Maternal Thyroid Hormone Research Articles

Associations between gestational exposure to perfluoroalkyl substances, fetal growth, and the mediation effect of thyroid hormones

Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances (PFASs) may cause adverse birth outcomes. Thyroid hormones may play a key role in mediating the effects of PFAS. We enrolled 374 mother-infant pairs from the Ezhou birth cohort study between 2019 and 2020. Eight PFASs and six thyroid hormones were measured in maternal serum during the first trimester of pregnancy. Neonatal growth metrics, including birth weight, length, head circumference, and gestational age, were acquired. Multivariate linear regression was performed to determine the associations between maternal serum PFAS and thyroid hormone levels and birth outcomes and a mediation analysis was also conducted. Except for perfluoroheptanoic acid (41.2%), the other seven PFAS detection rates were more than 85%, and the highest median concentration was observed for PFOSA with levels of 5.21 ng/mL. After controlling for typical confounders, we observed a decrease in birth length (cm) with increasing serum concentrations of perfluorononanoic acid (PFNA) (β = -0.54; 95% CI = -1.0, -0.08) and perfluorohexane sulfonate (PFHxS) (β = -0.64; 95% CI = -0.86, -0.42). Additionally, a decrease in birth head circumference was observed with increasing concentrations of perfluorooctanote (PFOA) (β = -0.73, 95% CI = -1.19, -0.27) and PFHxS (β = -0.30; 95% CI = -0.53, -0.07). Maternal free triiodothyronine (FT3) mediated 36.7% of the negative association between PFNA and birth length, and free thyroxine (FT4) mediated 30.8% of the effect of PFOA on head circumference. When performing stratified analysis by infant sex, the associations might differ between boys and girls. Our study suggested prenatal exposure to some PFASs was negatively associated with birth length and circumference, and FT3 and FT4 may partly mediate the association.

7912 Children's Neurodevelopmental Outcomes at School-Age After Conception with Hysterosalpingography Using Iodinated Contrast Media

Abstract Disclosure: S. Keestra: None. C. Kooper: None. N. van Welie: None. K. Dreyer: Grant Recipient; Self; research grants from Guerbet. Speaker; Self; travel and speaker fees Guerbet. R. van Eekelen: None. T. Roseboom: None. J. Oosterlaan: None. B. Mol: Consulting Fee; Self; Organon Laboratories, Norgine, Merck. Grant Recipient; Self; Merck. Stock Owner; Self; ObsEva. M. Finken: None. V. Mijatovic: Grant Recipient; Self; Guerbet, Merck, Ferring Pharmaceuticals. Speaker; Self; Guerbet, Merck, Ferring Pharmaceuticals. M. Königs: None. Thyroid hormone sufficiency in pregnancy is vital for children's neurodevelopment. Exposure to iodine excess can cause transient disruption of thyroid hormone synthesis through the Wolff-Chaikoff effect. Iodinated contrast media are commonly utilized in hysterosalpingography (HSG) as part of female fertility work-up. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone synthesis could jeopardize children's neurodevelopment. We compared the neurodevelopmental outcomes of 6-9-year-old children (n=69) conceived <6 months after HSG with 5-10 ml of oil-based contrast (iodine content: 480mg/ml) or water-based contrasts (iodine content: 250mg/ml) in the follow-up of a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). A community sample of naturally-conceived children (n=44) with similar age, sex and parental education was used as a comparison group (NTR9574). Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behaviour questionnaires for parents and teachers (Strengths and Difficulties Questionnaire (SDQ); Strengths and Weaknesses of ADHD Symptoms And Normal behaviour (SWAN)), and academic performance. Secondary outcomes were neurocognitive domains assessed in computerized tasks focussing on Processing & Control, Verbal Memory, Visual Memory, Verbal Working Memory, Visual Working Memory, and Visuomotor Integration (Emma Toolbox for Neurocognitive Functioning). We adjusted linear regression models for age, sex, and parental education, applying FDR correction for multiple comparisons. Additional analysis looked at children conceived within 4 weeks, 4-12 weeks, or >12 weeks after HSG. Children conceived <6 months after HSG had lower performance on intelligence tests (-6.81; 95%CI -10.97 to -2.65; p=0.02) and the neurocognitive domain Processing & Control (-0.52; 95%CI-0.84 to -0.19; p=0.02), with processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. In comparison to naturally-conceived children, children conceived <4 weeks after HSG had lower performance on intelligence tests, but there was no difference for children conceived 4-12 weeks and >12 weeks after HSG. Replication studies with higher power are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children's neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted. Presentation: 6/1/2024

