High thyroid hormone sensitivity is associated with the risk of hypertensive disorders during pregnancy in euthyroid women: the mediating role of triglycerides

High thyroid hormone sensitivity is associated with the risk of hypertensive disorders during pregnancy in euthyroid women: the mediating role of triglycerides | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article High thyroid hormone sensitivity is associated with the risk of hypertensive disorders during pregnancy in euthyroid women: the mediating role of triglycerides Zexin Chen, Xialidan Alifu, Wanli Li, Yunxian Yu This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8051840/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 7 You are reading this latest preprint version Abstract Background Few studies have focused on the relationship between thyroid hormone sensitivity and hypertensive disorders of pregnancy (HDP) in euthyroid women. This study aimed to investigate this association among euthyroid pregnant women and the potential mediating effects of serum lipids. Methods This study was conducted at Zhoushan Maternal and Child Health Hospital, Zhejiang Province. The general sociodemographic characteristics and lifestyle behaviors of the participants were collected. Blood pressure was measured during pregnancy. Thyroid function data were extracted from medical records. GEE and logistic regression were applied to assess the associations of thyroid hormone sensitivity with longitudinal BP changes and HDP risk, respectively. A nested case‒control study was further adopted to validate the relationship and explore the mediating effects of serum lipids. Results Among the 4,041 pregnant women, 92 developed HDP. Early-pregnancy FT3/FT4 was positively associated with longitudinal increases in SBP (β = 14.78, P < 0.001) and DBP (β = 6.76, P < 0.001). The TFQI was negatively associated with SBP (β= -1.05, P = 0.003). The mid-pregnancy FT3/FT4 ratio was strongly associated with SBP (β = 14.74, P < 0.001) and DBP (β = 7.71, P < 0.001). In contrast, higher mid-pregnancy TFQI, TT4RI, and TSHI were associated with decreased SBP (TFQI: β=-1.96, P < 0.001; TT4RI: β=-0.07, P < 0.001; TSHI: β=-1.07, P < 0.001). Moreover, early-pregnancy FT3/FT4 was associated with increased HDP risk (OR = 27.23, 95% CI: 1.83–406.26). A similar association was found in mid-pregnancy (OR = 38.93, 95% CI: 4.26–355.49). Higher mid-pregnancy TT4RI, TSHI, and TFQI were associated with reduced HDP risk (TT4RI: OR = 0.96, 95% CI: 0.93–1.00; TSHI: OR = 0.65, 95% CI: 0.43–0.99; TFQI: OR = 0.48, 95% CI: 0.27–0.85). Mediation analysis indicated that TG mediated 18.7% of the FT3/FT4-HDP associations (β = 0.153, 95% CI: 0.018–0.390, P = 0.008) and 15.4% of the TFQI-HDP associations (β=-0.031, 95% CI: -0.068–0.000, P = 0.026). Conclusions In euthyroid pregnant women, high thyroid hormone sensitivity is associated with an increased risk of HDP. TGs mediate the associations between thyroid sensitivity (FT3/FT4 ratio and TFQI) and HDP. Trial registration: not applicable Thyroid hormone sensitivity Hypertensive Disorders during Pregnancy Triglycerides (TG) Serum lipid mediated effect. Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Hypertensive disorders during pregnancy (HDP) are a leading cause of maternal mortality worldwide, accounting for approximately 14% of such deaths[ 1 ]. The prevalence of HDP varies significantly across regions, with a global prevalence of 116 cases per 100,000 women of reproductive age. Previous studies have indicated that the prevalence of HDP among pregnant women in China ranges from 5% to 10%[ 2 – 4 ]. HDP is positively associated with various adverse maternal and fetal outcomes, including maternal death, miscarriage, preterm birth, stillbirth, cardiovascular diseases, and neuropsychiatric disorders[ 5 – 8 ]. Both the American Heart Association and the European Society of Cardiology have recognized HDP as a female-specific risk factor for cardiovascular disease (CVD). According to the China Health Statistical Yearbook 2020, HDP remains one of the top three causes of maternal mortality in China, accounting for 10.4% of maternal deaths in 2017. Therefore, it is crucial to conduct an in-depth exploration of the relevant risk factors and potential mechanisms underlying HDP. Thyroid hormones are crucial hormones synthesized and secreted by the thyroid gland and play indispensable roles in human growth and development, metabolic regulation, and the maintenance of various physiological functions[ 9 ]. Several studies have reported that thyroid dysfunction, such as hyperthyroidism and hypothyroidism, is associated with an increased risk of cardiovascular diseases[ 10 – 12 ]. In recent years, increasing attention has been given to the relationship between thyroid hormones and blood pressure. A nationwide survey in Spain involving 384,182 participants revealed that the risk of hypertension was 2.16 times greater in hyperthyroid patients than in nonhyperthyroid individuals[ 13 ]. Moreover, hypothyroidism and subclinical hypothyroidism have also been associated with cardiovascular diseases[ 11 , 14 – 19 ]. Nevertheless, several large prospective cohort studies have not demonstrated a significant association[ 19 – 21 ]. Considering the above inconsistent findings, population heterogeneity may be a key factor. Pregnancy is a unique physiological state during which thyroid hormone secretion markedly differs from that of the general population. Hence, more in-depth research on thyroid hormone levels and blood pressure among pregnant women is needed. At present, the majority of studies have focused on overt thyroid dysfunction during pregnancy[ 22 – 26 ]. However, the prevalence of overt thyroid dysfunction is relatively low in clinical practice. A nationwide European study of 46,283 pregnant women reported a prevalence of thyroid dysfunction of only 1.3%[ 27 ]. The findings in Chinese populations are consistent: a cross-sectional study including 26,166 pregnant women from 31 provinces in China revealed that the prevalence rates of hyperthyroidism and hypothyroidism were only 1.08% and 1.28%, respectively, whereas the rate of subclinical hypothyroidism was 14.28%[ 28 ]. Thus, the majority of pregnant women are euthyroid, but few studies have examined the association between thyroid function and the risk of hypertensive disorders in this population. Therefore, this study focused specifically on euthyroid pregnant women. Recent studies have increasingly utilized composite parameters rather than isolated thyroid indices to assess thyroid homeostasis[ 29 ]. The inconsistency in findings regarding thyroid function and cardiovascular risk may be attributable to differences in hormonal sensitivity[ 30 ]. Some previous studies have also shown that indices of thyroid hormone sensitivity are associated with various metabolic abnormalities in euthyroid individuals[ 30 – 33 ]. Further investigations suggested that thyroid hormone sensitivity may also be correlated with heart rate[ 34 ] and homocysteine levels[ 32 ] in euthyroid populations. Therefore, we hypothesize that thyroid hormone sensitivity may be associated with BP or hypertension during pregnancy in euthyroid women. Regrettably, relevant studies have not been reported. Notably, dyslipidemia is the third major risk factor for atherosclerotic cardiovascular disease (ASCVD). Lipids and lipoprotein particles, as potential pathological factors of cardiovascular diseases, play crucial roles in atherosclerosis and affect the inflammatory process as well as the functions of white blood cells, blood vessels and cardiac cells, thereby influencing blood vessels and the heart[ 35 ]. Previous studies have shown that thyroid hormones may regulate lipid metabolism by stimulating lipid mobilization and degradation in the liver and the synthesis of new fatty acids[ 36 – 38 ]. Epidemiological studies have also revealed a significant positive correlation between blood lipids and thyroid hormone sensitivity[ 39 ]. Hence, we speculate that serum lipids may play a mediating role in the relationship between thyroid hormone sensitivity and HDP. In summary, this study comprises two main components. First, we investigated the association between thyroid hormone sensitivity and longitudinal changes in BP in euthyroid pregnant women, as well as its relationship with HDP. A nested case‒control study was subsequently performed on the same cohort to further examine the potential mediating effect of serum lipids on this association. Methods Study design The pregnant women included in this study were derived from the Zhoushan Pregnant Women Cohort (ZPWC) established by our research group at Zhoushan Maternal and Child Health Hospital in August 2011. This study included participants who entered the ZPWC between June 2015 and January 2020. Participants Inclusion criteria (must meet all the following conditions): 1) Maternal age between 18 and 45 years; 2) Pregnancy confirmed at 8–14 gestational weeks and registration for perinatal health care at the study hospital (gestational age was determined on the basis of the last menstrual period and confirmed by ultrasound); 3) Availability of blood pressure monitoring data after 20 weeks of gestation; 4) Agreement to participate in the study and provision of signed informed consent. Exclusion criteria (meeting any of the following conditions): 1) Preexisting essential hypertension; 2) Systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg detected before 20 weeks of gestation; 3) History of hyperthyroidism, hypothyroidism, subclinical hypothyroidism, positive thyroid antibodies, or other thyroid disorders requiring medication; 4) Pprepregnancy diagnosis of anxiety disorders, phobias, obsessive‒compulsive disorder, depression, or a history of psychotropic medication use; 5) Threatened abortion or miscarriage; 6) Fetal malformation or abnormal development; 7) Twin or multiple pregnancies; 8) Malignancies, syphilis, HIV, liver or kidney diseases, or the use of assisted reproductive technologies; 9) Lack of thyroid function indicators during the first and second trimesters; 10) Inability to comprehend questionnaire content due to cognitive or educational limitations. 