Maternal Thyroid-stimulating Hormone Research Articles

Effect of Gestational Weight Gain on Associations Between Maternal Thyroid Hormones and Birth Outcomes.

Purpose: The aim was to investigate the associations between maternal thyroid parameters within the normal ranges during early pregnancy and birth outcomes, and further to examine whether the associations were modified by gestational weight gain (GWG).Methods: Maternal serum thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) concentrations within the normal ranges during early pregnancy were measured from 8,107 pregnant women in Wuhan, China. The associations between maternal thyroid parameters and birth outcomes (birth weight, birth length, and low birth weight) were analyzed using multivariable adjusted regression models, and effect modification by pre-pregnancy body mass index (BMI) category and GWG were further evaluated.Results: Maternal TSH and FT4 concentrations were negatively associated with birth weight, and the latter only occurred in normal weigh women with inadequate and excessive GWG, as well as in both underweight and overweight women with excessive GWG (e.g., β = −359.33 g, 95% CI: −700.95, −17.72 in underweight women with excessive GWG for per unit increase of FT4 concentrations). Moreover, maternal FT4 and FT3 concentrations were associated with increased risk for low birth weight, and the latter only occurred in normal weigh women with inadequate GWG (OR = 2.52, 95% CI: 1.00, 6.36 for per unit increase of FT3 concentrations). These associations still persist when maternal thyroid parameters were modeled as quintiles.Main conclusion: Maternal normal thyroid function during early pregnancy with excessive and inadequate GWG may adversely influence fetal growth.

Associations Between Maternal Thyroid Function in Pregnancy and Obstetric and Perinatal Outcomes

Context The effects of maternal subclinical hypothyroidism on pregnancy outcomes are not clear. Objective We aimed to assess potential associations between maternal thyrotropin (thyroid-stimulating hormone [TSH]) levels in pregnancy and obstetric and perinatal outcomes. Design Retrospective cohort study. Setting Tertiary academic medical center. Patients Women aged ≥18 years with a singleton gestation and no known thyroid disease seen for prenatal care at Boston Medical Center from January 1, 2003 through May 22, 2014, and their fetuses and infants were included. Main outcome measures Risk ratios of adverse obstetric and perinatal outcomes. Results A total of 8,413 pregnant women (mean age 29.1 years, 15% white, 60% black, 13% Hispanic) and their fetuses and infants (mean gestational age at birth 38.5 weeks, 52% male, mean birth weight 3.2 kg) were included in the analyses. The median (interquartile range) TSH level was 1.06(0.62-1.60) mIU/L, and 130 women (1.6%) had TSH > 4 mIU/L. Maternal TSH levels > 4 mIU/L were associated with increased risks of prematurity (risk ratio [RR] 2.17 [95% confidence interval 1.15-4.07] P = .016) and neonatal respiratory distress syndrome (RDS) (RR 2.83 [95% confidence interval 1.02-7.86] P = .046) compared to TSH levels ≤ 4 mIU/L. Although not statistically significant, TSH levels > 4 mIU/L were also associated with increased RRs for fetal loss, preeclampsia/eclampsia, and low birth weight. TSH levels > 4 mIU/L were not associated with preterm labor, placental abruption, cesarean section, gestational hypertension or diabetes, or neonatal intensive care unit admission. Conclusion Maternal serum TSH concentration > 4 mIU/L in pregnancy was associated with approximately 2-fold increased risks of prematurity and RDS in offspring. Elevated TSH was also associated with statistically non-significant increases in the risk of fetal loss, preeclampsia/eclampsia, and low birth weight.

Dose-Dependent Influence of Antithyroid Drugs on the Difference in Free Thyroxine Levels between Mothers with Graves’ Hyperthyroidism and Their Neonates

Background: Several guidelines have recommended that the use of the lowest effective dose of antithyroid drugs (ATDs) that maintains maternal serum free thyroxine (FT4) levels at or moderately above the upper limit of the reference range is appropriate for fetal euthyroid status. However, little is known about whether ATD dosage affects the difference in serum FT4 levels between the mother and neonate. We conducted a retrospective study at a tertiary hospital in Japan to investigate the dose-dependent influence of ATDs on both maternal and fetal thyroid hormone status. Materials and Methods: We retrospectively examined 62 pregnant women who delivered between 2007 and 2016 and were treated for Graves’ hyperthyroidism with ATD at any stage during pregnancy. We selected individuals whose data on maternal FT4 level within 4 weeks of their deliveries and cord FT4 level of their infants at the time of delivery were available. Those with multiple pregnancies, iodine or glucocorticoid treatment, and fetal goiter detected by ultrasonography were excluded. Results: After the exclusion criteria were applied, we recruited 40 individuals. The cord FT4 levels were significantly lower than the maternal FT4 levels in patients treated with high-dosage ATDs (methimazole >5 mg daily or propylthiouracil >100 mg daily). However, there were no significant differences between maternal and cord FT4 levels in patients treated with low-dosage ATDs (methimazole ≤5 mg daily or propylthiouracil ≤100 mg daily). We selected 35 individuals whose data on maternal thyrotropin receptor-binding inhibitory immunoglobulin (TBII) level were available. Multiple linear regression analysis adjusted for ATD dosage, maternal TBII level, and gestational period found that ATD dosage was a significant predictor of the difference in serum FT4 levels between the mother and neonate. In terms of maternal complications, multiple logistic regression analysis identified maternal free triiodothyronine (FT3) level as a significant predictor of the incidence of preterm delivery. Conclusions: We found a dose-dependent influence of ATDs on the difference in serum FT4 levels between mothers with Graves’ hyperthyroidism and their neonates. Further studies to evaluate the optimal target FT4 and FT3 levels for the mother and neonate during pregnancy may improve the outcome of pregnant women with Graves’ hyperthyroidism.