The Mediating Role of Maternal Thyroid Hormones in the Relationship Between PAH Exposure and Neonatal Birth Weight

The Mediating Role of Maternal Thyroid Hormones in the Relationship Between PAH Exposure and Neonatal Birth Weight

Regulation of Thyroid Hormone: An Important Aspect During Pregnancy

Abstract: This paper provides a synopsis of maternal and fetal thyroid hormone stimulation during pregnancy. Treatment of thyroid illness during pregnancy is critical for avoiding negative maternal and fetal outcomes. Thyroid disorders are frequently asymptomatic and difficult to detect without specialized monitoring programs. Even mild maternal thyroid hormone insufficiency can result in fetal neurodevelopment difficulties. The thyroid is over-stimulated during pregnancy, resulting in alterations in thyroid hormone concentrations. Accurate thyroid function testing during pregnancy is crucial for both initiating thyroid hormone therapy and adjusting thyroid hormone dose in people who are already on thyroid hormone. Trimester-specific intervals are particularly critical during pregnancy, when thyroid insufficiency has been linked to poor obstetric outcomes and neuro-developmental impairments in the fetus. Knowing the natural changes in hormone concentrations that occur throughout pregnancy allows for customized supplementation of iodine when needed.

Maternal hypothyroidism and subsequent metabolic outcomes in children: a systematic review and meta-analysis

IntroductionAs the fetus relies on maternal thyroid hormones in early pregnancy, maternal hypothyroidism plays an important role in fetal development. However, the association between maternal hypothyroidism and metabolic disease in offspring is unclear.ObjectiveTo examine the association between maternal hypothyroidism in pregnancy and metabolic outcomes (obesity, hypertension, type 2 diabetes mellitus, and dyslipidemia) in children < 18 years.MethodsWe systematically searched 5 databases from inception to May 2023. Eligible studies included cohort, case-control, and randomized controlled trials involving children born to mothers with or without hypothyroidism in pregnancy. Data were pooled across studies using random-effects models for outcomes reported in at least three studies. Quality assessment was performed using the ROBINS-E tool for observational studies and the Cochrane Risk of Bias tool for trials.ResultsThe search identified 3221 articles, of which 7 studies were included (1 trial, 6 observational). All studies were conducted outside of North America and ranged in size from 250 to > 1 million children. The follow-up time ranged from 6 to 20 years. Included studies support an increased risk of hypertension and glucose dysregulation in offspring exposed to maternal hypothyroidism (hypertension: OR 1.08, 95% CI 0.75, 1.57 and HR 1.81, 95% CI 1.21, 2.69; diabetes: RR 2.7, 95% CI 0.7, 10). In the pooled analysis, maternal hypothyroidism was not associated with obesity in offspring (OR 1.04, 95% CI 0.64, 1.70).ConclusionThis study found inconsistent evidence on the association between maternal hypothyroidism in pregnancy and metabolic outcomes in offspring, though associations with hypertension and glucose dysregulation are possible.

Effects of gestational hypothyroidism on mouse brain development: Gabaergic systems and oxidative stress

