Optimization of the follow-up of pregnant women with autoimmune thyroid disease | Endocrinología, Diabetes y Nutrición (English ed.)

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TSH: thyroid stimulating hormone; FT4: free thyroxine." ] ] ] "textoCompleto" => "IntroductionThe reported prevalence of thyroid autoimmune disorders in pregnant women ranges from 3% to 18%,<a class="elsevierStyleCrossRef" href="#bib0110">1</a> and these disorders are associated with an increased risk of maternal and fetal complications, mainly miscarriage and preterm delivery.<a class="elsevierStyleCrossRefs" href="#bib0115">2–4</a> In addition, women with positive thyroid autoimmunity usually have higher thyroid stimulating hormone (TSH) levels at the start of pregnancy as compared to those without such autoimmunity.<a class="elsevierStyleCrossRefs" href="#bib0130">5,6</a> The presence of anti-thyroperoxidase (TPO) and anti-thyroglobulin antibodies (anti-Tg) in pregnant women has been related to different factors such as a family history of autoimmune thyroid disease, age, parity and iodine deficiency or excess.<a class="elsevierStyleCrossRefs" href="#bib0140">7–9</a>Anti-thyroid antibody titers are higher in the first trimester and then decrease considerably during pregnancy, with eventual negative conversion in some cases.<a class="elsevierStyleCrossRef" href="#bib0155">10</a> Despite this, it is considered that women with positive thyroid autoimmunity are at an increased risk of developing hypothyroidism during pregnancy; monitoring of thyroid function is therefore advised mainly during the first half of pregnancy.<a class="elsevierStyleCrossRefs" href="#bib0160">11,12</a>The purpose of this study was to determine the percentage of pregnant women with positive thyroid autoimmunity and TSH<2.5mIU/l in the first trimester who develop hypothyroidism during pregnancy, and to compare them with a control group of pregnant women with negative autoimmunity.Material and methodsStudy populationA prospective study was made of 400 women in the first trimester of pregnancy with no history of thyroid disease and no drug treatment capable of affecting thyroid function (amiodarone, lithium, levothyroxine, antithyroid drugs). The participants were recruited from two women's health care centers on the occasion of their first prenatal visit, and were assessed in person at the Department of Endocrinology of Complejo Hospitalario de Navarra (Pamplona, Spain) between May 2014 and May 2016. At this visit, a case history was compiled, with physical examination, thyroid ultrasound and the collection of a simple urine sample for measuring ioduria. Determinations were made of TSH, free thyroxine (FT4), and anti-TPO and anti-Tg antibodies, coinciding with the routine laboratory tests made during pregnancy (gestational weeks 9, 15, 25 and 36).For the present study, we excluded women with multiple pregnancy (n=14), thyroid nodules >1cm in size (n=24) and/or those with TSH in the first trimester ≥2.5mIU/l (n=62). The final study population thus comprised 300 pregnant women. The appearance of hypothyroidism was defined as a TSH elevation above 4mIU/l at any time during pregnancy.Miscarriages and preterm deliveries (before gestational week 37) occurring during the study were recorded.The study was approved by the Clinical Research Ethics Committee of Navarre, and all included pregnant women signed the corresponding informed consent form.Laboratory tests and ultrasound studyBlood samples for the determination of TSH, FT4, and anti-TPO and anti-Tg antibodies were analyzed by the core laboratory of Complejo Hospitalario de Navarra using chemiluminescence (Abbott method). All the samples were collected in the morning. Anti-TPO and anti-Tg positivity was considered in the presence of values above the upper limit of normal. The titers (numerical values) of both antibodies were also recorded.The determination of ioduria was carried out in the Public Health Standard Laboratory of the Basque Government in Derio (Vizcaya) using ion-pair reversed-phase liquid chromatography with electrochemical detection and a silver electrode (Waters Chromatography, Milford, MA, USA). Detailed information on the procedure and validation of the method and its within- and between-serial precision has been published elsewhere.<a class="elsevierStyleCrossRef" href="#bib0170">13</a> The urine samples were stored in the Biobank, frozen at −20°C, and duly identified, until submission for analysis.Thyroid ultrasound was performed with the patient in the dorsal decubitus position using a MicroMaxx® portable ultrasound device (Sonosite, Bothell, WA, USA) with a 5–12MHz linear probe. Thyroid volume (in ml) was calculated by summing the volume of both thyroid lobes (volume of each lobe=longitudinal axis [cm]×transverse axis [cm]×anteroposterior axis [cm]×0.479).Statistical analysisQualitative variables were reported as frequencies and percentages, while quantitative variables were expressed as measures of central tendency (mean, median) and dispersion (standard deviation [SD] and interquartile range [IQR]).Normal distribution of the variables was assessed using the Kolmogorov–Smirnov test. The TSH and FT4 levels according to positive thyroid autoimmune testing were compared using the parametric Student t-test or nonparametric Mann–Whitney test, as applicable. Associations between categorical variables were assessed using the χ2 test. The SPSS version 20 statistical package was used throughout. Statistical significance was considered for p<0.05.ResultsBaseline population characteristicsThe study comprised 300 pregnant women in the first trimester of pregnancy (95% Caucasians), evaluated in gestational week 10 (range 6–18). Median ioduria was 242μg/l (range 148.5–413), which is consistent with an iodine-sufficient population according to World Health Organization (WHO) criteria. A total of 98.3% of the women were receiving drug supplementation with potassium iodide at the time of evaluation (mean iodine dose: 202.6±30.1μg daily).Fifty-three of the pregnant women (17.7%) showed positive autoimmunity in the first trimester. Of these, 15.1% (n=8) had positive anti-TPO antibodies, 47.2% (n=25) had positive anti-Tg antibodies, and 37.7% (n=20) proved positive for both antibodies.There were no baseline differences between women with positive thyroid autoimmunity and those with negative autoimmunity (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Pregnant women with positive anti-TPO antibodies (n=28) and those with positive anti-Tg antibodies only (n=25) were analyzed separately, and both groups were compared with the autoimmune-negative control population (n=247). A family history of thyroid disease was more frequent in women with positive anti-TPO antibodies than in the control population (35.7% vs. 17.8%; p=0.024), with no differences between the two groups in terms of age, parity or baseline TSH levels (TSH 1.4±0.7 vs. 1.2±0.6mIU/l; p=0.328). No significant differences were found in any of the above variables between the pregnant women with positive anti-Tg antibodies alone and the control group. The baseline TSH concentration was 1.4±0.7mIU/l and 1.2±0.6mIU/l, respectively (p=0.123).Variation of thyroid antibodies over timeThe laboratory tests were performed in the following gestational weeks (median [P25–P75]): week 9 (8–9) (n=300), week 15 (14–15) (n=266), week 25 (25–26) (n=98) and week 36 (36–37) (n=248).The anti-TPO and anti-Tg antibody titers decreased significantly during pregnancy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Between the first and last laboratory tests (gestational weeks 9 and 36, respectively), the anti-TPO antibodies decreased by 76.8%, with negative conversion in 6 women (21.4%), while the anti-Tg antibodies decreased by 80.7%, with negative conversion in 18 women (40%).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Variation of thyroid function over time and the appearance of hypothyroidismThe TSH and FT4 levels during pregnancy were similar in women with autoimmune thyroid disease and those with negative autoimmunity (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). There were no significant differences in TSH and FT4 levels between the two groups in any of the gestational weeks in which laboratory tests were performed.