was read the article
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Covariate FT4 assessed at 1.1391<span class="elsevierStyleHsp" style=""></span>ng/mL to eliminate its significant effect (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) on FT3. BMI, body mass index; FT3, free triiodothyronine; FT4, free thyroxine. Significance: BMI <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05; smoking <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05; interaction between BMI and smoking <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Pregnancy represents an exceptional challenge for the thyroid gland, and normal pregnancy involves complex changes in thyroid physiology, causing an increased risk of thyroid dysfunction.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> At least 5% of pregnant women experience some thyroid dysfunction.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These dysfunctions are associated with complications of pregnancy, and also affect newborns. In pregnancy, they are mainly associated with abortion,<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3–5</span></a> premature delivery,<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4–6</span></a> postpartum anemia and bleeding,<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> and increased fetal loss (odds ratio: 13.5).<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> In newborns, complications include low weight and inadequate neurophysiological development, which may even cause a seven-point decrease in the intelligence quotient in children aged 7–9 years.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Iodine is an essential element for the synthesis of thyroid hormones, and iodination levels in pregnant women are highly variable in Spain. The geographic area of El Bierzo is characterized by lower than recommended urinary iodine levels in women in the first trimester of pregnancy (≥150<span class="elsevierStyleHsp" style=""></span>μg/L according to the World Health Organization),<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> a median of 118<span class="elsevierStyleHsp" style=""></span>μg/L, which causes a high prevalence of thyroid dysfunction in pregnant women.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">11,12</span></a> In one study only 15.6% of such women were found to be taking supplemental iodine.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Reference thyroid hormone levels in pregnant women are different from those for the general population because of physiological changes in pregnancy, particularly in the first trimester. Since neurological fetal development occurs during that first trimester, any intervention should occur at the beginning of pregnancy to achieve a good neurological development. A diagnosis of thyroid dysfunction should therefore be made during the first trimester of pregnancy. For this, thyroid-stimulating hormone (TSH) should primarily be measured, and when this is altered, free thyroxine (FT4) and free triiodothyronine (FT3) should also be measured.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Several scientific societies, such as the American Thyroid Association (ATA) and the Endocrine Society, have recently published new guidelines for the diagnosis and management of thyroid dysfunction in pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> A consensus document of the Spanish Society of Endocrinology and Nutrition (SEEN) intended to improve the diagnosis of a condition which is considered to be underdiagnosed is also available.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> There is some controversy among scientific bodies as to whether universal screening of thyroid hormones should be performed in the first trimester of pregnancy. The ATA and the Endocrine Society only recommend screening in high-risk patients,<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13,14</span></a> but in its document the SEEN advocates universal screening in Spain.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> The area of El Bierzo is defined as a high-risk area because of the low iodine intake, and all these societies would recommend the universal screening of pregnant women living in it. To diagnose thyroid dysfunction in pregnancy, all of these scientific bodies recommend verification that thyroid hormone levels are within the reference values for each trimester and area of the relevant laboratories.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13–15</span></a> When such reference values are not available, they recommend what they consider to be adequate reference values. Specifically, SEEN and ATA recommend the use of 2.5<span class="elsevierStyleHsp" style=""></span>μIU/mL as the cut-off value.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The purpose of this study was to establish reference values for TSH, FT4, and FT3 in women in the first trimester of pregnancy in our area that could be used for universal screening for thyroid dysfunction in the pregnant population. The study was also intended to find population factors which could explain the variability of TSH, FT4, and FT3 in pregnant women.