Hormonal imbalance during pregnancy is a risk factor for neuropsychiatric impairment in the offspring. It has been suggested that hypothyroidism leads to dysfunction of cortical GABAergic interneurons and inhibitory system development that in turn underlies impairment of the central nervous system. Here we investigated how gestational hypothyroidism affected offspring GABAergic system development as well as redox regulation parameters, because of previous links identified between the two. Experimental Gestational Hypothyroidism (EGH) was induced in CD-1 mice with 0.02% methimazole (MMI) in drinking water from embryonic day 9 (E9) until tissue collection at embryonic day 14 (E14) or E18. We examined GABAergic cell distribution and inhibitory system development gene expression as well as redox relevant gene expression and direct measures across all embryos regardless of sex. Intrauterine restriction of maternal thyroid hormones significantly impacted both of these outcomes in brain, as well as altering redox regulation in the placenta. GAD67+ neuronal migration was reduced, accompanied by a disruption in gene expression influencing GABAergic cell migration and cortical inhibitory neural system development. EGH also altered embryonic brain gene expression of Gpx1, Nfe2l2, Cat levels in the dorsal E14 brains. Additionally, EGH resulted in elevated TBARS, Gpx1 and Nfe2l2 in the ventral E18 brains. Furthermore, EGH downregulated placental Gpx1 gene expression at E14 and increased protein oxidation at E18. These findings support the hypothesis that sufficient maternal thyroid hormone supply to the fetus influences central nervous system development, including processes of GABAergic system development and redox equilibrium.

Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight: A Cross-Sectional Study from the Zunyi Birth Cohort

Maternal Thyroid Hormones as Mediators between Phthalate Exposure and Neonatal Birth Weight: A Cross-Sectional Study from the Zunyi Birth Cohort

P-756 Neurodevelopmental outcomes at school-age after conception with hysterosalpingography using iodinated contrast media - follow-up of the nationwide multicentre H2Oil trial

Abstract Study question How does conception &amp;lt;6 months after hysterosalpingography (HSG) with iodinated contrast media affect the neurodevelopment of the offspring compared to naturally-conceived peers at a school-age? Summary answer Children conceived &amp;lt;6 months after HSG with iodinated contrast media perform lower on intelligence tests and information processing and attention control compared to naturally-conceived peers. What is known already Tubal patency in subfertile women is commonly assessed using hysterosalpingography (HSG), but the potential risks of exposure to high iodine content in contrast media used remains unknown. Exposure to iodine excess can cause transient reduction in thyroid hormone synthesis due to the Wolff-Chaikoff effect. Thyroid hormone sufficiency in early pregnancy is vital for children’s neurodevelopment. When conception occurs shortly after HSG with iodinated contrast, a temporary reduction of maternal and/or foetal thyroid hormone supply could jeopardize children’s neurodevelopment. Study design, size, duration We evaluated neurodevelopmental outcomes of 6–9-year-old children conceived &amp;lt;6 months after HSG with oil-based (iodine content: 480mg/ml) or water-based contrast (iodine content: 240-300mg/ml) in a nationwide randomised controlled trial (H2Oil trial; Netherlands; 2012-2014; NCT05168228). Naturally-conceived children (n = 44) with similar age, sex and parental education were used as a comparison group (NTR9574). We also compared children conceived &amp;lt;4w, 4-12w, &amp;gt;12w after HSG with those conceived naturally. The study took place January 2022 until November 2023. Participants/materials, setting, methods We contacted 140 mothers from the H2Oil trial, 69 children conceived &amp;lt;6m after HSG participated, and parallelly we recruited 44 naturally-conceived children. Primary outcomes were intelligence (Wechsler’s Intelligence Scale for Children V), behavioural functioning (SDQ and SWAN, administered to parents and teachers), and academic performance. Secondary outcomes were neurocognitive function assessed by a battery of computerized tests. We used linear regression adjusted for age, sex, and parental education and applied FDR correction. Main results and the role of chance Compared to naturally conceived children, children conceived &amp;lt;6m after HSG had lower performance on intelligence tests (-6.81; 95%CI-10.97 to -2.65; p = 0.02) and the neurocognitive domain Processing &amp; Control (-0.52; 95%CI-0.84 to -0.19; p = 0.02), with functions relating to information processing speed and consistency affected. No differences were found for other neurocognitive domains, behaviour or academic performance. Considering time between HSG and conception, intelligence scores were lower for children conceived &amp;lt;4w after HSG compared to naturally-conceived peers (-11.47; 95%CI-17.98 to -4.95; p = 0.03), while no significant differences were found for the groups of children conceived 4-12 weeks after HSG (-7.17; 95%CI -12.28 to -2.06; p = 0.10) or &amp;gt; 12 weeks after HSG (-4.20; 95%CI -9.33 to 0.94; p = 0.52). The findings of this study warrant replication in larger independent samples in order to evaluate the long-term neurodevelopment of children conceived after HSG with iodinated contrast media. Limitations, reasons for caution We aimed to recruit 64 children for each group, but our study was not sufficiently powered for small- and medium-sized differences. We did not collect information on the thyroid or iodine status of the mothers following HSG, and there is limited knowledge about pharmacokinetics of iodinated contrast media in humans. Wider implications of the findings Replication studies with are needed to further evaluate the safety of iodinated contrast media use periconception, including their effects on thyroid function and children’s neurodevelopment. Closer monitoring and treatment of thyroid dysfunction in the months following HSG may be warranted. Trial registration number NCT05168228

