Maternal Thyroid Hormone Levels 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.

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.

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.

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.

OR14-03 The Thyroid Hormone Receptor Beta Genotype Of The Fetus Influences The Maternal Thyroid Function During Pregnancy

Abstract Disclosure: F. Salas Lucia: None. X. Liao: None. H. Jiang: None. A.M. Dumitrescu: None. S. Refetoff: None. J. Anselmo: None. When women with resistance to thyroid hormone beta (RTHβ) are pregnant, their high serum thyroid hormone (TH) levels are perceived as normal by affected fetuses (AfFe) carrying the same THRB mutation as their mothers. On the contrary, normal fetuses (NlFe) that do not carry the maternal THRB mutation are exposed to supraphysiologic TH levels and have unfavorable outcomes. This shows the impact maternal TH levels have on the fetus. However, whether the fetus might influence the maternal thyroid function remains unknown. To explore this possibility, we studied the maternal thyroid function tests (TFT) TSH, FT3, and FT4 throughout the pregnancies from 8 women harboring the R243Q THRB mutation (AfMo) during a total of 10 pregnancies: 6 carrying AfFe and 4 NlFe fetuses. Cord blood TFT from 3 of the NlFe and 3 AfFe at birth were also obtained. In addition, 8 pregnancies from 7 normal mothers (NlMo) carrying 4 AfFe who inherited the THRB mutation from the father and 4 NlFe were also evaluated for TFT. Cord blood from these pregnancies was not available. Results were compared to those in pregnancies of normal WT women. In all RTHβpregnancies, the maternal TSH values were within the range of pregnancies in WT women (0.35-4.94 mU/L) with an hCG-mediated nadir at the end of the first trimester. Maternal FT4 and FT3 values in RTHβpregnancies were above the upper limit of normal (ULN) of 100, peaking during weeks 5-16 (150±20% and 175±15% ULN, respectively) and progressively decreasing afterward. We found differences in maternal TFTdepending on the THRB genotype of the fetus. From weeks 25-32, the AfMo carrying an AfFe exhibited lower FT4 than when carrying a NlFe (96±2 vs. 108±5.3% ULN; p&amp;lt;0.05). Similarly, from weeks 25-40, the AfMo carrying an AfFe exhibited lower FT3 values than when carrying a NlFe ULN (110±11 vs. 134±13% ULN; p&amp;lt;0.05). While gestational age at delivery was similar in all RTHβ pregnancies, the NlFe had a lower birth body weight than the AfFe (2.3±0.1 vs. 3.1±0.2 kg; p&amp;lt;0.01). Cord blood TSH in NlFe was undetectable (&amp;lt;0.1 mU/L) but was 9.51 mU/L (2.2-10; range in normal neonates) in AfFe, which indicates that the thyroid function in NlFe could be restricted during pregnancy, but not in AfFe. Cord blood FT4 levels were similar in NlFe and AfFe (98.4±16.4 vs. 89.5±9.4% ULN). However, FT3 levels were significantly higher in NlFe than in AfFe (67.7±3.0 vs. 42.0±9.6% ULN; p&amp;lt;0.05) and represented ∼68, and ∼42% of the serum maternal FT3 level at birth, respectively. NlMo carrying either AfFe or NlFe showed similar TSH and FT3 levels during pregnancies. However, from weeks 33 to 40, FT4 levels were lower when carrying an AfFe than when carrying a NlFe (51.8±2.8 vs. 62.5±3.2% ULN; p&amp;lt;0.001). Our findings indicate that maternal thyroid function are influenced by THRB genotype of the fetus. The quantitation of placental and fetal TH transporters, deiodinases, and TH metabolites could provide insights into the mechanisms involved. Presentation: Friday, June 16, 2023

Ambient particulate matter, maternal thyroid function, and birth weight: A mediation analysis