Association of maternal serum trace elements with newborn screening-thyroid stimulating hormone

Abstract Objectives Trace elements are essential in thyroid functioning as they incorporate into biologically important enzymes as cofactors. The placenta can either activate or inhibit the transfer of maternal trace elements to the unborn. An imbalance of maternal trace elements in pregnancy may affect both maternal and newborn thyroid function. Methods Blood samples from 315 lactating mothers were collected in the first 48 h after delivery and evaluated for selenium (Se), copper (Cu), manganese (Mn), and zinc (Zn) using flame atomic absorption spectroscopy (FAAS) and quadrupole inductively coupled plasma-mass spectrometer (ICP-MS). Thyroid hormones and auto-antibodies (thyroid-stimulating hormone (TSH), free T3 (fT3), free T3 (fT4), anti–thyroid peroxidase (anti-TPO), and antithyroglobulin (anti-TG)) were analyzed in maternal blood using an electro-chemiluminescence immunoassay (ECLIA). Between 48 and 72 postpartum hours, spot blood samples were used for newborn screening-TSH measurement. Correlation and multivariate analyses were performed to evaluate the effect of maternal trace element levels on newborn screening-TSH levels. Results The medians (min-max) of maternal Se (45.16 µg/L (21.28–79.04)), Cu (210.10 µg/dL (117.04–390.64)), Mn (2.11 µg/L (0.20–3.46)), and Zn (0.43 mg/L (0.24–0.66)) were determined. A positive correlation was detected between Zn and maternal TSH levels (r=0.12, p < 0.05). Newborn screening-TSH was significantly correlated with maternal Cu (r=0.14, p < 0.01). Similarly, Cu exhibited weak associations in clustering analysis while others shared common clusters with newborn-screening TSH. Conclusions There was no significant association between most of the maternal serum trace elements and maternal thyroid hormone parameters, with an only exception between maternal Zn and maternal serum TSH. Finally, the association between maternal serum Cu levels and newborn screening-TSH levels may highlight the importance of maternal Cu levels on the newborn thyroid health.

Prenatal exposure to per- and polyfluoroalkyl substances and maternal and neonatal thyroid function in the Project Viva Cohort: A mixtures approach

BackgroundMaternal and neonatal thyroid function is critical for growth and neurodevelopment. Exposure to individual per- and polyfluoroalkyl substances (PFAS) can alter circulating thyroid hormone levels, but few studies have investigated effects of combined exposure to multiple PFAS. ObjectivesEstimate associations of exposure to multiple PFAS during early pregnancy with maternal and neonatal thyroid function. MethodsThe study population consisted of 726 mothers and 465 neonates from Project Viva, a Boston, Massachusetts area longitudinal pre-birth cohort. We measured six PFAS [perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), 2-(N-ethyl-perfluorooctane sulfonamido)acetate (EtFOSAA), and 2-(N-methyl-perfluorooctane sulfonamido)acetate (MeFOSAA)] and thyroxine (T4), Free T4 Index (FT4I), and thyroid stimulating hormone (TSH) in maternal plasma samples collected during early pregnancy, and neonatal T4 in postpartum heel sticks. We estimated individual and joint effects of PFAS exposure with thyroid hormone levels using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR), and evaluated potential non-linearity and interactions among PFAS using BKMR. ResultsHigher concentrations of the PFAS mixture were associated with significantly lower maternal FT4I, with MeFOSAA, EtFOSAA, PFOA, and PFHxS contributing most to the overall mixture effect in BKMR and WQS regression. In infants, higher concentrations of the PFAS mixture were associated with lower T4 levels, primarily in males, with PFHxS and MeFOSAA contributing most in WQS, and PFHxS contributing most in BKMR. The PFAS mixture was not associated with maternal T4 or TSH levels. However, in maternal BKMR analyses, ln-PFOS was positively associated with T4 levels (Δ25th to 75th percentile: 0.21 µg/dL; 95% credible interval: −0.03, 0.47) and ln-PFHxS was associated with a non-linear effect on TSH levels. ConclusionsThese findings support the hypothesis that there may be combined effects of prenatal exposure to multiple PFAS on maternal and neonatal thyroid function, but the direction and magnitude of these effects may vary across individual PFAS.