Maternal thyroid function in early pregnancy and offspring school performance and neurodevelopmental disorders.

Thyroid hormones are critical for neural development, and during the first trimester of pregnancy the fetus relies fully on maternal thyroid hormone production. To investigate the associations between maternal thyroid hormone levels in the first trimester with the child's school performance, risk of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). From the Copenhagen Primary Care Laboratory Pregnancy Database information on first trimester TSH and fT4 measurements in mothers of children born in 2000-2014 were linked with information on the child's standardized test scores in school, ADHD (patient record diagnoses and medication) and ASD (patient record diagnoses) until end of 2018. Associations of TSH and fT4 with the outcomes were individually assessed by linear mixed models and Cox regression models. The analyses were stratified by preexisting maternal thyroid disorders. TSH measurements were available for 17,909 mother-child dyads. Among those with children born in 2000-2009, 6,126 had a standardized school test score and were analyzed for the association between maternal thyroid hormone levels and child's school performance, and no support for an association was found. The association between thyroid hormone levels and child's risk of ADHD and ASD were analyzed for the 17,909 dyads and with no support for an association between thyroid hormone levels and these neurodevelopmental disorders. Stratification by preexisting maternal thyroid disorders did not affect the results. We found no evidence for associations between first trimester maternal thyroid hormone levels and child's school performance, or risk of ADHD or ASD.

Association between maternal and cord blood thyroid hormones, and urine iodine concentration with fetal growth.

We planned to evaluate the association of fetal and maternal thyroid hormones and maternal iodine status with neonates' anthropometric parameters. In this cross-sectional study, levels of thyrotropin were measured in maternal serum in the first trimester of pregnancy, and thyrotropin (TSH) and free thyroxin (fT4) were measured in cord blood serum samples at birth. Urinary iodine concentration (UIC) levels in random urine samples of mothers were measured in the third trimester of pregnancy. The relationship between UIC and thyroid hormone levels of mothers with neonates' anthropometric birth parameters of neonates was evaluated. One hundred eighty-eight mother-newborn pairs completed the study. Mean (SD) of cord blood TSH (CB-TSH), cord blood-free thyroxin (CB-FT4) values, and maternal TSH (M-TSH) levels were 8.8 (7.3) mIU/L, 1.01 (0.2) ng/dL, and 2.2 (0.9) mIU/L, respectively. After adjusting for confounders, there was a positive significant association between female neonate length and maternal TSH and log log-transformed CB TSH (LN_CB-TSH) (p<0.05). Median UIC (Q1-Q3) was 157 (53-241) μg/L, and there was no association between birth weight, birth length, and head circumferences of neonates and mothers' UIC (p>0.05). We found a positive correlation between maternal TSH in the first trimester of pregnancy and the birth length of newborns, and a negative correlation was observed between CB-TSH and birth length in girls, but it did not provide conclusive evidence for the relationship between maternal and neonatal thyroid hormone levels and birth weight. There was no association between maternal UIC levels in the third trimester and birth anthropometric parameters.

Neural harmony: revolutionizing thyroid nodule diagnosis with hybrid networks and genetic algorithms