BackgroundBirth weight (BW) is an indicator of fetal growth and development. Previous studies showed inconsistent results on the association of ambient particulate matter (PM) exposure with BW, and the role of maternal thyroid function has not been clarified. MethodsWe recruited 1711 gravidas between 2017 and 2019 in Henan, China. All participants were followed up until delivery. Daily concentrations of PM, including PM2.5 and PM10, were evaluated by using the spatial-temporal model. Maternal thyroid hormone (TH) levels were quantified by electrochemiluminescent microparticle immunoassay. Linear regression models were employed to examine the association among PM, BW, and maternal TH. Mediating effects of maternal TH interrelated with PM exposure on BW were investigated by causal mediation analyses. ResultsA total of 1049 gravidas were identified. We found that per 10 µg/m3 increase in PM2.5 and PM10 were associated with a decreased BW of 9.941 g, and 7.758 g (PM2.5: 95 %CI: −18.184, −1.698; PM10: 95 %CI: −14.436, −1.080). An inverse correlation of maternal FT4 levels with BW was found, with the pooled β of −319.983 g (95 %CI: −483.216, −156.750). We found a prominent positive correlation between gestational FT4 and PM exposure (PM2.5: β = 0.004, 95 %CI: 0.001, 0.007; PM10: β = 0.003, 95 %CI: 0.000, 0.006). Mediation analysis found that FT4 levels mediated the relationship between maternal PM exposure and BW, ranging from 5.55 % to 15.86 %. ConclusionsMaternal PM exposure may induce a reduction in newborn BW by affecting the maternal TH concentrations.

Roger Philip Ekins. 22 September 1926—26 July 2016

Roger Philip Ekins was born in London and educated at Westminster School. He studied natural sciences at Emmanuel College, Cambridge, and then returned to London, where he spent the rest of his career. His work initially focused on the thyroid gland and its disorders. In the 1950s, measurements of circulating hormones and other substances relied on biological assays. These were very time-consuming, inaccurate and unsuitable for routine clinical laboratories. In 1960, Ekins published the first radioactive assay for measuring the thyroid hormone thyroxine, using an approach he called ‘saturation analysis’; this and other work led to the systematic and accurate diagnosis of different forms of thyroid disease. He also developed tests for low-concentration biological substances, such as vitamin B 12 , always using simple and elegant techniques. In 1986, he was the first to propose the use of microarray ‘chip’ technologies for measuring these biological molecules simultaneously, recognizing that this could be applied to many other substances, such as oligonucleotides or peptides; he then worked with Boehringer Mannheim-Roche to develop the methodology. Meanwhile, he helped to identify the importance of thyroid hormones during human development, demonstrating that reduced levels of maternal thyroxine predicted the severity of the resulting ‘cretinism’ in their children. As a result, he went on to study the effects of abnormal levels of maternal thyroid hormones on fetal development, developing a rat model of maternal hypothyroidism. He travelled widely giving courses on standardization of the radioactive clinical assays, sponsored by the World Health Organization and the International Atomic Energy Agency. He received many UK and international awards for his work, including the Prince of Wales Award for Innovation in 1991 and the Dale Medal from the Society of Endocrinology in 1998. He was elected FRS in 2001.

Association of maternal urinary fluoride concentrations during pregnancy with size at birth and the potential mediation effect by maternal thyroid hormones: The Swedish NICE birth cohort

BackgroundObservational studies have indicated that elevated maternal fluoride exposure during pregnancy may impair child neurodevelopment but a potential impact on birth outcomes is understudied. ObjectivesTo evaluate the impact of gestational fluoride exposure on birth outcomes (birth size and gestational age at birth) and to assess the potential mediating role of maternal thyroid hormones. MethodsWe studied 583 mother-child dyads in the NICE cohort in northern Sweden. Maternal fluoride exposure was assessed by measuring urinary concentrations at late pregnancy (median: 29th gestational week) using an ion selective electrode. Plasma levels of free and total thyroxine (fT4, tT4) and triiodothyronine (fT3, tT3), and thyroid stimulating hormone (TSH) were measured with electrochemiluminescence immunoassays. The infant's weight, length, head circumference, and gestational age at birth were extracted from hospital records. ResultsMedian urinary fluoride concentration was 0.71 mg/L (5th-95th percentile 0.31–1.9 mg/L; specific gravity adjusted). In multivariable-adjusted regression models, every 1 mg/L increase of maternal urinary fluoride was associated with a mean increase in birth weight by 84 g (95%CI: 30, 138), length by 0.41 cm (95%CI: 0.18, 0.65), head circumference by 0.3 cm (95%CI: 0.1, 0.4), and with increased odds of being born large for gestational age (OR = 1.39, 95%CI: 1.03, 1.89). Every 1 mg/L increase of maternal urinary fluoride was also associated with a mean increase of the plasma fT3:fT4 ratio (B = 0.007, 95%CI: 0.000, 0.014), but not with the hormones or TSH. In mediation analyses, the maternal fT3:fT4 ratio did not explain the urinary fluoride-birth size relationships. DiscussionGestational urinary fluoride concentrations were associated with increased size at birth and even with increased odds of being born large for gestational age. The fluoride-related associations with increased size at birth were not explained by changes in maternal thyroid hormone levels.