11) Participants who had already been diagnosed with hypertensive disorders of pregnancy before thyroid function and lipid testing (exclusion criteria for the case group in the mediation analysis). Collection of epidemiological data Baseline Survey Trained research assistants conducted face‒to-face interviews via questionnaires to collect general sociodemographic information (e.g., age, education level, occupation, marital status), lifestyle behaviors (e.g., smoking, alcohol consumption), dietary habits (e.g., intake of fish, meat, eggs, dairy products, vegetables, and fruits), reproductive and obstetric history (e.g., age at menarche, menstrual history, number of pregnancies and deliveries), history of past diseases (e.g., uterine fibroids, ovarian tumors, diabetes, hypertension), and history of adverse pregnancy outcomes (e.g., miscarriage, stillbirth, and preterm birth). Follow-up during the second and third trimesters Trained research assistants performed face‒to-face interviews via epidemiological questionnaires to gather information on changes in lifestyle behaviors and nutritional status during pregnancy in the second and third trimesters. The information of ZPWC cohort and questionnaire used in our study has previously been published by Shao B et al[ 40 ]. Sampling Blood Specimens On the day of the questionnaire survey in pregnant women after an 8-hour fast during the first, second, and third trimesters of pregnancy, as well as at delivery, approximately 5 mL of peripheral venous blood was collected from the superficial veins of the elbow into vacuum blood collection tubes containing ethylenediaminetetraacetic acid (EDTA) as an anticoagulant. After collection, the tubes were gently inverted several times to ensure thorough mixing of the blood with the EDTA coating the tube walls. The blood samples were then centrifuged at 1500×g for 10 minutes. Following centrifugation, the upper plasma layer and the intermediate leukocyte layer were carefully aliquoted into separate 2 mL cryovials. All the samples were stored in a freezer at -80°C. Definition of Variables Blood Pressure Measurement Blood pressure was measured via an electronic sphygmomanometer. After the pregnant woman had rested quietly for at least 5 minutes, she was instructed to sit upright with her back supported, her feet flat on the floor, and her limbs relaxed, ensuring that her arm was positioned at heart level. An appropriately sized cuff was selected. Initial measurements were taken on both arms, and the arm with the higher reading was selected for subsequent measurements. Two measurements were taken on the selected arm, with an interval of 1–2 minutes between each. The average of the two readings was recorded. If the systolic blood pressure (SBP) or diastolic blood pressure (DBP) differed by more than 5 mmHg between the two measurements, an additional measurement was taken after further rest, and the average of all three readings was used. Blood pressure measurements were obtained at the following six time points throughout pregnancy: ≤20 weeks, 20–24 weeks, 24–28 weeks, 28–32 weeks, 32–36 weeks, and ≥ 36 weeks. Definition of HDP Most international guidelines define gestational hypertension as a blood pressure (BP) reading of ≥ 140/90 mmHg[ 41 ]. This study adopted the following criteria: SBP ≥ 140 mmHg and/or DBP ≥ 90 mmHg after 20 weeks of gestation was used to diagnose HDP. This study focused exclusively on women who developed new-onset hypertension after 20 weeks of gestation. Thyroid hormone testing Thyroid hormone levels were routinely measured during pregnancy in the study participants. The thyroid function data used in this study were obtained from the electronic medical records system of Zhoushan Maternal and Child Health Hospital. Venous blood samples were collected from pregnant women after an 8-hour fast. The concentrations of thyroid hormones—including TSH, FT3, and FT4—were measured via a Beckman Coulter UniCel Dxl 800 Access immunoassay analyzer and its corresponding reagents. Measurements were taken at two time points: during the first trimester (before 14 weeks of gestation) and during the second trimester (20–24 weeks of gestation). Thyroid hormone sensitivity indices Thyroid hormone sensitivity was categorized into central and peripheral measures. Indicators used to assess central thyroid hormone sensitivity include the thyroid-stimulating hormone index (TSHI), the thyroid T4 resistance index (TT4RI), and the thyroid feedback quantile-based index (TFQI). Higher values of TSHI and TT4RI indicate lower central thyroid hormone sensitivity[ 42 , 43 ]. The specific formulas are as follows: TSHI = ln(TSH) + 0.1345×FT4 TT4RI = FT4 × TSH The TFQI is calculated via the following formula: TFQI = cdf(FT4) - [1 - cdf(TSH)] The TFQI values range from − 1 to 1. A negative value indicates greater pituitary sensitivity to thyroid hormones, whereas a positive value suggests reduced sensitivity[ 30 ]. Peripheral thyroid hormone sensitivity is evaluated via the FT3/FT4 ratio. A higher ratio of FT3 (the active form of thyroid hormone) to FT4 suggests increased peripheral metabolic activity and greater peripheral sensitivity to thyroid hormones. FT3/FT4 ratio = FT3/FT4 Units: TSH (mIU/L), FT3 (pmol/L), FT4 (pmol/L) Serum lipid measurement The mid-pregnancy serum lipid data in this study were extracted from the biochemical database of the study hospital. For lipid profiling, venous blood samples were collected from pregnant women after an 8-hour fast. The concentrations of blood lipids were measured via a Beckman AU5800 biochemical analyzer and its corresponding reagents. The lipid indicators included in this analysis were total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs). The lipid measurements were conducted during the second trimester, after the assessment of thyroid hormone levels and prior to blood pressure evaluation at 24–28 weeks of gestation. Statistical analysis In this study, descriptive statistics were performed for thyroid hormones and thyroid hormone sensitivity in the study population. The quantitative data are expressed as the means ± SDs, and the categorical data are presented as numbers and percentages. For continuous variables with a normal distribution, an independent samples t test was used for comparisons between two groups, and one-way analysis of variance (ANOVA) was applied for comparisons among multiple groups. For continuous variables with an abnormal distribution, the Kruskal‒Wallis test was used for intergroup comparisons. For categorical data, the chi-square test was employed for intergroup comparisons; in special cases, Fisher’s exact test or nonparametric tests were used instead. Considering that blood pressure monitoring during pregnancy involves longitudinal repeated measurements, a generalized estimating equation (GEE) regression model was subsequently used to analyze the associations between thyroid hormone/thyroid hormone sensitivity and longitudinal changes in blood pressure throughout pregnancy. Specifically, when the impact of second-trimester thyroid hormone sensitivity on longitudinal blood pressure was explored, only the four blood pressure measurements taken after the second-trimester thyroid hormone test were analyzed. Next, a restricted cubic spline (RCS) method was applied, with three knots set at the 25th, 50th, and 75th percentiles, to assess whether there was a potential nonlinear association between thyroid hormone sensitivity and HDP. This process was performed via the "plotRCS" package in R software. Furthermore, on the basis of the results of the RCS analysis, an unconditional logistic regression model was used to investigate the associations between different thyroid hormone sensitivity indices and the risk of developing HDP. Similarly, when the associations between second-trimester thyroid hormone sensitivity indices and HDP were analyzed, 5 participants who developed HDP before second-trimester thyroid hormone testing were excluded. Considering the substantial amount of missing lipid profile data among subjects during the second trimester, a nested case‒control study design was employed to further explore the mediating role of serum lipids. The matching criteria were as follows: age within ± 1 year, obesity status, and primiparity. Patients and controls were matched at a 1:2 ratio. Patients were defined as women with mid-pregnancy lipid profiles who developed HDP after lipid measurement. The data of thyroid hormone sensitivity indices in the first trimester, TG in the second trimester and HDP occurring after TG measurement were used for mediating effect analysis. The mediating effect of serum lipids was analyzed via R software (with the "Mediation" package, version 4.5.0), and the random seed number was set to 123456. On the basis of previous reports, all multivariate models above were adjusted for maternal age (continuous variable), parity, BMI, educational level, smoking, alcohol consumption, and gestational weight gain. Statistical analyses were performed via R software, and a two-tailed test with P < 0.05 was considered statistically significant. Results Associations between thyroid sensitivity and HDP Characteristics of the Study Population The detailed flow chart of the subjects is shown in Fig. 1 . The characteristics of the final 4,041 pregnant women are presented in Table 1 . The median age was 28.0 years (IQR: 26.0–32.0 years), and the median BMI was 21.08 kg/m² (IQR: 19.31–23.07 kg/m²). A total of 126 patients were prepregnant obese, accounting for 3.1% of the sample. A total of 2,326 cases were primiparas, accounting for 57.6% of the total. Few of the subjects reported