Maternal FT4 Research Articles

Maternal Thyroid Function and Biochemical Markers of Placental Function in Early Pregnancy.

A link between maternal thyroid function and the placental biomarkers, soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), has been brought forward. This study aimed to describe their association in early pregnancy. Retrospective cohort study. Eight hundred and fifty-eight pregnant women from the North Denmark Region, 2013, with blood samples drawn in early pregnancy. Thyroid-stimulating hormone (TSH), free thyroxine (fT4), thyroid-peroxidase antibodies (TPO-Ab), thyroglobulin antibodies (Tg-Ab) (ADVIA Centaur XPT, Siemens Healthineers), sFlt-1 and PlGF (Kryptor Compact, ThermoFisher Scientific) were measured. The association between maternal TSH and fT4 and percentile (pc) levels of sFlt-1 and PlGF (< 25th pc, 25-75th pc, > 75th pc) was evaluated using regression analysis and reported as adjusted beta coefficient (aβ). The frequency of maternal thyroid autoantibodies (TPO-Ab > 60 U/mL or Tg-Ab > 33 U/mL) by pc levels of sFlt-1 and PlGF was compared using chi-squared test. Higher levels (> 75th pc) of sFlt-1 associated with lower TSH (aβ 0.62, 95% CI: 0.51-0.76) and higher fT4 (aβ 1.03, 95% CI: 1.01-1.05). Higher levels of PlGF associated with lower TSH (aβ 0.82, 95% CI: 0.69-0.98), but not with levels of fT4 (aβ 1.00, 95% CI: 0.97-1.02). No association with maternal thyroid autoantibodies was found (TPO-Ab: sFlt-1: p-value 0.5 and PlGF: p-value 0.1; Tg-Ab: sFlt-1: p-value 0.7 and PlGF: p-value 0.1). In a large cohort of Danish pregnant women, higher levels of sFlt-1 and PlGF associated with maternal thyroid function in early pregnancy, while there was no association with maternal thyroid autoantibodies.

Thyroid function monitoring during pregnancy in euthyroid women with thyroid autoimmunity.

Thyroid autoimmunity (TAI) may be present in 1-17% of pregnant women. Monitoring of thyroid function in euthyroid pregnant women positive for anti-thyroperoxidase antibodies (TPOAb+) is recommended. To determine the prevalence and possible clinical and biological risk factors of biochemical progression (rise in serum thyroid-stimulating hormone (TSH) > 2.5 mU/L) at second blood sampling during pregnancy, in euthyroid women (TSH ≤ 2.5 mU/L) according to their TPOAb status. This study included demographic and biological data from two previously published cohorts (n = 274 women from August 1996 to May 1997 Copenhagen cohort, and n = 66 women from January 2013 to December 2014 Brussels cohort) having at least two measurements of TSH and free thyroxine (FT4) and at least one of TPOAb during spontaneously achieved singleton pregnancies. The majority of women studied did not show biochemical progression. Only 4.2% progressed, significantly more frequently among TPOAb+ women, as compared to TPOAb- group (9.4 vs 2.7%, P = 0.015). No rise in serum TSH > 4 mU/L at 2nd sampling was observed. Higher baseline TSH levels were associated with biochemical progression in both TPOAb+ (P = 0.05) and TPOAb- women (P < 0.001), whereas maternal age, BMI, multiparity, smoking, FT4, and TPOAb concentrations were not significantly different between women with and without progression. Only a minority of euthyroid women with thyroid autoimmunity presented biochemical progression and none with a TSH > 4 mU/L. Larger studies are needed to better target the subset of women who would benefit most from repeated thyroid function monitoring during pregnancy.