Impact of High-Throughput Model Parameterization and Data Uncertainty on Thyroid-Based Toxicological Estimates for Pesticide Chemicals.

Chemical-induced alteration of maternal thyroid hormone levels may increase the risk of adverse neurodevelopmental outcomes in offspring. US federal risk assessments rely almost exclusively on apical endpoints in animal models for deriving points of departure (PODs). New approach methodologies (NAMs) such as high-throughput screening (HTS) and mechanistically informative in vitro human cell-based systems, combined with in vitro to in vivo extrapolation (IVIVE), supplement in vivo studies and provide an alternative approach to calculate/determine PODs. We examine how parameterization of IVIVE models impacts the comparison between IVIVE-derived equivalent administered doses (EADs) from thyroid-relevant in vitro assays and the POD values that serve as the basis for risk assessments. Pesticide chemicals with thyroid-based in vitro bioactivity data from the US Tox21 HTS program were included (n = 45). Depending on the model structure used for IVIVE analysis, up to 35 chemicals produced EAD values lower than the POD. A total of 10 chemicals produced EAD values higher than the POD regardless of the model structure. The relationship between IVIVE-derived EAD values and the in vivo-derived POD values is highly dependent on model parameterization. Here, we derive a range of potentially thyroid-relevant doses that incorporate uncertainty in modeling choices and in vitro assay data.

Maternal Thyroid Anomalies and Attention-Deficit Hyperactivity Disorder in Progeny.

Previous epidemiologic investigations suggested that maternal thyroid anomalies are a possible causal factor in attention-deficit hyperactivity disorder (ADHD) in progeny, yet clinical trials indicated that levothyroxine treatment was ineffective in preventing neurodevelopmental impairments. We used an Israeli cohort of 385,542 singleton births from 1999-2012 to explore the interrelated roles of maternal thyroid conditions, laboratory gestational thyroid hormone measurements, use of thyroid medications, and offspring ADHD. Analyses were performed using Cox proportional hazards models. Results indicated that maternal hypothyroidism diagnosis was associated with an elevated progeny ADHD hazard (adjusted hazard ratio= 1.14, 95% confidence interval= 1.10, 1.18). However, this association was unmitigated by gestational use of levothyroxine and was unexplained by maternal gestational thyroid hormone levels. Associations with gestational thyrotropin values and hypothyroxinemia were also observed but were robust only in mothers without other records indicative of a thyroid problem. Results indicated that maternal thyroid hypofunction was associated with progeny ADHD but possibly not due to a direct causal relationship. Instead, maternal thyroid hypofunction may serve as a proxy indicator for other factors that affect neurodevelopment through thyroid hormone independent pathways, which are thus unaffected by pharmaceutical treatments for thyroid hypofunction. Factors known to disrupt thyroid functioning should be examined for their independent ADHD-related effects.

