EGFR targeting PhosTACs as a dual inhibitory approach reveals differential downstream signaling.

We recently developed a heterobifunctional approach [phosphorylation targeting chimeras (PhosTACs)] to achieve the targeted protein dephosphorylation (TPDephos). Here, we envisioned combining the inhibitory effects of receptor tyrosine kinase inhibitors (RTKIs) and the active dephosphorylation by phosphatases to achieve dual inhibition of kinases. We report an example of tyrosine phosphatase-based TPDephos and the effective epidermal growth factor receptor (EGFR) tyrosine dephosphorylation. We also used phosphoproteomic approaches to study the signaling transductions affected by PhosTAC-related molecules at the proteome-wide level. This work demonstrated the differential signaling pathways inhibited by PhosTAC compared with the TKI, gefitinib. Moreover, a covalent PhosTAC selective for mutated EGFR was developed and showed its inhibitory potential for dysregulated EGFR. Last, EGFR PhosTACs, consistent with EGFR dephosphorylation profiles, induced apoptosis and inhibited cancer cell viability during prolonged PhosTAC treatment. PhosTACs showcased their potential of modulating RTKs activity, expanding the scope of bifunctional molecule utility.

First alongside midwifery led unit in a high complexity public hospital in Spain: Maternal and neonatal outcomes.

PROBLEM: Midwifery led units are rare in Spain. BACKGROUND: Midwife-Led Care (MLC) is a widely extended model of care and, within this, the alongside midwifery-led units (AMLU) are those hospital-based and located in close connection with obstetric units. In Spain, CL is the first center belonging to the National Health System of these characteristics. AIM: To evaluate the first year of activity of this pioneering unit. METHODS: An observational cross-sectional study was carried out to assess maternal and neonatal outcomes of births facilitated at CL by comparing with those births that fulfilled the criteria to be admitted at the AMLU but were assisted at the standard obstetric care unit of the hospital. FINDINGS: 174 (20,3%) women and birthing people decided to give birth at CL, whereas 684 (79,7%) gave birth at the Obstetric Unit of the Hospital. Women assisted at the AMLU had lower intervention rates (episiotomy, epidural analgesia) and a higher rate of breastfeeding practice. There were no statistical differences in maternal outcomes (postpartum hemorrhage, third-or-four-degree laceration) or neonatal outcomes (Apgar< 7 at 5 min; birth weight < 2500 gr; macrosomia; shoulder dystocia, neonatal care transfer). DISCUSSION: There were differences in transfers from MLU to OU between nulliparous and multiparous; the main reason for transfer is the request for analgesia. Epidural analgesia should be considered when analyzing maternal outcomes. CONCLUSION: An alongside midwifery-led unit is a safe option with a low incidence of complications. This model of care can be positively implemented at the Public Healthcare System.

Longitudinal trajectories of maternal TSH in healthy pregnant women in Catalonia.

Objective: Longitudinal evaluation of thyroid function throughout pregnancy in the same subject could offer precise information about its dynamics as a physiological mechanism of adaption to the requirements. In this study, we evaluated longitudinal trajectories of maternal thyroid function during pregnancy by a latent class growth analysis and explored their association with maternal-fetal outcomes. Methods: A prospective observational study was carried out, including 414 healthy pregnant women, from the first trimester to delivery. Thyroid function and autoimmunity were measured in the three trimesters. Clinical data during pregnancy were obtained. Longitudinal mixed model techniques were performed to explore trajectories of gestational thyroid function. Results: Three different longitudinal trajectories were obtained from maternal thyrotropin (TSH) levels: low-increasing TSH (class 1) in 86% of cases, high-increasing TSH (class 2) in 9.7%, and decreasing TSH (class 3) in 4.3%. No statistical differences in free thyroxine levels were found among the three classes. Differences in maternal age (P = 0.027) and initial maternal weight (P = 0.043) were observed among the groups. In logistic regression analysis, maternal age correlated with longitudinal trajectories. The three longitudinal classes remain when women with thyroid autoimmunity (TAI) are excluded. Multinomial logistic regression showed maternal age correlated with longitudinal trajectories independently of TAI status. Conclusions: Three differentiated TSH trajectories were found in healthy pregnant women living in Catalonia, as previously described. No association with obstetric outcomes was observed in these different chronological thyroid pathways, but maternal age might condition the longitudinal mechanism of thyroid function regulation throughout pregnancy.

