First- and Second-Trimester Reference Intervals for Thyroid Hormones during Pregnancy in “Rhea” Mother-Child Cohort, Crete, Greece

Estimation and interpretation of thyroid function tests in pregnant women is of utmost importance for maternal, fetal and neonatal health. Our objective was to calculate laboratory- and geography-specific reference intervals for thyroid hormones during pregnancy in an iodine-sufficient area of the Mediterranean, Crete, Greece. This project was performed in the context of “Rhea” mother-child cohort. Fulfillment of extensive questionnaires and estimation of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and antithyroid antibodies were performed. The reference population was defined using inclusion criteria regarding thyroidal, obstetric, and general medical status of women. Reference interval for TSH was 0.05–2.53 μIU/mL for the first and 0.18–2.73 μIU/mL for the second trimester. 6,8% and 5,9% of women in the first and second trimester, respectively, had TSH higher than the upper reference limit. These trimester-specific population-based reference ranges are essential in everyday clinical practice for the correct interpretation of thyroid hormone values and accurate classification of thyroid disorders

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Estimation and interpretation of thyroid function tests in pregnant women is of utmost importance for maternal, fetal and neonatal health. Our objective was to calculate laboratory-and geography-specific reference intervals for thyroid hormones during pregnancy in an iodine-sufficient area of the Mediterranean, Crete, Greece. This project was performed in the context of "Rhea" mother-child cohort. Fulfillment of extensive questionnaires and estimation of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and antithyroid antibodies were performed. The reference population was defined using inclusion criteria regarding thyroidal, obstetric, and general medical status of women. Reference interval for TSH was 0.05-2.53 μIU/mL for the first and 0.18-2.73 μIU/mL for the second trimester. 6,8% and 5,9% of women in the first and second trimester, respectively, had TSH higher than the upper reference limit. These trimester-specific population-based reference ranges are essential in everyday clinical practice for the correct interpretation of thyroid hormone values and accurate classification of thyroid disorders

Metabolic syndrome in early pregnancy and risk of preterm birth

The authors determined the association between metabolic syndrome in early pregnancy (mean, 11.96 weeks) and the risk of preterm birth in the mother-child cohort study (>Rhea> Study) in Crete, Greece, 2007-2009. Maternal fasting serum samples were collected, and blood pressure was measured at the time of the first major ultrasound examination (n=625). Multivariable log-binomial regression models were used. Women with metabolic syndrome were at high risk for preterm birth (relative risk (RR)=2.93, 95% confidence interval (CI): 1.53, 5.58), with the highest risk observed for medically indicated preterm births (RR=5.13, 95% CI: 1.97, 13.38). Among the components of metabolic syndrome, the most significant risk factor was hypertension (RR=2.32, 95% CI: 1.28, 4.20). An elevation of 10 mm Hg in diastolic blood pressure increased the relative risk for preterm birth by 29% (RR= 1.29, 95% CI: 1.08, 1.53), while a per unit increase in the low density lipoprotein/high density lipoprotein cholesterol ratio increased this risk by 19% (RR=1.19, 95% CI: 1.02, 1.39). Fetal weight growth restriction was associated with elevated levels of insulin (RR=1.14, 95% CI: 1.08, 1.20) and diastolic blood pressure (RR=1.27, 95% CI: 1.00, 1.61) in early pregnancy. These findings suggest that women with metabolic syndrome in early pregnancy had higher risk for preterm birth.This work was partly supported by the European Union Integrated Project NewGeneris, 6th Framework Program (contract FOOD-CT-2005-016320), and by the European Union-funded project HiWATE, 6th Framework Program (contract Food-CT-2006-036224).Peer Reviewe

Thyroid dysfunction and autoantibodies in early pregnancy are associated with increased risk of gestational diabetes and adverse birth outcomes

Context: Maternal thyroid dysfunction, especially in early pregnancy, may lead to pregnancy complications and adverse birth outcomes. Few population-based prospective studies have evaluated these effects and results are discrepant. Objective: We examined the association of thyroid function and autoimmunity in early pregnancy with adverse pregnancy and birth outcomes. Setting and Participants: The study used data from the prospective mother-child cohort >Rhea> study in Crete, Greece. A total of 1170 women with singleton pregnancies participated in this analysis. Maternal serum samples in the first trimester of pregnancy were tested for thyroidhormones (TSH, free T4, and free T3) and thyroid antibodies (thyroid peroxidase antibody and thyroglobulin antibody). Multivariable log-Poisson regression models were used adjusting for confounders. Main Outcome Measures: Outcomes included gestational diabetes, gestational hypertension/preeclampsia, cesarean section, preterm delivery, low birth weight, and small-for-gestational-age neonates. Results: The combination of high TSH and thyroid autoimmunity in early pregnancy was associated with a 4-fold increased risk for gestational diabetes [relative risk (RR) 4.3, 95% confidence interval (CI) 2.1- 8.9)] and a 3-fold increased risk for low birth weight neonates (RR 3.1,95%CI 1.2- 8.0) after adjustment for several confounders. Women positive for thyroid antibodies without elevated TSH levels in early pregnancy were at high risk for spontaneous preterm delivery (RR 1.7, 95% CI 1.1-2.8), whereas the combined effect of high TSH and positive thyroid antibodies did not show an association with preterm birth. Conclusions: High TSH levels and thyroid autoimmunity in early pregnancy may detrimentally affect pregnancy and birth outcomes. Copyright © 2012 by The Endocrine Society.This work was supported by the European Uniuon Integrated Projects NewGeneris, Sixth Framework Programme (Contract FOOD-CT-2005-016320), and Chicos, Seventh Framework Programme (Contract Health-F2-2009-241604).Peer Reviewe

Nonlinear responses to waterborne cadmium exposure in zebrafish. An in vivo study

Cadmium (Cd) has proved to be associated with numerous toxic effects in aquatic organisms via waterbome exposure. With a view to investigate Cd toxicity along a broad spectrum of exposures reaching from environmental to toxic, we employed adult zebrafish (Danio rerio) for an in vivo study. A number of 10 fish per tank were placed in 40 L tanks and were exposed for 30 days to 0.0, 5.0, 25, 50, 75, 100 and 1000 mu g Cd per liter. There were 2 tanks for each Cd exposure (duplicate experiment). Mortality was recorded daily, dead fish were collected and tissue samples were obtained for histologic observation, whereas remaining tissues were stored for Cd burden determination. Surviving fish were collected at the end of the experiment. Median overall survival (OS) in days was found to be 9.0, 11.0, 8.0 and 7.0 for 25 mu g/L, 50 mu g/L, 75 mu g/L and 100 mu g/L respectively, with all of them showing mortality greater than 50%. Remarkably, fish exposed to the highest Cd concentration (1000 mu g/L) survived the longest exhibiting a mean OS of 29.2 days. Cd determination in fish tissue was conducted with an in house ICP-MS method and levels ranged from 3.1 to 29.1 ng/mg. Log Cd tissue levels were significantly correlated with the log Cd exposure levels (r = 0.535, p lt 0.001). The highest Cd burden was determined for fish exposed to 1000 mu g Cd /L (mean = 12.2 ng/mg). Histopathology supported these results. Our findings disclose a deviation in toxic responses through the range of Cd concentrations, leading to nonlinear responses. These differentiated responses, could be linked to hormesis phenomena