Identifying a critical window of maternal metal exposure for maternal and neonatal thyroid function in China: A cohort study

BackgroundChina, a developing country, has a particularly serious problem with metal pollution. We evaluated the association of metal exposure during pregnancy with maternal and neonatal thyroid function, and identified the critical window for maternal metal exposure effects on maternal and neonatal thyroid functions. MethodsThe maternal urinary concentrations of mercury (Hg), cadmium (Cd), arsenic (As) and cesium (Cs) were determined in pregnant women during their first (n = 389) or third (n = 257) trimesters in a prospective cohort from 2014 to 2015 in Nanjing, China, using an inductively coupled plasma mass spectrometry (ICP-MS) instrument. Maternal serum-free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured by electrochemiluminescent microparticle immunoassays in the second and third trimesters. Neonatal TSH levels were detected 72 h after birth. ResultsHg (>0.162 µg/L), Cd (>0.084 µg/L), As (>0.348 µg/L) and Cs (>0.093 µg/L) were detectable in 76.9%, 90.1%, 100% and 100% of maternal urine samples from women in the first trimester of pregnancy. In the multiple adjusted linear regression models, maternal exposures to Hg and Cd in the first trimester were positively associated with maternal TSH levels in the second trimester (P < 0.01, P = 0.02). Moreover, maternal exposures to Cd and Cs in the first trimester were positively associated with neonatal TSH levels (P = 0.04, P = 0.02). In the Bayesian kernel machine regression (BKMR) model, the results were stable and consistent with the linear regression model. ConclusionsMaternal exposure to Hg, Cd and Cs in the first trimester was related to TSH levels in mothers and newborns. Efforts to identify maternal and neonatal thyroid disruptors should carefully consider the effects of exposure to these metals.

Maternal serum perfluoroalkyl substance mixtures and thyroid hormone concentrations in maternal and cord sera: The HOME Study

BackgroundPer- and polyfluoroalkyl substances (PFAS) are ubiquitous. Previous studies have found associations between PFAS and thyroid hormones in maternal and cord sera, but the results are inconsistent. To further address this research question, we used mixture modeling to assess the associations with individual PFAS, interactions among PFAS chemicals, and the overall mixture. MethodsWe collected data through the Health Outcomes and Measures of the Environment (HOME) Study, a prospective cohort study that between 2003 and 2006 enrolled 468 pregnant women and their children in the greater Cincinnati, Ohio region. We assessed the associations of maternal serum PFAS concentrations measured during pregnancy with maternal (n = 185) and cord (n = 256) sera thyroid stimulating hormone (TSH), total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), and free triiodothyronine (FT3) using two mixture modeling approaches (Bayesian kernel machine regression (BKMR) and quantile g-computation) and multivariable linear regression. Additional models considered thyroid autoantibodies, other non-PFAS chemicals, and iodine deficiency as potential confounders or effect measure modifiers. ResultsPFAS, considered individually or as mixtures, were generally not associated with any thyroid hormones. A doubling of perfluorooctanesulfonic acid (PFOS) had a positive association with cord serum TSH in BKMR models but the 95% Credible Interval included the null (β = 0.09; 95% CrI: −0.08, 0.27). Using BKMR and multivariable models, we found that among children born to mothers with higher thyroid peroxidase antibody (TPOAb), perfluorooctanoic acid (PFOA), PFOS, and perfluorohexanesulfonic acid (PFHxS) were associated with decreased cord FT4 suggesting modification by maternal TPOAb status. ConclusionsThese findings suggest that maternal serum PFAS concentrations measured in the second trimester of pregnancy are not strongly associated with thyroid hormones in maternal and cord sera. Further analyses using robust mixture models in other cohorts are required to corroborate these findings.

Prenatal dioxin exposure and thyroid hormone levels in the Seveso second generation study

BackgroundIn animal studies, perinatal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters thyroid homoeostasis and thyroid hormone concentrations; epidemiologic evidence is limited. ObjectivesWe aimed to determine the association of prenatal exposure to TCDD with thyroid hormone concentrations in the Seveso Second Generation Study, a unique cohort of children born to TCDD-exposed women resulting from a 1976 chemical factory explosion in Seveso, Italy. MethodsWe included 570 children (288 female, 282 male) with complete follow-up data, including a fasting blood draw. Serum levels of total and free thyroxine (T4), free triiodothyronine (T3), and thyroid stimulating hormone (TSH) were measured using immunoassays. We defined prenatal TCDD exposure as: 1) maternal initial TCDD concentration measured in serum collected soon after the explosion and 2) maternal TCDD estimated at pregnancy. ResultsCompared to the lowest quartile (Q1), maternal initial serum TCDD was associated with lower free T3 (Q2: adj-β = −0.13, 95%CI -0.26, 0.00; Q3: adj-β = −0.22, 95%CI -0.35, −0.09; Q4: adj-β = −0.14, 95%CI -0.28, 0.00; p-trend = 0.02). In participants with high thyroid antibody status, inverse associations between maternal initial serum TCDD and free T3 were significantly stronger than in participants with normal antibody status (p-interaction = 0.02). We also observed a positive association between maternal initial serum TCDD and TSH concentrations in participants with high thyroid antibody status (Q2: adj-β = 11.4%, 95%CI -25.2, 66.1; Q3: adj-β = 49.0%, 95%CI 3.0, 115.5; Q4: adj-β = 105.5, 95%CI 36.6, 209.2; p-trend < 0.01) but not in those participants with normal antibody status (p-interaction < 0.01). Similar results were found for TCDD estimated at pregnancy. DiscussionOur results suggest prenatal exposure to TCDD, a potent endocrine-disrupting compound, may alter thyroid function later in life. Populations with additional thyroid stress may be particularly susceptible to in utero exposure of thyroid disrupting chemicals.