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Subjects and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">A retrospective study was conducted on 412 pregnant women consecutively attending Hospital del Bierzo from February 2011 to April 2012 for screening for chromosome diseases in the first trimester. The results of TSH, FT4, and FT3 measurements performed on serum samples between weeks 8 and 13 of pregnancy were collected. The clinical histories of the pregnant women and the database of chromosome disease screening were consulted to collect population data at the time of sampling for thyroid hormone measurement. The population data collected included age, weight, height, body mass index (BMI), prior and/or current diseases (thyroid and non thyroid), and the smoking of three or more cigarettes daily.</p><p id="par0035" class="elsevierStylePara elsevierViewall">Pregnant women with endocrine changes, with no thyroid hormone data available between 8 and 13 weeks of pregnancy, with no information available on population data or prior diseases, and with twin and Down syndrome pregnancies were excluded from the study. Endocrine causes included treatment with thyroxine or other drugs altering thyroid hormones, positive anti-thyroid antibodies, a prior diagnosis of hypothyroidism or hyperthyroidism, or nutritional problems, and a diagnosis of diabetes mellitus or gestational diabetes. As smoking may alter thyroid hormone levels,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> pregnant women who smoked at least three cigarettes daily were excluded from the calculation of reference values in the first trimester.</p><p id="par0040" class="elsevierStylePara elsevierViewall">TSH, FT4, and FT3 measurements were performed using an ADVIA CENTAUR XP analyzer from Siemens Healthcare Diagnostics<span class="elsevierStyleSup">®</span>. TSH was measured using a double-antibody ultrasensitive assay with a range from 0.008 to 150<span class="elsevierStyleHsp" style=""></span>mIU/L and with the following interassay coefficients of variation (iCV) for three levels: level 1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.418<span class="elsevierStyleHsp" style=""></span>mIU/L, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.1%; level 2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5.685<span class="elsevierStyleHsp" style=""></span>mIU/L, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.4%; level 3<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>36.4<span class="elsevierStyleHsp" style=""></span>mIU/L, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.1%. FT4 was measured using a competitive assay, with a range from 0.1 to 12<span class="elsevierStyleHsp" style=""></span>ng/dL (1.3–155<span class="elsevierStyleHsp" style=""></span>pmol/L) and iCV for three levels: level 1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.883<span class="elsevierStyleHsp" style=""></span>ng/dL, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5.9%; level 2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.155<span class="elsevierStyleHsp" style=""></span>ng/dL, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5.1%; level 3<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>4.1<span class="elsevierStyleHsp" style=""></span>ng/dL, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>5.2%. FT3 was measured using a competitive assay, with a range from 0.2 to 20<span class="elsevierStyleHsp" style=""></span>μg/mL (0.3–30.8<span class="elsevierStyleHsp" style=""></span>μmol/L) and iCV for three levels: level 1<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.53<span class="elsevierStyleHsp" style=""></span>μg/mL, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.2%; level 2<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6.31<span class="elsevierStyleHsp" style=""></span>μg/mL, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>2.2%; level 3<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>11.24<span class="elsevierStyleHsp" style=""></span>μg/mL, iCV<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.4%.</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0045" class="elsevierStylePara elsevierViewall">Data were collected in Excel version 2003, and CBStat version 5.1 software was used to calculate reference values.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Normal thyroid hormone distribution was analyzed using an Anderson–Darling test,<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> and variables not normally distributed were transformed to adjust them to a parametric distribution.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> FT3 followed a parametric distribution, but FT4 required transformation by natural logarithms and TSH required dual exponential and modular transformation.<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20,21</span></a> Potential stratification by weeks of pregnancy, age, and BMI were studied,<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> and possible outliers were analyzed to discard them or not.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> Reference values were established between the 2.5th and 97.5th percentiles, with 90% confidence intervals as recommended by the International Federation of Clinical Chemistry.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> Group comparison was performed using a Student's t test, a Mann–Whitney <span class="elsevierStyleItalic">U</span> test, a Kruskal–Wallis <span class="elsevierStyleItalic">H</span> test, or a one-factor ANOVA test as appropriate.