smoking (including passive smoking) or drinking, with 22 (0.5%) and 41 (1.0%) cases, respectively. Table 1 The characteristics of the 4041 finally included pregnant women Variable Total subjects Non-HDP HDP P value N = 4041 N = 3949 N = 92 Age, years 28.0(26.0,32.0) 28.0(26.0, 32.0) 29.0(27.0, 33.0) 0.007 Parity Firstborn 2326 (57.6) 2270 (57.5) 56 (60.9) 0.793 Non-firstborn 1497 (37.0) 1466 (37.1) 31 (33.7) Unknown 218 (5.4) 213 (5.4) 5 (5.4) Height, cm 160.0(158.0,164.0) 160.0(158.0,164.0) 160.0(158.0,165.0) 0.781 Weight, kg 55.0(50.0, 60.0) 54.8(50.0, 60.0) 59.5(53.9, 69.0) < 0.001 Pre-pregnancy BMI, kg/m 2 21.08(19.31,23.07) 21.04(19.29,23.03) 23.39(21.05,26.46) < 0.001 Obesity No 3914 (96.9) 3836 (97.2) 78 (84.8) < 0.001 Yes 126(3.1) 112 (2.8) 14 (15.2) Education Junior high school or below 716 (17.7) 696 (17.6) 20 (21.7) 0.439 High school 699 (17.3) 681 (17.2) 18 (19.6) Junior college or above 2267 (56.1) 2223 (56.3) 44 (47.8) Unknown 359 (8.9) 349 (8.8) 10 (10.9) Smoking No 3995 (98.9) 3903 (98.8) 92 (100.0) 0.582 Yes 22 (0.5) 22 (0.6) 0 (0.0) Unknown 24 (0.6) 24 (0.6) 0 (0.0) Drinking No 3972 (98.3) 3881 (98.3) 91 (98.9) 0.719 Yes 41 (1.0) 40 (1.0) 1 (1.1) Unknown 28 (0.7) 28 (0.7) 0 (0.0) Among the 4,041 pregnant women, 92 (2.3%) developed HDP. In the HDP group, the median age and BMI were 29.0 years (IQR: 27.0–33.0 years) and 23.39 kg/m² (IQR: 21.05–26.46 kg/m²), respectively. Compared with those of non-HDP subjects, the age, weight, and prepregnancy BMI of HDP patients were significantly greater (all P < 0.05). In addition, obesity in the HDP group was also significantly greater than that in the non-HDP group ( P < 0.001). No significant differences were found in parity, height, educational level, smoking status or drinking status between the two groups. Distribution of thyroid hormone sensitivity As shown in Table 2 , in the first trimester of pregnancy, the levels of FT3/FT4, TT4RI, TSHI, and TFQI were 0.44 (0.39, 0.49), 11.80 (6.41, 18.15), 1.55 (0.95, 1.98), and − 0.01 (-0.22, 0.21), respectively. The FT3/FT4 ratio was significantly greater in the HDP group than in the non-HDP group ( P < 0.05). In the second trimester, the median levels of FT3/FT4, TT4RI, TSHI, and TFQI were 0.52 (0.46, 0.58), 13.85 (9.96, 18.87), 1.64 (1.31, 1.95), and − 0.01 (-0.27, 0.28), respectively. The FT3/FT4 ratio was significantly greater, and the TT4RI, TSHI, and TFQI were significantly lower in the HDP group than in the non-HDP group ( P < 0.05). Table 2 The distribution of thyroid hormone and thyroid hormone sensitivity Non-HDP HDP P value First-trimester Total N = 3949 N = 92 FT3, pmol/L 4.89 (4.53, 5.28) 4.88 (4.53, 5.28) 5.02 (4.68, 5.49) 0.011 FT4, pmol/L 11.03 (10.09, 12.17) 11.04 (10.10, 12.18) 10.50 (9.66, 11.90) 0.018 TSH, mIU 1.08 (0.59, 1.66) 1.08 (0.58, 1.66) 1.15 (0.72, 1.50) 0.577 F3/F4 0.44 (0.39, 0.49) 0.44 (0.39, 0.49) 0.47 (0.42, 0.51) < 0.001 TT4RI 11.80 (6.41, 18.15) 11.80 (6.41, 18.17) 12.24 (6.64, 16.51) 0.824 TSHI 1.55 (0.95, 1.98) 1.55 (0.94, 1.99) 1.61 (1.01, 1.92) 0.931 TFQI -0.01 (-0.22, 0.21) -0.01 (-0.22, 0.21) -0.05 (-0.24, 0.14) 0.104 Second-trimester Total N = 3949 N = 87 FT3, pmol/L 4.41 (4.09, 4.73) 4.40 (4.09, 4.72) 4.50 (4.22, 4.86) 0.022 FT4, pmol/L 8.48 (7.76, 9.29) 8.49 (7.77, 9.30) 8.02 (7.35, 8.77) < 0.001 TSH, mIU 1.64 (1.18, 2.22) 1.64 (1.19, 2.23) 1.59 (1.16, 2.04) 0.284 F3/F4 0.52 (0.46, 0.58) 0.52 (0.46, 0.58) 0.56 (0.50, 0.63) < 0.001 TT4RI 13.85 (9.96, 18.87) 13.88 (9.97, 18.96) 12.38 (9.13, 16.46) 0.027 TSHI 1.64 (1.31, 1.95) 1.64 (1.31, 1.95) 1.53 (1.21, 1.83) 0.021 TFQI -0.01 (-0.27, 0.28) 0.00 (-0.26, 0.28) -0.21 (-0.42, 0.14) < 0.001 Associations between thyroid hormone sensitivity and longitudinal changes in blood pressure during pregnancy In the first trimester, the multivariate GEE model analysis indicated that an increase in the FT3/FT4 ratio was positively associated with longitudinal SBP and DBP (SBP: β = 14.78, SE = 1.61, P < 0.001; DBP: β = 6.76, SE = 1.23, P < 0.001), whereas an increase in the TFQI was negatively associated with a longitudinal change in SBP (β= -1.05, SE = 0.36, P = 0.003) (Table 3.1 ). Table 3.1. Association between thyroid hormone sensitivity and longitudinal changes in blood pressure during first-trimester pregnancy(GEE model) Variables SBP P DBP P β (se) β (se) Univariate FT3/FT4 14.68(1.61) <0.001 6.64(1.22) <0.001 TFQI -0.89(0.35) 0.01 -0.08(0.27) 0.774 TT4RI -0.004(0.01) 0.761 -0.002(0.01) 0.982 TSHI 0.13(0.13) 0.346 -0.002(0.10) 0.988 Multivariate* FT3/FT4 14.78(1.62) <0.001 6.76(1.23) <0.001 TFQI -1.05(0.36) 0.003 / / TT4RI / / / / TSHI / / / / *:Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain Similarly, we also analyzed the relationship in the second trimester. This analysis included only the four blood pressure measurements taken after the second-trimester thyroid hormone assessment (Table 3.2). Multivariate GEE regression analysis revealed that an increased FT3/FT4 ratio was significantly associated with increases in both SBP and DBP (SBP: β = 14.74, SE = 1.51, P < 0.001; DBP: β = 7.71, SE = 1.13, P < 0.001). Conversely, increases in the TFQI, TT4RI, and TSHI were significantly associated with decreases in SBP (TFQI: β=-1.96, SE = 0.34, P < 0.001; TT4RI: β=-0.07, SE = 0.02, P < 0.001; TSHI: β=-1.07, SE = 0.26, P < 0.001). Furthermore, increased TFQI was also associated with a decrease in DBP (β=-0.86, SE = 0.26, P = 0.001). Table 3.2. Association between thyroid hormone sensitivity and longitudinal changes in blood pressure during second-trimester pregnancy(GEE model) Variables SBP P DBP P β (se) β (se) Univariate FT3/FT4 15.29(1.50) <0.001 7.89(1.11) <0.001 TFQI -1.87(0.33) <0.001 -0.79(0.26) 0.002 TT4RI -0.06(0.02) <0.001 -0.02(0.01) 0.132 TSHI -0.93(0.26) <0.001 -0.38(0.20) 0.057 Multivariate* FT3/FT4 14.74(1.51) <0.001 7.71(1.13) <0.001 TFQI -1.96(0.34) <0.001 -0.86(0.26) 0.001 TT4RI -0.07(0.02) <0.001 / / TSHI -1.07(0.26) <0.001 / / *:Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain Associations between thyroid hormone sensitivity and HDP As shown in Fig. 2 , the RCS results revealed significant nonlinear associations between each thyroid hormone sensitivity index and HDP risk (all P values for nonlinearity > 0.05). As shown in Table 4 , multivariate logistic regression analysis revealed that a higher FT3/FT4 ratio was significantly associated with an increased risk of HDP (OR = 27.23, 95% CI: 1.83–406.26, P = 0.017) after adjusting for covariates. Additionally, in the second trimester, the analysis was conducted after five subjects who developed HDP prior to the second-trimester thyroid hormone measurement were excluded. A similar association was found between the FT3/FT4 ratio and HDP (OR = 38.93, 95% CI: 4.26–355.49; P = 0.001). Interestingly, increases in three central thyroid sensitivity indices were associated with a reduced risk of HDP (TT4RI: OR = 0.96, 95% CI: 0.93–1.00, P = 0.038; TSHI: OR = 0.65, 95% CI: 0.43–0.99, P = 0.047; TFQI: OR = 0.48, 95% CI: 0.27–0.85, P = 0.012). Table 4 Association between thyroid hormone sensitivity and HDP Table 3.2. Association between thyroid hormone sensitivity and longitudinal changes in blood pressure during second-trimester pregnancy(GEE model) Variables SBP P DBP P β (se) β (se) Univariate FT3/FT4 15.29(1.50) < 0.001 7.89(1.11) < 0.001 TFQI -1.87(0.33) < 0.001 -0.79(0.26) 0.002 TT4RI -0.06(0.02) < 0.001 -0.02(0.01) 0.132 TSHI -0.93(0.26) < 0.001 -0.38(0.20) 0.057 Multivariate* FT3/FT4 14.74(1.51) < 0.001 7.71(1.13) < 0.001 TFQI -1.96(0.34) < 0.001 -0.86(0.26) 0.001 TT4RI -0.07(0.02) < 0.001 / / TSHI -1.07(0.26) < 0.001 / / *:Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain Mediating effect of blood lipids on the association between thyroid hormone sensitivity and HDP Finally, a total of 201 women, comprising 67 cases with HDP and 134 controls, were matched at a 1:2 ratio. The sociodemographic characteristics of the two groups were comparable, as shown in Table 5 . Interestingly, only the TG level was significantly elevated in the cases compared with the controls ( P = 0.0114). No statistically significant differences in TC, HDL-C, or LDL-C levels were detected between the two groups ( P > 0.05, Table 6 ). The necessary conditions for the mediation analysis of TG in the FT3/FT4-HDP and TFQI-HDP associations are all satisfied; the details are shown in Fig. 3 and Table 7 . Table 5 The characteristics of subjects in nested case-control study Variables OR(95%CI) P OR(95%CI)* P First-trimester F3/F4 185.76 (15.18-2272.63) < 0.001 27.23 (1.83-406.26) 0.017 TT4RI 1.00 (0.97–1.02) 0.906 / / TSHI 1.09 (0.85–1.39) 0.495 / / TFQI 0.60 (0.32–1.13) 0.111 / / Second-trimester F3/F4 176.40 (23.23-1339.43) < 0.001 38.93 (4.26-355.49) 0.001 TT4RI 0.96 (0.93-1.00) 0.025 0.96 (0.93-1.00) 0.038 TSHI 0.64 (0.43–0.95) 0.028 0.65 (0.43–0.99) 0.047 TFQI 0.38 (0.22–0.65) 0.001 0.48 (0.27–0.85) 0.012 *: Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain Table 6 The distribution of thyroid hormone sensitivity and serum lipid of subjects in nested case-control study (second-trimester) Variables Total Non-HDP HDP P value N = 201 N = 134 N = 67 Age, years 29.0(27.0, 33.0) 29.0(27.0, 33.0) 29.0(27.0, 33.5) 0.932 Parity Firstborn 126 (62.7) 84 (62.7) 42 (62.7) 0.911 Non-firstborn 62 (30.8) 42 (31.3) 20 (29.9) Unknown 13 (6.5) 8 (6.0) 5 (7.5) Height, cm 160.0(158.0, 164.0) 160.5(158.0, 164.0) 160.0(158.0, 165.0) 0.458 Weight, kg 56.0 (51.0, 62.0) 55.7 (50.0, 60.0) 58.0 (53.5, 66.3) 0.015 Pre-pregnancy BMI, kg/m 2 21.64 (19.81,24.03) 21.05 (19.41,23.41) 22.83 (20.54,25.21) 0.009 Obesity No 180 (89.6) 120 (89.6) 60 (89.6) 1.00 Yes 21 (10.4) 14 (10.4) 7 (10.4) Education Junior high school or below 39 (19.4) 26 (19.4) 13 (19.4) 0.695 High school 30 (14.9) 18 (13.4) 12 (17.9) junior college or above 112 (55.7) 78 (58.2) 34 (50.7) Unknown 20 (10.0) 12 ( 9.0) 8 (11.9) Smoking No 197 (98.0) 130 (97.0) 67 (100.0) 0.360 Yes 3 (1.5) 3 (2.2) 0 (0.0) Unknown 1 (0.5) 1 (0.7) 