Correlating maternal iodine status with neonatal thyroid function in two hospital populations in Ghana: a multicenter cross-sectional pilot study

BackgroundCongenital hypothyroidism is a common, yet easily treatable cause of poor growth and intellectual disability. Newborn screening programs play an important role in the early detection and treatment of congenital hypothyroidism. However, an estimated 71% of children are born in countries such as Ghana, which does not have a screening program. Iodine deficiency, a common cause of congenital hypothyroidism, is present in the Ghanaian population. Mild to moderate maternal iodine deficiency may negatively impact cognitive function in children. A structured approach to examine the association between maternal iodine levels and infant thyroid function may have important ramifications on our understanding of congenital hypothyroidism in Ghana. We investigated the hypothesis that maternal iodine deficiency impacts infant thyroid function, using Thyroid Stimulating Hormone (TSH) as a marker of thyroid function. We also explored potential opportunities and barriers to newborn screening for congenital hypothyroidism in Ghana.MethodsThis was a cross-sectional, multicenter pilot study of 250 women and their neonates recruited from post-natal clinics in Accra and Tamale, Ghana. We compared maternal urine iodine concentration and infant TSH, as well as maternal sociodemographic and nutrition information. Regression models were used to model the relationship between variables.ResultsMedian infant TSH was 4.7 μIU/ml (95% CI: 3.9–5.5) in Accra. In Tamale, the median infant TSH was 3.5 μIU/ml (95%CI: 3.3 to 3.6) (Δ: 1.3 μIU/ml, 95% CI: 0.5–2.1, p = 0.002). Median maternal urine iodine concentrations were 141.0 μg/L (95% CI: 115.7 to 166.3) and 142.5 μg/L (95% CI: 125.1 to 160.0) in Accra and Tamale, respectively (Δ: − 1.5 μIU/ml, 95% CI: − 32.2 – 29.2, p = 0.925). There was a weakly positive correlation between maternal urine iodine and infant TSH (rho 0.1, p = 0.02). Almost one-third (30%) of women in both locations had biochemical evidence of iodine deficiency. Mothers with any formal education were more likely to have higher iodine levels than their counterparts who had no formal education (coefficient 0.31, p = 0.006).ConclusionsMaternal iodine deficiency is prevalent in Ghana and is correlated to infant thyroid function. We recommend studies with larger sample sizes to assess the true scope of this relationship.

Maternal urinary bisphenol A concentration and thyroid hormone levels of Chinese mothers and newborns by maternal body mass index.

Animal studies indicated that bisphenol A (BPA) exposure during pregnancy may disrupt thyroid function which is critical for fetal development. However, few epidemiological studies have examined this topic and the results were inconsistent. We aimed to evaluate whether prenatal BPA exposure is associated with thyroid hormone levels in Chinese mothers and newborns with stratification by maternal body mass index (BMI). BPA concentration were measured in urine samples collected from 555 women at late pregnancy. Maternal serum free thyroxin (FT4), thyroid-stimulating hormone (TSH) and thyroid peroxidase antibody (TPO-Ab) concentrations at the third trimester were abstracted from medical records. Cord serum-free triiodothyronine (FT3), FT4, TSH, and TPO-Ab levels were measured in 398 newborns. Prenatal urinary BPA was detected in 98.5% of mothers with a geometric mean of 1.32ng/mL (95% CI 1.17-1.49ng/mL). With each 10-fold increase in BPA concentrations, maternal log10_(TSH) mIU/L was 0.10 lowered (95% CI - 0.20, - 0.005, p < 0.05) among pre-pregnancy BMI>23kg/m2, with adjustment for maternal age, maternal education, gestation diabetes mellitus (GDM), husband smoking during pregnancy, parity, and gestational age at thyroid parameters measured, but no association was observed in pre-pregnancy BMI < 18.5, or 18.5-22.9kg/m2 stratum. No BPA-associated changes were observed in maternal FT4 level or odds of positive TPO-Ab in all BMI stratum. Also, no associations were observed between prenatal urinary BPA concentration and cord serum FT4, FT3, TSH levels, and odds of positive TPO-Ab in both male and female newborns among pre-pregnancy BMI < 18.5, 18.5-22.9 or>23kg/m2 stratum. In this study, prenatal urinary BPA concentration was associated with lower maternal TSH among women with overweight, but not associated with other maternal thyroid parameters or cord serum thyroid parameters across maternal BMI categories. More research on pregnant women and newborns cohort with BPA exposure are warranted.

