Maternal Thyroxine Research Articles

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.

Do maternal urinary iodine concentration or thyroid hormones within the normal range during pregnancy affect growth parameters at birth? A systematic review and meta-analysis.

Iodine, an essential constituent of thyroid hormones, is required for proper growth and development. To investigate whether growth parameters at birth are associated with maternal urinary iodine concentration (UIC) or normal ranges of thyroid hormones during pregnancy. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, electronic databases (namely, MEDLINE, Web of Science, the Cochrane Library, Scopus, and Google Scholar) were searched between January 1988 and November 2018 to identify relevant articles. Data from the studies included were independently extracted by 2 investigators using standardized forms developed for this review. The pooled mean birth weight, length, and head circumference values, and 95% confidence intervals were estimated in newborns born to women with UIC < 150 and UIC ≥150 μg/L during pregnancy. Possible linear or nonlinear associations between maternal UIC and the aforementioned anthropometric measures were evaluated. A narrative synthesis of the data was performed for thyroid hormones with levels within the normal range. Of the 123 studies identified, 11 were eligible for inclusion in the meta-analysis. The pooled mean birth weight, length, and head circumference in newborns whose mothers had UIC < 150 μg/L vs UIC ≥150 μg/L were 2898 g vs 2900 g (P = 0.970), 49.6 cm vs 49.4 cm (P = 0.880), and 34.0 cm vs 34.1 cm (P = 0.933), respectively. Dose-response meta-analyses revealed no significant linear or nonlinear associations between maternal UIC during pregnancy and anthropometric measures at birth. Among the different thyroid function parameters evaluated, high-normal values of maternal free thyroxine and thyrotropin during pregnancy were inversely associated with neonatal birth weight. This systematic review showed that birth weight may be affected by even mild variations in the normal concentrations of maternal thyroid hormones. However, in the current meta-analysis, birth anthropometric measures were not associated with maternal UIC during pregnancy.

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

Controlled Antenatal Thyroid Screening II: Effect of Treating Maternal Suboptimal Thyroid Function on Child Behavior.

The Controlled Antenatal Thyroid Screening (CATS) study was the first randomized controlled trial to investigate effects of treating suboptimal gestational thyroid function (SGTF) on child cognition. Since observational studies indicated that SGTF may also increase symptoms of autism and attention-deficit/hyperactivity disorder (ADHD), the CATS cohort was used to investigate whether treatment of mothers affected their children's behavior. Mothers (N = 475) completed 3 questionnaires: the Strengths and Difficulties Questionnaire (SDQ), the Child ADHD Questionnaire, and the Social Communication Questionnaire (SCQ, used as a screen for autism spectrum disorder [ASD]), about their children (mean age 9.5 years). Group comparisons of total scores, numbers of children above clinical thresholds, and association between high maternal free thyroxine (FT4) (> 97.5th percentile of the UK cohort, "overtreated") and child neurodevelopment were reported. There were no differences in total scores between normal gestational thyroid function (GTF) (n = 246), treated (n = 125), and untreated (n = 104) SGTF groups. More children of treated mothers scored above clinical thresholds, particularly the overtreated. Scores were above thresholds in SDQ conduct (22% vs 7%), SCQ total scores (7% vs 1%), and ADHD hyperactivity (17% vs 5%) when comparing overtreated (n = 40) and untreated (N = 100), respectively. We identified significantly higher mean scores for SDQ conduct (adjusted mean difference [AMD] 0.74; 95% confidence interval [CI], 0.021-1.431; P = 0.040, effect size 0.018) and ADHD hyperactivity (AMD 1.60, 95% CI, 0.361-2.633; P = 0.003, effect size 0.028) comparing overtreated with normal-GTF children. There was no overall association between SGTF and offspring ADHD, ASD, or behavior questionnaire scores. However, children of "overtreated" mothers displayed significantly more ADHD symptoms and behavioral difficulties than those of normal-GTF mothers. Thyroxine supplementation during pregnancy requires monitoring to avoid overtreatment.

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.

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.