<elsevierMultimedia ident="fig0010"></elsevierMultimedia>During follow-up, TSH increased to above 4mIU/l in one of the 53 pregnant women in the autoimmune-positive group (1.9%), and in 5 of the 247 women with negative autoimmunity (2%). Hypothyroidism was detected in week 15 in two of these women and in week 36 in the other four women. In no case did TSH increase to above 5mIU/l (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). The pregnant women who developed hypothyroidism (n=6) had higher TSH levels at the start of pregnancy than the women who maintained TSH≤4mIU/l during pregnancy (TSH 1.8 vs. 1.3mIU/l; p=0.047), with no other significant differences.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Twelve miscarriages were recorded during follow-up: one in the group of pregnant women with positive autoimmunity and 11 in the control group (1.9% vs. 4.5%; p=0.387). The incidence of preterm delivery was 7.5% and 5.2%, respectively (p=0.547). Likewise, no significant differences were found in the miscarriage or preterm delivery rates on separately comparing the women with positive anti-TPO antibodies and those with only positive anti-Tg antibodies versus the pregnant women with negative autoimmunity.DiscussionThe results of our study show that pregnant women with positive thyroid autoimmunity and TSH<2.5mIU/l at the start of pregnancy have a minimal risk of developing hypothyroidism, similar to that seen in women with negative autoimmunity.The prevalence of positive thyroid autoimmunity in pregnant women reported in the literature is highly variable.<a class="elsevierStyleCrossRefs" href="#bib0110">1,11</a> This variability is probably due to the different analytical methods used, the cut-off points employed, and the characteristics of the study population (ethnicity, iodine status, etc.). In our study, 17.7% of the pregnant women had positive thyroid antibodies in the first trimester. Of note is the observation that almost half of them were positive only for anti-Tg antibodies. Although the presence of thyroid antibodies has been associated in some studies with age and parity,<a class="elsevierStyleCrossRef" href="#bib0140">7</a> we found no relationship between the presence of autoimmunity and these variables. Similarly to as was reported in previous studies,<a class="elsevierStyleCrossRefs" href="#bib0155">10,14,15</a> the anti-TPO and anti-Tg antibody titers decreased by about 80% during pregnancy, with negative conversion in 21% and 40% of the women, respectively. Therefore, in those cases where it is considered clinically appropriate, thyroid autoimmunity should be tested as early as possible in pregnancy, since the diagnostic usefulness of thyroid antibody testing in the second half of pregnancy is limited.With regard to the main adverse events associated with thyroid autoimmunity (miscarriage and preterm delivery), we found no significant differences between the antibody-positive women and the control group. In this regard, it should be emphasized that the personal visit took place in gestational week 10 (range 6–18), and so in some cases miscarriage would have already occurred. The fact that the women included in our study presented baseline TSH<2.5mIU/l (and did not develop hypothyroidism during pregnancy) probably reflects the existence of mild or early forms of autoimmune thyroid disease.Women with autoimmune thyroid disease are considered to be at an increased risk of developing hypothyroidism in pregnancy due to the inability of the thyroid gland to respond to the increased hormone production associated with pregnancy.<a class="elsevierStyleCrossRef" href="#bib0185">16</a> Two previous studies in euthyroid pregnant women with positive autoimmunity recorded progression to hypothyroidism in close to 20% of the cases.<a class="elsevierStyleCrossRefs" href="#bib0180">15,17</a> The risk of hypothyroidism was higher in pregnant women with baseline TSH levels >2mIU/l and in those with high anti-TPO antibody titers. Based on the results of these studies, the clinical guides recommend periodic monitoring of thyroid function during pregnancy in women with autoimmune thyroid disease.<a class="elsevierStyleCrossRefs" href="#bib0160">11,18,19</a> However, the occurrence of hypothyroidism in our study was very low. In addition, hypothyroidism was detected at the end of pregnancy in most cases, and the TSH levels were <5mIU/l in all patients. The main differences between our study and the previous publications concern the baseline TSH cut-off point of the women on the one hand, and the prevalence of positivity of the different antithyroid antibodies on the other. With regard to the first point, the above-mentioned studies included women with basal TSH levels of up to 4mIU/l, while in our study pregnant women with TSH levels ranging from 2.5 to 4mIU/l were not included, because most of them started treatment with levothyroxine. With regard to antithyroid antibodies, the pregnant women in the studies published by Glinoer et al. and Negro et al. were predominantly positive for anti-TPO antibodies (84% and 100% of the women, respectively), while anti-Tg positivity predominated in our population. In addition, unlike the previous studies, our population was iodine-sufficient, and such improved iodination may have influenced a lesser frequency of progression to hypothyroidism. Two later studies also found a high frequency of hypothyroidism in women with autoimmune thyroid disease, this largely being explained by the definition of hypothyroidism used in both studies (i.e., TSH≥2.5mIU/l in the first trimester or ≥3mIU/l thereafter).<a class="elsevierStyleCrossRefs" href="#bib0205">20,21</a> Our findings are similar to those of a recent study in 140 Australian pregnant women with basal TSH<2.5mIU/l, in which none of the patients developed gestational hypothyroidism.<a class="elsevierStyleCrossRef" href="#bib0155">10</a>ConclusionsIn our population, the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and TSH<2.5mIU/l in the first trimester was minimal, and similar to that seen in women with negative autoimmunity.The results obtained suggest the convenience of optimizing the follow-up of euthyroid women with autoimmune thyroid disease during pregnancy, based on the TSH levels in the first trimester. In this way, women at greater risk of developing hypothyroidism could be identified, and those at very low risk would not have to undergo needless monitoring.Pregnant women with TSH<2.5mIU/l would not need further studies, because even if they had positive autoimmunity (known before pregnancy), the risk of developing hypothyroidism during pregnancy would be minimal.In women with TSH levels ranging from 2.5 to 4mIU/l, the measurement of thyroid antibodies is recommended. If autoimmunity proves positive, treatment with levothyroxine may be considered (especially in the case of a history of adverse events in previous pregnancies, or assisted reproduction treatments).<a class="elsevierStyleCrossRef" href="#bib0160">11</a> With regard to the risk of hypothyroidism in this group, our results do not allow for the drawing of conclusions (it was at the time of the study that the pregnant women with TSH>2.5mIU/l started treatment with levothyroxine). However, based on data from previous studies, these women would appear to be more at risk of developing hypothyroidism during pregnancy, and thyroid function monitoring is therefore advisable if such treatment is not started.To sum up, women with autoimmune thyroid disease and TSH<2.5mIU/l in the first trimester of pregnancy have a minimal risk of gestational hypothyroidism; the monitoring of thyroid function therefore should not be required during pregnancy in these cases.Authorship/collaboratorsM. Dolores Ollero, Javier Pineda, Juan Pablo Martínez de Esteban, Marta Toni and Emma Anda made substantial contributions to the conception and design of the study, and to data acquisition, analysis and interpretation. They also contributed to a critical review of the manuscript and to the final approval of the submitted version. Mercedes Espada contributed to the data analysis, as well as to the critical review and to the final approval of the submitted version of the manuscript.FundingThis study was funded in part by the Endocrinology, Nutrition and Diabetes Foundation of Navarre (Fundación de Endocrinología, Nutrición y Diabetes de Navarra).Conflicts of interestThe authors declare that they have no conflicts of interest." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres1201935" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1120000" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1201936" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1120001" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Laboratory tests and ultrasound study" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Baseline population characteristics" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Variation of thyroid antibodies over time" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Variation of thyroid function over time and the appearance of hypothyroidism" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Authorship/collaborators" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Funding" ] 11 => array:2 [ "identificador" => "sec0070" "titulo" => "Conflicts of interest" ] 12 => array:2 [ "identificador" => "xack411185" "titulo" => "Acknowledgments" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-06-13" "fechaAceptado" => "2018-08-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1120000" "palabras" => array:4 [ 0 => "Hypothyroidism" 1 => "Pregnancy" 2 => "Autoimmune thyroid disease" 3 => "Thyrotropin" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1120001" "palabras" => array:4 [ 0 => "Hipotiroidismo" 1 => "Gestación" 2 => "Enfermedad tiroidea autoinmune" 3 => "Tirotropina" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo determine the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and thyrotropin (TSH)<2.5mIU/l at the beginning of pregnancy. MethodsProspective longitudinal study of pregnant women with no personal history of thyroid disease, and with TSH<2.5mIU/l in the first trimester. TSH, free thyroxine (FT4), anti peroxidase (TPO) and anti thyroglobulin antibodies were measured in the 3 trimesters of pregnancy. We compared thyroid function throughout pregnancy, and the development of gestational hypothyroidism (TSH>4mIU/l) among pregnant women with positive thyroid autoimmunity and those with negative autoimmunity. ResultsWe included 300 pregnant women with mean baseline TSH 1.3±0.6mIU/l (9th gestational week). Positive thyroid autoimmunity was detected in 17.7% of women (n=53) at the first trimester. Between the first and the third trimesters, TPO and anti thyroglobulin antibodies titers decreased 76.8% and 80.7% respectively. Thyroid function during pregnancy was similar among the group with positive autoimmunity and the group with negative autoimmunity, and the development of hypothyroidism was 1.9% (1/53) and 2% (5/247) respectively. Pregnant women in whom TSH increased above 4mIU/l (n=6), had higher baseline TSH levels compared to those who maintained TSH≤4mIU/l during pregnancy (1.8 vs. 1.3mIU/l; p=0.047). ConclusionIn our population, women with TSH levels <2.5mIU/l at the beginning of pregnancy have a minimal risk of developing gestational hypothyroidism regardless of thyroid autoimmunity." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoDeterminar el riesgo de hipotiroidismo en gestantes con enfermedad tiroidea autoinmune y tirotropina (TSH) < 2,5 mUI/l al inicio del embarazo. MétodosEstudio prospectivo longitudinal en gestantes de primer trimestre sin antecedentes de patología tiroidea y con TSH en primer trimestre < 2,5 mUI/l. Se determinaron TSH, tiroxina libre (T4l) y anticuerpos antiperoxidasa (TPO) y antitiroglobulina en los 3 trimestres. Se comparó la evolución de la función tiroidea y la aparición de hipotiroidismo gestacional (TSH > 4 mUI/l), entre las gestantes con autoinmunidad positiva y autoinmunidad negativa. ResultadosSe incluyeron 300 gestantes con TSH basal 1,3±0,6 mUI/l (semana gestacional 9). El 17,7% (n = 53) tenían autoinmunidad positiva en el primer trimestre. Los títulos de anticuerpos TPO y antitiroglobulina disminuyeron entre el primer y el tercer trimestre un 76,8% y un 80,7% respectivamente. La evolución de la función tiroidea fue similar en el grupo con autoinmunidad positiva y el grupo con autoinmunidad negativa, y la aparición de hipotiroidismo fue del 1,9% (1/53) y del 2% (5/247) respectivamente. Las gestantes en las que la TSH aumentó por encima de 4 mUI/l (n = 6) tenían cifras superiores de TSH basal en comparación con las que mantuvieron TSH≤4 mUI/l a lo largo del embarazo (1,8 vs. 1,3 mUI/l; p = 0,047). ConclusiónEn nuestra población, las mujeres con TSH < 2,5 mUI/l al inicio del embarazo tienen un riesgo mínimo de desarrollar hipotiroidismo durante la gestación, independientemente de la autoinmunidad tiroidea." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Ollero MD, Pineda J, Martínez de Esteban JP, Toni M, Espada M, Anda E. Optimización del seguimiento de gestantes con enfermedad tiroidea autoinmune. Endocrinol Diabetes Nutr. 2019;66:305–311." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 867 "Ancho" => 2199 "Tamanyo" => 72260 ] ] "descripcion" => array:1 [ "en" => "Anti-TPO (A) and anti-thyroglobulin (B) antibody titers during pregnancy in women with positive autoimmunity. Anti-Tg antibodies: anti-thyroglobulin antibodies; anti-TPO antibodies: anti-thyroperoxidase antibodies. *p-value <0.05 in relation to gestational week 9." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 653 "Ancho" => 2329 "Tamanyo" => 100690 ] ] "descripcion" => array:1 [ "en" => "Variation of TSH (A) and FT4 (B) levels during pregnancy in pregnant women with positive autoimmunity and negative autoimmunity. TSH: thyroid stimulating hormone; FT4: free thyroxine." ] ] 2 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "Values are reported as mean±standard deviation, except for ioduria, which is expressed as median (P25–P75). TSH (mIU/l) and FT4 (ng/dl) correspond to gestational week 9, and thyroid volume and ioduria to gestational week 10.Family hist.: family history; thyroid vol.: thyroid volume." "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"><th 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" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Total population (n=300) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Positive autoimmunity (n=53) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Negative autoimmunity (n=247) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">p<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age (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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.4±4.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.4±4.1 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">33.4±4.1 \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">0.989 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BMI \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">23.7±4.4 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">23.5±4.5 \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">23.7±4.4 \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">0.739 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Family hist. (%) \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">19 \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">24.5 \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">17.8 \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">0.258 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nulliparity (%) \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">47.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.8 \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">0.111 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">No. of previous offspring \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">0.6±0.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.8±0.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.6±0.7 \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">0.083 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Thyroid vol. (ml) \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">8.0±2.6 \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">8.4±2.3 \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">7.9±2.7 \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">0.300 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ioduria (μg/l) \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">242 (148.5–413.0) \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">294 (169.8–430.8) \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">234 (140.5–409.0) \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">0.114 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">TSH (mIU/l) \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">1.3±0.6 \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">1.4±0.7 \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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.2±0.6 \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">0.091 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">FT4 (ng/dl) \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">1.04±0.99 \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">1.04±0.11 \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">1.05±0.10 \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">0.780 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2054417.