Maternal thyroid function and offspring birth anthropometrics in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) and thyroid disorders have both been linked to adverse pregnancy and neonatal outcomes. Even small variations in thyroid function within the normal range may influence fetal growth. Our aim was to investigate whether maternal thyroid function is associated with newborn anthropometrics in PCOS and explore the potential modifying effect of metformin. Post-hoc analyses of two RCTs in which pregnant women with PCOS were randomized to metformin or placebo, from first trimester to delivery. Maternal serum levels of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at gestational weeks (gw) 5-12, 19, 32 and 36 in 309 singleton pregnancies. The mean z-scores of birthweight, birth length, and head circumference were estimated in the offspring. Associations of maternal thyroid parameters with offspring anthropometrics and the outcomes large for gestational age (LGA) and small for gestational age (SGA) were studied using linear and logistic regression models, with adjustment for body mass index (BMI) when relevant. Maternal fT4 at baseline was negatively associated with birth length (b= -0.09, p=0.048). Furthermore, ΔfT4 during pregnancy correlated positively to z-score of both birth weight and length (b=0.10, p=0.017 and b=0.10, p=0.047 respectively), independently of treatment group. TSH at baseline and gw19 was inversely associated with LGA (OR 0.47, p=0.012 and OR 0.58, p=0.042), while ΔTSH was positively associated with LGA (OR 1.99, p=0.023). There were inverse associations between TSH at baseline and SGA (OR 0.32, p=0.005) and between ΔfT4 and SGA (OR 0.59, p=0.005) in the metformin group only. There were no associations between maternal thyroid function and head circumference of the newborns. In women with PCOS, a higher maternal fT4 in early pregnancy and a greater decrease in fT4 during pregnancy was associated with a lower offspring birthweight and shorter birth length. Higher TSH by mid-gestation and smaller increase in TSH during pregnancy was associated with less risk of LGA. Subclinical variations in maternal thyroid function might play a role for birth anthropometrics of PCOS offspring.

Associations of Ambient Particulate Matter with Maternal Thyroid Autoimmunity and Thyroid Function in Early Pregnancy.

This prospective birth cohort study evaluated the association of exposure to PM2.5 (diameter ≤2.5 μm), PM1-2.5 (1-2.5 μm), and PM1 (≤1 μm) with maternal thyroid autoimmunity and function during early pregnancy. A total of 15,664 pregnant women were included at 6 to 13+6 gestation weeks in China from 2018 to 2020. Single-pollutant models using generalized linear models (GLMs) showed that each 10 μg/m3 increase in PM2.5 and PM1-2.5 was related with 6% (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.01, 1.12) and 15% (OR = 1.15, 95% CI: 1.08, 1.22) increases in the risk of thyroid autoimmunity, respectively. The odds of thyroid autoimmunity significantly increased with each interquartile range increase in PM2.5 and PM1-2.5 exposure (P for trend <0.001). PM1 exposure was not significantly associated with thyroid autoimmunity. GLM with natural cubic splines demonstrated that increases in PM2.5 and PM1-2.5 exposure were associated with lower maternal FT4 levels, while a negative association between PM1 and FT4 levels was found when exposure exceeded 32.13 μg/m3. Only PM2.5 exposure was positively associated with thyrotropin (TSH) levels. Our findings suggest that high PM exposure is associated with maternal thyroid disruption during the early pregnancy.

Thyroid autoimmunity in euthyroid pregnant women is associated with slower productive language acquisition: the Odense child cohort study.

Maternal thyroid autoimmunity and thyroid function in early pregnancy may impact fetal neurodevelopment. We aimed to investigate how thyroid autoimmunity and thyroid function in early pregnancy were associated with language acquisition in offspring at 12-36 months of age. This study was embedded in the prospective Odense child cohort. Mother-child dyads were excluded in case of maternal intake of thyroid medication during pregnancy. The parents completed MacArthur-Bates Communicative Development Inventories (MB-CDI) every third month to assess their offspring's productive vocabulary. All completed reports for each child were included in the analyses. Logistic growth curve models evaluated associations between MB-CDI scores and levels of maternal thyroid peroxidase antibodies (TPOAb), free thyroxine (FT4), and thyrotropin, respectively, measured in early pregnancy (median gestational week 12). All models were stratified by offspring sex and adjusted for maternal age, education, pre-pregnancy body mass index, parity, breastfeeding, and offspring age. The study included 735 mother-child dyads. Children born to mothers with TPOAb ≥11 kIU/L, opposed to TPOAb <11 kIU/L, had a lower probability of producing words at age 18-36 months for girls (OR = 0.78, P < 0.001) and 33-36 months for boys (OR = 0.83, P < 0.001). The probability of producing words was higher in girls at 30-36 months of age with low-normal maternal FT4 vs high-normal FT4 (OR = 0.60, P < 0.001), and a similar trend was seen in boys. Results were ambiguous for thyrotropin. In women without known thyroid disease, TPOAb positivity in early pregnancy was negatively associated with productive vocabulary acquisition in girls and boys. This association was not mediated by a decreased thyroid function, as low-normal maternal FT4, unexpectedly, indicated better vocabulary acquisition. Our results support that maternal thyroid autoimmunity per se may affect fetal neurodevelopment.