Evaluation of Maternal Exposure to PM2.5 and Its Components on Maternal and Neonatal Thyroid Function and Birth Weight: A Cohort Study.

Background: Particulate matter (PM) air pollution is an environmental risk to public health. The prevalence of thyroid disease during pregnancy has increased rapidly in recent decades, but the available data on the relationships among air pollution, thyroid function, and birth outcomes in pregnant women, particularly in China, are scarce. We aimed to evaluate the association between maternal exposure to PM2.5 and its components and maternal and neonatal thyroid function and to investigate whether thyroid function acts as a mediator between air pollution and birth weight. Methods: In this prospective birth cohort study, the levels of maternal exposure to PM2.5 and its components during the first trimester were assessed in 433 pregnant women in Nanjing, China, enrolled during 2014-2015. We evaluated the levels of maternal exposure to PM2.5 and its six main constituents-organic matter (OM), black carbon (BC), sulfate (SO42-), nitrate (NO3-), ammonium (NH4+), and soil dust-using the V4.CH.02 product of the Dalhousie University Atmospheric Composition Analysis Group. The maternal serum-free thyroxine (fT4), thyrotropin (TSH), and thyroid peroxidase antibody (TPOAb) levels during the second trimester were measured through electrochemiluminescent microparticle immunoassays. The neonatal TSH levels were detected using an AutoDELFIA Neonatal TSH kit within 72 hours after birth, and the birth weight Z-score of each newborn was estimated. Results: Higher exposure to maternal PM2.5 and some components (BC and NH4+) decreased the maternal fT4 level (p < 0.05), and the birth weight Z-score was decreased (p < 0.05) by higher exposure to maternal PM2.5 and some components (OM, BC, NO3-, and NH4+). A mediation analysis clarified that the maternal fT4 levels explained 15.9%, 18.4%, and 20.9% of the associations of maternal PM2.5, BC, and NH4+ exposure with the birth weight Z-score, respectively (p < 0.05). After additional sensitivity analyses including only nonpreterm participants (n = 418) and non-TPOAb-positive participants (n = 415), the models remained stable. Conclusions: Our results suggest an inverse association between maternal exposure to PM2.5 and its components and the maternal fT4 levels. Maternal fT4 might act as a mediator between exposure to PM2.5 and its components and birth weight.

Maternal thyroid function during pregnancy and child brain morphology: a time window-specific analysis of a prospective cohort

Adequate thyroid hormone availability during pregnancy is necessary for optimal fetal brain development. During the first 18-20 weeks of gestation, fetal thyroid hormone availability largely depends on the placental transfer of maternal thyroxine. Although various studies have shown that maternal thyroid dysfunction is associated with suboptimal child neurodevelopmental outcomes, the most vulnerable time window remains to be identified. The aim of this study is to examine the association of maternal thyroid function with child brain morphology and to study whether any association depends on the timing of thyroid assessment. This prospective cohort study was part of the Generation R Study in Rotterdam, Netherlands, with a prospective population-based birth cohort. Pregnant women living in Rotterdam with an expected delivery date between April 1, 2002, and Jan 1, 2006, were eligible. Other inclusion criteria were maternal serum thyroid-stimulating hormone (TSH) and free thyroxine (FT4) measurement in early or mid-pregnancy (≤18 weeks) and available brain MRI data for child at age 10 years. Exclusion criteria were pre-existing thyroid disorder, thyroid disorder treatment, twin pregnancy, in-vitro fertilisation-induced pregnancy, and suboptimal-quality MRI data or major incidental finding on MRI. The main outcome was the association between maternal TSH and FT4 concentrations with brain MRI outcomes of children. Regression analyses accounted for gestational age at blood sampling, maternal age, ethnicity, education level, smoking, thyroid peroxidase antibody positivity, child sex, age at MRI, and total intracranial volume. Effect modification by gestational age at blood sampling was also investigated. Between Dec 1, 2001, and June 30, 2005, 7069 women were enrolled during early or mid-pregnancy (≤18 weeks of gestation), of whom 5088 were not included because they did not have available data on maternal serum TSH or FT4 concentrations (n=1175), their child did not have brain MRI done (n=3377), or they met exclusion criteria (n=536). Thus, 1981 mother-child pairs were included in the study, with TSH and FT4 concentrations measured during pregnancy at a median of 13·1 weeks of gestation (IQR 12·1-14·5) and offspring brain morphology assessed by MRI at a median age of 9·9 years (9·7-10·2). Maternal TSH had an inverted U-shaped association with offspring total grey matter volume (p=0·007) and with cortical grey matter volume (p=0·022). The association of maternal TSH with child total grey matter volume (pinteraction=0·053) and cortical volume (pinteraction=0·086) differed by the duration of gestation. Analyses stratified for gestational age at blood sampling showed an inverted U-shaped association of maternal TSH with child total grey matter volume and cortical grey matter volume, which was most evident at 8 weeks gestation. After about 14 weeks of gestation, TSH was no longer associated with child brain morphology. Maternal FT4 concentrations were not associated with child total grey matter volume after adjusting for total intracranial volume (p=0·75). Here, we show that both low and high maternal thyroid function are associated with smaller child total grey matter and cortical volume. To the best of our knowledge, this study is the first to show that an association with a neurodevelopmental outcome is most evident when maternal thyroid function is measured early in pregnancy. These novel findings suggest that embryonic brain development is particularly vulnerable to altered maternal thyroid function. Netherlands Organisation for Health Research and Development and the Sophia Children's Hospital Foundation.