Universal screening programme for cytomegalovirus infection in the first trimester of pregnancy: study protocol for an observational multicentre study in the area of Barcelona (CITEMB study).

INTRODUCTION: Congenital cytomegalovirus (cCMV) is the leading cause of non-genetic sensorineural hearing loss and one of the main causes of neurological disability. Despite this, no universal screening programme for cCMV has been implemented in Spain. A recent study has shown that early treatment with valaciclovir, initiated in the first trimester and before the onset of signs in the fetus, reduces the risk of fetal infection. This finding favours the implementation of a universal screening programme for cCMV.The aim of this study is to evaluate the performance of a universal screening programme for cCMV during the first trimester of pregnancy in a primary care setting. METHODS AND ANALYSIS: This is an observational multicentre cohort study. The study will be conducted in four primary care settings from the Northern Metropolitan Barcelona area and three related hospitals and will last 3 years and will consist of a recruitment period of 18 months.In their first pregnancy visit, pregnant women will be offered to add a CMV serology test to the first trimester screening tests. Pregnant women with primary infection will be referred to the reference hospital, where they will continue treatment and follow-up according to the clinical protocol of the referral hospital, which includes treatment with valacyclovir. A CMV-PCR will be performed at birth on newborns of mothers with primary infection, and those who are infected will undergo neonatal follow-up for at least 12 months of life.For the analysis, the acceptance rate, the prevalence of primary CMV infections and the CMV seroprevalence in the first trimester of pregnancy will be studied. ETHICS AND DISSEMINATION: Ethical approval was obtained from the University Institute Foundation for Primary Health Care Research Jordi Gol i Gurina Ethics Committee 22/097-P dated 27 April 2022.

Executive summary of the SEEN (Sociedad Española de Endocrinología y Nutrición[Spanish Society of Endocrinology and Nutrition])-SEGO (Sociedad Española deGinecología y Obstetricia [Spanish Society of Gynaecology and Obstetrics]) consensusdocument on the management of thyroid dysfunction during pregnancy.

During pregnancy, thyroid function disorders are associated with multiple complications, both maternal and foetal. In recent years, numerous Clinical Practice Guidelines have been developed to facilitate the identification and correct management of thyroid disease in pregnant women. However, this proliferation of guidelines has led to confusion by proposing different cut-off points for reference values and different recommendations for similar situations. For this reason, the Sociedad Española de Endocrinología y Nutrición and the Sociedad Española de Ginecología y Obstetricia have prepared this Consensus Document, with the aim of creating a framework for joint action to unify criteria for the diagnosis and treatment of thyroid dysfunction in these patients. The document is structured to answer the most frequently asked questions in clinical practice, grouped into five sections: 1/Reference values for thyroid function tests and screening during pregnancy 2/Iodine nutrition 3/Hypothyroidism and pregnancy 4/Hyperthyroidism and pregnancy 5/ Thyroid autoimmunity.

Maternal mental health and breastfeeding amidst the Covid-19 pandemic: cross-sectional study in Catalonia (Spain).

BACKGROUND: Covid-19 pandemic became an unexpected stressor for the entire population and, particularly, for pregnant women and lactating mothers. The alarming infectious risk together with the lockdown period could affect the emotional state of mothers-to-be, as well as breastfeeding rates, mother-baby bonding, or neonatal weight gain. The aim of this study is to describe the impact of this world health emergency in mother-baby pairs right after the first wave of Sars-Cov-2 pandemic (from March to May 2020). STUDY DESIGN: A prospective observational study was carried out in mother-child dyads from those women who gave birth between June and August 2020 in a tertiary hospital. 91 mother-baby pairs were initially enrolled and 56 of them completed the follow-up. The study design had two separate steps: i) Step one: A clinical interview plus three psychometric tests (EPDS: Edinburgh Postnatal Depression Scale, PBQ: Postpartum Bonding Questionnaire and STAI-S: State-Trait Anxiety Inventory); ii) Step two: mother-child dyads were followed using a round of three brief telephone interviews (conducted at the newborn's 7, 14 and 28 days of age) to accurately depict the newborn's outcome in the neonatal period. RESULTS: In terms of maternal mental health, 25% of the sample screens positively in the EPDS, requiring further evaluation to rule out depressive symptoms. STAI-state and PBQ detect no abnormalities in either anxiety levels or mother-child bonding in our sample, as 100% of the mothers score below the cut-off points in each test (34 and 26 respectively). When comparing feeding practices (breast/bottle feeding) in 2020 to those practices during pre-pandemic years (2017-2019), a significant increase in breastfeeding was found in pandemic times. All newborns in the sample showed an adequate weight gain during their first month of life. CONCLUSION: Women and newborns in our sample did not experience an increase in adverse outcomes in the neonatal period in terms of maternal mental health, breastfeeding rates, bonding and further neonatal development.