Association of exposure to PM2.5-bound metals with maternal thyroid function in early pregnancy

Epidemiological evidence linking metals bound to ambient particulate matters with aerodynamic diameter less than 2.5 μm (PM2.5) and maternal thyroid function is limited. In this study, we investigated the association of PM2.5-bound metals with maternal thyroid hormones (TH) during the first trimester. We retrospectively reviewed data for 2528 pregnant women attending prenatal care in Jinhua Maternal and Child Health Care Hospital, Jinhua, China, from January to December 2018. Information including thyroid hormone levels and demographics was retrieved from existing medical records. We analyzed the concentration of 10 metals for collected particulate samples, and estimated their exposure levels during the first trimester for each woman. We employed multivariate linear regression models to estimate the association of exposure to individual PM2.5-bound metals with serum levels of maternal TH, and weighted quantile sum (WQS) to estimate the overall association of exposure to PM2.5-bound metals within a mixture. Higher exposures to most of the PM2.5-bound metals were associated with lower levels of maternal free thyroxine (FT4) and free triiodothyronine (FT3). The thyroid peroxidase antibody (TPOAb) or thyroglobulin antibody (TgAb) status had no effect modification on the observed associations. WQS analyses further suggested that Be, Ni, Tl and Ba contributed the most to the associations. These findings highlight the associations of exposure to PM2.5-bound metals with maternal thyroid function, and emphasize the public health significance of commitments to improve air quality.

Perinatal effects of maternal FT3/FT4 ratio on gestational transient thyrotoxicosis.

The effects of maternal thyroid hormone levels on the course of pregnancy and birth weight have attracted interest. The aim of the present study was to consider FT3 and FT3/FT4 ratio in the evaluation of the effects of maternal thyroid functions in gestational transient thyrotoxicosis (GTT). This case-control study included 45 patients with GTT and 45 healthy pregnant women. Maternal history before pregnancy, thyroid function tests, thyroid autoantibodies, and thyroid ultrasonography results in 6th to 10th weeks of pregnancy were used in the differential diagnosis of GTT. In both groups, the effects of FT3, FT4 and FT3/FT4 ratios on gestational age and birth weight were evaluated. There was no significant difference in the gestational age between the GTT and control groups (39,3±1,0 weeks and 39,2±1,2 weeks, respectively). Birth weights were similar in both groups (3205,2±4899 g and 3196,6±309,3 g, respectively). When maternal weight was adjusted, a positive correlation was observed between maternal FT3/FT4 ratio and birth weight (r=0,317, p=0,017). Additionally there was a positive correlation between the gestational age and the birth weight in the control group (ρ=0,726, p=0,001). GTT had no significant effect on the gestational age and the birth weight. On the other hand an increase in the maternal FT3/FT4 ratio had a positive effect on the birth weight in the patient with GTT. Maternal characteristics (age, weight, BMI) and FT3/FT4 ratio should be taken into consideration in future impact assessment studies on this issue.

Maternal essential metals, thyroid hormones, and fetal growth: Association and mediation analyses in Chinese pregnant women

BackgroundEssential metals play critical roles in fetal growth and development, but results from human studies are inconsistent. Additionally, whether maternal thyroid hormone (TH) levels mediate the associations between essential metals and fetal growth remains unknown. MethodsData for analysis were extracted from the Information System of Guangdong Women and Children Hospital between January 2017 and December 2019. Maternal levels of essential metals [copper (Cu), zinc (Zn), magnesium (Mg), and iron (Fe)] and THs were measured at the second trimester. Multivariate linear models were introduced to evaluate the potential associations between maternal essential metals, thyroid functions, and fetal growth, and the possible mediation effects of thyroid functions were explored in the median analyses. ResultsA total of 4186 mother-infant pairs were included in the present study. Maternal Fe levels were found to significantly increase birth weight in 272.91 g (95 % CI: 15.59, 530.22) among anemia group. Maternal Cu levels were positively associated with increased free triiodothyronine/free thyroxine ratio (FT3/FT4). Negative associations of Fe and Mg levels with thyroid-stimulating hormone (TSH) concentrations were observed, accompanied with the positive associations in relation to FT3, FT4 and FT3/FT4 ratio. Mediation analyses suggested that 72.01 % of the associations between Fe levels and birth length might be mediated by FT3 levels. Additionally, 25.85 % of the Cu-birth length association and 44.53 % of the Fe-birth length association could be explained by FT3/FT4 ratio. ConclusionOur findings suggest that maternal Cu, Mg, and Fe levels can alter TH concentrations, and maternal FT3 and FT3/FT4 ratio might be potential mediators on the developmental effects of Cu and Fe levels.

Associations of Prenatal Exposure to Triclosan and Maternal Thyroid Hormone Levels: A Systematic Review and Meta-Analysis.