Two Sources of Maternal Iodine Intake and Their Effect on Maternal and Infant Iodine Status and Thyroid Function and Infant Information Processing in Southern Ethiopia (P11-007-19)

ObjectivesThe objective of this study was to assess the effects of two sources of iodine supplementation on maternal and infant thyroid function and on visual information processing (VIP) of infants in southern Ethiopia MethodsA community-based, randomized, supplementation trial was conducted. Mother infant dyads (n = 106) were recruited within the first week 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 appropriately iodized salt weekly for 26 weeks for household consumption. 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. ResultsAt baseline, neither mothers nor infants in the two groups (capsule and iodized salt groups) were significantly different in any of the biomarkers and anthropometry measurements. Maternal TSH and goiter rate significantly decreased following iodine supplementation but T3, T4 and Tg didn’t change. Maternal UIC and BMIC and infant UIC were not different among groups. ConclusionsA maternal dose of 225 μg iodine daily or adequately iodized salt initiated within a week after delivery decreased goiter and TSH but did not impact infant T4, TSH or VIP. The two treatment groups didn’t differ in any of the outcome variables. Funding SourcesThe study was funded by Nestlé Foundation and Oklahoma State University.

Para-occupational exposure to pesticides, PON1 polymorphisms and hypothyroxinemia during the first half of pregnancy in women living in a Mexican floricultural area