0 (0.0) Drinking No 198 (98.5) 131 (97.8) 67 (100.0) 0.467 Yes 2 (1.0) 2 (1.5) 0 (0.0) Unknown 1 (0.5) 1 (0.7) 0 (0.0) Table 7 Association between thyroid sensitivity, TG and HDP of subjects in nested case-control study (second-trimester) Variables Total Non-HDP HDP P value N = 201 N = 134 N = 67 FT3/FT4 0.54(0.48, 0.59) 0.53(0.46, 0.58) 0.55(0.50, 0.62) 0.006 TT4RI 13.94(10.14, 18.84) 14.57(10.99, 21.23) 12.67(9.16, 16.46) 0.027 TSHI 1.64(1.34, 1.95) 1.69(1.40, 2.05) 1.54(1.21, 1.83) 0.023 TFQI -0.01(-0.31, 0.26) 0.04(-0.25, 0.32) -0.18(-0.39, 0.17) 0.008 Cholesterol, mmol/L 6.07(5.41, 6.76) 6.08(5.38, 6.85) 6.01(5.44, 6.56) 0.615 HDL-C, mmol/L 1.80(1.52, 2.10) 1.81(1.59, 2.18) 1.75(1.47, 2.03) 0.081 LDL-C, mmol/L 3.20(2.47, 3.87) 3.30(2.48, 3.96) 3.16(2.45, 3.58) 0.252 TG, mmol/L 2.32(1.85, 2.92) 2.27(1.80,2.78) 2.48(2.05, 3.24) 0.014 We subsequently employed a mediation analysis. Regarding the mediating effect of TG on the FT3/FT4-HDP association (Table 8.1 ), the average causal mediating effect (ACME) was 0.153 (95% CI: 0.018–0.390, P = 0.008). The proportion of mediation was 18.7% ( P = 0.030). The overall relationships among TG, FT3/FT4 and HDP are shown in Fig. 4.1 . Furthermore, the mediating effect of TG on the TFQI-HDP association is shown in Table 8.2 . The ACME was − 0.031 (95% CI: -0.068–0.000, P = 0.026), and the proportion of mediation was 15.4% ( P = 0.028). The mediating relationships among TG, the TFQI, and HDP are visually summarized in Fig. 4.2 . Table 8.1. The mediating effect of TG in the association between FT3/FT4 and HDP in second-trimester. Indicators of mediating effects Estimated value 95%CI P value ACME (control) 0.096 0.005 ~ 0.340 0.008 ACME (case) 0.210 0.029 ~ 0.470 0.008 ADE (control) 0.492 -0.056 ~ 0.880 0.072 ADE (case) 0.607 -0.083 ~ 0.930 0.072 Total Effect 0.703 0.155 ~ 0.940 0.022 Prop. Mediated (control) 0.088 0.002 ~ 0.990 0.030 Prop. Mediated (case) 0.287 0.018 ~ 1.000 0.030 ACME (average) 0.153 0.018 ~ 0.390 0.008 ADE (average) 0.550 -0.066 ~ 0.900 0.072 Prop. Mediated (average) 0.187 0.010 ~ 0.990 0.030 ACME (control)：The average causal mediating effect in control group. ACME (case)：The average causal mediating effect in case group. ADE (control)：The average causal direct effect in control group. ADE (case)：The average causal direct effect in case group. Prop. Mediated (control)：The proportion of the mediating effect in control group to the total effect。 Prop. Mediated (case)：The proportion of the mediating effect in case group to the total effect. ACME (average)：Average causal mediating effect. ADE (average)：Average causal direct effect. Prop. Mediated (average)：The proportion of the average mediating effect to the total effect. Adjusting for pregnant woman's age, BMI, parity, educational level, and weight gain(considering the stability of the model, smoking and drinking were not included, for there are 0 categories in each variable). Table 8.2 The mediating effect of TG in the association between TFQI and HDP in second-trimester. Indicators of mediating effects Estimated value 95%CI P 值 ACME (control) -0.038 -0.082 ～ 0.000 0.026 ACME (case) -0.024 -0.057 ～ 0.000 0.026 ADE (control) -0.164 -0.251 ～ -0.050 0.008 ADE (case) -0.150 -0.234 ～ -0.050 0.008 Total Effect -0.188 -0.268 ～ -0.090 0.002 Prop. Mediated (control) 0.197 0.013 ～ 0.520 0.028 Prop. Mediated (case) 0.112 0.006 ～ 0.440 0.028 ACME (average) -0.031 -0.068 ～ 0.000 0.026 ADE (average) -0.157 -0.240 ～ -0.050 0.008 Prop. Mediated (average) 0.154 0.010 ～ 0.480 0.028 ACME (control)：The average causal mediating effect in control group. ACME (case)：The average causal mediating effect in case group. ADE (control)：The average causal direct effect in control group. ADE (case)：The average causal direct effect in case group. Prop. Mediated (control)：The proportion of the mediating effect in control group to the total effect。 Prop. Mediated (case)：The proportion of the mediating effect in case group to the total effect. ACME (average)：Average causal mediating effect. ADE (average)：Average causal direct effect. Prop. Mediated (average)：The proportion of the average mediating effect to the total effect. Adjusting for pregnant woman's age, BMI, parity, educational level, and weight gain(considering the stability of the model, smoking and drinking were not included, for there are 0 categories in each variable). Discussion In this study, increased FT3/FT4 in the first trimester was positively associated with longitudinal changes in both SBP and DBP, whereas the TFQI was negatively correlated with SBP. Similar results were observed in the second trimester. Furthermore, higher FT3/FT4 ratios in the first trimester were significantly associated with an increased risk of HDP, and similar results were observed in the second trimester. However, increased levels of three central thyroid hormone sensitivity indices in the second trimester were associated with a reduced risk of HDP. Furthermore, our analysis revealed that TG had a mediating effect on approximately 15% of the associations between both FT3/FT4 and the TFQI with HDPs. Levels of thyroid hormone sensitivity during pregnancy In the present study, the median FT3 and FT4 levels during the first trimester were 4.89 (IQR: 4.53, 5.28) pmol/L and 11.03 (IQR: 10.09, 12.17) pmol/L, respectively. The first-trimester FT3 level was similar to that reported in the Belgian cohort of 597 pregnant women (5.0 ± 0.8 pmol/L). However, their FT4 level was notably higher than that in our study (14.9 ± 2.4 pmol/L). Consequently, the value of the FT3/FT4 ratio was lower than our result (0.34 ± 0.06 vs 0.44, 0.39–0.49). Similar differences were found in the second trimester[ 44 ]. Additionally, the FT3/FT4 ratio of a Chinese cohort study by Wang was 2.75 (IQR: 2.44, 3.15), which was also lower than our result[ 45 ]. The subjects of the above two cohorts were from the general pregnant population, including individuals with thyroid dysfunction, which may limit comparability. However, in 2023, a study conducted by Zhao among euthyroid pregnant women also reported a lower FT3/FT4 ratio than previously reported[ 46 ]. This pattern may be related to physiological thyroid enlargement during pregnancy, which increases hormone production capacity by approximately 40% to meet gestational demands. This adaptation is accompanied by alterations in FT3 and FT4 secretion and an overall increase in metabolic activity. The FT3/FT4 ratio reflects the conversion rate of T4 to T3, indicating peripheral tissue responsiveness to thyroid hormones[ 47 ]. A higher ratio suggests increased peripheral metabolic activity and heightened sensitivity to thyroid hormones, which has been associated with conditions such as insulin resistance[ 48 ], metabolic syndrome[ 49 ], and cardiometabolic dysfunction[ 50 ]. The TFQI is a novel resistance index derived from the empirical joint distribution of FT4 and TSH. It is increasingly used to assess central thyroid hormone sensitivity in relation to conditions such as diabetes, obesity, and metabolic syndrome[ 30 ]. The TFQI values range from − 1 to 1, with negative values indicating increased pituitary sensitivity to thyroid hormones and positive values indicating reduced sensitivity. A key advantage of the TFQI is its robustness against extreme values, offering greater stability than other central sensitivity indices, such as the TT4RI and TSHI. In our study, the median TFQI values were − 0.01 (IQR: -0.22, 0.21) and − 0.01 (IQR:-0.27, 0.28) in the first trimester and second trimester, respectively, which were similar to the findings of Zhao in a euthyroid pregnant population[ 46 ] but were slightly lower than those reported in Chinese euthyroid women[ 33 ] and the euthyroid general population[ 29 , 51 ]. In addition, a study of 1,075 Greek singleton pregnancies in 2024 reported a mean TFQI of -0.06 during pregnancy, which was lower than our findings[ 52 ]. Our results indicated that central thyroid hormone sensitivity in euthyroid pregnant individuals may be slightly greater than that in the general Chinese population but may be lower than that in the European population. Thyroid Hormone Sensitivity and Blood Pressure/Hypertension during Pregnancy Previous studies have typically focused on the relationships between individual thyroid hormone indicators and blood pressure and have rarely focused on the associations between thyroid hormone sensitivity and blood pressure in pregnant women[ 13 , 15 , 19 – 21 ]. Our study revealed that an elevated FT3/FT4 ratio was positively correlated with longitudinal increases in SBP and DBP and an increased risk of HDP. To our knowledge, this is the first study to report such an association in euthyroid pregnant women. However, to date, several studies in other populations have been reported. In 2024, Chen[ 53 ] reported a similar positive association among 107,301 Chinese euthyroid type 2 diabetes mellitus patients who were overweight or obese. Conversely, Samet reported no significant difference in FT3/FT4 between hypertensive and nonhypertensive obese subjects[ 54 ], and Birck[ 55 ], Yuan[ 56 ] and Xu[ 39 ] reported no significant associations. These discrepant results may be attributed to variations in the study populations, including differences in health status, age, and ethnicity, especially in the pregnant population, whose hormonal status differs substantially from that of the general population. The FT3/FT4 ratio reflects the peripheral conversion of T4 to T3 and is considered an indicator of peripheral thyroid hormone sensitivity. An elevated ratio may result from increased type 2 deiodinase (DIO2) activity in response to adverse metabolic conditions[ 48 ], serving as an early marker of metabolic alterations[ 57 ] and a predictor of cardiovascular mortality[ 58 ]. This may explain the association between higher FT3/FT4 ratios and increased HDP risk. Moreover, the FT3/FT4 ratio may be a more precise and clinically