Maternal and neonatal iodine status in Dakshina Kannada district of Karnataka, India.

This study was designed to assess iodine status of mother-fetus dyad by estimation of spot urine iodine concentration (UIC) in the study district. It is a cross-sectional study of 250 pregnant women with euthyroid status and their term neonates residing in Dakshina Kannada district. Neonates with foetal growth restriction or requiring intensive care were excluded. Median UIC was quantified using modified Sandell-Kolthoff reaction by microplate method. World Health Organization (WHO) classification was used to categorise the iodine status of pregnant women. Among 250 pregnant women, the majority were primigravida (38%). Median maternal thyroid stimulating hormone (TSH) was 1.54 mIU/l, and median UIC was 352 mcg/l. Urine iodine levels were insufficient (<150 mcg/l) in 1.2% (n = 3), adequate (150-249 mcg/l) in 9.2% (n = 23) and above requirement (250-499 mcg/l) in 89.6% (n = 224); none had excess (> 500 mcg/l). Median birth weight was 3,000 g and head circumference was 34 cm. Median cord blood TSH was 8.1 mIU/l, and median UIC 344.5 mcg/l. All the newborns had adequate (> 100 mcg/l) iodine status, including those born to mothers with insufficient values. Maternal and newborn median UIC showed positive correlation (r = 0.139; p = 0.028). Iodine statuses were above requirement or adequate in pregnant women from the study district and their neonates, respectively, indicating successful salt iodisation.

Associations Between Maternal Thyroid Function in Pregnancy and Obstetric and Perinatal Outcomes.

The effects of maternal subclinical hypothyroidism on pregnancy outcomes are not clear. We aimed to assess potential associations between maternal thyrotropin (thyroid-stimulating hormone [TSH]) levels in pregnancy and obstetric and perinatal outcomes. Retrospective cohort study. Tertiary academic medical center. Women aged ≥18 years with a singleton gestation and no known thyroid disease seen for prenatal care at Boston Medical Center from January 1, 2003 through May 22, 2014, and their fetuses and infants were included. Risk ratios of adverse obstetric and perinatal outcomes. A total of 8,413 pregnant women (mean age 29.1 years, 15% white, 60% black, 13% Hispanic) and their fetuses and infants (mean gestational age at birth 38.5 weeks, 52% male, mean birth weight 3.2 kg) were included in the analyses. The median (interquartile range) TSH level was 1.06(0.62-1.60) mIU/L, and 130 women (1.6%) had TSH > 4 mIU/L. Maternal TSH levels > 4 mIU/L were associated with increased risks of prematurity (risk ratio [RR] 2.17 [95% confidence interval 1.15-4.07] P = .016) and neonatal respiratory distress syndrome (RDS) (RR 2.83 [95% confidence interval 1.02-7.86] P = .046) compared to TSH levels ≤ 4 mIU/L. Although not statistically significant, TSH levels > 4 mIU/L were also associated with increased RRs for fetal loss, preeclampsia/eclampsia, and low birth weight. TSH levels > 4 mIU/L were not associated with preterm labor, placental abruption, cesarean section, gestational hypertension or diabetes, or neonatal intensive care unit admission. Maternal serum TSH concentration > 4 mIU/L in pregnancy was associated with approximately 2-fold increased risks of prematurity and RDS in offspring. Elevated TSH was also associated with statistically non-significant increases in the risk of fetal loss, preeclampsia/eclampsia, and low birth weight.

Perfluoroalkyl Substances and Maternal Thyroid Hormones in Early Pregnancy; Findings in the Danish National Birth Cohort.