Reference Intervals of Thyroid Function Tests Assessed by Immunoassay and Mass Spectrometry in Healthy Pregnant Women Living in Catalonia.

BACKGROUND: Recent guidelines recommend establishing a local reference interval (RI) for thyroid function. We aimed to establish trimester-specific RIs for thyrotropin (TSH) and free thyroxine (FT4) in a cohort of healthy pregnant women in Catalonia (Spain). METHODS: A prospective observational study was conducted with 332 healthy pregnant women, from the first trimester (1T) to delivery. TSH was measured using an Architect® immunoassay (Abbott) and FT4 by two immunoassays, Architect® (Abbott) and Cobas® (Roche), in the three trimesters. FT4 was also measured by liquid chromatography mass spectrometry (LC/MS/MS) in the 1T. RESULTS: TSH (µUI/mL) increased throughout pregnancy (1T: 0.03-3.78; 2T: 0.51-3.53; 3T: 0.50-4.32; p < 0.0001) and FT4 (pmol/L) progressively decreased (Architect® 1T: 10.42-15.96; 2T: 8.37-12.74; 3T: 8.24-12.49; p < 0.0001; and Cobas®: 1T: 11.46-19.05; 2T: 9.65-14.67; 3T: 8.88-14.54; p < 0.0067). The FT4 RI during 1T determined LC/MS/MS was 8.75-18.27. Despite the 1T FT4 results measured by LC/MS/MS and with the two immunoassays being significantly correlated, the results obtained by the three methods were found to be non-interchangeable. CONCLUSIONS: We established trimester-specific RIs for TSH and for FT4 with immunoassays in our population. We also validated the 1T FT4 using LC/MS/MS to confirm the results of FT4 lower than the 2.5th percentile or higher than the 97.5th percentile.

Indications for treatment of subclinical hypothyroidism and isolated hypothyroxinaemia in pregnancy.

Thyroid hormones are essential for maintaining a pregnancy and optimal fetal neurological development. Pregnancy places additional demands on the thyroid axis and around 5% of women who have their thyroid function checked during gestation will have borderline low thyroid function (subclinical hypothyroidism or isolated hypothyroxinemia) identified. These borderline low thyroid states are associated with adverse obstetric and offspring outcomes. Whilst it is well established that overt hypothyroidism requires treatment with levothyroxine, it is less clear whether there is any benefit of treating borderline low thyroid states. This review summarizes the potential indications for treatment of subclinical hypothyroidism and isolated hypothyroxinemia.

Iodine Status, Thyroid Function, and Birthweight: A Complex Relationship in High-Risk Pregnancies.

(1) Background: The consequences of iodine deficiency and/or thyroid dysfunction during pregnancy have been extensively studied, emphasizing on infant neurodevelopment. However, the available information about the relationship between iodine, thyroid hormones, and fetal growth in high-risk pregnancies is limited. We aim to investigate if iodine metabolism and/or thyroid parameters can be affected by adverse antenatal/perinatal conditions. (2) Methods: A cross-sectional study examined differences in iodine status, thyroid function, and birthweight between high-risk (HR group; n = 108)) and low-risk pregnancies (LR group; n = 233) at the time of birth. Urinary iodine concentration (UIC), iodine levels in amniotic fluid, and thyroid parameters [thyroid-stimulating hormone (TSH), free thyroxine (FT4)] were measured in mother-baby pairs. (3) Results: There were significant differences between HR and LR groups, free thyroxine (FT4) concentration in cord blood was significantly higher in the LR group compared with HR pregnancies (17.06 pmol/L vs. 15.30 pmol/L, respectively; p < 0.001), meanwhile iodine concentration in amniotic fluid was significantly lower (13.11 µg/L vs. 19.65 µg/L, respectively; p < 0.001). (4) Conclusions: Our findings support the hypothesis that an adverse intrauterine environment can compromise the availability of FT4 in cord blood as well as the iodine metabolism in the fetus. These differences are more noticeable in preterm and/or small fetuses.