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "p-Value between pregnant women with positive autoimmunity and negative autoimmunity." ] ] ] "descripcion" => array:1 [ "en" => "Baseline characteristics of the study population in the first trimester of pregnancy." ] ] 3 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "TSH (mIU/l) and FT4 (ng/dl) levels in gestational weeks 9, 15 and 36 in the women who developed hypothyroidism during follow-up.Pat.: patient; Wk: gestational week." "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"><th class="td-with-role" title="\n \t\t\t\t\ttable-head\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col">Pat. \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col">Autoimmunity \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TSH (mIU/l)</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="3" align="center" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">FT4 (ng/dl)</th></tr><tr title="table-row"><th 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" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 9 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 15 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 36 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 9 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 15 \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 36 \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Positive \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">2.01 \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">4.07<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \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">— \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">0.87 \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">1.07 \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">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \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">1.64 \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">2.87 \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">4.61 \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">1.15 \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">1.14 \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">0.85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \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">Negative \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">0.95 \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">2.76 \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">4.51 \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">1.08 \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">0.94 \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">0.86 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">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="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Negative \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">1.85 \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">4.11<a class="elsevierStyleCrossRef" href="#tblfn0010">a</a> \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">— \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">0.88 \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">0.87 \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">— \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 \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">Negative \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">2.45 \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">3.67 \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">4.35 \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">0.86 \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">0.98 \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">0.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \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">Negative \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">1.69 \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">1.72 \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">4.45 \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">1.16 \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">1.04 \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">0.91 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2054418.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "a" "nota" => "Patients in whom treatment with levothyroxine was started." ] ] ] "descripcion" => array:1 [ "en" => "Variation of thyroid function over time in the women who developed hypothyroidism during follow-up." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Autoimmune thyroid disease during pregnancy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "S. De Leo" 1 => "E.N. Pearce" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S2213-8587(17)30402-3" "Revista" => array:3 [ "tituloSerie" => "Lancet Diabetes Endocrinol" "fecha" => "2017" "paginaInicial" => "12" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0115" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association between thyroid autoantibodies and miscarriage and preterm birth: meta-analysis of evidence" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "S. Thangaratinam" 1 => "A. Tan" 2 => "E. Knox" 3 => "M.D. Kilby" 4 => "J. Franklyn" 5 => "A. Coomarasamy" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/bmj.d2616" "Revista" => array:5 [ "tituloSerie" => "BMJ" "fecha" => "2011" "volumen" => "342" "paginaInicial" => "d2616" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21558126" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0120" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thyroid autoimmunity and miscarriage: a meta-analysis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "L. Chen" 1 => "R. Hu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/j.1365-2265.2010.03974.x" "Revista" => array:5 [ "tituloSerie" => "Clin Endocrinol (Oxf)" "fecha" => "2011" "volumen" => "74" "paginaInicial" => "513" "paginaFinal" => "519" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0125" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Thyroid antibodies and risk of preterm delivery: a meta-analysis of prospective cohort studies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "X. He" 1 => "P. Wang" 2 => "Z. Wang" 3 => "X. He" 4 => "D. Xu" 5 => "B. Wang" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1530/EJE-12-0379" "Revista" => array:7 [ "tituloSerie" => "Eur J Endocrinol" "fecha" => "2012" "volumen" => "167" "paginaInicial" => "455" "paginaFinal" => "464" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22826476" "web" => "Medline" ] ] "itemHostRev" => array:3 [ "pii" => "S0959804916325412" "estado" => "S300" "issn" => "09598049" ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0130" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "High prevalence of thyroid disorders in pregnant women in a mildly iodine-deficient country: a population-based study" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Moreno-Reyes" 1 => "D. Glinoer" 2 => "H. van Oyen" 3 => "S. Vandevijvere" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2013-2149" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2013" "volumen" => "98" "paginaInicial" => "3694" "paginaFinal" => "3701" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23846819" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0135" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Association of first-trimester thyroid function test values with thyroperoxidase antibody status, smoking, and multivitamin use" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "E.N. Pearce" 1 => "E. Oken" 2 => "M.W. Gillman" 3 => "S.L. Lee" 4 => "B. Magnani" 5 => "D. 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Optimization of the follow-up of pregnant women with autoimmune thyroid disease