BackgroundAdequate maternal thyroxine (T4) concentrations during the first half of pregnancy are fundamental to the embryo’s or fetus’ neural development. Organophosphate pesticides (OP) can act as thyroid disruptors and genetic polymorphisms for paraoxonase 1 (PON1), an enzyme that detoxifies OP, could be involved in individual’s susceptibility to them. We assessed the association between para-occupational exposure to pesticides, including OP, during pregnancy and maternal hypothyroxinemia, as well as the potential genetic susceptibility conferred by PON1 polymorphisms.MethodsWe analyzed information from 381 healthy pregnant women (< 17 gestational weeks), who lived in a floricultural region of Mexico where pesticides, including OP, are routinely used. Women who were para-occupationally exposed to pesticides were those whose partner had an occupation involving contact with these products. Thyroid-Stimulating Hormone (TSH) and free T4 concentrations were determined using ELISA, and hypothyroxinemia was defined as free T4 concentrations <0.76 ng/dL. PON1192QR, PON155LM and PON1–108CT polymorphisms were determined through Polymerase Chain Reaction (PCR). The association between para-occupational exposure and genetic polymorphisms and hypothyroxinemia was estimated using logistic regression models.ResultsOne hundred and sixty two women (42.52%) were classified as para-occupationally exposed to pesticides. Hypothyroxinemia prevalence was 54%, and it was not significantly associated with pesticide para-occupational exposure (OR: 1.21 95% CI 0.75–1.94). Independently of para-occupational exposure, the likelihood of hypothyroxinemia was higher among women who were carriers of PON155MM than in those with PON155LL genotype (OR MM vs LL: 3.03; 95%CI 1.62, 5.70). PON1192 RR (OR RR vs QQ: 1.72; 95%CI 0.93, 3.17) and PON1–108TT (OR TT vs CC: 1.60; 95%CI 0.90, 2.70) genotypes were marginally associated with hypothyroxinemia. No significant interaction was observed between pesticides para-occupational exposure and PON1 polymorphisms.ConclusionsThese results suggest that PON1 polymorphisms could affect thyroid function during pregnancy in women living in areas where pesticides, including OP, are routinely used. Low exposure variability in this population, could be a possible explanation for the lack of association between para-occupational exposure and thyroid function.

Pregnancy Week-Specific Reference Ranges for Thyrotropin and Free Thyroxine in the North Denmark Region Pregnancy Cohort.

Physiological changes in maternal thyroid function during pregnancy necessitate the use of pregnancy-specific reference ranges. Dynamic changes in thyrotropin (TSH) within the first trimester of pregnancy have been reported, but more evidence is needed to substantiate the findings. The objective of this study was to estimate pregnancy week-specific reference ranges for maternal TSH and free thyroxine (fT4) in early pregnancy. The study consecutively recruited serum residues from blood samples collected as part of the prenatal screening in the North Denmark Region, 2011-2015. TSH, fT4, thyroid peroxidase antibodies (TPOAb), and thyroglobulin antibodies (TgAb) were measured using an ADVIA Centaur XPT immunoassay. The reference cohort included 10,337 pregnant women who had no thyroid disease or other autoimmune diseases and were TPOAb- and TgAb negative. The main outcome measures were lower and upper reference limits (2.5th and 97.5th percentiles) for TSH and fT4 stratified by week of pregnancy. Blood samples were drawn in pregnancy weeks 4-20 (median week 10), and 92% of the pregnancies ended with a live birth. TSH varied considerably in the first trimester of pregnancy, and the levels were highest in early pregnancy (weeks 4-6: 0.6-3.7 mIU/L) followed by a gradual decline to lower levels in weeks 9-11 (0.1-2.8 mIU/L) and 12-14 (0.03-2.8 mIU/L). Maternal fT4 showed less variation (weeks 4-6: 12-20 pmol/L; weeks 9-11: 13-21 pmol/L; weeks 12-14: 13-20 pmol/L). The results corroborate dynamic week-specific changes in maternal TSH in early pregnancy. The use of uniform lower and upper reference limits for TSH in early pregnancy may be too simple.

Isolated effect of maternal thyroid-stimulating hormone, free thyroxine and antithyroid peroxidase antibodies in early pregnancy on gestational diabetes mellitus: a birth cohort study in China.