La nutrición de yodo en España. Necesidades para el futuro / Iodine nutrition status in Spain Needs for the future

Aunque la nutrición de yodo en España ha mejorado en los últimos años, el problema no está resuelto del todo. Es preciso que las Instituciones sanitarias establezcan medidas para garantizar que la nutrición de yodo de toda la población sea la adecuada, especialmente entre los colectivos de mayor riesgo (niños y adolescentes, mujeres en edad fértil, mujeres embarazadas y madres lactantes). Debe aconsejarse un bajo consumo de sal, pero que esta sea yodada. También es imprescindible que las agencias de control alimentario establezcan un control efectivo sobre una adecuada yodación de la sal. En las futuras encuestas de salud debería incluirse indicadores sobre la nutrición de yodo. El estudio EUthyroid y la Declaración de Cracovia sobre la nutrición de yodo brindan una oportunidad para establecer un plan paneuropeo para la prevención de la deficiencia de yodo que debería ser considerada y aprovechada por las autoridades sanitarias

Although iodine nutrition in Spain has improved in recent years, the problem is not completely resolved. It is necessary that health institutions establish measures to ensure an adequate iodine nutrition of the population, especially among the highest risk groups (children and adolescents, women of childbearing age, pregnant women and nursing mothers). A low salt intake should be advised, but it should be iodized. It is also imperative that food control agencies establish effective control over adequate iodization of salt. Indicators on iodine nutrition should be included in future health surveys. The EUthyroid study and the Krakow Declaration on iodine nutrition provide an opportunity to set up a pan-European plan for the prevention of iodine deficiency that should be considered and used by health authorities

Iodine nutrition status in Spain Needs for the future. / La nutrición de yodo en España. Necesidades para el futuro.

Although iodine nutrition in Spain has improved in recent years, the problem is not completely resolved. It is necessary that health institutions establish measures to ensure an adequate iodine nutrition of the population, especially among the highest risk groups (children and adolescents, women of childbearing age, pregnant women and nursing mothers). A low salt intake should be advised, but it should be iodized. It is also imperative that food control agencies establish effective control over adequate iodization of salt. Indicators on iodine nutrition should be included in future health surveys. The EUthyroid study and the Krakow Declaration on iodine nutrition provide an opportunity to set up a pan-European plan for the prevention of iodine deficiency that should be considered and used by health authorities.

Iodine as Essential Nutrient during the First 1000 Days of Life.

Iodine is an essential micronutrient incorporated into thyroid hormones. Although iodine deficiency can lead to a broad spectrum of disorders throughout life, it is most critical in the early stages of development, as the foetal brain is extremely dependent on iodine supply. During the last two decades, our understanding of thyroid physiology during gestation has substantially improved. Furthermore, thyroid hormone receptors have been identified and characterised in placental and embryonic tissues, allowing us to elucidate the maternal-foetal transfer of thyroid hormones. Experimental studies have demonstrated that the cyto-architecture of the cerebral cortex can be irreversibly disturbed in iodine deficiency causing abnormal neuron migratory patterns which are associated with cognitive impairment in children. In this context, the role of iodine as key factor in the programming of foetal and infant neurodevelopment, needs to be revisited with a special focus on areas of mild to moderate iodine deficiency. The objective of this review is to summarize the available evidence from both animals and human studies, for the effect of iodine deficiency (particularly, of maternal hypothyroxinemia) on brain development and neurological or behavioural disorders, such as lower intelligence quotient (IQ) or attention deficit hyperactivity disorder (ADHD).

Hypothyroidism during pregnancy and its association to perinatal and obstetric morbidity: a review.

There is currently no consensus among the different scientific societies on screening for thyroid dysfunction in the first trimester of pregnancy. Indeed, diagnosis and treatment of subclinical hypothyroidism during pregnancy are controversial, as no cut-off value for thyrotropin (TSH) is universally accepted. TSH measurement may be influenced by different factors throughout pregnancy, but especially during the first trimester. The association between overt hypothyroidism during pregnancy and obstetric and perinatal complications is well established. It is also accepted that thyroid hormones are important for neurodevelopment of the offspring. However, there is no scientific evidence available about the impact of subclinical hypothyroidism and its treatment during the first trimester of pregnancy on children's neurodevelopment. In recent years, studies conducted in the offspring of mothers with subclinical hypothyroidism have reported new biochemical parameters which may eventually serve as biomarkers of offspring neurodevelopment and which are more reproducible and are measured at an earlier time than the conventional clinical tests.