Optimización del seguimiento de gestantes con enfermedad tiroidea autoinmune

M. Dolores Olleroa,b,

Corresponding author

lolaollero@hotmail.com

Corresponding author.

, Javier Pinedaa,b, Juan Pablo Martínez de Estebanc, Marta Tonib,c, Mercedes Espadad, Emma Andaa,b

a Servicio de Endocrinología y Nutrición, Complejo Hospitalario de Navarra, Pamplona, Navarra, Spain

b Instituto de Investigación Sanitaria de Navarra (IdisNa), Pamplona, Navarra, Spain

c Sección de Endocrinología, Hospital García Orcoyen, Estella, Navarra, Spain

d Unidad de Química Clínica, Laboratorio de Salud Pública del Gobierno Vasco, Derio, Vizcaya, Spain

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and anti-thyroglobulin antibodies &#40;anti-Tg&#41; in pregnant women has been related to different factors such as a family history of autoimmune thyroid disease&#44; age&#44; parity and iodine deficiency or excess&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">7&#8211;9</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Anti-thyroid antibody titers are higher in the first trimester and then decrease considerably during pregnancy&#44; with eventual negative conversion in some cases&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a> Despite this&#44; it is considered that women with positive thyroid autoimmunity are at an increased risk of developing hypothyroidism during pregnancy&#59; monitoring of thyroid function is therefore advised mainly during the first half of pregnancy&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;12</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The purpose of this study was to determine the percentage of pregnant women with positive thyroid autoimmunity and TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in the first trimester who develop hypothyroidism during pregnancy&#44; and to compare them with a control group of pregnant women with negative autoimmunity&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study population</span><p id="par0020" class="elsevierStylePara elsevierViewall">A prospective study was made of 400 women in the first trimester of pregnancy with no history of thyroid disease and no drug treatment capable of affecting thyroid function &#40;amiodarone&#44; lithium&#44; levothyroxine&#44; antithyroid drugs&#41;&#46; The participants were recruited from two women&#39;s health care centers on the occasion of their first prenatal visit&#44; and were assessed in person at the Department of Endocrinology of Complejo Hospitalario de Navarra &#40;Pamplona&#44; Spain&#41; between May 2014 and May 2016&#46; At this visit&#44; a case history was compiled&#44; with physical examination&#44; thyroid ultrasound and the collection of a simple urine sample for measuring ioduria&#46; Determinations were made of TSH&#44; free thyroxine &#40;FT4&#41;&#44; and anti-TPO and anti-Tg antibodies&#44; coinciding with the routine laboratory tests made during pregnancy &#40;gestational weeks 9&#44; 15&#44; 25 and 36&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">For the present study&#44; we excluded women with multiple pregnancy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>14&#41;&#44; thyroid nodules &#62;1<span class="elsevierStyleHsp" style=""></span>cm in size &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>24&#41; and&#47;or those with TSH in the first trimester &#8805;2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>62&#41;&#46; The final study population thus comprised 300 pregnant women&#46; The appearance of hypothyroidism was defined as a TSH elevation above 4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l at any time during pregnancy&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Miscarriages and preterm deliveries &#40;before gestational week 37&#41; occurring during the study were recorded&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">The study was approved by the Clinical Research Ethics Committee of Navarre&#44; and all included pregnant women signed the corresponding informed consent form&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Laboratory tests and ultrasound study</span><p id="par0040" class="elsevierStylePara elsevierViewall">Blood samples for the determination of TSH&#44; FT4&#44; and anti-TPO and anti-Tg antibodies were analyzed by the core laboratory of Complejo Hospitalario de Navarra using chemiluminescence &#40;Abbott method&#41;&#46; All the samples were collected in the morning&#46; Anti-TPO and anti-Tg positivity was considered in the presence of values above the upper limit of normal&#46; The titers &#40;numerical values&#41; of both antibodies were also recorded&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The determination of ioduria was carried out in the Public Health Standard Laboratory of the Basque Government in Derio &#40;Vizcaya&#41; using ion-pair reversed-phase liquid chromatography with electrochemical detection and a silver electrode &#40;Waters Chromatography&#44; Milford&#44; MA&#44; USA&#41;&#46; Detailed information on the procedure and validation of the method and its within- and between-serial precision has been published elsewhere&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">13</span></a> The urine samples were stored in the Biobank&#44; frozen at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C&#44; and duly identified&#44; 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while quantitative variables were expressed as measures of central tendency &#40;mean&#44; median&#41; and dispersion &#40;standard deviation &#91;SD&#93; and interquartile range &#91;IQR&#93;&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Normal distribution of the variables was assessed using the Kolmogorov&#8211;Smirnov test&#46; The TSH and FT4 levels according to positive thyroid autoimmune testing were compared using the parametric Student <span class="elsevierStyleItalic">t</span>-test or nonparametric Mann&#8211;Whitney test&#44; as applicable&#46; Associations between categorical variables were assessed using the <span class="elsevierStyleItalic">&#967;</span><span class="elsevierStyleSup">2</span> test&#46; The SPSS version 20 statistical package was used throughout&#46; Statistical significance was considered for <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Baseline population characteristics</span><p id="par0065" class="elsevierStylePara elsevierViewall">The study comprised 300 pregnant women in the first trimester of pregnancy &#40;95&#37; 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had positive anti-TPO antibodies&#44; 47&#46;2&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; had positive anti-Tg antibodies&#44; and 37&#46;7&#37; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>20&#41; proved positive for both antibodies&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">There were no baseline differences between women with positive thyroid autoimmunity and those with negative autoimmunity &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">Pregnant women with positive anti-TPO antibodies &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41; and those with positive anti-Tg antibodies only &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>25&#41; were analyzed separately&#44; and both groups were compared with the autoimmune-negative control population &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>247&#41;&#46; A family history of thyroid disease was more frequent in women with positive anti-TPO antibodies than in the control population &#40;35&#46;7&#37; vs&#46; 17&#46;8&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;024&#41;&#44; with no differences between the two groups in terms of age&#44; parity or baseline TSH levels &#40;TSH 1&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7 vs&#46; 1&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;328&#41;&#46; No significant differences were found in any of the above variables between the pregnant women with positive anti-Tg antibodies alone and the control group&#46; The baseline TSH concentration was 1&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7<span class="elsevierStyleHsp" style=""></span>mIU&#47;l and 1&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;123&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Variation of thyroid antibodies over time</span><p id="par0085" class="elsevierStylePara elsevierViewall">The laboratory tests were performed in the following gestational weeks &#40;median &#91;P25&#8211;P75&#93;&#41;&#58; week 9 &#40;8&#8211;9&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>300&#41;&#44; week 15 &#40;14&#8211;15&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>266&#41;&#44; week 25 &#40;25&#8211;26&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>98&#41; and week 36 &#40;36&#8211;37&#41; &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>248&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The anti-TPO and anti-Tg antibody titers decreased significantly during pregnancy &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; Between the first and last laboratory tests &#40;gestational weeks 9 and 36&#44; respectively&#41;&#44; the anti-TPO antibodies decreased by 76&#46;8&#37;&#44; with negative conversion in 6 women &#40;21&#46;4&#37;&#41;&#44; while the anti-Tg antibodies decreased by 80&#46;7&#37;&#44; with negative conversion in 18 women &#40;40&#37;&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Variation of thyroid function over time and the appearance of hypothyroidism</span><p id="par0095" class="elsevierStylePara elsevierViewall">The TSH and FT4 levels during pregnancy were similar in women with autoimmune thyroid disease and those with negative autoimmunity &#40;<a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a>&#41;&#46; There were no significant differences in TSH and FT4 levels between the two groups in any of the gestational weeks in which laboratory tests were performed&#46;</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">During follow-up&#44; TSH increased to above 4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in one of the 53 pregnant women in the autoimmune-positive group &#40;1&#46;9&#37;&#41;&#44; and in 5 of the 247 women with negative autoimmunity &#40;2&#37;&#41;&#46; Hypothyroidism was detected in week 15 in two of these women and in week 36 in the other four women&#46; In no case did TSH increase to above 5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; The pregnant women who developed hypothyroidism &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41; had higher TSH levels at the start of pregnancy than the women who maintained TSH<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l during pregnancy &#40;TSH 1&#46;8 vs&#46; 1&#46;3<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41;&#44; with no other significant differences&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">Twelve miscarriages were recorded during follow-up&#58; one in the group of pregnant women with positive autoimmunity and 11 in the control group &#40;1&#46;9&#37; vs&#46; 4&#46;5&#37;&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;387&#41;&#46; The incidence of preterm delivery was 7&#46;5&#37; and 5&#46;2&#37;&#44; respectively &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;547&#41;&#46; Likewise&#44; no significant differences