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.

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

The Effects of Maternal Smoking on Thyroid Function: Findings from Routine First-Trimester Sonographic Anomaly Screening.

This study aimed to assess the effect of tobacco exposure on maternal thyroid function and investigate its relationship to subclinical hypothyroidism in pregnant women during the first trimester. A comparison of maternal thyroid function was made on 45 smokers, who composed the study group, and 72 non-smokers, pregnant women, who constituted the control group. After determining smokers by questionnaire, carbon monoxide (CO) levels in the expiratory air of the participants in both groups were measured and recorded, and the smokers' exposure was objectively confirmed. Smoking and non-smoking pregnant women were similar regarding body mass index (BMI). While the TSH and fT4 levels were respectively 1.48 mlU/L and 11.43 pmol/L in pregnant women who smoked, that ratio changed to 1.72 mlU/L and 11.17 pmol/L in the non-smokers' group. But the differences between the groups were not statistically significant (p=0.239, p=0.179). Even though the rate of subclinical hypothyroidism was 8.9% in the smoking group, it was approximately 19.4% in the non-smoker group; the difference was not statistically significant (p=0.187). This study proved that there is no statistically significant difference between maternal serum TSH and fT4 levels and the rate of subclinical hypothyroidism in smokers during pregnancy in the first trimester.

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.

Maternal Thyroid Function During Pregnancy and Offspring White Matter Microstructure in Early Adulthood: A Prospective Birth Cohort Study.

Background: The fetus is fully dependent on maternal thyroid hormones until mid-gestation and suboptimal maternal thyroid function has been associated with alterations in the neurodevelopment of the offspring. We used maternal free thyroxine (fT4) and thyrotropin (TSH) levels in early gestation to study the association of maternal thyroid function during early pregnancy and offspring brain white matter (WM) integrity in early adulthood. Methods: Our study population consisted of a total of 292 mother-child pairs. Maternal fT4 and TSH were used as predictors and offspring multimodal imaging measures of fractional anisotropy, mean diffusivity, and magnetization transfer ratio (FA, MD, and MTR) as dependent variables. First, as Global analysis, all analyzed 14 WM tracts were studied simultaneously using linear-mixed effect models. Second, if a global effect was detected, a post hoc Tract-wise analysis was carried out using linear models individually in each WM tract. Study population was stratified by sex. Results: We found a positive association between maternal fT4 and offspring Global FA in males when adjusted for all maternal and offspring covariates (n = 114; β = 0.154; confidence interval = 0.045-0.263; p = 0.006). The finding was observed to be driven by multiple WM tracts, of which three projection fiber tracts and the forceps minor survived correcting for multiple comparisons in Tract-wise analysis. Conclusions: Maternal thyroid function in early pregnancy was observed to be associated with WM microstructure in male offspring in early adulthood. Our results suggest that maternal fT4 levels in early pregnancy may modulate axonal characteristics, with a long-term effect on offspring WM development.

Association of Maternal TSH, FT4 With Children's BMI Trajectories, and Obesity: A Birth Cohort Study.

To investigate the association between maternal TSH, free thyroxine (FT4), and children's body mass index (BMI) trajectories and obesity. Based on the Ma'anshan Birth Cohort in China, we repeatedly assayed maternal thyroid functions in 3 trimesters of pregnancy. Children's height and weight were measured 15 times before they were age 6 years. Body fat was assessed when children were aged 6 years. Mplus software was used to fit maternal thyroid hormone trajectories and BMI trajectories. Multivariate logistic regression models and generalized linear models were used in data analysis. Low maternal FT4 trajectory was observed to be related to an increased risk of a high children's BMI trajectory and overweight, with an odds ratio and 95% CI of 1.580 (1.169-2.135) and 1.505 (1.064-2.129), respectively. Increased maternal FT4 concentrations in the first, second, and third trimesters were associated with a decreased risk of high children's BMI trajectories and obesity. There was a positive association between low maternal FT4 trajectory and 6-year-old children's body fat ratio with β and 95% CI of 0.983 (0.138-1.829). Furthermore, negative correlations between maternal FT4 concentration in the first, second, and third trimesters of pregnancy and body fat ratio were observed. Low maternal FT4 trajectory during pregnancy may predict a high BMI trajectory in children and relate to overweight and high body fat ratio in 6-year-old children. High maternal FT4 concentrations throughout pregnancy may be associated with the decreasing risk of obesity and low body fat ratio in 6-year-old children.