ObjectiveTo quantitatively evaluate associations between exposure to triclosan during pregnancy and maternal thyroid hormone levels.MethodThe databases of PubMed, Embase, Web of Science and Cochrane Library were systematically searched to identify relevant studies on the relationship between prenatal exposure to triclosan and maternal levels of serum thyroid hormone published before October 22, 2019. Stata 12.0 was used to examine the heterogeneity among the eligible studies.ResultsSeven studies involving a total of 4,136 participants were included. Overall, descriptive analysis provided no indication that exposure to TCS during pregnancy was related to either maternal FT4 levels (ES = 0.01, 95% CI: −0.03 to 0.05, P = 0.00) or TSH levels (ES = −0.03, 95% CI: −0.13 to 0.07, P = 0.412). Although the results were statistically insignificant, with the increase of urine TCS concentration, maternal FT4 levels exhibited a tendency to increase while TSH levels had a tendency to decrease during pregnancy.ConclusionThe results indicated that exposure to triclosan during pregnancy has no significant influence on maternal levels of thyroid hormone. On account of the inconsistency of existing research designs and study locations, further studies and replication are necessary to confirm these findings.

Hyperthyroidism in pregnancy: evidence and hypothesis in fetal programming and development.

The management of hyperthyroidism in pregnant patients has been a topic of raised clinical awareness for decades. It is a strong recommendation that overt hyperthyroidism of Graves’ disease in pregnant women should be treated to prevent complications. The consequences of hyperthyroidism in pregnancy are less studied than hypothyroidism, and a literature review illustrates that the main burden of evidence to support current clinical guidance emerges from early observations of severe complications in Graves’ disease patients suffering from untreated hyperthyroidism in the pregnancy. On the other hand, the more long-term consequences in children born to mothers with hyperthyroidism are less clear. A hypothesis of fetal programming by maternal hyperthyroidism implies that excessive levels of maternal thyroid hormones impair fetal growth and development. Evidence from experimental studies provides clues on such mechanisms and report adverse developmental abnormalities in the fetal brain and other organs. Only few human studies addressed developmental outcomes in children born to mothers with hyperthyroidism and did not consistently support an association. In contrast, large observational human studies performed within the last decade substantiate a risk of teratogenic side effects to the use of antithyroid drugs in early pregnancy. Thus, scientific and clinical practice are challenged by the distinct role of the various exposures associated with Graves’ disease including the hyperthyroidism per se, the treatment, and thyroid autoimmunity. More basic and clinical studies are needed to extend knowledge on the effects of each exposure, on the potential interaction between exposures and with other determinants, and on the underlying mechanisms.

Understanding the Relationship Between Maternal Thyroid Hormones and Neurodevelopmental Outcomes

Background: In utero exposures to endocrine disrupting chemicals can impact a range of health outcomes for the offspring. Specifically, when considering potential disruptions to proper maternal thyroid functioning due to chemical exposures there is increasing concern that adverse neurodevelopmental outcomes may occur in the offspring. A preclinical outcome, hypothyroxinemia (low free thyroxine and thyroid stimulating hormone within the reference rage) is being recognized as a potential outcome of interest in understanding alterations in maternal thyroid functioning. Methods: A literature review on the associations between maternal thyroid hormone levels, including maternal hypothyroxinemia and offspring neurodevelopmental outcomes was conducted. Studies were categorized if the main analysis presented evaluated the risk of adverse neurological outcomes as a result of incremental changes in maternal fT4 or the categorical outcome of yes/no hypothyroxinemia. Results: We found that altered free thyroxine (fT4) in early pregnancy has the most evidence regarding the relationship between altered maternal thyroid hormone homeostasis and adverse neurodevelopmental outcomes in offspring. We will present multiple approaches to utilize data from the literature to evaluate the magnitude of impact from altered maternal fT4 levels on offspring neurodevelopment. These approaches consist of both evaluating dose-response relationships between maternal fT4 and offspring neurodevelopment and examining how shifts in distributions of thyroid hormone levels may place additional proportions of a population at risk. Conclusions: The presented methods can be used to assess the potential neurodevelopmental impacts on the fetus of a pregnant mother exposed to a chemical that may potentially alter homeostatic thyroid functioning (e.g., PCBs, perchlorate, PBDEs, PFAs, BPA)