Hypothyroidism during pregnancy and its association to perinatal and obstetric morbidity: a review / Hipotiroidismo durante la gestación y su asociación con la morbilidad perinatal y obstétrica: revisión

There is currently no consensus among the different scientific societies on screening for thyroid dysfunction in the first trimester of pregnancy. Indeed, diagnosis and treatment of subclinical hypothyroidism during pregnancy are controversial, as no cut-off value for thyrotropin (TSH) is universally accepted. TSH measurement may be influenced by different factors throughout pregnancy, but especially during the first trimester. The association between overt hypothyroidism during pregnancy and obstetric and perinatal complications is well established. It is also accepted that thyroid hormones are important for neurodevelopment of the offspring. However, there is no scientific evidence available about the impact of subclinical hypothyroidism and its treatment during the first trimester of pregnancy on children's neurodevelopment. In recent years, studies conducted in the offspring of mothers with subclinical hypothyroidism have reported new biochemical parameters which may eventually serve as biomarkers of offspring neurodevelopment and which are more reproducible and are measured at an earlier time than the conventional clinical tests (AU)

En la actualidad no existe un consenso entre las diferentes sociedades científicas para la detección de la disfunción tiroidea en el primer trimestre del embarazo. De hecho, el diagnóstico y tratamiento del hipotiroidismo subclínico durante el embarazo es controvertido, ya que no se acepta universalmente el valor límite para la tirotropina (TSH). La determinación de TSH puede estar influenciada por diferentes factores durante todo el embarazo, pero especialmente durante el primer trimestre. La asociación entre el hipotiroidismo clínico durante el embarazo y las complicaciones obstétricas y perinatales está bien establecida. También se acepta que las hormonas tiroideas son importantes para el desarrollo neurológico del feto. Sin embargo, falta evidencia científica sobre el impacto en el neurodesarrollo infantil del tratamiento del hipotiroidismo subclínico en el primer trimestre de gestación. En los últimos años, los estudios realizados en hijos de madres con hipotiroidismo subclínico han descrito nuevos parámetros bioquímicos que eventualmente pueden servir como biomarcadores del neurodesarrollo fetal, siendo más reproducibles y pudiendo determinarse en un período anterior al de las pruebas clínicas clásicas (AU)

The role of levothyroxine in obstetric practice.

Thyroid hormones play a pivotal role in somatic growth, metabolic regulation and neurodevelopment. There is growing evidence regarding adverse obstetric and perinatal consequences of maternal thyroid hypofunction during early stages of pregnancy. These include: early pregnancy loss, preterm delivery and lower intelligence quotient (IQ) in children. Different clinical guidelines have been published by scientific societies for the management of thyroid diseases during pregnancy and levothyroxine (LT4) has become a therapeutic agent increasingly prescribed by obstetricians. The aim of this work was to search for both similarities and controversial clinical aspects from the currently available literature. Guidelines published from 2011 onwards have been analysed and compared, in order to clarify the evidence about the involvement of thyroid dysfunction in pregnancy complications and the impact of LT4 use in their prevention and/or treatment. This review summarizes the most updated knowledge about the effectiveness of LT4 for pregnancy complications, the current recommendations and its application into clinical practice. KEY MESSAGES The use of levothyroxine in obstetric practices requires a correct diagnosis and to consider the specific recommendations for each thyroid dysfunction entity. The effectiveness and safety of levothyroxine treatment in preventing adverse perinatal events in pregnant women with clinical hypothyroidism is supported by all the current guidelines. Levothyroxine therapy is strongly recommended in all cases of overt hypothyroidism and in cases of subclinical hypothyroidism associated to positive thyroid autoimmunity.

Identifying and treating subclinical thyroid dysfunction in pregnancy: emerging controversies.