In the contemporary world, thyroid disease poses a prevalent health issue, particularly affecting women’s well-being. Recognizing the significance of maternal thyroid (MT) hormones in fetal neurodevelopment during the first half of pregnancy, this study introduces the HNN-GSO model. This groundbreaking hybrid approach, utilizing the MT dataset, integrates ResNet-50 and Artificial Neural Network (ANN) within a Glow-worm Swarm Optimization (GSO) framework for optimal parameter tuning. With a comprehensive methodology involving dataset preprocessing and Genetic Algorithm (GA) for feature selection, our model leverages ResNet-50 for feature extraction and ANN for classification tasks. Implemented in Python, the HNN-GSO model outperforms existing models, including K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Logistic Regression (LR), Random Forest (RF), ResNet, GoogleNet, and ANN, achieving an impressive accuracy rate of 98%. This success underscores the effectiveness of our approach in complex classification tasks within machine learning (ML) and pattern recognition, specifically tailored to the Thyroid Ultrasound Images (TUI) Dataset. To provide a comprehensive understanding of performance, additional statistical measures such as precision, recall, and F1 score were considered. The HNN-GSO model consistently outperformed competitors across these metrics, showcasing its superiority in MT classification. The HNN-GSO model seamlessly combines ResNet-50's feature extraction, ANN's classification robustness, and GSO's optimization for unparalleled performance. This research offers a promising framework for advancing ML methodologies, enhancing accuracy, and efficiency in classification tasks related to MT health.

EVALUATION OF ADVERSE EFFECTS OF HYPOTHYROIDISM DURING ANTENATAL PERIOD WITH MATERNAL AND FETAL OUTCOMES IN SUBJECTS WITH SUBCLINICAL AND OVERT HYPOTHYROIDISM

Objectives: Maternal thyroid hormone excess or deficiency can influence the outcome of the mother and fetus at all stages of pregnancy as well as interfere with ovulation and infertility. In females who suffer from thyroid diseases before pregnancy or during pregnancy, these hormonal changes are magnified leading to adverse maternal and fetal outcomes. This study is done to evaluate the adverse effects of hypothyroidism during the antenatal period, maternal and fetal outcomes in patients with subclinical and overt hypothyroidism (OH). Methods: The present prospective case–control study was conducted in the Department of Obstetrics and Gynaecology, Government Medical College and Rajindra Hospital Patiala, Punjab, from August 2018 to July 2019. The study was conducted among 150 antenatal patients, who had singleton pregnancy irrespective of age and parity. A complete thyroid profile was done to segregate them into euthyroid, subclinical hypothyroidism, and OH. Patients were divided into two groups, In group I, there were 75 antenatal patients who were euthyroid, and in group II, there were 75 antenatal patients with subclinical or OH diagnosed in pregnancy or already on treatment. The adverse maternal and fetal complications were noted in two groups. Data were compared using t-test for parametric data and Chi-square test for non-parametric data. Data presented as mean and standard deviation with p≤0.05 was considered statistically significant. Results: In the current study, 4 (5.33%) patients in group II, 0 patient in group I had abortions giving p=0.011. 7 (9.3%) patients of group II, 0 patient in group I had intra uterine death giving a p=0.001. In group I, 1 (1.33%) patient, 8 (10.6%) patients in group II developed pregnancy-induced hypertension giving p=0.025. In group I, 6 (8%) patients, 25 (33.3%) in group II had preterm delivery giving p=0.018. In group I, 7 (9.33%) patients underwent induction of labor, and in group II, 19 (25.3%) patients were induced giving p=0.009. In group I, 2 (2.67%) patients, 10 (13.3%) patients in group II had undergone C-section giving p=0.006. In group I, 2 (2.67%) patients had fetal growth restriction babies as compared to 10 (13.3%) in group II giving p=0.006. In group I, 1 (1.33%) baby had an APGAR score &lt;9 at 5 min and 15 (20%) in group II patients giving p=0.001. Neonatal intensive care unit admissions were 7 (9.33%) in group I as compared to 19 (25.33%) in group II giving p=0.018. Conclusion: In the present study, it was observed that the prevalence of thyroid disorder in pregnant women is considerably high with subclinical hypothyroidism being most common followed by OH. A simple screening test of thyroid profile, if used to timely diagnose hypothyroidism a large number of maternal and fetal complications can be prevented.

Effect of thyroid function on offspring neurodevelopment in people receiving ART therapy: a prospective cohort study.