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Thyroid hormone variability was analyzing using SPSS software (PASW Statistics 18<span class="elsevierStyleSup">®</span>). Multivariate linear regression tests were done to obtain an approximation of significant variables, followed by a comprehensive study of multifactorial covariance (ANCOVA) for TSH, FT4, and FT3, in order to ascertain the main factors and interactions accounting for thyroid hormone variability. The variability factors analyzed included age ≥30 years, IMC<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, and smoking three or more cigarettes daily (smoker). TSH, FT4, or FT3 were introduced in the models as covariates if they were significant, in order to better differentiate the variability of the factors. FT4 was the covariate in the TSH model, while TSH was the covariate in the FT4 model and FT4 was the covariate in the FT3 model. Homogeneity and model lack-of-fit tests were performed, and residuals charts were analyzed to see whether the covariance models were correct. A value of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 was considered significant for all tests.</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall">A total of 412 women aged 16–43 years in the first trimester of pregnancy were studied. Of these, 163 were excluded from the study of reference values, and 193 from the variability study. The reasons for exclusion are given in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The prevalence of anti-thyroid antibodies in pregnant women was 5.1%. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the characteristics of the study population, which were not significantly different between the pregnant women included and excluded.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows the reference values obtained in the first trimester of pregnancy for TSH, FT4, and FT3, with their corresponding confidence intervals. Upon stratification between weeks 8 and 13 of pregnancy, no significant differences were found between pregnancy weeks in TSH (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.502), FT4 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.979), and FT3 (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.564), applying one-factor ANOVA taking into account the means of these parameters in each week (data not shown). A significant age-related decrease in TSH was seen (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> also shows TSH reference values for pregnant women aged <30 years and ≥30 years. A significant BMI-related increase in FT3 was also seen (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001), but no stratification was made because of the small number of cases with BMI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>24).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">The ANCOVA test showed that TSH decreased with age, mainly in pregnant women ≥30 years (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05), but that TSH levels in pregnant smokers did not differ from those in non-smokers (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.471). However, an interaction was seen to exist between the two variables, so that women ≥30 years of age who smoked had the lowest TSH levels (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> shows a profile plot of the marginal means estimated by the TSH model.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Age, BMI, or smoking had no influence on FT4 variability. As regards FT3, ANCOVA showed that FT3 increased with BMI, mainly in pregnant women with BMI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). Smoking also increased FT3 levels in pregnant women (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). An interaction was also seen between BMI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> and smoking, so that pregnant women who smoked and had BMIs<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) had higher FT3 levels. This interaction is better seen in the profile plot (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">The issue of the various recommendations made by scientific bodies and the lack of reference values for TSH, FT4, and FT3 in El Bierzo, an area where a high proportion of pregnant women have iodine deficiency, led us to calculate more precisely the reference values for those hormones in the first trimester of pregnancy. Although this was a retrospective study, maximum precautions were taken in our exclusion criteria. Any pregnant woman in whom there was the least doubt as to whether a treatment or disease would influence thyroid function was excluded from the study. This explains the high proportion of women excluded (39.6%). However, as shown in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, pregnant women included in and excluded from the study did not differ in the population data, and a homogeneous population could be assumed.</p><p id="par0080" class="elsevierStylePara elsevierViewall">To calculate reference values, distributions were normalized to obtain reference values with confidence intervals as adjusted as possible, which made the number of individuals less relevant. The upper TSH reference value (97.5th percentile<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>3.595<span class="elsevierStyleHsp" style=""></span>μIU/mL) was somewhat higher than 2.5<span class="elsevierStyleHsp" style=""></span>μIU/mL, the value recommended by the guidelines if no local reference values are available.