feasible indicator of thyroid hormone metabolic variability than FT3 or FT4 alone[ 56 , 59 , 60 ]. The TFQI is a recently developed index for assessing central thyroid hormone sensitivity [ 30 ]. Previous studies have reported positive associations between the TFQI and BP or HDP risk. Mehran[ 61 ] reported that a higher TFQI was associated with greater BP in an Iranian community-based population (OR = 1.14, 95% CI: 1.06–1.23). Similarly, Yang[ 29 ] reported that the TFQI was positively correlated with both SBP (β = 3.22) and DBP (β = 2.32), and high TFQI levels were associated with increased HDP risk (OR = 1.27, 95% CI: 1.07–1.51). In contrast, our study revealed that the first-trimester TFQI was negatively correlated with longitudinal changes in SBP, and a higher second-trimester TFQI was associated with a reduced risk of HDP. Our results were consistent with findings in Chinese [ 53 ] and Latin American middle-aged and older adults[ 62 ]. Moreover, one study of 5,124 adults from the Tehran Thyroid Study revealed that both TSHI (OR = 1.22, 95% CI: 1.08–1.38) and TT4RI (OR = 1.08, 95% CI: 1.01–1.16) were associated with increased HDP risk[ 61 ]. Conversely, a study of 34,310 participants reported negative associations between these indices and HDP risk[ 53 ]. Another study of 1,789 adults from a Spanish subcohort also reported a trend toward a negative association [ 63 ]. Similarly, our study revealed that higher TT4RI and TSHI in the second trimester were associated with a reduced risk of HDP. These results suggest that reduced central thyroid hormone sensitivity may be protective against HDP; in other words, increased sensitivity may increase HDP risk. This may be due to links between central sensitivity and metabolic disorders and dyslipidemia[ 30 , 64 ]. The current evidence remains controversial, and many more large-scale prospective studies are needed to clarify these relationships. In summary, our findings indicate that high thyroid hormone sensitivity (both central and peripheral) may be associated with elevated BP and a greater risk of HDP in euthyroid pregnant women. Potential mechanisms may include the following: ①Thyroid hormones influence cardiac contractility, heart rate, peripheral vascular resistance, endothelial function, and renin synthesis and secretion, thereby modulating BP through multiple pathways[ 65 – 67 ]. Altered thyroid hormone sensitivity may affect hormone activity and vascular function. ② Type 2 iodothyronine deiodinase (DIO2), which plays a key role in thyroid feedback regulation, has been linked to increased hypertension risk[ 68 – 70 ]. Increased thyroid hormone sensitivity may affect hypertension development through changes in DIO2 activity. Further research is needed to elucidate the regulatory mechanisms underlying these associations. Mediating Role of TG in the Association between FT3/FT4, TFQI, and HDP The present study revealed that TG significantly mediated the association between FT3/FT4 and HDP, with 10.5% of the total effect. Similarly, the relationship between the TFQI and HDP (12.1% of the total effect) was investigated. These results suggested that TG mediates approximately 10% of the association between both peripheral and central thyroid hormone sensitivity and HDP, and the dominant effect remains the direct influence of thyroid hormone sensitivity on HDP. Thyroid hormones modulate cardiovascular function through genomic and nongenomic mechanisms, primarily affecting vascular smooth muscle and endothelial cells. Potential pathways include ion channel activation (Na⁺, K⁺, Ca²⁺) and the regulation of specific signaling cascades. Among these pathways, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway plays a central role. Its activation promotes endothelial nitric oxide (NO) production, thereby reducing systemic vascular resistance through effects on vascular smooth muscle cells[ 71 , 72 ]. These mechanisms have been corroborated by multiple interventional studies[ 73 – 75 ]. T3 is recognized as an inotropic vasodilator that is particularly effective in treating diastolic dysfunction because of its unique pharmacological profile[ 76 ]. Additionally, thyroid hormones regulate lipid metabolism by stimulating hepatic lipid mobilization, degradation, and de novo fatty acid synthesis[ 77 , 78 ]. Notably, recent evidence highlights the critical role of free fatty acids (FFAs), which are key metabolites of TG, in endothelial function. As García-Prieto[ 79 ] demonstrated, a high-fat diet downregulates the AMPK-PI3K-Akt-eNOS pathway in endothelial cells, leading to endothelial dysfunction, which is correlated with elevated plasma FFAs and TG levels. FFAs may impair insulin-mediated NO production and peripheral blood flow via two primary mechanisms: reducing tyrosine phosphorylation of IRS-1/2 (insulin receptor substrate-1/2) and inhibiting the PI3K/Akt signaling pathway, which regulates eNOS-derived NO synthesis in endothelial cells[ 80 , 81 ]. Thus, the PI3K/Akt pathway appears to be a key mechanistic link underlying the partial mediating effect of TG on the relationship between thyroid hormone sensitivity and HDP. However, further biological investigations are warranted to elucidate more detailed mechanisms involved. Strengths and Limitations This is a prospective cohort study with longitudinal blood pressure measurements at six time points, enhancing the reliability of causal inference and providing a comprehensive assessment of blood pressure changes throughout pregnancy. This approach also allows for more accurate and timely identification of HDPs. Furthermore, the study exclusively enrolled pregnant women with normal thyroid function, thereby minimizing the potential confounding effects of thyroid dysfunction. Additional exclusions included women with preexisting hypertension, those with other serious pregnancy complications, and those diagnosed with abnormal liver or kidney function during pregnancy, which may significantly reduce the influence of potential confounders on the relationship between thyroid hormone sensitivity and blood pressure changes or HDP. Unlike previous studies that focused on individual thyroid hormones, our study employed composite indices to assess thyroid hormone sensitivity, which provides more stable and robust results. In addition, we are the first to evaluate the mediating role of TG in the relationship between thyroid hormone sensitivity (both peripheral and central) and HDP, offering new insights and evidence for potential mechanisms modulating thyroid hormone sensitivity and HDP risk. Nevertheless, this study has several limitations. First, a substantial proportion of the original cohort was excluded because of missing thyroid function tests or blood pressure measurements, which may affect the generalizability of the findings. Second, although the proportion of missing data at various time points was less than 5%, this minor missingness could still reduce the statistical power and introduce potential selection bias. Finally, the relatively small number of HDP cases in the cohort resulted in a wide confidence interval in the regression models. However, we conducted a nested case‒control study to further validate our findings. Conclusions In conclusion, we found that thyroid hormone sensitivity is greater in pregnant women than in the general population. Our results suggest that increased thyroid hormone sensitivity may be associated with a greater risk of HDP. Interestingly, we further revealed the mediating role of TG in the associations of both FT3/FT4 and the TFQI with HDPs. These findings provide important clues and a foundation for further investigations into the potential mechanisms of HDP. Abbreviations HDP hypertensive disorders of pregnancy GEE generalized estimating equation SBP systolic blood pressure DBP diastolic blood pressure TSHI thyroid-stimulating hormone index TT4RI the thyroid T4 resistance index TFQI the thyroid feedback quantile-based index CVD cardiovascular disease ASCVD atherosclerotic cardiovascular disease EDTA ethylenediaminetetraacetic acid TC total cholesterol HDL-C high-density lipoprotein cholesterol LDL-C low-density lipoprotein cholesterol TG triglycerides ANOVA one-way analysis of variance RCS restricted cubic spline ACME average causal mediating effect Declarations Ethics approval and consent to participate: This study was approved by the Ethics Committee of the Zhejiang University School of Medicine. Signed informed consent forms were obtained from all participants prior to the survey. Consent for publication: Not applicable Availability of data and materials: Data that underlie the results reported in this article (text, tables, figures, and appendices) will be made available upon request following publication, with no end date, to anyone who wishes to access the data for any purpose. Proposals should be directed to the corresponding author to gain access. Competing interests: The authors report that there are no competing interests to declare. Funding: This work was supported by the National Key R&D Program of China [grant numbers 2022YFC2703505 and 2021YFC2701901]. Authors' contributions: Zexin Chen and Yunxian Yu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: Zexin Chen and Yunxian Yu. Acquisition, analysis, or interpretation of data: Zexin Chen, Xialidan Alifu, Wanli Li, Yunxian Yu. Drafting of the manuscript: Zexin Chen. Critical review of the manuscript: Yunxian Yu. Statistical analysis: Zexin Chen, Xialidan Alifu. Acknowledgements: Not applicable References Say L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Global health. 2014;2(6):e323–333. Zhuang C, Gao J, Liu J, Wang X, He J, Sun J, Liu X, Liao S. Risk factors and potential protective factors of pregnancy-induced hypertension in China: A cross-sectional study. J Clin Hypertens. 