and the decreased Txnrd2 (r = −0.909, p = 0.012; r = −0.912, p = 0.011). In maternal rats of 10 HI group, cardiac hyperfunction with increased LVEF, LVFS and decreased LVESD were observed. The increased LVEF and decreased LVESD were significantly correlated with UIC, STIC and SNBIC (r = 0.976, p = 0.001; r = 0.945, p = 0.005; r = 0.953, p = 0.003; r = −0.917, p = 0.01; r = −0.859, p = 0.028; r = −0.847, p = 0.033), LVEF, LVFS and LVESD were significant correlated with KLF9 (r = 0.950, p = 0.004; r = 0.963, p = 0.002; r = −0.990, p = 0.0002) and Txnrd2 expression (r = −0.979, p = 0.001; r = −0.915, p = 0.01; r = 0.933, p = 0.007), and the decreased LVESD was correlated with decreased epoxyeicosatrienoic acid (EET) metabolites: 5,6-EET, 8,9-DHET and 11,12-DHET (r = 0.999, p = 0.034; r = 1.000, p = 0.017; r = 1.000, p = 0.017). While in offspring rats, no significant change in SBP and cardiac function was found. STIC and SNBIC were much lower than those in maternal rats, and eicosapentaenoic acid (EPA) metabolites (9-HEPE, 15-HEPE and 14,15 DiHETE) were significantly increased.ConclusionIn addition to thyroid hormones, STIC, SNBIC, KLF9, Txnrd2, EET and EPA metabolites might be promising biomarkers in high iodide intake-induced thyroid and cardiovascular function.     

No association between genetic variants in angiogenesis and inflammation pathway genes and breast cancer survival among Chinese women

Background: Angiogenesis and inflammation are implicated in breast cancer prognosis; however, the role of individual germline variation in related genes is unknown. Methods: A two-stage candidate pathway association study was conducted among 6983 Chinese women. Stage 1 included 2884 women followed for a median of 5.7 years; Stage 2 included 4099 women followed for a median of 4.0 years. Cox proportional hazards regression was used to estimate the effects of genetic variants on disease-free survival (DFS) and overall survival (OS). Results: Stage 1 included genotyping of 506 variants in 22 genes; analysis was conducted for 370 common variants. Nominally significant associations with DFS and/or OS were found for 20 loci in ten genes in Stage 1; variants in 19 loci were successfully genotyped and evaluated in Stage 2. In analyses of both study stages combined, nominally significant associations were found for nine variants in seven genes; none of these associations surpassed a significance threshold level corrected for the total number of variants evaluated in this study. Conclusions: No association with survival was found for 370 common variants in 22 angiogenesis and inflammation pathway genes among Chinese women with breast cancer. Impact: Our data do not support a large role for common genetic variation in 22 genes in breast cancer prognosis; research on angiogenesis and inflammation genes should focus on common variation in other genes, rare host variants, or tumor alterations.