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13–15</span></a> Some authors relate this higher value to a low iodine intake in the population,<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> but others think that no association exists between urinary iodine and TSH levels in the first trimester of pregnancy.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> Despite the stratification by age of pregnant women for subsequent use in screening for thyroid dysfunction in the first trimester of pregnancy, we think that it would be advisable to define the reference values of the total population, with no stratification by age, because it is more practical.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Since TSH and FT4 and FT3 levels did not differ between weeks 8 and 13 of pregnancy, a differentiation of reference values by week is not required, and they are grouped as reference values for the first trimester. Some reports provide reference values by weeks of pregnancy,<a class="elsevierStyleCrossRefs" href="#bib0135"><span class="elsevierStyleSup">27,28</span></a> while others do not,<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">29,30</span></a> but even García de Guadiana Romualdo et al.,<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> who give values according to gestational age, state that there are no significant differences in TSH by gestational week in the first trimester.</p><p id="par0090" class="elsevierStylePara elsevierViewall">A direct comparison of reference values found in this and other studies, even with the same procedures, is very difficult for several reasons. Many retrospective population studies use positive anti-thyroid antibodies as the only criterion, but as suggested by Spencer et al.,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> this procedure biases the upper reference TSH value due to other occult thyroid dysfunctions. Other studies used populations that were not comparable to ours both with regard to race<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> and because the nutritional iodine status of the population had not been studied.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> Moreover, there is no recognized reference method for the standardization of free thyroid hormone tests.</p><p id="par0095" class="elsevierStylePara elsevierViewall">The ANCOVA test showed that TSH levels of pregnant women are influenced by age and by interaction between age and smoking. As in some studies, smoking alone did not result in different TSH levels,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> although differences were found in other studies.<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">32,33</span></a> As regards age as an isolated factor, there are no reports in the literature suggesting that TSH levels decrease with an increase in the age of pregnant women, in particular from 30 years of age. Age-related increases<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a> or decreases<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> in TSH levels have however been seen in the general population. Specifically, Völzke et al.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a> hypothesized that an inverse relationship between TSH and age is seen in iodine-deficient populations, presumably due to prevailing nodular disease and increased thyroid autonomy with age. No references suggesting a potential interaction between age and smoking that causes pregnant women aged ≥30 years who are smokers to have lower TSH levels have been found either. This is a new finding which should be investigated in other studies so as to confirm it with a greater number of cases. If this finding is confirmed, TSH reference values in the first trimester of pregnancy for thyroid dysfunction screening will have to be stratified according to the age and smoking status of the women.</p><p id="par0100" class="elsevierStylePara elsevierViewall">As regards FT4 levels, they were not influenced by age ≥30 years, BMI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span>, or smoking. Other studies also reached the same conclusion with regard to smoking.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">As regards FT3 levels, other studies suggested that they increase with BMI<a class="elsevierStyleCrossRefs" href="#bib0175"><span class="elsevierStyleSup">35,36</span></a> and also with smoking,<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> but independently. No study reported an interaction between BMI<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>kg/m<span class="elsevierStyleSup">2</span> and smoking, as seen in this study. This interaction may be due to increased peripheral metabolism induced by smoking<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> and increased by the greater body surface area.</p><p id="par0110" class="elsevierStylePara elsevierViewall">We conclude that the reference values obtained for TSH, FT4, and FT3 may be used for thyroid dysfunction screening in the first trimester of pregnancy in El Bierzo. TSH levels in the first trimester of pregnancy are influenced by the age of the mother and by the interaction between age and smoking. FT3 levels in the first trimester of pregnancy depend on BMI and the smoking status of the mother, and an interaction between both factors also exists.