2019;21(5):618–23. Wen SW, Tan H, Retnakaran R, Shen M, Zhou S, Xie RH, Smith GN, Davidge ST, Trasler J, Walker MC. Pre-gravid predictors of new onset hypertension in pregnancy - Results from a pre-conception cohort study in China. Eur J Obstet Gynecol Reprod Biol. 2017;214:140–4. Li F, Qin J, Zhang S, Chen L. Prevalence of hypertensive disorders in pregnancy in China: A systematic review and meta-analysis. Pregnancy Hypertens. 2021;24:13–21. Abalos E, Cuesta C, Carroli G, Qureshi Z, Widmer M, Vogel JP, Souza JP. Maternal WHOMSo, Newborn Health Research N: Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG: Int J Obstet Gynecol. 2014;121(Suppl 1):14–24. Vogel JP, Souza JP, Mori R, Morisaki N, Lumbiganon P, Laopaiboon M, Ortiz-Panozo E, Hernandez B, Perez-Cuevas R, Roy M, et al. Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG: Int J Obstet Gynecol. 2014;121(Suppl 1):76–88. Brown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol. 2013;28(1):1–19. Leffert LR, Clancy CR, Bateman BT, Bryant AS, Kuklina EV. Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes. Obstet Gynecol. 2015;125(1):124–31. Arthur JR, Beckett GJ. Thyroid function. Br Med Bull. 1999;55(3):658–68. Colzani RM, Emdin M, Conforti F, Passino C, Scarlattini M, Iervasi G. Hyperthyroidism is associated with lengthening of ventricular repolarization. Clin Endocrinol. 2001;55(1):27–32. Rodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365–74. Takamura N, Hayashida N, Maeda T. Risk of coronary heart disease and mortality for adults with subclinical hypothyroidism. JAMA. 2010;304(22):2481–2. author reply 2482. Iglesias P, Diez JJ. Hyperthyroidism and cardiovascular risk factors: A nationwide study. Endocrinologia diabetes y nutricion. 2023;70(4):255–61. Pearce EN. Update in lipid alterations in subclinical hypothyroidism. J Clin Endocrinol Metab. 2012;97(2):326–33. Saito I, Ito K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension. 1983;5(1):112–5. Cappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab. 2003;88(6):2438–44. Klein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116(15):1725–35. Klein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344(7):501–9. Zhang J, Huang C, Meng Z, Fan Y, Yang Q, Zhang W, Gao Y, Yang Z, Cai H, Bian B et al. Gender-Specific Differences on the Association of Hypertension with Subclinical Thyroid Dysfunction. International journal of endocrinology 2019, 2019:6053068. Volzke H, Ittermann T, Schmidt CO, Dorr M, John U, Wallaschofski H, Stricker BH, Felix SB, Rettig R. Subclinical hyperthyroidism and blood pressure in a population-based prospective cohort study. Eur J Endocrinol. 2009;161(4):615–21. Cai Y, Ren Y, Shi J. Blood pressure levels in patients with subclinical thyroid dysfunction: a meta-analysis of cross-sectional data. Hypertens research: official J Japanese Soc Hypertens. 2011;34(10):1098–105. Alves Junior JM, Bernardo WM, Ward LS, Villagelin D. Effect of Hyperthyroidism Control During Pregnancy on Maternal and Fetal Outcome: A Systematic Review and Meta-Analysis. Front Endocrinol. 2022;13:800257. Cooper DS, Laurberg P. Hyperthyroidism in pregnancy. lancet Diabetes Endocrinol. 2013;1(3):238–49. Toloza FJK, Derakhshan A, Mannisto T, Bliddal S, Popova PV, Carty DM, Chen L, Taylor P, Mosso L, Oken E, et al. Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis. lancet Diabetes Endocrinol. 2022;10(4):243–52. Lai H, Zhan ZY, Liu H. Association between thyroid hormone parameters during early pregnancy and gestational hypertension: a prospective cohort study. J Int Med Res. 2020;48(2):300060520904814. Maraka S, Ospina NM, O'Keeffe DT, De Espinosa AE, Gionfriddo MR, Erwin PJ, Coddington CC 3rd, Stan MN, Murad MH, Montori VM. Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid: official J Am Thyroid Association. 2016;26(4):580–90. Vella K, Vella S, Savona-Ventura C, Vassallo J. Thyroid dysfunction in pregnancy - a retrospective observational analysis of a Maltese cohort. BMC Pregnancy Childbirth. 2022;22(1):941. Li Y, Shan Z, Teng W, Thyroid Disorders IS, Diabetes Epidemiological Survey G. The Iodine Status and Prevalence of Thyroid Disorders Among Women of Childbearing Age in China: National Cross-sectional Study. Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2021;27(10):1028–33. Yang S, Wang Z, Li J, Fu J, Guan H, Wang W. Thyroid Feedback Quantile-Based Index Is Associated With Blood Pressure and Other Hemodynamic Measures: A Cross-sectional Study. Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2022;28(10):1055–61. Laclaustra M, Moreno-Franco B, Lou-Bonafonte JM, Mateo-Gallego R, Casasnovas JA, Guallar-Castillon P, Cenarro A, Civeira F. Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome. Diabetes Care. 2019;42(2):303–10. Zhang X, Chen Y, Ye H, Luo Z, Li J, Chen Z, Zhang E, Li W. Correlation between thyroid function, sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease in euthyroid subjects with newly diagnosed type 2 diabetes. Endocrine. 2023;80(2):366–79. Ding X, Wang Y, Liu J, Wang G. Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Homocysteine Levels in the Euthyroid Population. J Clin Endocrinol Metab. 2022;107(9):e3731–7. Wei Y, Li X, Cui R, Liu J, Wang G. Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity. Front Endocrinol. 2024;15:1366830. Ye G, Zhang Y, Peng L, Yu Z, Bai Y, Wu M, Lu D, Ding C. Impaired sensitivity to thyroid hormones is associated with lower heart rate in the euthyroid population. Heart rhythm 2025. Soppert J, Lehrke M, Marx N, Jankowski J, Noels H. Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting. Adv Drug Deliv Rev. 2020;159:4–33. Damiano F, Rochira A, Gnoni A, Siculella L. Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms. Int J Mol Sci 2017, 18(4). Obregon MJ. Adipose tissues and thyroid hormones. Front Physiol. 2014;5:479. Katz LS, Xu S, Ge K, Scott DK, Gershengorn MC. T3 and Glucose Coordinately Stimulate ChREBP-Mediated Ucp1 Expression in Brown Adipocytes From Male Mice. Endocrinology. 2018;159(1):557–69. Xu R, Huang F, Zhang S, Lv Y, Liu Q. Thyroid function, body mass index, and metabolic risk markers in euthyroid adults: a cohort study. BMC Endocr disorders. 2019;19(1):58. Shao B, Mo M, Xin X, Jiang W, Wu J, Huang M, Wang S, Muyiduli X, Si S, Shen Y, et al. The interaction between prepregnancy BMI and gestational vitamin D deficiency on the risk of gestational diabetes mellitus subtypes with elevated fasting blood glucose. Clin Nutr. 2020;39(7):2265–73. Garovic VD, Dechend R, Easterling T, Karumanchi SA, McMurtry Baird S, Magee LA, Rana S, Vermunt JV, August P, American Heart Association Council on H. Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association. Hypertension. 2022;79(2):e21–41. Cappelli C, Rotondi M, Pirola I, Agosti B, Gandossi E, Valentini U, De Martino E, Cimino A, Chiovato L, Agabiti-Rosei E, et al. TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care. 2009;32(9):1589–90. Yagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity. J Clin Endocrinol Metab. 1997;82(5):1608–14. Raets L, Minschart C, Van den Bruel A, Van den Bogaert E, Van Crombrugge P, Moyson C, Verhaeghe J, Vandeginste S, Verlaenen H, Vercammen C et al. Higher Thyroid fT3-to-fT4 Ratio Is Associated with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes. J Clin Med 2022, 11(17). Wang Y, Sun F, Wu P, Huang Y, Ye Y, Yang X, Yuan J, Liu Y, Zeng H, Wen Y, et al. A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus. J Clin Endocrinol Metab. 2022;107(2):e804–14. Zhao X, Sun J, Yuan N, Zhang X. Free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio identified as a risk factor for gestational diabetes in euthyroid pregnant women: insights from a Chinese population cohort study. Front Endocrinol. 2023;14:1281285. Nie X, Ma X, Xu Y, Shen Y, Wang Y, Bao Y. Increased Serum Adipocyte Fatty Acid-Binding Protein Levels Are Associated with Decreased Sensitivity to Thyroid Hormones in the Euthyroid Population. Thyroid: official J Am Thyroid Association. 2020;30(12):1718–23. Park SY, Park SE, Jung SW, Jin HS, Park IB, Ahn SV, Lee S. Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects. Clin Endocrinol. 2017;87(1):87–96. Wolffenbuttel BHR, Wouters H, Slagter SN, van Waateringe RP, Muller Kobold AC, van Vliet-Ostaptchouk JV, Links TP, van der Klauw MM. Thyroid function and metabolic syndrome in the population-based LifeLines cohort study. BMC Endocr disorders. 2017;17(1):65. Roef GL, Rietzschel ER, Van Daele CM, Taes YE, De Buyzere ML, Gillebert TC, Kaufman JM. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid: official J Am Thyroid Association. 2014;24(2):223–31. Liu C, Hua L, Liu K, Xin Z. Impaired sensitivity to thyroid hormone correlates to osteoporosis and fractures in euthyroid individuals. J Endocrinol Investig. 2023;46(10):2017–29. Ilias I, Milionis C, Alexiou M, Michou E, Karavasili C, Venaki E, Markou K, Mamali I, Koukkou E. Changes in Central Sensitivity to Thyroid Hormones vs. Urine Iodine during Pregnancy. Med Sci 2024, 12(4). Chen F, Chen R, Zhou J, Xu W, Zhou J, Chen X, Gong X, Chen Z. Impaired Sensitivity to Thyroid Hormones is Associated with Central Obesity in Euthyroid Type 2 Diabetes Mellitus Patients with Overweight and Obesity. Diabetes metabolic syndrome obesity: targets therapy. 2024;17:3379–96. Ozer S, Butun I, Sonmezgoz E, Yilmaz R, Demir O. Relationships among Thyroid Hormones and Obesity Severity, Metabolic Syndrome and Its Components in Turkish Children with Obesity. Nutr Hosp. 2015;32(2):645–51. Birck MG, Janovsky C, Goulart AC, Meneghini V, Pititto BA, Sgarbi JA, Teixeira PFS, Bensenor IM. Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Archives Endocrinol metabolism. 2024;68:e230301. Yuan D, Zhang C, Jia S, Liu Y, Jiang L, Xu L, Zhang Y, Xu J, Xu B, Hui R, et al. Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease. Nutr metabolism Cardiovasc diseases: NMCD. 2021;31(2):579–86. Gokmen FY, Ahbab S, Ataoglu HE, Turker BC, Cetin F, Turker F, Mamac RY, Yenigun M. FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism. Clinics. 2016;71(4):221–5. Yu T, Tian C, Song J, He D, Wu J, Wen Z, Sun Z, Sun Z. Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study. BMC Cardiovasc Disord. 2018;18(1):181. Lang X, Li Y, Zhang D, Zhang Y, Wu N, Zhang Y. FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007–2012. Front Endocrinol. 2022;13:964822. Zhao X, Sun J, Xin S, Zhang X. Predictive Effects of FT3/FT4 on Diabetic Kidney Disease: An Exploratory Study on Hospitalized Euthyroid Patients with T2DM in China. Biomedicines 2023, 11(8). Mehran L, Delbari N, Amouzegar A, Hasheminia M, Tohidi M, Azizi F. Reduced Sensitivity to Thyroid Hormone Is Associated with Diabetes and Hypertension. J Clin Endocrinol Metab. 2022;107(1):167–76. Szili-Torok T, Xu Y, de Borst MH, Bakker SJL, Tietge UJF. Normal Fasting Triglyceride Levels and Incident Hypertension in Community-Dwelling Individuals Without Metabolic Syndrome. J Am Heart Association. 2023;12(16):e028372. Abasilim C, Persky V, Sargis RM, Argos M, Daviglus M, Freels S, Cai J, Tsintsifas K, Isasi CR, Peters BA, et al. Thyroid-related Hormones and Hypertension Incidence in Middle-Aged and Older Hispanic/Latino Adults: The HCHS/SOL Study. J Endocr Soc. 2024;8(6):bvae088. Liu Y, Ma M, Li L, Liu F, Li Z, Yu L, Yang T, Wang Y, Gao S, Gao S, et al. Association between sensitivity to thyroid hormones and dyslipidemia in patients with coronary heart disease. Endocrine. 2023;79(3):459–68. Rivas AM, Pena C, Kopel J, Dennis JA, Nugent K. Hypertension and Hyperthyroidism: Association and Pathogenesis. Am J Med Sci. 2021;361(1):3–7. Berta E, Lengyel I, Halmi S, Zrinyi M, Erdei A, Harangi M, Pall D, Nagy EV, Bodor M. Hypertension in Thyroid Disorders. Front Endocrinol. 2019;10:482. Marvisi M, Balzarini L, Mancini C, Mouzakiti P. Thyroid gland and pulmonary hypertension. What's the link? Panminerva Med. 2013;55(1):93–7. Castagna MG, Dentice M, Cantara S, Ambrosio R, Maino F, Porcelli T, Marzocchi C, Garbi C, Pacini F, Salvatore D. DIO2 Thr92Ala Reduces Deiodinase-2 Activity and Serum-T3 Levels in Thyroid-Deficient Patients. J Clin Endocrinol Metab 2017, 102(5):1623–30. Gereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeold A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008;29(7):898–938. Gumieniak O, Perlstein TS, Williams JS, Hopkins PN, Brown NJ, Raby BA, Williams GH. Ala92 type 2 deiodinase allele increases risk for the development of hypertension. Hypertension. 2007;49(3):461–6. Jabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat reviews Cardiol. 2017;14(1):39–55. Carrillo-Sepulveda MA, Ceravolo GS, Fortes ZB, Carvalho MH, Tostes RC, Laurindo FR, Webb RC, Barreto-Chaves ML. Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. Cardiovascular Res. 2010;85(3):560–70. Papaioannou GI, Lagasse M, Mather JF, Thompson PD. Treating hypothyroidism improves endothelial function. Metab Clin Exp. 2004;53(3):278–9. Taddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Salvetti A, Ferrannini E, Monzani F. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab. 2003;88(8):3731–7. Razvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007;92(5):1715–23. Razvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, Peeters R, Zaman A, Iervasi G. Thyroid Hormones and Cardiovascular Function and Diseases. J Am Coll Cardiol. 2018;71(16):1781–96. Tarpey T, Kinateder KKJ. Clustering Functional Data. J Classif. 2003;20(1):093–114. Rossi F, Conan-Guez B, Golli AE. Clustering functional data with the SOM algorithm. In: European Symposium on Artificial Neural Networks: 2004 ; 2004. Garcia-Prieto CF, Hernandez-Nuno F, Rio DD, Ruiz-Hurtado G, Aranguez I, Ruiz-Gayo M, Somoza B, Fernandez-Alfonso MS. High-fat diet induces endothelial dysfunction through a down-regulation of the endothelial AMPK-PI3K-Akt-eNOS pathway. Mol Nutr Food Res. 2015;59(3):520–32. Kosmas CE, Bousvarou MD, Kostara CE, Papakonstantinou EJ, Salamou E, Guzman E. Insulin resistance and cardiovascular disease. J Int Med Res. 2023;51(3):3000605231164548. Ghosh A, Gao L, Thakur A, Siu PM, Lai CWK. Role of free fatty acids in endothelial dysfunction. J Biomed Sci 2017, 24(1):50. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Reviews received at journal 21 Dec, 2025 Reviewers agreed at journal 12 Dec, 2025 Reviewers invited by journal 12 Dec, 2025 Editor invited by journal 21 Nov, 2025 Editor assigned by journal 14 Nov, 2025 Submission checks completed at journal 13 Nov, 2025 First submitted to journal 13 Nov, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8051840","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":560041857,"identity":"2f7e4f05-915a-41c9-9162-64c594cc5926","order_by":0,"name":"Zexin Chen","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Zexin","middleName":"","lastName":"Chen","suffix":""},{"id":560041858,"identity":"cf0f82c4-f0ec-4bbc-a29e-b2eb779ed798","order_by":1,"name":"Xialidan Alifu","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Xialidan","middleName":"","lastName":"Alifu","suffix":""},{"id":560041859,"identity":"510d4e29-a952-449b-91b0-8198b0075195","order_by":2,"name":"Wanli Li","email":"","orcid":"","institution":"Zhejiang University","correspondingAuthor":false,"prefix":"","firstName":"Wanli","middleName":"","lastName":"Li","suffix":""},{"id":560041860,"identity":"42092e75-9fb0-4e19-8ceb-6ef7325d29c9","order_by":3,"name":"Yunxian Yu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIie3RsQrCMBCA4ZNCXIpzHUQf4UpAF1F8kxTBSV1cHBwCgqO74EP0ESIFu/gALTpkqouzOKnXuqd1E8w/5G64bwqAzfarifypS0AaNVmduOobUuQVsALBZHb09OoShOlVL1zot0LlZNpM5mMUxywIz0JwFyY8VKyHZjL1tWBRThQRWpTLvBKCSjzpMj1IIq9KxNfBhkjiABFVTpqnG8dgG/HdaQL+Hsd8F7GukTTiabf5uEetbRxneFsOaFlnRtJRnzmSAAyLz3RM91RbfuYwv9UlxzabzfanvQH9WVD+Lb+lewAAAABJRU5ErkJggg==","orcid":"","institution":"Zhejiang University","correspondingAuthor":true,"prefix":"","firstName":"Yunxian","middleName":"","lastName":"Yu","suffix":""}],"badges":[],"createdAt":"2025-11-07 00:53:12","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8051840/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8051840/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":98749541,"identity":"1b502ff3-cb0f-4243-bbbb-59a516f4e174","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":971173,"visible":true,"origin":"","legend":"","description":"","filename":"reviewedManuscriptcleanincludingtablesandfiguresv3.docx","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/de8d11c5149d075a8a514d72.docx"},{"id":98777027,"identity":"11bf2b50-16d5-4660-adc7-9e1c155e8a4a","added_by":"auto","created_at":"2025-12-22 12:25:08","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":7000,"visible":true,"origin":"","legend":"","description":"","filename":"b9bbfe7c8ac14ebd911b2eeea6618043.json","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/bd57a17cec806e1846acbaf7.json"},{"id":98779293,"identity":"430f6b1d-60ce-4266-88c3-a7d35181832e","added_by":"auto","created_at":"2025-12-22 12:30:10","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":261818,"visible":true,"origin":"","legend":"","description":"","filename":"b9bbfe7c8ac14ebd911b2eeea66180431enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/1c55a249b5f4cfcf4bbed319.xml"},{"id":98777324,"identity":"2e0774ba-39b6-4394-b92a-db5d0e691be7","added_by":"auto","created_at":"2025-12-22 12:26:32","extension":"png","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":60678,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/79e1edacc67611b4eaf2e012.png"},{"id":98779576,"identity":"0b6a7a18-080f-4d0a-8e69-cf09dd7e0479","added_by":"auto","created_at":"2025-12-22 12:30:28","extension":"png","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":190305,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/aff43c237ce71f2a8acaa546.png"},{"id":98749553,"identity":"cf6777da-7540-4715-b3a8-3f3bc1b84838","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":360687,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/4c6e00539f8c470b142897c5.png"},{"id":98749548,"identity":"ec09df62-c44e-4f35-bf10-d80a7d3e1cef","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72733,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/75e5737be0c1360892c76134.png"},{"id":98749552,"identity":"0899460b-ca25-4359-8f76-0823cfd6ce0b","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"png","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":72633,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/ee61dd1df2f742be88fedf5d.png"},{"id":98780096,"identity":"398a9203-f358-4b83-aab1-27c89c7c7197","added_by":"auto","created_at":"2025-12-22 12:31:02","extension":"png","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":26269,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/503ff9aaea33d8660b833185.png"},{"id":98777123,"identity":"6d55d3f5-7905-45da-9e8c-a4d08bf07dd5","added_by":"auto","created_at":"2025-12-22 12:25:27","extension":"png","order_by":9,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":34201,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/b7bf9b34810b670782839cdb.png"},{"id":98777424,"identity":"88849a58-8770-4086-8c44-a7a160b63a54","added_by":"auto","created_at":"2025-12-22 12:27:04","extension":"png","order_by":10,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":38788,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/9bd4f0fe371fd44efc6cca44.png"},{"id":98777490,"identity":"19688824-8068-4d2f-9da2-c70773a1d533","added_by":"auto","created_at":"2025-12-22 12:27:40","extension":"png","order_by":11,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23884,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/4d35aaf0db3598d467136937.png"},{"id":98777455,"identity":"5df9601c-6130-4091-874f-b4a8c3a5fd14","added_by":"auto","created_at":"2025-12-22 