Background:Maternal thyroid hormones are essential for fetal brain development in early gestation. Perfluoroalkyl substances (PFASs)—widespread and persistent pollutants—have been suggested to interfere with maternal thyroid hormones in the second or third trimesters, but evidence for an association in the early pregnancy period is sparse.Objectives:Our goal was to evaluate the gestational-week specific associations of maternal thyroid-stimulating hormone (TSH) and free thyroxine (fT4) levels with plasma concentrations of six PFAS chemicals in the first and second pregnancy trimester.Methods:A cross-sectional analysis was conducted using 1,366 maternal blood samples collected between gestational weeks (GWs) 5 and 19 (median, 8 gestational weeks) in the Danish National Birth Cohort (DNBC) during 1996–2002. We estimated the percentage changes of serum TSH and fT4 levels according to concentrations (in nanograms per milliliter) of six PFAS chemicals modeled as per interquartile range (IQR) increase or by exposure quartiles. Moreover, we contrasted the estimated week-specific TSH or fT4 levels by PFAS quartile and estimated ORs for binary high or low TSH and fT4 status based on the week-specific distribution according to IQR increase of PFAS.Results:TSH levels followed a U-curve trend in early pregnancy with a nadir at GW10, whereas fT4 levels were less fluctuated in the samples. There were no apparent associations between any of the PFASs and changes of average TSH or fT4 levels in total samples. In gestational-week–specific analyses, we found that the estimated TSH values were higher among the highest perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorohexane sulfonate (PFHxS), and perfluoroheptane sulfonate (PFHpS) quartiles compared with the lower quartiles from GW5 to GW10, but the difference became null or even reversed after GW10. For binary outcomes, perfluorodecanoic acid (PFDA) was associated with high fT4 status before GW10 [ (95% CI: 1.04, 2.05)].Conclusions:We observed some gestational-week–specific associations between high exposure to several PFAS and TSH level in early gestations. Further research of the biology and the potential clinical impact regarding thyroid hormones disruptions in early pregnancy is needed. https://doi.org/10.1289/EHP5482

Iodine supplementation of lactating women and assessment of infant visual information processing and maternal and infant thyroid function: A randomized trial.

Iodine deficiency is one of the major causes of brain damage in childhood. However, iodine supplementation during early pregnancy and lactation can prevent the ill effects of iodine deficiency. This study evaluated maternal and infant thyroid function and infant visual information processing (VIP) in the context of maternal iodine supplementation. A community-based, randomized, supplementation trial was conducted. Mother infant dyads (n = 106) were enrolled within the first 10 days after delivery to participate in this study. Mothers were randomly assigned either to receive a potassium iodide capsule (225 μg iodine) daily for 26 weeks or iodized salt weekly for 26 weeks. Maternal thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone (TSH), thyroglobulin (Tg), urinary iodine concentration (UIC), breast milk iodine concentration (BMIC) and infant T4, TSH, UIC and VIP were measured as outcome variables. At baseline, neither mothers nor infants in the two groups were significantly different in any of the biomarkers or anthropometric measurements. Maternal TSH and goiter prevalence significantly decreased following iodine supplementation. The percentage of infants who preferentially remembered the familiar face was 26% in the capsule and 51% in the I-salt groups. Infant sex, length for age Z score, BMIC, maternal education and household food security were strong predictors of novelty quotient. In conclusion supplementation daily for six months with an iodine capsule or the use of appropriately iodized salt for an equivalent time was sufficient to reduce goiter and TSH in lactating women. Higher BMIC and LAZ as well as better household food security, maternal education, and male sex predicted higher novelty quotient scores in the VIP paradigm.

Association between prenatal exposure to multiple metals and maternal and child thyroid hormone levels

OPS 39: Metals and biomarkers, Room 411, Floor 4, August 26, 2019, 1:30 PM - 3:00 PM Background/Aim: Metals and trace elements may affect thyroid homeostasis, but the role of prenatal exposure is unclear. We evaluated the association of pregnancy exposure to mixtures of trace elements with maternal and child thyroid function in 800 mother-child pairs from the RHEA pregnancy cohort in Crete, Greece. Methods: Concentrations of 11 essential and non-essential trace elements were determined in first trimester maternal urine using inductively coupled plasma mass spectrometry. Thyroid hormones (thyroid stimulating hormone (TSH), free T(4), and free T(3)) were measured in serum samples collected from mothers (1st trimester) and their children at 4 years of age. Associations of each element and mixtures with thyroid hormone levels were assessed using linear regression and Bayesian Kernel Machine Regression (BKMR), respectively. Results: In BKMR analysis, higher total urinary element concentration was associated with lower maternal TSH and higher FT3 levels, while there was no association with FT4. Results from BKMR were in line with findings from linear models, with negative associations of urinary copper (adj. b=-49.7 %, 95%CI: -65.6, -26.5), selenium (b=-51.2 %, 95%CI: -66.8, -28.1) and cadmium (b=-23.1 %, 95%CI: -38.1, -4.5) with maternal TSH levels. Exposure to urinary copper was positively associated with maternal FT3 levels (b= 0.6 pg/mL, 95%CI: 0.2, 1.0). Cobalt was associated with lower maternal FT4 levels (b=-0.05 ng/dL, 95%CI: -0.1, -0.01) while copper (b=0.1 ng/dL, 95%CI: 0.02, 0.2), zinc (b=0.1 ng/dL, 95%CI: 0.02, 0.1), selenium (b=0.1 ng/dL, 95%CI: 0.1, 0.2) and cadmium (b=0.1 ng/dL, 95%CI: 0.02, 0.11) were associated with higher maternal FT4 levels. We observed no interactions between the different elements. No associations were observed with child thyroid hormones. Conclusions: The present results suggest that exposure to metals and trace elements at exposure levels relevant for the general population, can alter maternal thyroid homeostasis.