This article aims to understand the isolated effect of maternal thyroid-stimulating hormone (TSH), free thyroxine (FT4) and antithyroid peroxidase antibodies (TPOAb) in early pregnancy on gestational diabetes mellitus (GDM). Based on a birth cohort, pregnant women presented to maternity hospitals for the first antenatal care from Nov 2008 to Oct 2010 were invited to participate in the study. A self-administered questionnaire was asked to complete to collect data on socio-economic variables, previous adverse pregnancy outcomes, method of conception, previous endocrinic and metabolic diseases, and pregnancy-related anxiety in 1st trimester of the index pregnancy. Pre-pregnancy BMI was measured. Serum samples were collected, and TSH, FT4 and TPOAb were assayed. GDM was confirmed from medical records screened on 24-28 gestational weeks by using oral glucose tolerance test (OGTT). The prevalence of isolated subclinical hypothyroidism, hypothyroidemia and positive TPOAb in early pregnancy was 2.0%, 2.0% and 12.8%. Prevalence of GDM in women with the isolated sub-clinical hypothyroidism, hypothyroxinemia and positive TPOAb was 2.9%, 2.8% and 3.1%, respectively, which were all higher than that detected in euthyroidism women (1.2%). Women with isolated positive TPOAb had significantly higher TSH and lower FT4 level compared with euthyroidism women. It was found that isolated positive TPOAb in early pregnancy increased the risk of GDM, adjusted RR and 95%CI being 2.541(1.037-6.226). No significant relationships were identified between isolated sub-clinical hypothyroidism or hypothyroxinemia with GDM. In conclusion, isolated thyroid autoimmunity, represented by positive TPOAb, in early pregnancy were associated with GDM independent of TSH and FT4.

Resistance to thyroid hormone \u03b2 in autoimmune thyroid disease: a case report and review of literature

BackgroundResistance to thyroid hormone beta (RTHβ) results in symptoms of both increased and decreased thyroid hormone action. The effect of thyroid hormone changes in different types of autoimmune thyroid disease (AITD) in RTHβ is dynamic.Case presentationA 25-year-old Asian female had a RTHβ Y321C mutation with Hashimoto’s thyroiditis and type 2 diabetes mellitus. She was followed-up through gestation and two years postpartum, revealing development of postpartum thyroiditis (PPT) with characteristic wide fluctuations in serum thyrotropin levels, and of spontaneous recovery from an episode of transient hypothyroidism. The presence of RTHβ did not prolong thyroiditis duration nor progressed toward permanent hypothyroidism. Prenatal genetic analysis was not performed on the unaffected fetus, and did not result in congenital hypothyroidism, possibly because maternal free thyroxine (FT4) levels were mildly elevated at less than 50% above the reference range in early gestation and gradually decreased to less than 20% after the 28th gestational week.ConclusionIn RTHβ patients with autoimmune thyroid disease, episodes of thyroid dysfunction can significantly alter thyrotropin levels. During pregnancy, mildly elevated maternal free thyroxine levels less than 20% above the upper limit may not be harmful to unaffected fetuses. Unnecessary thyroid hormone control and fetal genetic testing was avoided during the gestational period with monthly follow-up.

Maternal thyroid function and child educational attainment: prospective cohort study

Objective: To determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment. Design: Prospective cohort study. Setting: Avon Longitudinal Study of Parents and Children cohort in the UK. Participants: 4615 mother-child pairs with an available first trimester sample (median 10 weeks gestation, interquartile range 8-12). Exposures: Free thyroxine, thyroid stimulating hormone, and thyroid peroxidase antibodies assessed as continuous measures and the seven clinical categories of maternal thyroid function. Main outcome measures: Five age-specific national curriculum assessments in 3580 children at entry stage assessment at 54 months, increasing up to 4461 children at their final school assessment at age 15. Results: No strong evidence of clinically meaningful associations of first trimester free thyroxine and thyroid stimulating hormone levels with entry stage assessment score or Standard Assessment Test scores at any of the key stages was found. Associations of maternal free thyroxine or thyroid stimulating hormone with the total number of General Certificates of Secondary Education (GCSEs) passed (range 0-16) were all close to the null: free thyroxine, rate ratio per pmol/L 1.00 (95% confidence interval 1.00 to 1.01); and thyroid stimulating hormone, rate ratio 0.98 (0.94 to 1.02). No important relationship was observed when more detailed capped scores of GCSEs allowing for both the number and grade of pass or when language, mathematics, and science performance were examined individually or when all educational assessments undertaken by an individual from school entry to leaving were considered. 200 (4.3%) mothers were newly identified as having hypothyroidism or subclinical hypothyroidism and 97 (2.1%) subclinical hyperthyroidism or hyperthyroidism. Children of mothers with thyroid dysfunction attained an equivalent number of GCSEs and equivalent grades as children of mothers with euthyroidism. Conclusions: Maternal thyroid dysfunction in early pregnancy does not have a clinically important association with impaired child performance at school or educational achievement.