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conflicts of interest</span><p id="par0115" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:2 [ "identificador" => "xres311193" "titulo" => array:5 [ 0 => "Abstract" 1 => "Background and objectives" 2 => "Patients and methods" 3 => "Results" 4 => "Conclusion" ] ] 1 => array:2 [ "identificador" => "xpalclavsec294345" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres311192" "titulo" => array:5 [ 0 => "Resumen" 1 => "Antecedentes y objetivos" 2 => "Pacientes y métodos" 3 => "Resultados" 4 => "Conclusión" ] ] 3 => array:2 [ "identificador" => "xpalclavsec294346" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Subjects and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-02-11" "fechaAceptado" => "2013-04-22" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec294345" "palabras" => array:7 [ 0 => "Thyroid-stimulating hormone" 1 => "Free thyroxine" 2 => "Free triiodothyronine" 3 => "Pregnancy" 4 => "Body mass index" 5 => "Smoking" 6 => "Age" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec294346" "palabras" => array:7 [ 0 => "Tirotropina" 1 => "Tiroxina libre" 2 => "Triyodotironina libre" 3 => "Embarazo" 4 => "Índice de masa corporal" 5 => "Fumar" 6 => "Edad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0010">Background and objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">El Bierzo area is characterized by low urinary iodine levels in the pregnant population. Guidelines recommend that local reference values are established for the diagnosis of thyroid dysfunction in pregnancy. Our objectives were to establish reference values for thyroid-stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyronine (FT3) in women in the first trimester of pregnancy and to explore the factors influencing variability in these hormones.</p> <span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A retrospective study of 412 women in the first trimester of pregnancy who were measured serum levels of TSH, FT4, and FT3; 163 women with conditions with a potential influence on thyroid function were excluded. Thirty smoking pregnant women were also excluded from the study of reference values. Factors examined in the variability study included age, body mass index (BMI), and smoking. A multifactorial analysis of covariance was performed.</p> <span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Reference values in first-trimester pregnant women were: TSH: 0.497–3.595<span class="elsevierStyleHsp" style=""></span>mIU/L; FT4: 0.90–1.42<span class="elsevierStyleHsp" style=""></span>ng/dL; FT3: 2.49–3.56<span class="elsevierStyleHsp" style=""></span>pg/mL. TSH levels depended on mother age and on interaction between age and smoking. FT3 levels depended on the mother's BMI and smoking, and there was also an interaction between both factors.</p> <span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The reference values found may be used to assess thyroid dysfunction in pregnant women from El Bierzo. TSH and FT3 levels are influenced by age and BMI of the mother and by smoking, in addition to the interaction of these factors.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span class="elsevierStyleSectionTitle" id="sect0035">Antecedentes y objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La zona de El Bierzo se caracteriza por una baja yoduria en la población gestante. Las guías recomiendan establecer valores de referencia locales para el diagnóstico de la disfunción tiroidea en el embarazo. Los objetivos fueron obtener valores de referencia de tirotropina (TSH), tiroxina libre (T4L) y triyodotironina libre (T3L) en gestantes de primer trimestre y estudiar los factores que intervienen en la variabilidad de estas hormonas.</p> <span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio retrospectivo de 412 gestantes con determinaciones en suero de TSH, T4L y T3L en el primer trimestre; se excluyeron 163 por condiciones con posible influencia sobre la función tiroidea. Para el estudio de los valores de referencia se excluyeron además 30 mujeres fumadoras. El estudio de la variabilidad se realizó para los factores edad, índice de masa corporal (IMC) y fumar, mediante análisis de la covarianza multifactorial.</p> <span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los valores de referencia en gestantes de primer trimestre fueron: TSH: 0,497–3,595<span class="elsevierStyleHsp" style=""></span>mUI/l; T4L: 0,90–1,42<span class="elsevierStyleHsp" style=""></span>ng/dl; T3L: 2,49–3,56<span class="elsevierStyleHsp" style=""></span>pg/ml. La TSH depende de la edad de la madre y de la interacción entre la edad y fumar. La T3L depende del IMC de la madre y de fumar, existiendo además una interacción entre ambos factores.</p> <span class="elsevierStyleSectionTitle" id="sect0050">Conclusión</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Los valores de referencia obtenidos pueden utilizarse para valorar la disfunción tiroidea en mujeres gestantes de El Bierzo. Los valores de TSH y T3L están influidos por la edad de la madre, el IMC y fumar, además de por las interacciones entre estos factores.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as: Lombardo Grifol M, Gutiérrez Menéndez ML, García Menéndez L, Valdazo Revenga MV. Valores de referencia y estudio de la variabilidad de hormonas tiroideas en gestantes de El Bierzo. Endocrinol Nutr. 2013;60:549–554.