Does Iodine Intake Modify the Effect of Maternal Dysglycemia on Birth Weight in Mild-to-Moderate Iodine-Deficient Populations? A Mother-Newborn Prospective Cohort Study.

It is unclear how maternal glycemic status and maternal iodine status influence birth weight among individuals with mild-to-moderate iodine deficiency (ID). We studied the association between birth weight and both maternal glucose levels and iodine intake among pregnant women with mild-to-moderate ID. Glucose values were assessed using a glucose challenge test (GCT) and non-fasting glucose levels that were determined before delivery; individuals' iodine statuses were assessed using an iodine food frequency questionnaire; and serum thyroglobulin (Tg) and urinary iodine concentrations (UIC) were used to assess each group's iodine status. Thyroid antibodies and free thyroxine (FT4) levels were measured. Obstetric and anthropometric data were also collected. Large-for-gestational age (LGA) status was predicted using a Cox proportional hazards model with multiple confounders. Tg > 13 g/L was independently associated with LGA (adjusted hazard ratio = 3.4, 95% CI: 1.4-10.2, p = 0.001). Estimated iodine intake correlated with FT4 among participants who reported consuming iodine-containing supplements (ICS) after adjusting for confounders (β = 0.4, 95% CI: 0.0002-0.0008, p = 0.001). Newborn weight percentiles were inversely correlated with maternal FT4 values (β = -0.2 95% CI:-0.08--56.49, p = 0.049). We conclude that in mild-to-moderate ID regions, insufficient maternal iodine status may increase LGA risk. Iodine status and ICS intake may modify the effect that maternal dysglycemia has on offspring weight.

Mediation by Thyroid Hormone in the Relationships Between Gestational Exposure to Methylmercury and Birth Size

Our previous studies have linked gestational methylmercury exposure, originating from seafood, to changes in maternal thyroid hormones and infant birth size in a Swedish birth cohort. Herein we aimed to determine associations between maternal thyroid hormones and infant birth size and elucidate if maternal hormones could mediate the relationship between methylmercury and lower birth size. In 515 women, without known thyroid disease, we assessed metal exposure by erythrocyte mercury concentrations (mainly methylmercury, reflecting exposure over the past months) in early third trimester measured with inductively coupled plasma-mass spectrometry. Plasma concentrations of total and free thyroxine (tT4 and fT4) and triiodothyronine (tT3 and fT3), and thyroid-stimulating hormone (TSH) were measured at an accredited clinical laboratory. In multivariable-adjusted linear regression models, maternal tT3 (per 1 nmol/L increase) was positively associated with birth weight (B: 125 g; 95% CI 36, 214) and length (B: 0.59 cm; 95% CI 0.21, 0.97). Maternal fT4 was inversely associated with birth weight (B: − 33 g; 95% CI − 57, − 9.5), driven by obese women (n = 76). Causal mediation analyses suggested that a doubling of erythrocyte mercury (> 1 µg/kg; n = 374) was associated with a mean tT3-mediated decrease in birth weight of 11 g (95% CI − 25, − 1.6) and in birth length of 0.1 cm (95% CI − 0.12, − 0.01), both equivalent to about 12% of the total effect. To conclude, tT3 was positively associated with infant birth size. Reduced tT3 levels appeared to mediate a minor part of the inverse association between methylmercury exposure and birth size.

Triglycerides Mediate the Relationship Between Maternal Free Thyroxine and Birth Weight: A Prospective Cohort Study from China.