Adequate maternal thyroid hormone is vital for fetal neurodevelopment. Abnormal thyroid function can cause developmental defects in offspring from spontaneous pregnancies; however, research in assisted reproduction is lacking. To investigate the association between thyroid disorders and offspring neurodevelopment from assisted reproduction. Prospective cohort study. In this prospective and longitudinal birth cohort study (Jiangsu, China), we included 729 women who had their thyroid function tested before ART cycle and delivered liveborn babies between November 2015 and June 2020. Maternal thyroid function was assessed by measuring thyroid antibodies, free thyroxine, and serum thyroid-stimulating hormone. The third edition Bayley Scales of Infant and Toddler Development screening test (Bayley-III screening test) is used to assess the infant's neurodevelopment. In multivariate corrected linear regression analysis, infants of women with subclinical hypothyroidism demonstrated a significantly lower receptive communication score (β = -0.63, 95% CI [-1.12, -0.14], P = 0.013), with stratified analysis showing a significant association among female offspring (β = -0.87, 95% CI [-1.59, -0.15], P = 0.018) but null association among male offspring (β = -0.44, 95% CI [-1.03, 0.15], P = 0.145). No significant differences were found in assisted pregnancy population with normal thyroid function and positive antibodies according to the diagnostic cut-offs applied to normal pregnant women. Subclinical hypothyroidism in assisted pregnancies correlates with lower communication scores in 1-year-olds, especially in girls. Recommending medication for subclinical hypothyroidism throughout, regardless of thyroid autoantibody status.

Fluoride exposure and thyroid hormone levels in pregnancy: The MIREC cohort

BackgroundFluoride exposure may increase the risk of hypothyroidism, but results from previous studies are inconsistent at low-level fluoride exposure (i.e., ≤0.7 mg/L). Human studies of fluoride and thyroid hormone levels in pregnancy are scarce. ObjectivesWe examined associations between fluoride exposure and maternal thyroid hormone levels in a Canadian pregnancy cohort, with consideration for fetal sex-specific effects. MethodsWe measured fluoride concentrations in drinking water and spot urine samples collected during each trimester from 1876 pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) study. We also measured maternal thyroid stimulating hormone (TSH), free thyroxine (FT4), and total thyroxine (TT4) levels during the first trimester of pregnancy. We used linear and non-linear regression models to estimate associations between fluoride exposure and levels of TSH, FT4, and TT4. We explored effect modification by fetal sex and considered maternal iodine status as a potential confounder. ResultsA 1 mg/L increase in urinary fluoride was associated with a 0.30 (95 %CI: 0.08, 0.51) logarithmic unit (i.e., 35.0 %) increase in TSH among women pregnant with females, but not males (B = 0.02; 95 %CI: −0.16, 0.19). Relative to women with urinary fluoride concentrations in the first quartile (0.05–0.32 mg/L), those with levels in the third quartile (0.49–0.75 mg/L) had higher FT4 and TT4 (i.e., inverted J-shaped associations), but the association was not statistically significant after adjustment for covariates (p = 0.06). Water fluoride concentration showed a U-shaped association with maternal FT4, whereby women with water fluoride concentrations in the second (0.13–0.52 mg/L) and third (0.52–0.62 mg/L) quartiles had significantly lower FT4 compared to those with levels in the first quartile (0.04–0.13 mg/L). Adjustment for maternal iodine status did not change the results. DiscussionFluoride exposure was associated with alterations in maternal thyroid hormone levels, the magnitude of which appeared to vary by fetal sex. Given the importance of maternal thyroid hormones for fetal neurodevelopment, replication of findings is warranted.

Perinatal maternal exposure to high-dose sodium phenobarbital in the modified Comparative Thyroid Assay: no significant reduction in thyroid hormones in pups despite notable effects in dams.