Thyroid hormones are essential for an adequate growth and development of the fetus. In addition to the classical association between maternal hypothyroidism and neurological impairment in the progeny, other adverse reproductive events have been associated with maternal thyroid dysfunction including infertility, miscarriage and preterm delivery. Although all scientific societies endorse the treatment of overt hypothyroidism; the management and/or treatment of subclinical hypothyroidism, hypothyroxinemia or antithyroid antibody-positive women should be considered with caution. Important trials have found no clear benefit of treatment of subclinical hypothyroidism in terms of cognitive outcomes; however, other interventional studies appear to reduce some of the obstetric and perinatal complications. As a result, the dilemma between universal screening or selective screening of women at high risk of thyroid dysfunction during pregnancy remains unresolved. Despite this, levothyroxine is also now regularly prescribed by gynaecologists and centres for reproductive medicine. In this context, there is increasing concern regarding the risk of over diagnosis and subsequent potential overtreatment. Taken together, we need to reconsider how thyroid dysfunction should be identified in pregnant women and highlight the arguments for and against the use of levothyroxine in obstetric practices. Our main findings: the mismatch between the guidelines recommendations and the use of LT4 in clinical settings as well as the disparity of criteria between scientific societies from different medical specialties. In conclusion, it is essential to reach agreements between both endocrinologists and obstetricians.

Intra-individual variability in TSH levels of healthy women during the first half of pregnancy / Variabilidad intra-individual de los niveles TSH en mujeres sanas en primer trimestre de gestación

Objective: TSH is the parameter most widely accepted to assess thyroid function, especially in pregnant women. The aim of this current study was to analyze intra-individual changes in TSH during the first half of pregnancy in women with TSH levels higher than 2.5mIU/L in early pregnancy. Methods: An observational, prospective study was conducted on 243 healthy pregnant women in the first trimester of pregnancy. Thyroid function was assessed by testing TSH and free T4 levels. A subgroup of women with TSH levels >2.5mIU/L underwent additional tests (TSH, free T4, peroxidase antibodies). Information on dietary iodine intake and/or iodine supplements was also recorded. Results: Mean TSH level was 1.89mIU/L (range 0.024-6.48mIU/L), and mean FT4 level was 1.19ng/dL (range 0.80-1.90ng/dL). Fifty-eight women (23.8%) had TSH levels>2.5mIU/L in the first trimester of pregnancy, and additional thyroid function tests were performed in 27 women. TSH levels significantly decreased from the first to the second test (3.59±0.92mIU/L vs 2.81±1.06mIU/L respectively; p<0.01), and the decrease was significantly greater in pregnant women who used iodized salt as compared to those who did not (1.16±0.65mIU/L vs 0.19±0.93mIUI/L respectively; p<0.01). A positive correlation was found between the time elapsed to the second measurement (24.3±17.2 days; range 8-58) and the decrease in TSH levels (r=0.40; p=0.038). Conclusion: TSH levels showed a continuous, uniform decrease during the first half of pregnancy in women with values slightly above the normal range. Pregnant women who used iodized salt were more likely to have decreased TSH levels in a second test (AU)

Objetivo: La TSH es el parámetro más aceptado para evaluar la función tiroidea, especialmente en mujeres embarazadas. El objetivo del presente estudio fue analizar los cambios intraindividuales de TSH durante la primera mitad de la gestación, en aquellos casos en los que la TSH en las primeras etapas de la gestación fue superior a 2,5 mUI/L. Métodos: Estudio observacional prospectivo que incluyó a 243 mujeres embarazadas sanas en el primer trimestre de gestación. Se estudió función tiroidea mediante TSH y T4 libre. Un subgrupo de mujeres con TSH> 2,5 mUI/L fueron sometidas a un segundo análisis (TSH, T4 libre, anticuerpos antiperoxidasa). También se registró información sobre la ingesta de yodo con la dieta y/o suplementos. Resultados: La TSH media fue de 1,89 mUI/L (rango 0,024-6,48 mUI/L), y la T4 libre media fue de 1,19 ng/dL (rango 0,80-1,90ng/dL). El 23,8% (58 mujeres) presentaron TSH> 2,5 mUI/L en el primer trimestre de gestación, realizándose una segunda valoración en 27 pacientes. La TSH disminuyó significativamente del primer al segundo análisis (3,59±0,92 mUI/L vs. 2,81±1,06 mUI/L respectivamente, p <0,01). La TSH disminuyó significativamente más en aquellas mujeres embarazadas que consumieron sal yodada que en aquellas que no lo hicieron (1,16±0,65 mUI/L vs. 0,19±0,93 mUI/L respectivamente, p<0,01). Hubo una correlación positiva entre el tiempo transcurrido para una segunda determinación (24,3±17,2 días, rango 8-58 días), y la reducción en los niveles de TSH (r= 0,40; p=0,038). Conclusión: La disminución de los niveles de TSH con la edad gestacional es uniformemente continua a lo largo de la primera mitad de la gestación en aquellos casos con TSH ligeramente por encima del rango sugerido de normalidad. Las mujeres embarazadas que consumían sal yodada tenían más probabilidades de reducir los niveles de TSH en un segundo análisis (AU)