</p>" ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1519 "Ancho" => 1669 "Tamanyo" => 79175 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">TSH profile plots. Covariate FT4 assessed at 1.1391<span class="elsevierStyleHsp" style=""></span>ng/mL to eliminate its significant effect (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) on TSH. TSH: thyroid-stimulating hormone; FT4: free thyroxine. Significance: age <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05; smoking <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.471; interaction between age and smoking <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1350 "Ancho" => 1682 "Tamanyo" => 79333 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">FT3 profile plots. Covariate FT4 assessed at 1.1391<span class="elsevierStyleHsp" style=""></span>ng/mL to eliminate its significant effect (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05) on FT3. BMI, body mass index; FT3, free triiodothyronine; FT4, free thyroxine. Significance: BMI <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05; smoking <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05; interaction between BMI and smoking <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] 2 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>412 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Reason for exclusion \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Number of cases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " rowspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Excluded</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive anti-thyroid antibodies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">21 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other endocrine causes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No hormone data in first trimester (weeks 8–13) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No data on prior diseases \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Other diseases that may affect thyroid hormones \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Twin and Down syndrome pregnancies \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2.2 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Excluded from the variability study</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">163 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">39.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Excluded \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smokers \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Excluded from the study of reference values</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">193 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46.8 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab457220.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Description of reasons for study exclusion.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">BMI, body mass index.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Study (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>249) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Excluded (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>163) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span><a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (mean) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Weight (mean) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">65.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">67.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Height (mean) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">162.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">162.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI (mean) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">24.51 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.11 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Smoker (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.19 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab457222.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005"><span class="elsevierStyleItalic">p</span>: significance estimated by Student's test or comparison of proportions.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Description of study population.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:3 [ "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">CI, confidence interval; P, percentile; TSH, thyroid-stimulating hormone; FT3, triiodothyronine not bound to protein; FT4, thyroxine not bound to protein.</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Median urinary iodine levels in women in the first trimester of pregnancy in El Bierzo: 118<span class="elsevierStyleHsp" style=""></span>μg/L.</p><p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Reference values appear in bold.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">n<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="4" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">Reference values</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">P2.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">(CI) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">P97.