We propose a modified Comparative Thyroid Assay (CTA, USEPA) utilizing a smaller number of Sprague-Dawley rats (N=10/group) that assesses brain thyroid hormone (TH) concentrations and periventricular heterotopia while maintaining assay sensitivity. Our recent findings demonstrated that a prenatal test cohort of the modified CTA detected a dose-dependent decrease in maternal serum T3 (up to -26%) and T4 (up to -44%) with sodium phenobarbital (NaPB) exposure at 1000 ppm and 1500 ppm, equivalent to intakes of 60 and 84 mg/kg/day, respectively. On gestation day (GD) 20, fetuses exhibited reduced serum (-26%) and brain (-29%) TH concentrations, although these reductions were not dose dependent. The present study expanded the treatment in a postnatal test cohort, with maternal exposure to NaPB (81-93 mg/kg/day) from GD6 to lactation day (LD) 21. We assessed serum and brain TH concentrations, and periventricular heterotopia in pups on postnatal days (PND) 4, 21, and 28. While LD21 dams showed significant reductions in serum T3 (up to -34%) and T4 (up to -54%), the pups did not exhibit significant TH suppression or periventricular heterotopia at any test point. Instead, a compensatory increase in T4 was observed in serum and brain of PND21 pups. The present study confirmed that perinatal maternal exposure to high doses of NaPB leads to a moderate decrease in maternal TH concentrations; however, the exposure of maternal rats to a similar dose of NaPB did not significantly reduce serum or brain TH concentrations in their postnatal offspring.

ISCHEMIA-MODIFIED ALBUMIN AND THYROID HORMONE LEVELS IN FIRST-TRIMESTER ABORTIONS: A RELATIONSHIP?

Objectives: The objectives are to estimate maternal thyroid hormone levels and ischemia-modified albumin (IMA) levels in first-trimester pregnancy loss and to study the correlation between the maternal thyroid hormone levels and the IMA. Patients and Methods: We recruited 45 pregnant women with recurrent pregnancy loss (RPL) from our obstetric clinic as cases and 45 healthy pregnant women with the same gestational age and successful pregnancy outcomes as controls. Results: There is no correlation between the maternal thyroid hormone levels and the IMA levels in first-trimester pregnancy loss. Maternal IMA levels appear to be elevated in women with early RPL. Conclusion: In cases of first-trimester pregnancy loss, there is no association between maternal thyroid hormone levels and IMA levels. IMA cannot be used for the diagnosis and follow-up of early RPL because maternal IMA levels appear to be higher in women with early RPL.

3 Fluoride Exposure and Hypothyroidism in Pregnant Women: A Potential Mechanism of Fluoride Neurotoxicity

Objective:Fluoride exposure has been associated with thyroid dysfunction, but fluoride's impact on thyroid function in pregnancy is unclear, especially during early gestation when the fetus is dependent on maternal thyroid hormone. We examined the potential thyroid-disrupting effects of maternal fluoride exposure in pregnancy and tested whether thyroid disruption in pregnancy mediates the association between maternal fluoride exposure and child intelligence quotient (IQ) among Canadian mother-child dyads living in areas with optimal fluoridation.Participants and Methods:We measured fluoride concentrations in drinking water and in spot urine samples collected in each trimester from pregnant women enrolled in the Maternal-Infant Research on Environmental Chemicals study. We also measured thyroid hormone (thyroid stimulating hormone [TSH], free thyroxine [FT4], and total thyroxine [TT4]) levels during the first trimester of pregnancy and categorized women as euthyroid (n=1301), subclinical hypothyroid (n=100), or primary hypothyroid (n=28). Those categorized as primary hypothyroid were combined with an additional 79 women who reported clinical diagnoses at time of study enrolment (total n=107). In a sample of 1508 women, we used logistic regression to estimate the association between fluoride exposure and risk of either subclinical or primary hypothyroidism, separately, and linear regression to estimate associations between fluoride exposure and women's thyroid hormone levels (TSH, FT4, TT4). We tested effect modification by child sex and thyroid peroxidase (TPO) antibody status. In a subsample of 439 mother-child pairs, we measured child Full-Scale IQ (FSIQ) at 3-4 years of age using the Wechsler Preschool and Primary Scale of Intelligence. We used linear regression to test associations between maternal hypothyroidism or thyroid hormone levels, and children's FSIQ scores. Finally, mediation analysis in the counterfactual framework was used to estimate the proportion of the effect of maternal fluoride exposure on child FSIQ mediated by maternal hypothyroidism, through evaluation of the natural direct (not through hypothyroidism) and indirect (through hypothyroidism) effects.Results:Using categorical measures of thyroid status, a 0.5 mg/L increase in water fluoride concentration was associated with a 1.64 (95% confidence interval [CI], 1.04 to 2.58) increased odds of primary hypothyroidism. This association was stronger among women with normal TPO antibody levels (&lt; 5.61 IU/mL) (odds ratio, 2.80; 95% CI, 1.24 to 6.36). In contrast, we did not find a significant association between maternal urinary fluoride and hypothyroidism. For continuous measures of thyroid hormone levels, a 1 mg/L increase in maternal urinary fluoride was associated with a 35% (p=0.01) increase in TSH among women pregnant with a female fetus. In our subsample analyses, children born to women with primary hypothyroidism had lower FSIQ than children of euthyroid women, especially among boys (B, 8.78; 95% CI, -16.78 to -0.79). In contrast, maternal TSH, FT4, and TT4 levels were not significantly associated with child FSIQ scores. Maternal primary hypothyroidism did not significantly mediate the relationship between maternal water fluoride concentration and child FSIQ (p natural indirect effect= .35).Conclusions:Fluoride in drinking water may increase the risk of hypothyroidism in pregnancy. Thyroid dysfunction in pregnancy may be one mechanism underlying developmental neurotoxicity of fluoride.