Fetal overgrowth (large for gestational age, LGA), is associated with an increased risk of maternal and fetal morbidity and adverse health outcomes. Thyroid hormones are key regulators of metabolism during pregnancy and fetal development. Lower maternal free thyroxine (FT4) and higher maternal triglyceride (TG) levels during early pregnancy are associated with higher birth weight. We aimed to examine the mediating role of maternal TG in the association between maternal FT4 and birth weight. We performed a large prospective cohort study including pregnant Chinese women who were treated at a tertiary obstetric center during the period of January 2016 to December 2018. We included 35,914 participants with complete medical records. We performed causal mediation analysis to decompose the overall effect of FT4 on birth weight and LGA with maternal TG as the mediator. We observed statistically significant associations between maternal FT4, TG levels and birth weight (all p<0.0001). Using a four-way decomposition model, we identified a controlled direct effect (coefficient [95% confidence interval, CI], -0.038 [-0.047 to -0.029], p<0.0001) that accounted for 63.9% of the total effect, in addition to the other three estimated effects (reference interaction, coefficient [95% CI]= -0.006 [-0.009 to -0.001], p=0.008; mediated interaction, coefficient [95% CI]= 0.0004 [0.000 to 0.001], p=0.008; and pure indirect effect, coefficient [95% CI]= -0.009 [-0.013 to -0.005], p<0.0001) of TG on the association between FT4 and birth weight z-score. Moreover, maternal TG accounted for 21.6% and 20.7% (via mediation) and 13.6% and 41.6% (via maternal FT4 and TG interaction) of the total effect of maternal FT4 on fetal birth weight and LGA, respectively. The proportions of the total associations that could be reduced by "eliminating" the effect of maternal TG were 36.1% for birth weight and 65.1% for LGA, respectively. High maternal TG levels may play substantial mediating roles in the relationship between low FT4 levels in early pregnancy and increased birth weight and a higher risk of LGA. Furthermore, the occurrence of fetal overgrowth may also be influenced by possible synergistic effects between FT4 and TG.

Thyroid hormones in canine pregnancy and lactation

It is believed that thyroid function has a significant effect on fertility and fetal development in mammals. So far, however, only few studies have been published about potential effects of the reproductive cycle stage on thyroid hormone concentrations in dogs. Therefore, over the course of 122 pregnant and non-pregnant cycles in healthy bitches, Thyroid stimulating hormone (TSH), free Thyroxine (fT4), total Thyroxine (tT4) and Progesterone (P4) were measured six times to assess the influence of the cycle stage and pregnancy on hormone concentrations. The aim was to evaluate established reference intervals for the thyroid hormones in a female study population. Of the 122 bitches, 98 became pregnant. Blood samples were collected during estrus, three times in pregnancy, during lactation and after weaning, or at equivalent times during and after estrus in non-pregnant dogs. No differences between pregnant and non-pregnant animals in any of the thyroid hormones were found. Hormone concentrations, however, differed significantly between the six samplings (p < .01). TSH initially declined during pregnancy, then rose again. The mean concentration of all dogs exceeded the overall upper reference limit of 0.70 ng/mL during lactation. Concentrations of tT4 and ft4 increased during the first third of pregnancy and then subsequently declined. The overall reference limits for tT4 were 0.47–3.20 μg/dL, and for fT4 4.86–29.60 pmol/L, but the reference intervals varied between the sampling dates. The observed patterns may reflect that maternal tT4 and fT4 seem to have important effects during early pregnancy, including a pronounced negative feedback effect on TSH. The initial increase and subsequent decline of tT4 and fT4 concentrations during the course of pregnancy is in accordance with findings in humans and may support the development of fetal thyroid function. The observed peak of TSH concentrations during lactation suggests that the demand for thyroid hormones in this phase is largest. Even if the underlying causes and mechanisms of thyroid regulation are not fully understood, the results of this study show relevant changes of hormone concentrations in the course of the sexual cycle and pregnancy. In that regard, cycle stage needs to be considered when assessing thyroid function in bitches.

Incidence of and Risk Factors for Neonatal Hypothyroidism Among Women with Graves' Disease Treated with Antithyroid Drugs Until Delivery.