Low thyroid-stimulating hormone and its persistence beyond the first trimester of pregnancy.

To investigate predictors of low thyroid-stimulating hormone (TSH) persisting beyond the first trimester and associated pregnancy outcomes. We retrospectively assessed the association between low first-trimester TSH and obstetric outcomes of singleton pregnancies in southern Israel between 2001 and 2011. We included women with first-trimester TSH and at least one other THS measurement. Clinical data were from maternity and community medical records. Among 3761 women, 185 (4.9%) had a TSH of 0.10mIU/L or less in the first trimester. Multiple of the median human chorionic gonadotropin was higher in women with TSH of 0.40mIU/L or less versus 0.41-4.0mIU/L, but was not associated with higher rates of persistent low TSH. Maternal age (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.00-1.16; per yearly increment), free thyroxine (FT4; OR 1.11, 95% CI 1.03-1.20; per ng/dL increment), and TSH of 0.10mIU/L or less (OR 3.06, 95% CI 1.38-6.80 vs 0.21-0.40mIU/L) were independent predictors of persistent low TSH. No adverse pregnancy outcomes occurred in women with low first-trimester TSH. Low TSH persisting beyond the first trimester was more common with increasing maternal age, elevated FT4, and TSH below 0.10mIU/L, but was not associated with obstetric complications.

The cognitive dissonance

The first 1000 days of life (the period between conception and the second birthday) is a window of opportunity for brain development, a unique period when the foundations for optimal growth and development of the nervous system are laid throughout the entire life. Previously it was believed that the main factor that negatively affects the psychomotor development of a child is maternal hypothyroidism in the early stages of pregnancy. However, numerous experimental and epidemiological studies have shown that the development of the nervous system of the fetus is disrupted when a woman has isolated hypothyroxinemia in early pregnancy. The cause of neuropsychiatric disorders in this case is the inadequate availability of maternal thyroxin for the developing brain. Universal salt iodization and fortification of flour with folic acid and iron is a reliable means of preventing micronutrient deficiency in the first 1000 days of life. It is important that this prevention begins before conception and lasts until the end of the neurogenesis period. However, in practice, effective mass methods of prevention are ignored in favor of certain “individual” approaches, the possibilities of which are severely limited.

Disruption in Thyroid Signaling Pathway: A Mechanism for the Effect of Endocrine-Disrupting Chemicals on Child Neurodevelopment.

Thyroid hormones are crucial in normal brain development. Transient and mild thyroid hormone insufficiency in pregnancy is also associated with impaired neurodevelopment in the offspring (e.g., 3–4 IQ score loss in association with maternal free thyroxine in the lowest fifth percentile). While inadequate iodine intake remains the most common underlying cause of mild thyroid hormone insufficiency in vulnerable populations including pregnant women, other factors such as exposure to environmental contaminants have recently attracted increasing attention, in particular in interaction with iodine deficiency. Endocrine-disrupting chemicals (EDCs) are natural and synthetic substances with ubiquitous exposure in children and adults including pregnant women. EDCs interfere, temporarily or permanently, with hormonal signaling pathways in the endocrine system by binding to hormone receptors and modifying gene expression. Other mechanisms involve alterations in production, metabolism, and transfer of hormones. Experimental studies have shown that exposures to EDCs affect various brain processes such as neurogenesis, neural differentiation and migration, as well as neural connectivity. Neuroimaging studies confirm brain morphological abnormalities (e.g., cortical thinning) consistent with neurodevelopmental impairments as a result of EDC exposures at standard use levels. In this review, we provide an overview of present findings from toxicological and human studies on the anti-thyroid effect of EDCs with a specific attention to fetal and early childhood exposure. This brief overview highlights the need for additional multidisciplinary studies with a focus on thyroid disruption as an underlying mechanism for developmental neurotoxicity of EDC, which can provide insight into modifiable risk factors of developmental delays in children.