In Vitro and In Vivo Supplementation with Curcumin Promotes Hippocampal Neuronal Synapses Development in Rats by Inhibiting GSK-3β and Activating β-catenin.

The human fetal thyroid gland is not capable of producing thyroid hormones independently until 20 weeks of gestation, and if maternal thyroid hormone synthesis is inadequate in early pregnancy, fetal brain and nerve development may be affected by maternal hypothyroidism. Curcumin, which is isolated from turmeric (Curcuma longa), has been shown to be effective in repairing neurological disorders and is effective in relieving nerve damage when consumed over a long period of time. In this experiment, we investigated the effect of curcumin supplementation on synaptic development of rat hippocampal neurons. A cell model of oxidative damage and a young rat model of hypothyroidism were constructed, and model cells and rats were treated with triiodothyronine (T3), tetraiodothyronine (T4), and curcumin, respectively. Damage of nerve cells and animal brain tissues was examined, and the effect of curcumin in alleviating the blocked neurodevelopment was investigated. Further modulation of GSK-3β/β-catenin was performed to investigate the mechanism of action of curcumin. Ultimately, we found that T3-, T4-, and curcumin-treated model cells and young rats had increased numbers of synapses and good neurodevelopment. At the same time, we found that curcumin inhibited the production of GSK-3β and Axin to activate β-catenin. The inhibition of β-catenin weakened the therapeutic effect of curcumin, and the differences between the indicators and the model group disappeared. Both cellular and animal experiments supported that curcumin effectively alleviated the oxidative cell damage caused by thyroxine deficiency and activated the synaptogenic ability of nerve synapses by inhibiting GSK-3β and protecting β-catenin activity.

Maternal thyroid hormone receptor β activation in mice sparks brown fat thermogenesis in the offspring

It is well established that maternal thyroid hormones play an important role for the developing fetus; however, the consequences of maternal hyperthyroidism for the offspring remain poorly understood. Here we show in mice that maternal 3,3’,5-triiodothyronine (T3) treatment during pregnancy leads to improved glucose tolerance in the adult male offspring and hyperactivity of brown adipose tissue (BAT) thermogenesis in both sexes starting early after birth. The activated BAT provides advantages upon cold exposure, reducing the strain on other thermogenic organs like muscle. This maternal BAT programming requires intact maternal thyroid hormone receptor β (TRβ) signaling, as offspring of mothers lacking this receptor display the opposite phenotype. On the molecular level, we identify distinct T3 induced alterations in maternal serum metabolites, including choline, a key metabolite for healthy pregnancy. Taken together, our results connect maternal TRβ activation to the fetal programming of a thermoregulatory phenotype in the offspring.

Effect of in utero and lactational exposure to a thyroid hormone system disrupting chemical on mouse metabolome and brain transcriptome

Mice were exposed to a low dose of the model thyroid hormone disruptor, propylthiouracil. Although this had only a modest effect on maternal thyroid hormones production, postnatal analysis of the pups’ plasma by mass spectrometry and the brain striatum by RNA sequencing gave evidence of low lasting changes that could reflect an adverse effect on neurodevelopment. Overall, these methods proved to be sensitive enough to detect minor disruptions of thyroid hormone signalling in vivo.