were found in the miscarriage or preterm delivery rates on separately comparing the women with positive anti-TPO antibodies and those with only positive anti-Tg antibodies versus the pregnant women with negative autoimmunity&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0110" class="elsevierStylePara elsevierViewall">The results of our study show that pregnant women with positive thyroid autoimmunity and TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l at the start of pregnancy have a minimal risk of developing hypothyroidism&#44; similar to that seen in women with negative autoimmunity&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The prevalence of positive thyroid autoimmunity in pregnant women reported in the literature is highly variable&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">1&#44;11</span></a> This variability is probably due to the different analytical methods used&#44; the cut-off points employed&#44; and the characteristics of the study population &#40;ethnicity&#44; iodine status&#44; etc&#46;&#41;&#46; In our study&#44; 17&#46;7&#37; of the pregnant women had positive thyroid antibodies in the first trimester&#46; Of note is the observation that almost half of them were positive only for anti-Tg antibodies&#46; Although the presence of thyroid antibodies has been associated in some studies with age and parity&#44;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">7</span></a> we found no relationship between the presence of autoimmunity and these variables&#46; Similarly to as was reported in previous studies&#44;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">10&#44;14&#44;15</span></a> the anti-TPO and anti-Tg antibody titers decreased by about 80&#37; during pregnancy&#44; with negative conversion in 21&#37; and 40&#37; of the women&#44; respectively&#46; Therefore&#44; in those cases where it is considered clinically appropriate&#44; thyroid autoimmunity should be tested as early as possible in pregnancy&#44; since the diagnostic usefulness of thyroid antibody testing in the second half of pregnancy is limited&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">With regard to the main adverse events associated with thyroid autoimmunity &#40;miscarriage and preterm delivery&#41;&#44; we found no significant differences between the antibody-positive women and the control group&#46; In this regard&#44; it should be emphasized that the personal visit took place in gestational week 10 &#40;range 6&#8211;18&#41;&#44; and so in some cases miscarriage would have already occurred&#46; The fact that the women included in our study presented baseline TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;and did not develop hypothyroidism during pregnancy&#41; probably reflects the existence of mild or early forms of autoimmune thyroid disease&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Women with autoimmune thyroid disease are considered to be at an increased risk of developing hypothyroidism in pregnancy due to the inability of the thyroid gland to respond to the increased hormone production associated with pregnancy&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">16</span></a> Two previous studies in euthyroid pregnant women with positive autoimmunity recorded progression to hypothyroidism in close to 20&#37; of the cases&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">15&#44;17</span></a> The risk of hypothyroidism was higher in pregnant women with baseline TSH levels &#62;2<span class="elsevierStyleHsp" style=""></span>mIU&#47;l and in those with high anti-TPO antibody titers&#46; Based on the results of these studies&#44; the clinical guides recommend periodic monitoring of thyroid function during pregnancy in women with autoimmune thyroid disease&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">11&#44;18&#44;19</span></a> However&#44; the occurrence of hypothyroidism in our study was very low&#46; In addition&#44; hypothyroidism was detected at the end of pregnancy in most cases&#44; and the TSH levels were &#60;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in all patients&#46; The main differences between our study and the previous publications concern the baseline TSH cut-off point of the women on the one hand&#44; and the prevalence of positivity of the different antithyroid antibodies on the other&#46; With regard to the first point&#44; the above-mentioned studies included women with basal TSH levels of up to 4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#44; while in our study pregnant women with TSH levels ranging from 2&#46;5 to 4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l were not included&#44; because most of them started treatment with levothyroxine&#46; With regard to antithyroid antibodies&#44; the pregnant women in the studies published by Glinoer et al&#46; and Negro et al&#46; were predominantly positive for anti-TPO antibodies &#40;84&#37; and 100&#37; of the women&#44; respectively&#41;&#44; while anti-Tg positivity predominated in our population&#46; In addition&#44; unlike the previous studies&#44; our population was iodine-sufficient&#44; and such improved iodination may have influenced a lesser frequency of progression to hypothyroidism&#46; Two later studies also found a high frequency of hypothyroidism in women with autoimmune thyroid disease&#44; this largely being explained by the definition of hypothyroidism used in both studies &#40;i&#46;e&#46;&#44; TSH<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in the first trimester or &#8805;3<span class="elsevierStyleHsp" style=""></span>mIU&#47;l thereafter&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">20&#44;21</span></a> Our findings are similar to those of a recent study in 140 Australian pregnant women with basal TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#44; in which none of the patients developed gestational hypothyroidism&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">10</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0130" class="elsevierStylePara elsevierViewall">In our population&#44; the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in the first trimester was minimal&#44; and similar to that seen in women with negative autoimmunity&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The results obtained suggest the convenience of optimizing the follow-up of euthyroid women with autoimmune thyroid disease during pregnancy&#44; based on the TSH levels in the first trimester&#46; In this way&#44; women at greater risk of developing hypothyroidism could be identified&#44; and those at very low risk would not have to undergo needless monitoring&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Pregnant women with TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l would not need further studies&#44; because even if they had positive autoimmunity &#40;known before pregnancy&#41;&#44; the risk of developing hypothyroidism during pregnancy would be minimal&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In women with TSH levels ranging from 2&#46;5 to 4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#44; the measurement of thyroid antibodies is recommended&#46; If autoimmunity proves positive&#44; treatment with levothyroxine may be considered &#40;especially in the case of a history of adverse events in previous pregnancies&#44; or assisted reproduction treatments&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">11</span></a> With regard to the risk of hypothyroidism in this group&#44; our results do not allow for the drawing of conclusions &#40;it was at the time of the study that the pregnant women with TSH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l started treatment with levothyroxine&#41;&#46; However&#44; based on data from previous studies&#44; these women would appear to be more at risk of developing hypothyroidism during pregnancy&#44; and thyroid function monitoring is therefore advisable if such treatment is not started&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">To sum up&#44; women with autoimmune thyroid disease and TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in the first trimester of pregnancy have a minimal risk of gestational hypothyroidism&#59; the monitoring of thyroid function therefore should not be required during pregnancy in these cases&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authorship&#47;collaborators</span><p id="par0155" class="elsevierStylePara elsevierViewall">M&#46; Dolores Ollero&#44; Javier Pineda&#44; Juan Pablo Mart&#237;nez de Esteban&#44; Marta Toni and Emma Anda made substantial contributions to the conception and design of the study&#44; and to data acquisition&#44; analysis and interpretation&#46; They also contributed to a critical review of the manuscript and to the final approval of the submitted version&#46; Mercedes Espada contributed to the data analysis&#44; as well as to the critical review and to the final approval of the submitted version of the manuscript&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Funding</span><p id="par0160" class="elsevierStylePara elsevierViewall">This study was funded in part by the <span class="elsevierStyleGrantSponsor" id="gs1">Endocrinology&#44; Nutrition and Diabetes Foundation of Navarre</span> &#40;Fundaci&#243;n de Endocrinolog&#237;a&#44; Nutrici&#243;n y Diabetes de Navarra&#41;&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0165" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
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              "titulo" => "Variation of thyroid antibodies over time"
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              "titulo" => "Variation of thyroid function over time and the appearance of hypothyroidism"
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            3 => "Thyrotropin"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To determine the risk of hypothyroidism in pregnant women with autoimmune thyroid disease and thyrotropin &#40;TSH&#41;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l at the beginning of pregnancy&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Prospective longitudinal study of pregnant women with no personal history of thyroid disease&#44; and with TSH<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l in the first trimester&#46; TSH&#44; free thyroxine &#40;FT4&#41;&#44; anti peroxidase &#40;TPO&#41; and anti thyroglobulin antibodies were measured in the 3 trimesters of pregnancy&#46; We compared thyroid function throughout pregnancy&#44; and the development of gestational hypothyroidism &#40;TSH<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#41; among pregnant women with positive thyroid autoimmunity and those with negative autoimmunity&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">We included 300 pregnant women with mean baseline TSH 1&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;9th gestational week&#41;&#46; Positive thyroid autoimmunity was detected in 17&#46;7&#37; of women &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>53&#41; at the first trimester&#46; Between the first and the third trimesters&#44; TPO and anti thyroglobulin antibodies titers decreased 76&#46;8&#37; and 80&#46;7&#37; respectively&#46; Thyroid function during pregnancy was similar among the group with positive autoimmunity and the group with negative autoimmunity&#44; and the development of hypothyroidism was 1&#46;9&#37; &#40;1&#47;53&#41; and 2&#37; &#40;5&#47;247&#41; respectively&#46; Pregnant women in whom TSH increased above 4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>6&#41;&#44; had higher baseline TSH levels compared to those who maintained TSH<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>4<span class="elsevierStyleHsp" style=""></span>mIU&#47;l during pregnancy &#40;1&#46;8 vs&#46; 1&#46;3<span class="elsevierStyleHsp" style=""></span>mIU&#47;l&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;047&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">In our population&#44; women with TSH levels &#60;2&#46;5<span class="elsevierStyleHsp" style=""></span>mIU&#47;l at the beginning of pregnancy have a minimal risk of developing gestational hypothyroidism regardless of thyroid autoimmunity&#46;</p></span>"