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" style="border-bottom: 2px solid black">(CI) \t\t\t\t\t\t\n \t\t\t\t</td></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">TSH (μIU/mL) (age 16–43 years)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">219 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">0.497</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(0.415–0.584) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">3.595</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(3.298–3.914) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>TSH (μIU/mL)<span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>30 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">140 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">0.499</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(0.401–0.605) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">3.459</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(3.079–3.888) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>TSH (μIU/mL) <30 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">0.481</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(0.331–0.647) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">3.798</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(3.352–4.275) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">FT4 (ng/dL)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">219 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">0.90</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(0.88–0.92) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">1.42</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(1.39–1.45) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">FT3 (pg/mL)</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">219 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">2.49</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(2.44–2.54) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">3.56</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">(3.51–3.61) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab457221.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Thirty women who smoked three or more cigarettes daily were excluded.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Reference values in women in the first trimester of pregnancy (weeks 8–13) in El Bierzo.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:36 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thyroid disorders during pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.F. 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Year/Month | Html | Total | |
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2024 October | 32 | 14 | 46 |
2024 September | 45 | 31 | 76 |
2024 August | 55 | 27 | 82 |
2024 July | 27 | 17 | 44 |
2024 June | 39 | 12 | 51 |
2024 May | 16 | 11 | 27 |
2024 April | 28 | 22 | 50 |
2024 March | 58 | 7 | 65 |
2024 February | 57 | 10 | 67 |
2024 January | 44 | 7 | 51 |
2023 December | 44 | 17 | 61 |
2023 November | 41 | 9 | 50 |
2023 October | 42 | 15 | 57 |
2023 September | 34 | 4 | 38 |
2023 August | 31 | 8 | 39 |
2023 July | 19 | 15 | 34 |
2023 June | 30 | 6 | 36 |
2023 May | 20 | 6 | 26 |
2023 April | 13 | 3 | 16 |
2023 March | 26 | 5 | 31 |
2023 February | 20 | 11 | 31 |
2023 January | 19 | 7 | 26 |
2022 December | 30 | 11 | 41 |
2022 November | 19 | 8 | 27 |
2022 October | 19 | 18 | 37 |
2022 September | 25 | 15 | 40 |
2022 August | 39 | 12 | 51 |
2022 July | 21 | 14 | 35 |
2022 June | 23 | 10 | 33 |
2022 May | 25 | 19 | 44 |
2022 April | 23 | 16 | 39 |
2022 March | 35 | 19 | 54 |
2022 February | 25 | 11 | 36 |
2022 January | 35 | 17 | 52 |
2021 December | 36 | 17 | 53 |
2021 November | 22 | 12 | 34 |
2021 October | 34 | 18 | 52 |
2021 September | 30 | 11 | 41 |
2021 August | 29 | 8 | 37 |
2021 July | 24 | 9 | 33 |
2021 June | 30 | 7 | 37 |
2021 May | 34 | 10 | 44 |
2021 April | 69 | 9 | 78 |
2021 March | 33 | 10 | 43 |
2021 February | 23 | 8 | 31 |
2021 January | 43 | 14 | 57 |
2020 December | 26 | 11 | 37 |
2020 November | 26 | 7 | 33 |
2020 October | 11 | 9 | 20 |
2020 September | 23 | 9 | 32 |
2020 August | 27 | 9 | 36 |
2020 July | 39 | 15 | 54 |
2020 June | 20 | 9 | 29 |
2020 May | 29 | 11 | 40 |
2020 April | 22 | 9 | 31 |
2020 March | 27 | 3 | 30 |
2020 February | 32 | 7 | 39 |
2020 January | 32 | 8 | 40 |
2019 December | 27 | 8 | 35 |
2019 November | 12 | 12 | 24 |
2019 October | 19 | 10 | 29 |
2019 September | 13 | 5 | 18 |
2019 August | 18 | 11 | 29 |
2019 July | 30 | 18 | 48 |
2019 June | 38 | 15 | 53 |
2019 May | 124 | 15 | 139 |
2019 April | 38 | 17 | 55 |
2019 March | 13 | 6 | 19 |
2019 February | 15 | 9 | 24 |
2019 January | 17 | 3 | 20 |
2018 December | 8 | 10 | 18 |
2018 November | 20 | 6 | 26 |
2018 October | 15 | 5 | 20 |
2018 September | 13 | 5 | 18 |
2018 August | 5 | 1 | 6 |
2018 July | 7 | 3 | 10 |
2018 June | 8 | 3 | 11 |
2018 May | 15 | 3 | 18 |
2018 April | 12 | 2 | 14 |
2018 March | 5 | 1 | 6 |
2018 February | 8 | 1 | 9 |
2018 January | 14 | 1 | 15 |
2017 December | 12 | 0 | 12 |
2017 November | 12 | 1 | 13 |
2017 October | 12 | 1 | 13 |
2017 September | 10 | 3 | 13 |
2017 August | 13 | 4 | 17 |
2017 July | 17 | 6 | 23 |
2017 June | 10 | 5 | 15 |
2017 May | 21 | 4 | 25 |
2017 April | 24 | 6 | 30 |
2017 March | 32 | 24 | 56 |
2017 February | 50 | 3 | 53 |
2017 January | 21 | 0 | 21 |
2016 December | 25 | 6 | 31 |
2016 November | 27 | 6 | 33 |
2016 October | 51 | 6 | 57 |
2016 September | 42 | 6 | 48 |
2016 August | 29 | 1 | 30 |
2016 July | 24 | 2 | 26 |
2016 June | 30 | 16 | 46 |
2016 May | 20 | 5 | 25 |
2016 April | 17 | 0 | 17 |
2016 March | 19 | 6 | 25 |
2016 February | 25 | 12 | 37 |
2016 January | 21 | 8 | 29 |
2015 December | 22 | 13 | 35 |
2015 November | 14 | 6 | 20 |
2014 November | 1 | 0 | 1 |
2014 August | 0 | 1 | 1 |
2014 May | 1 | 0 | 1 |