Maternal Thyroid-Stimulating Hormone Level and Thyroid Peroxidase Antibody Status in the First and Second Trimester of Pregnancy and Their Relationship with the Risk of Gestational Diabetes Mellitus

Abstract Objective: To investigate thyroid-stimulating hormone (TSH) levels and thyroid peroxidase antibody (TPOAb) in early pregnancy and to estimate the risk of development of gestational diabetes mellitus (GDM). Methods: The levels of TSH, free thyroxine, free triiodothyronine, and TPOAb were retrospectively evaluated in 2333 pregnant women. All women recruited were divided into groups of TSH high (H), TSH low (L), TSH (H) TPOAb positive (+), TSH (H)TPOAb negative (−), TSH normal (N)TPOAb (+), TSH (L)TPOAb (+), TSH (L)TPOAb (−), and estimated the risk of GDM. Results: TSH level (X 2 = 13.0024, P = 0.0015) and TSH combined TPOAb (X 2 = 20.0038, P = 0.0012) were correlated to development of GDM. The level of TSH in 95 women was increased, and in 216 women were decreased. Of the 2333 pregnant women, 546 patients were diagnosed with GDM, with a prevalence of 23.40%. The prevalence of GDM was 35.78% and 28.70% for the TSH high (H) and TSH low (L) pregnant women, respectively. The increased TSH (P = 0.0013, odds ratio: 2.09, confidence interval:1.34–3.28) was correlated to increase GDM incidence. TSH (H) TPOAb (+) (n = 29), TSH (H) TPOAb (−) (n = 58), TSH normal (N) TPOAb (+) (n = 265), TSH (L) TPOAb (+) (n = 30), TSH (L) TPOAb (−) (n = 154) were in this study. The prevalence of GDM was 51.72%, 29.31%, 23.02%, 26.67%, and 29.87% for the TSH (H) TPOAb (+), TSH (H) TPOAb (−), TSH (N) TPOAb (+), TSH (L) TPOAb (+), and TSH (L) TPOAb (−) pregnant women, respectively. Only the TSH (H) TPOAb (+) pregnant women had a significant higher incidence of GDM (P = 0.0018, odds ratio: 3.63, confidence interval: 1.62–8.16). Trimester specific results showed that only second trimester had higher GDM risk either analyze TSH or the combination of TSH and TPOAb. Conclusion: Elevated TSH level and TPOAb positive in the second trimester of pregnancy were correlated to an increased risk of GDM.

Fetal Heart Rate as an Indirect Indicator of Treatment Response in Fetal Hyperthyroidism Secondary to Transplacental Passage of Maternal Thyrotropin Receptor Antibodies

Maternal hyperthyroidism is prevalent in 0.2-0.4% of pregnancies. Graves’ disease accounts for 85% of these cases. Approximately 1-5% of neonates born to these mothers develop hyperthyroidism. Transplacental passage of thyrotropin receptor antibodies (TRAbs) are considered to be the likely cause of transient fetal and neonatal hyperthyroidism. An 18-year-old G1P0 with a history of Graves’ disease treated by radioactive ablation presented with persistent fetal tachycardia at 23 weeks gestational age. TRAb was elevated and fetal hyperthyroidism secondary to transplacental crossing of maternal TRAb was suspected. There was no evidence of overt fetal hyperthyroidism or goiter on ultrasound examination. Oral methimazole was initiated and the fetal tachycardia resolved. Upon decrease of the methimazole dosage, the fetal tachycardia returned. Methimazole dosing was again increased and stabilized at a higher dose and the fetal tachycardia remained resolved. At birth at 40 weeks gestation, the neonate was tachycardic with elevated TRAb. She was initiated on methimazole. At 1 month of life, the methimazole dose was halved. At 2 months of life, all medication was held. On further testing, the thyroid function test remained normal. In our patient who did not display evidence of fetal hyperthyroidism on ultrasound examination, as there were no abnormal fetal markers on ultrasound to evaluate treatment response, fetal heart rate on non-stress testing was successfully used as an indirect indicator of fetal thyroid status and guided appropriate titration of methimazole. J Clin Gynecol Obstet. 2019;8(3):91-96 doi: https://doi.org/10.14740/jcgo564

Maternal Thyroid Function in Early Pregnancy and Child Attention-Deficit Hyperactivity Disorder: An Individual-Participant Meta-Analysis.