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            "titulo" => "Objective"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Methods"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Determinar el riesgo de hipotiroidismo en gestantes con enfermedad tiroidea autoinmune y tirotropina &#40;TSH&#41; &#60; 2&#44;5 mUI&#47;l al inicio del embarazo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo longitudinal en gestantes de primer trimestre sin antecedentes de patolog&#237;a tiroidea y con TSH en primer trimestre &#60; 2&#44;5 mUI&#47;l&#46; Se determinaron TSH&#44; tiroxina libre &#40;T4l&#41; y anticuerpos antiperoxidasa &#40;TPO&#41; y antitiroglobulina en los 3 trimestres&#46; Se compar&#243; la evoluci&#243;n de la funci&#243;n tiroidea y la aparici&#243;n de hipotiroidismo gestacional &#40;TSH &#62; 4 mUI&#47;l&#41;&#44; entre las gestantes con autoinmunidad positiva y autoinmunidad negativa&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 300 gestantes con TSH basal 1&#44;3&#177;0&#44;6 mUI&#47;l &#40;semana gestacional 9&#41;&#46; El 17&#44;7&#37; &#40;n &#61; 53&#41; ten&#237;an autoinmunidad positiva en el primer trimestre&#46; Los t&#237;tulos de anticuerpos TPO y antitiroglobulina disminuyeron entre el primer y el tercer trimestre un 76&#44;8&#37; y un 80&#44;7&#37; respectivamente&#46; La evoluci&#243;n de la funci&#243;n tiroidea fue similar en el grupo con autoinmunidad positiva y el grupo con autoinmunidad negativa&#44; y la aparici&#243;n de hipotiroidismo fue del 1&#44;9&#37; &#40;1&#47;53&#41; y del 2&#37; &#40;5&#47;247&#41; respectivamente&#46; Las gestantes en las que la TSH aument&#243; por encima de 4 mUI&#47;l &#40;n &#61; 6&#41; ten&#237;an cifras superiores de TSH basal en comparaci&#243;n con las que mantuvieron TSH&#8804;4 mUI&#47;l a lo largo del embarazo &#40;1&#44;8 vs&#46; 1&#44;3 mUI&#47;l&#59; p &#61; 0&#44;047&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">En nuestra poblaci&#243;n&#44; las mujeres con TSH &#60; 2&#44;5 mUI&#47;l al inicio del embarazo tienen un riesgo m&#237;nimo de desarrollar hipotiroidismo durante la gestaci&#243;n&#44; independientemente de la autoinmunidad tiroidea&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
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            "identificador" => "abst0035"
            "titulo" => "Resultados"
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          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusi&#243;n"
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      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Ollero MD&#44; Pineda J&#44; Mart&#237;nez de Esteban JP&#44; Toni M&#44; Espada M&#44; Anda E&#46; Optimizaci&#243;n del seguimiento de gestantes con enfermedad tiroidea autoinmune&#46; Endocrinol Diabetes Nutr&#46; 2019&#59;66&#58;305&#8211;311&#46;</p>"
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        "etiqueta" => "Figure 1"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Anti-TPO &#40;A&#41; and anti-thyroglobulin &#40;B&#41; antibody titers during pregnancy in women with positive autoimmunity&#46; Anti-Tg antibodies&#58; anti-thyroglobulin antibodies&#59; anti-TPO antibodies&#58; anti-thyroperoxidase antibodies&#46; &#42;<span class="elsevierStyleItalic">p</span>-value &#60;0&#46;05 in relation to gestational week 9&#46;</p>"
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      1 => array:7 [
        "identificador" => "fig0010"
        "etiqueta" => "Figure 2"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
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        "descripcion" => array:1 [
          "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Variation of TSH &#40;A&#41; and FT4 &#40;B&#41; levels during pregnancy in pregnant women with positive autoimmunity and negative autoimmunity&#46; TSH&#58; thyroid stimulating hormone&#59; FT4&#58; free thyroxine&#46;</p>"
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      2 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
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        "detalles" => array:1 [
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Values are reported as mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#44; except for ioduria&#44; which is expressed as median &#40;P25&#8211;P75&#41;&#46; TSH &#40;mIU&#47;l&#41; and FT4 &#40;ng&#47;dl&#41; correspond to gestational week 9&#44; and thyroid volume and ioduria to gestational week 10&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Family hist&#46;&#58; family history&#59; thyroid vol&#46;&#58; thyroid volume&#46;</p>"
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                  \t\t\t\t">23&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">23&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;4&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;739&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Family hist&#46; &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">No&#46; of previous offspring&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Thyroid vol&#46; &#40;ml&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">8&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&nbsp;\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
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                  \t\t\t\t">8&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3&nbsp;\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">7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;300&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Ioduria &#40;&#956;g&#47;l&#41;&nbsp;\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
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                  \t\t\t\t">242 &#40;148&#46;5&#8211;413&#46;0&#41;&nbsp;\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
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                  \t\t\t\t">294 &#40;169&#46;8&#8211;430&#46;8&#41;&nbsp;\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">234 &#40;140&#46;5&#8211;409&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;114&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">TSH &#40;mIU&#47;l&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">1&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;99&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;04<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;11&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">1&#46;05<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;780&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td-with-role" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Pat&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col">Autoimmunity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">TSH &#40;mIU&#47;l&#41;</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " colspan="3" align="center" valign="\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Wk 9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Wk 15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th 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" scope="col" style="border-bottom: 2px solid black">Wk 36&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \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
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                  \t\t\t\t">Positive&nbsp;\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
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                  \t\t\t\t">2&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;07<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;87&nbsp;\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
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                  \t\t\t\t">1&#46;07&nbsp;\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">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\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">Negative&nbsp;\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
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                  \t\t\t\t">1&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#46;87&nbsp;\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">4&#46;61&nbsp;\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&#46;15&nbsp;\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&#46;14&nbsp;\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&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\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">Negative&nbsp;\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&#46;95&nbsp;\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&#46;76&nbsp;\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">4&#46;51&nbsp;\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&#46;08&nbsp;\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&#46;94&nbsp;\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&#46;86&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\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">Negative&nbsp;\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&#46;85&nbsp;\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">4&#46;11<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">a</span></a>&nbsp;\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">&#8212;&nbsp;\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&#46;88&nbsp;\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&#46;87&nbsp;\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">&#8212;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\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">Negative&nbsp;\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&#46;45&nbsp;\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">3&#46;67&nbsp;\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">4&#46;35&nbsp;\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&#46;86&nbsp;\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&#46;98&nbsp;\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&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\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">Negative&nbsp;\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&#46;69&nbsp;\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&#46;72&nbsp;\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
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Article information