Maternal Thyroid Anomalies and Risk of Attention Deficit Hyperactivity Disorder in Progeny

Background. The fetus is dependent on adequate maternal supply of thyroid hormones, which have important neurodevelopmental roles. Impaired thyroid function was linked with exposure to several environmental toxicants, and these thyroid-related effects may be a mechanism through which environmental toxicants affect neurodevelopment. Extreme maternal thyroid dyshomeostasis causes adverse neurodevelopmental effects, but impacts of subtler thyroid disruption remain unclear. We evaluated the risk of Attention Deficit Hyperactivity Disorder (ADHD) in children of mothers with thyroid anomalies, and the relation between gestational maternal thyroid hormone levels and child ADHD risk. Methods. The study included 445,477 singletons born in 1999-2012 in a large Israeli health fund, with data on ADHD diagnoses retrieved through 2019. Maternal thyroid conditions were ascertained through ICD-9 codes with subsequent validation through review of drug dispensing and laboratory data. ADHD cases were identified through ICD-9 codes, with additional information on dispensing of stimulants and nonstimulants medications. Analyses were performed using Cox proportional hazard and additive Poisson regression models employing a robust variance estimator. Results. Children of mothers who experienced hypothyroidism had a higher ADHD risk compared to children of mothers without thyroid conditions (HR=1.11, 95% C.I:1.07-1.15), with more robust results in the subgroup of ADHD children who also received pharmaceutical ADHD treatments. Hyperthyroidism results were less consistent. Results were materially unchanged when restricting to mothers gestationally treated with levothyroxine. Analysis of maternal gestational thyrotropin and free-thyroxine levels did not show consistent associations with ADHD risk. Conclusions. Maternal hypothyroidism was associated with increased child ADHD risk, but seemingly not due to direct effects of thyroid hormones. Instead, factors that influence maternal thyroid function may have etiologic roles in ADHD through pathways independent of maternal gestational thyroid hormones, and thus be unaffected by medication treatment. Environmental factors known to disrupt thyroid function should be examined for possible involvement in ADHD etiology.

Associations between prenatal exposure to organochlorine pesticides and thyroid hormone levels in mothers and infants: The Hokkaido study on environment and children's health

Organochlorine pesticides (OCPs) are environmental contaminants with potentially adverse effects on neurodevelopment. Previous findings on the association between prenatal exposure to OCPs and the maternal or infant thyroid hormone system are inconsistent. Moreover, the influence of exposure to multiple OCPs and other chemical compounds is not clearly understood. Our study therefore aimed to examine the association between OCP exposure and both maternal and infant thyroid hormone systems. We also explored multiple exposure effects of OCPs and the influence of each compound using weighted quantile sum (WQS) methods. The study population included 514 participants in the Hokkaido study, recruited from 2002 to 2005 at one hospital in Sapporo, Japan. To quantify 29 OCPs, maternal blood samples were analyzed using gas chromatography/mass spectrometry. Blood samples for measuring thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels were obtained from mothers during the early gestational stage (mean 11.4 weeks), and from infants between 7 and 43 days of age. The data of 333 mother child pairs with OCP and thyroid hormone measurements were included in the final analyses. Multivariate regression models showed a negative association between maternal FT4 and levels of o,p’-dichlorodiphenyldichloroethylene (DDE), o,p’-dichlorodiphenyltrichloroethane (DDT), and dieldrin. The WQS analysis showed that o,p’-DDT (48.6%), cis-heptachlorepoxide (22.8%), dieldrin (15.4%) were the primary contributors to the significant multiple exposure effect of OCPs on maternal FT4. For infants, we found a positive association between FT4 and cis-nonachlor and mirex. The most contributory compounds in the multiple exposure effect were trans-nonachlor (27.1%) and cis-nonachlor (13.8%), while several compounds contributed to the WQS via small weights (0.4–9.1%). These results indicate that OCPs, even at very low levels, may influence maternal and child thyroid hormone levels, which could modulate child development.