Background: Thyroid hormone is essential for optimal fetal brain development. Evidence suggests that both low and high maternal thyroid hormone availability may have adverse effects on child neurodevelopmental outcomes, but the effect on behavioral problems remains unclear. We studied the association of maternal thyrotropin (TSH) and free thyroxine (fT4) concentrations during the first 18 weeks of pregnancy with child attention-deficit hyperactivity disorder (ADHD). Methods: A total of 7669 mother-child pairs with data on maternal thyroid function and child ADHD were selected from three prospective population-based birth cohorts: INfancia y Medio Ambiente (INMA; N = 1073, Spain), Generation R (N = 3812, The Netherlands), and Avon Longitudinal Study of Parents and Children (ALSPAC; N = 2784, United Kingdom). Exclusion criteria were multiple pregnancy, fertility treatment, usage of medication affecting the thyroid, and pre-existing thyroid disease. We used logistic regression models to study the association of maternal thyroid function with the primary outcome, ADHD, assessed via the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) criteria by parents and/or teachers at a median child age of 4.5 to 7.6 years, and with the secondary outcome, an ADHD symptom score above the 90th percentile. Effect modification by gestational age and sex was tested with interaction terms and stratified analyses. Results: Overall, 233 (3%) children met the criteria for ADHD. When analyzed continuously, neither fT4 nor TSH was associated with a higher risk of ADHD (odds ratio [OR] 1.1, 95% confidence interval [CI 1.0-1.3], p = 0.060 and OR 0.9 [CI 0.9-1.1], p = 0.385, respectively) or with high symptom scores. When investigating effect modification by gestational age, a higher fT4 was associated with symptoms above the 90th percentile but only in the first trimester (for fT4 per 1 SD: OR 1.2 [CI 1.0-1.4], p = 0.027). However, these differential effects by gestational age were not consistent. No significant effect modification by sex was observed. Conclusions: We found no clear evidence of an association between maternal thyroid function and child ADHD.

Organophosphate pesticides exposure in pregnant women and maternal and cord blood thyroid hormone concentrations

BackgroundAnimal studies suggest that organophosphate (OP) pesticides exposure affects thyroid function, but evidence in humans remains sparse and inconclusive. Gestational exposure is of particular interest, since thyroid hormone is essential for fetal brain development. OP pesticides are able to cross the placental and blood-brain barrier and may interfere with fetal development processes regulated by thyroid hormone. ObjectiveTo investigate the association of gestational OP pesticides exposure during pregnancy with maternal and cord blood thyroid hormone concentrations. MethodsThis study was embedded within Generation R (Rotterdam, the Netherlands), a prospective population-based birth cohort. Mother-child pairs with OP pesticides assessment and maternal (N = 715) or cord blood (N = 482) thyroid hormone measurements were included. OP pesticides exposure was assessed at <18, 18–25, and >25 weeks gestation by measuring six urinary dialkylphosphate (DAP) metabolites. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in maternal and cord blood. Maternal measures also included total thyroxine (TT4) and TPO antibodies (TPOAbs). To study the association of creatinine-adjusted DAP metabolite concentrations with thyroid function and TPO antibodies, multivariable linear regression models including relevant confounders were used. ResultsThere was no association of DAP metabolites with maternal TSH, FT4, TT4 or TPOAb concentrations during pregnancy. Similarly, there was no association of DAP metabolites with cord blood TSH or FT4. Results did not change when DAP concentrations were analyzed at individual time points or as mean gestational exposure. ConclusionGestational OP pesticides exposure, as assessed by repeatedly measured urinary DAP metabolite concentrations in an urban population, was not associated with maternal or cord blood thyroid hormone concentrations. These findings do not support a mediating role for serum thyroid hormone availability in the relation of early life exposure to low levels of OP pesticides with child neurodevelopment. However, disruption of the thyroid system at tissue level cannot be excluded. In addition, this is one of the first studies on this subject and measurement error in DAP metabolites might have resulted in imprecise estimates. Future studies should use more urine samples to increase precision and should investigate specific OP pesticide metabolites.

Higher thyroid-stimulating hormone levels in the first trimester are associated with gestational diabetes in a Chinese population.

To evaluate the relationship between maternal thyroid-stimulating hormonelevels during the first trimester and gestational diabetes risk. In Tianjin, China, 7258 women underwent a thyroid-stimulating hormone screening test within 12 gestational weeks and then had a glucose challenge test at 24-28 weeks of gestational age. The women with a glucose challenge test ≥7.8 mmol/l underwent a 75 g oral glucose tolerance test. Gestational diabetes was diagnosed following International Association of Diabetes and Pregnancy Study Group criteria. Restricted cubic spline analysis was performed to explore full-range risk associations of thyroid-stimulating hormone levels with gestational diabetes. Logistic regression was performed to obtain odds ratios and 95% confidence intervals. In all, 594 women (8.2%) had gestational diabetes. Among women with thyroid-stimulating hormone ≤3.2 mIU/l, a positive association between thyroid-stimulating hormone levels and gestational diabetes risk was found (adjusted OR: 1.13, 95% CI: 1.00-1.27). There was no relationship between thyroid-stimulating hormone levels and gestational diabetes risk in univariable and multivariable analyses among women with thyroid-stimulating hormone >3.2 mIU/l. In subgroup analyses, among women with thyroid-stimulating hormone ≤3.2 mIU/l and BMI ≥25 kg/m2 , the adjusted odds ratio for thyroid-stimulating hormone levels with gestational diabetes was enhanced to 1.25 (95% CI: 1.02-1.53). In pregnant Chinese women, thyroid-stimulating hormone levels even within normal range in the first trimester were positively related to gestational diabetes risk, especially for pre-pregnancy overweight/obese women.