Intra-individual variability in TSH levels of healthy women during the first half of pregnancy.

OBJECTIVE: TSH is the parameter most widely accepted to assess thyroid function, especially in pregnant women. The aim of this current study was to analyze intra-individual changes in TSH during the first half of pregnancy in women with TSH levels higher than 2.5mIU/L in early pregnancy. METHODS: An observational, prospective study was conducted on 243 healthy pregnant women in the first trimester of pregnancy. Thyroid function was assessed by testing TSH and free T4 levels. A subgroup of women with TSH levels >2.5mIU/L underwent additional tests (TSH, free T4, peroxidase antibodies). Information on dietary iodine intake and/or iodine supplements was also recorded. RESULTS: Mean TSH level was 1.89mIU/L (range 0.024-6.48mIU/L), and mean FT4 level was 1.19ng/dL (range 0.80-1.90ng/dL). Fifty-eight women (23.8%) had TSH levels>2.5mIU/L in the first trimester of pregnancy, and additional thyroid function tests were performed in 27 women. TSH levels significantly decreased from the first to the second test (3.59±0.92mIU/L vs 2.81±1.06mIU/L respectively; p<0.01), and the decrease was significantly greater in pregnant women who used iodized salt as compared to those who did not (1.16±0.65mIU/L vs 0.19±0.93mIUI/L respectively; p<0.01). A positive correlation was found between the time elapsed to the second measurement (24.3±17.2 days; range 8-58) and the decrease in TSH levels (r=0.40; p=0.038). CONCLUSION: TSH levels showed a continuous, uniform decrease during the first half of pregnancy in women with values slightly above the normal range. Pregnant women who used iodized salt were more likely to have decreased TSH levels in a second test.

Selenium, selenoproteins and selenometabolites in mothers and babies at the time of birth.

The deficiency of Se, an essential micronutrient, has been implicated in adverse pregnancy outcomes. Our study was designed to determine total serum Se, selenoproteins (extracellular glutathione peroxidase (GPx-3), selenoprotein P (SeP)), selenoalbumin (SeAlb) and selenometabolites in healthy women and their newborns at delivery. This cross-sectional study included eighty-three healthy mother-baby couples. Total Se and Se species concentrations were measured in maternal and umbilical cord sera by an in-series coupling of two-dimensional size-exclusion and affinity HPLC. Additional measurements of serum SeP concentration and of serum GPx-3 enzyme activity were carried out using ELISA. Total Se concentration was significantly higher in maternal serum than in cord serum (68·9 (sd 15·2) and 56·1 (sd 14·6) µg/l, respectively; P<0·01). There were significant correlations between selenoprotein and SeAlb concentrations in mothers and newborns, although they also showed significant differences in GPx-3 (11·2 (sd 3·7) v. 10·5 (sd 3·5) µg/l; P<0·01), SeP (42·5 (sd 9·5) v. 28·1 (sd 7·7) µg/l; P<0·01) and SeAlb (11·6 (sd 3·6) v. 14·1 (sd 4·3) µg/l; P<0·01) concentrations in maternal and cord sera, respectively. Serum GPx-3 activity and concentration were positively correlated in mothers (r 0·33; P=0·038) but not in newborns. GPx-3 activity in cord serum was significantly correlated with gestational age (r 0·44; P=0·009). SeAlb concentration was significantly higher in babies, whereas SeP and GPx-3 concentrations were significantly higher in mothers. The differences cannot be explained by simple diffusion; specific transfer mechanisms are probably involved. GPx-3 concentrations in mothers, at delivery, are related to maternal Se status, whereas the GPx-3 activity in cord serum depends on gestational age.