Maternal environment and craniofacial growth: geometric morphometric analysis of mandibular shape changes with in utero thyroxine overexposure in mice.

An estimated 3% of US pregnancies are affected by maternal thyroid dysfunction, with between one and three of every 1000 pregnancies being complicated by overactive maternal thyroid levels. Excess thyroid hormones are linked to neurological impairment and excessive craniofacial variation, affecting both endochondral and intramembranous bone. Using a geometric morphometric approach, this study evaluates the role of in utero thyroxine overexposure on the growth of offspring mandibles in a sample of 241 mice. Canonical variate analysis utilized 16 unilateral mandibular landmarks obtained from 3D micro-computed tomography to assess shape changes between unexposed controls (n = 63) and exposed mice (n = 178). By evaluating shape changes in the mandible among three age groups (15, 20 and 25 days postnatal) and different dosage levels (low, medium and high), this study found that excess maternal thyroxine alters offspring mandibular shape in both age- and dosage-dependent manners. Group differences in overall shape were significant (P < 0.001), and showed major changes in regions of the mandible associated with muscle attachment (coronoid process, gonial angle) and regions of growth largely governed by articulation with the cranial base (condyle) and occlusion (alveolus). These results compliment recent studies demonstrating that maternal thyroxine levels can alter thecranial base and cranial vault of offspring, contributing to a better understanding of both normal and abnormal mandibular development, as well as the medical implications of craniofacial growth and development.

Maternal urinary phthalate metabolites during pregnancy and thyroid hormone concentrations in maternal and cord sera: The HOME Study.

Phthalates, endocrine-disrupting chemicals that are commonly found in consumer products, may adversely affect thyroid hormones, but findings from prior epidemiologic studies are inconsistent. In a prospective cohort study, we investigated whether maternal urinary phthalate metabolite concentrations and phthalate mixtures measured during pregnancy were associated with thyroid hormones among pregnant women and newborns. We measured nine phthalate metabolites [monoethyl phthalate (MEP), mono-n-butyl phthalate, mono-isobutyl phthalate, monobenzyl phthalate (MBzP), and four monoesthers of di(2-ethylhexyl) phthalate] in urine collected at approximately 16 and 26 weeks' gestation among women in the Health Outcomes and Measures of the Environment Study (2003-2006, Cincinnati, Ohio). Thyroid stimulating hormone (TSH) and free and total thyroxine and triiodothyronine were measured in maternal serum at 16 weeks' gestation (n = 202) and cord serum at delivery (n = 276). We used multivariable linear regression to assess associations between individual urinary phthalate metabolites and concentrations of maternal or cord serum thyroid hormones. We used weighted quantile sum regression (WQS) to create a phthalate index describing combined concentrations of phthalate metabolites and to investigate associations of the phthalate index with individual thyroid hormones. With each 10-fold increase in 16-week maternal urinary MEP, maternal serum total thyroxine (TT4) decreased by 0.52 μg/dL (95% CI: -1.01, -0.03). For each 10-fold increase in average (16- and 26-week) maternal urinary MBzP, cord serum TSH decreased by 19% (95% CI: -33.1, -1.9). Among mothers, the phthalate index was inversely associated with maternal serum TT4 (WQS beta = -0.60; 95% CI: -1.01, -0.18). Among newborns, the phthalate index was inversely associated with both cord serum TSH (WQS beta = -0.11; 95% CI: -0.20, -0.03) and TT4 (WQS beta = -0.53; 95% CI: -0.90, -0.16). Our results suggest that co-exposure to multiple phthalates was inversely associated with certain thyroid hormones (TT4 in pregnant women and newborns, and TSH in newborns) in this birth cohort. These findings highlight the need to study chemical mixtures in environmental epidemiology.

Maternal thyroid function and child educational attainment: prospective cohort study

ObjectiveTo determine if first trimester maternal thyroid dysfunction is a critical determinant of child scholastic performance and overall educational attainment.DesignProspective cohort study.SettingAvon Longitudinal Study of Parents and Children cohort in...