ISSN: 25300180
Original language: English

DOI:10.1016/j.endien.2018.08.010

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Year/Month	Html	Pdf	Total

2024 November	4	2	6
2024 October	14	6	20
2024 September	11	7	18
2024 August	12	7	19
2024 July	13	10	23
2024 June	7	9	16
2024 May	11	7	18
2024 April	18	6	24
2024 March	33	6	39
2024 February	32	5	37
2024 January	19	9	28
2023 December	15	3	18
2023 November	12	3	15
2023 October	12	8	20
2023 September	10	1	11
2023 August	12	1	13
2023 July	7	3	10
2023 June	18	6	24
2023 May	49	2	51
2023 April	40	3	43
2023 March	24	4	28
2023 February	28	9	37
2023 January	12	14	26
2022 December	23	9	32
2022 November	21	9	30
2022 October	17	7	24
2022 September	20	11	31
2022 August	23	9	32
2022 July	21	6	27
2022 June	28	7	35
2022 May	36	6	42
2022 April	38	6	44
2022 March	77	8	85
2022 February	79	5	84
2022 January	69	9	78
2021 December	60	7	67
2021 November	45	8	53
2021 October	15	9	24
2021 September	37	8	45
2021 August	37	8	45
2021 July	25	11	36
2021 June	27	11	38
2021 May	42	8	50
2021 April	46	20	66
2021 March	18	12	30
2021 February	14	8	22
2021 January	15	4	19
2020 December	11	9	20
2020 November	19	11	30
2020 October	6	5	11
2020 September	10	6	16
2020 August	14	7	21
2020 July	20	10	30
2020 June	12	4	16
2020 May	18	5	23
2020 April	17	4	21
2020 March	24	2	26
2020 February	19	0	19
2020 January	7	3	10
2019 December	9	7	16
2019 November	4	7	11

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