Background: The incidence of neonatal hypothyroidism among newborns born to mothers with Graves' disease (GD) who continued antithyroid drug (ATD) treatment until delivery has never been reported. Objective: Our primary objective was to investigate the incidence of neonatal hypothyroidism among newborns born to mothers with GD who were treated with ATD until delivery. Our secondary objective was to identify the cutoff ATD daily doses for neonatal hypothyroidism risk, based on maternal thyrotropin (TSH) receptor antibody (TRAb) levels. Methods: We conducted a retrospective cohort study. We included 305 pregnant women with GD who were treated with an ATD until delivery (63 treated with methimazole [MMI] and 242 treated with propylthiouracil [PTU]). Umbilical cord TSH, free thyroxine (fT4), and TRAb levels were measured at delivery, and we investigated the respective relationships between neonatal hypothyroidism at delivery and maternal fT4 levels, TRAb levels, and daily ATD doses during pregnancy. Neonatal hypothyroidism was diagnosed when the umbilical cord fT4 level was below the lower limit of the reference range. Results: The incidence of neonatal hypothyroidism at delivery was 19.0% ([confidence interval, CI, 11.2-30.4]; 12/63) in the MMI group and 12.8% ([CI, 9.2-17.6]; 31/242) in the PTU group. Neonatal goiter was observed in one neonate in the PTU group, and two infants in the PTU group required levothyroxine treatment. The daily ATD dose in the third trimester was the strongest predictor of neonatal hypothyroidism at delivery; the cutoff MMI dose was 10 mg/day, and the cutoff PTU dose was 150 mg/day. When the maternal TRAb level in the third trimester was above three times the upper limit of the normal range, the cutoff MMI dose was 20 mg/day, and the cutoff PTU dose was 150 mg/day. Conclusions: Maternal fT4 and TRAb levels were higher in the neonatal hypothyroid group, which suggested prolonged GD activity. Careful follow-up is necessary when maternal GD remains active and the ATD dose to control maternal thyrotoxicosis cannot be reduced.

Effect of Iodine Nutrition Status on Thyroid Function and Pregnancy Outcomes.

Iodine is essential for normal thyroid function, supporting healthy fetal and child development. The relevance between maternal iodine nutrition status and pregnancy outcomes remains controversial. The aim was to explore whether urinary iodine concentrations (UIC)/urinary creatinine (UCr) was associated with thyroid function and adverse pregnancy outcomes. This study was performed in the Department of Endocrinology and Metabolism of the First Affiliated Hospital of Nanjing Medical University. A total of 212 pregnant women were enrolled from May 2018 to November 2021, from the first visit until postpartum. Maternal serum samples were obtained in the second half of pregnancy, and then thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine (FT3), UIC, and UCr were tested. The correlation of UIC/UCr, which represented maternal iodine nutrition status, with TSH, FT4, and FT3 was studied using linear regression. And we assessed associations between UIC/UCr and pregnancy outcomes. Notably, we explored consistency between UIC/UCr and the incidence of low birth weight (LBW) by application of logistic regression analysis. A total of 212 women were divided into 3 groups according to the upper and lower quartiles of UIC/UCr. There were 53 women in group 1 (UIC/UCr < 106.96 ug/g), 106 women in group 2 (UIC/UCr 106.96-259.08 ug/g), and 53 women in group 3 (UIC/UCr > 259.08 ug/g). The level of UIC/UCr had a negative correlation with FT4 (r = - 0.139, p = 0.043) but a positive correlation with TSH (r = 0.096, p = 0.162 > 0.05). There was a significant difference in the incidence of LBW among the 3 groups (p = 0.007). Logistic regression analysis found that the level of UIC/UCr was an independent factor for LBW (p = 0.048, OR = 0.991, 95%CI (0.982, 0.999)). The receiver operating characteristic (ROC) curve showed that the area under the curve (AUC) for UIC/UCr predicting the incidence of low birth weight was 0.687 (p = 0.013, 95%CI 0.575, 0.799). Lower UIC/UCr during pregnancy was associated with higher FT4 and lower TSH. And iodine deficiency during pregnancy is a risk factor for low birth weight. Our findings indicated that more attention should be paid to the appropriate iodine nutrition status in pregnant women, which can help prevent suffering from adverse pregnancy outcomes.

Triclosan in paired-maternal and cord blood, and their relationships with congenital heart disease of baby.

Prenatal triclosan (TCS) exposure has been reported to be associated with various birth outcomes and thyroid function, while the study of TCS exposure for congenital heart disease (CHD) patients is limited. In the present study, paired mother-fetus blood samples from CHD and healthy participants were collected to measure TCS exposure levels, and then check their relationship. Coupled with the concentrations of thyroid function biomarkers [free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), and thyroid antibodies (TgAb)] in maternal blood, we aimed to investigate whether the hormone-disrupting properties of TCS will affect its association with CHD. Our results indicated that the maternal TCS concentrations in the CHD group (median 0.31 ng/mL) were significantly lower than those in the control group (0.48 ng/mL, Mann Whitney U test, p = 0.01). Higher interquartile of TCS levels in maternal blood was associated with decrease odds of CHD (adjusted OR = 0.61, 95%CI: 0.41-0.91, p = 0.02). Maternal blood TCS higher than the cut-off value (25th quantile, 0.17 ng/mL) was significantly negatively associated with CHD risk (adjusted OR = 0.24, 95%CI: 0.09-0.62, p < 0.01). Besides, none of the thyroid biomarkers were significantly associated with maternal TCS exposure. However, maternal FT4 concentrations were positively correlated with TCS transplacental transfer rate and cord blood TCS levels (general linear regression, both p < 0.01). The results of molecular docking and dynamics simulation suggested that these correlations might be related to the transthyretin, a thyroid hormone-binding protein involved in the placental thyroid hormone transport system. Overall, our findings indicated that at normal exposure levels, the increase of maternal blood TCS concentration may have an inverse association with CHD, which merits further investigation.

Serum lipid profile in relation to free thyroxine and the effect of levothyroxine treatment on lipids in patients with isolated hypothyroxinemia during pregnancy: a single-center retrospective study

BackgroundThyroid function is widely considered a lipid metabolism regulator. However, studies on lipid metabolism in pregnant women with low free thyroxine (FT4) levels are limited and inconclusive. Furthermore, the association between maternal FT4 deficiency and adverse lipid metabolic parameters is unknown. Therefore, we aimed to investigate this association and the effects of levothyroxine (L-T4) treatment on these metabolic indicators.MethodsThis retrospective study included 164 patients with isolated hypothyroidism (IH) (FT4 levels below the 5th percentile with normal thyroid stimulating hormone levels according to the gestational-specific reference range) and 407 euthyroidism patients (control group who had regular antenatal examinations at Zhejiang Provincial People's Hospital, Hangzhou, China) between January 1, 2019, and December 31, 2020. Patients with IH were divided into levothyroxine (L-treatment group, n = 77) and dietary iodine supplement treatment groups (dietary treatment group, n=87) according to the hospital’s treatment policy and clinical experience. The intervention lasted for at least 8 weeks. Metabolic indicators, including thyroid function and lipid parameters, were collected at least twice before and after the intervention. Other data collected included maternal age, history of abortion, prepregnancy BMI, and gestational weight gain (Fig. 1).ResultsCompared with the control group, Patients with IH had a higher degree of dyslipidemia, reflected in elevated total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (Apo B) levels. In IH patients, an inverse correlation was found between FT4 and TG levels, which remained after adjusting for prepregnancy BMI. The L-treatment group demonstrated a significantly slower rate of hypercholesterolemia progression during pregnancy than the dietary treatment group. In addition, there was a relationship between the therapeutic effect and the degree of disease, with the main factors being FT4, TSH and TG levels prior to starting treatment.ConclusionsLow FT4 levels were associated with elevated blood lipid levels. Serum FT4 and lipid levels in patients could be improved by medical intervention.

Association of maternal TSH and neonatal metabolism: A large prospective cohort study in China.

Neonatal metabolites are very important in neonatal disease screening, and maternal thyroid hormones play an important role in fetal and neonatal health. Our study aimed to explore the association of maternal thyroid hormones with neonatal metabolites and identify an important time windows. Pregnant women were recruited in Jinan Maternity and Child Care Hospital and followed up until delivery. Multivariate generalized linear regression models (GLMs) and restricted cubic spline (RCS) regression analysis models were used to investigate the associations of maternal TSH and FT4 with neonatal metabolites. In total, 6,653 pairs of mothers and newborns were enrolled in our study. We identified 5 neonatal metabolites, including arginine/ornithine (Arg/Orn), C14:1/C2, C18:1, C3DC+C4OH and C8:1, that were significantly associated with maternal serum TSH during the whole pregnancy (P < 0.05), especially in the first trimester. Moreover, 10 neonatal metabolites were significantly associated with maternal serum FT4 (P < 0.05), most of which had positive correlations with maternal FT4 in the first trimester (P < 0.05). Some neonatal metabolites also had linear or nonlinear dose-effect relationships with maternal serum TSH and FT4 during the whole pregnancy, particularly in the first trimester. Our study, for the first time, provides epidemiological evidence that maternal serum TSH and FT4, especially during the first trimester, are associated with linear or nonlinear variations in neonatal metabolites. Efforts to identify newborn metabolism levels should carefully consider the effects of maternal thyroid function.