12:27:26","extension":"png","order_by":12,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":23698,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/bd0e4a67a07b88fc04823067.png"},{"id":98749555,"identity":"dfdc2f2d-aa11-4a50-a10b-3bc7b4d588c4","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"xml","order_by":13,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":259452,"visible":true,"origin":"","legend":"","description":"","filename":"b9bbfe7c8ac14ebd911b2eeea66180431structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/1966f1531d99d7a756bf0ec5.xml"},{"id":98749554,"identity":"8a0abd42-1fcf-4577-aeb8-4075a08f7ac6","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"html","order_by":14,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":278674,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/81454e471da81052f3103637.html"},{"id":98749539,"identity":"8fd61013-89c3-4d3b-ada6-e31220b4abfd","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":108408,"visible":true,"origin":"","legend":"\u003cp\u003eThe screening flow chart of subjects\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/7aa67f933ab686f46f35f159.png"},{"id":98749538,"identity":"f99f3376-2546-4a38-80bc-e524bfb1fc4d","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":131797,"visible":true,"origin":"","legend":"\u003cp\u003eRCS analysis results of the relationship between thyroid sensitivity and HDP\u003c/p\u003e\n\u003cp\u003e(adjusted for pregnant women's age, educational level, smoking, drinking, parity, pre-pregnancy BMI, and pregnancy weight gain)\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/44bb64c22f72372a9bfe0091.png"},{"id":98777076,"identity":"3f77256c-c1cd-4286-bba1-d9bcf5ad50af","added_by":"auto","created_at":"2025-12-22 12:25:19","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":254375,"visible":true,"origin":"","legend":"\u003cp\u003ecorrelation between thyroid sensitivity and TG in second-trimester pregnancy\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/de4fffac015ece9d67c92368.png"},{"id":98749544,"identity":"b0dc9f4a-d583-4f6c-8483-7495062e9802","added_by":"auto","created_at":"2025-12-22 09:02:09","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":90596,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend.\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/8b2c90ef34cea65896131296.png"},{"id":98786407,"identity":"61e7a01b-ae6d-4df6-89b7-aec6a7dc0d38","added_by":"auto","created_at":"2025-12-22 12:43:36","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2190070,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8051840/v1/88c4f753-b53d-4a92-ad85-1a2d3525a1b4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"High thyroid hormone sensitivity is associated with the risk of hypertensive disorders during pregnancy in euthyroid women: the mediating role of triglycerides","fulltext":[{"header":"Background","content":"\u003cp\u003eHypertensive disorders during pregnancy (HDP) are a leading cause of maternal mortality worldwide, accounting for approximately 14% of such deaths[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. The prevalence of HDP varies significantly across regions, with a global prevalence of 116 cases per 100,000 women of reproductive age. Previous studies have indicated that the prevalence of HDP among pregnant women in China ranges from 5% to 10%[\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. HDP is positively associated with various adverse maternal and fetal outcomes, including maternal death, miscarriage, preterm birth, stillbirth, cardiovascular diseases, and neuropsychiatric disorders[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Both the American Heart Association and the European Society of Cardiology have recognized HDP as a female-specific risk factor for cardiovascular disease (CVD). According to the China Health Statistical Yearbook 2020, HDP remains one of the top three causes of maternal mortality in China, accounting for 10.4% of maternal deaths in 2017. Therefore, it is crucial to conduct an in-depth exploration of the relevant risk factors and potential mechanisms underlying HDP.\u003c/p\u003e \u003cp\u003eThyroid hormones are crucial hormones synthesized and secreted by the thyroid gland and play indispensable roles in human growth and development, metabolic regulation, and the maintenance of various physiological functions[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Several studies have reported that thyroid dysfunction, such as hyperthyroidism and hypothyroidism, is associated with an increased risk of cardiovascular diseases[\u003cspan additionalcitationids=\"CR11\" citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In recent years, increasing attention has been given to the relationship between thyroid hormones and blood pressure. A nationwide survey in Spain involving 384,182 participants revealed that the risk of hypertension was 2.16 times greater in hyperthyroid patients than in nonhyperthyroid individuals[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. Moreover, hypothyroidism and subclinical hypothyroidism have also been associated with cardiovascular diseases[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan additionalcitationids=\"CR15 CR16 CR17 CR18\" citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Nevertheless, several large prospective cohort studies have not demonstrated a significant association[\u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Considering the above inconsistent findings, population heterogeneity may be a key factor. Pregnancy is a unique physiological state during which thyroid hormone secretion markedly differs from that of the general population. Hence, more in-depth research on thyroid hormone levels and blood pressure among pregnant women is needed.\u003c/p\u003e \u003cp\u003eAt present, the majority of studies have focused on overt thyroid dysfunction during pregnancy[\u003cspan additionalcitationids=\"CR23 CR24 CR25\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. However, the prevalence of overt thyroid dysfunction is relatively low in clinical practice. A nationwide European study of 46,283 pregnant women reported a prevalence of thyroid dysfunction of only 1.3%[\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. The findings in Chinese populations are consistent: a cross-sectional study including 26,166 pregnant women from 31 provinces in China revealed that the prevalence rates of hyperthyroidism and hypothyroidism were only 1.08% and 1.28%, respectively, whereas the rate of subclinical hypothyroidism was 14.28%[\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. Thus, the majority of pregnant women are euthyroid, but few studies have examined the association between thyroid function and the risk of hypertensive disorders in this population. Therefore, this study focused specifically on euthyroid pregnant women.\u003c/p\u003e \u003cp\u003eRecent studies have increasingly utilized composite parameters rather than isolated thyroid indices to assess thyroid homeostasis[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. The inconsistency in findings regarding thyroid function and cardiovascular risk may be attributable to differences in hormonal sensitivity[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Some previous studies have also shown that indices of thyroid hormone sensitivity are associated with various metabolic abnormalities in euthyroid individuals[\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]. Further investigations suggested that thyroid hormone sensitivity may also be correlated with heart rate[\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] and homocysteine levels[\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e] in euthyroid populations. Therefore, we hypothesize that thyroid hormone sensitivity may be associated with BP or hypertension during pregnancy in euthyroid women. Regrettably, relevant studies have not been reported.\u003c/p\u003e \u003cp\u003eNotably, dyslipidemia is the third major risk factor for atherosclerotic cardiovascular disease (ASCVD). Lipids and lipoprotein particles, as potential pathological factors of cardiovascular diseases, play crucial roles in atherosclerosis and affect the inflammatory process as well as the functions of white blood cells, blood vessels and cardiac cells, thereby influencing blood vessels and the heart[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]. Previous studies have shown that thyroid hormones may regulate lipid metabolism by stimulating lipid mobilization and degradation in the liver and the synthesis of new fatty acids[\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]. Epidemiological studies have also revealed a significant positive correlation between blood lipids and thyroid hormone sensitivity[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]. Hence, we speculate that serum lipids may play a mediating role in the relationship between thyroid hormone sensitivity and HDP.\u003c/p\u003e \u003cp\u003eIn summary, this study comprises two main components. First, we investigated the association between thyroid hormone sensitivity and longitudinal changes in BP in euthyroid pregnant women, as well as its relationship with HDP. A nested case‒control study was subsequently performed on the same cohort to further examine the potential mediating effect of serum lipids on this association.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy design\u003c/h2\u003e \u003cp\u003eThe pregnant women included in this study were derived from the Zhoushan Pregnant Women Cohort (ZPWC) established by our research group at Zhoushan Maternal and Child Health Hospital in August 2011. This study included participants who entered the ZPWC between June 2015 and January 2020.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eInclusion criteria (must meet all the following conditions):\u003c/p\u003e \u003cp\u003e1) Maternal age between 18 and 45 years;\u003c/p\u003e \u003cp\u003e2) Pregnancy confirmed at 8\u0026ndash;14 gestational weeks and registration for perinatal health care at the study hospital (gestational age was determined on the basis of the last menstrual period and confirmed by ultrasound);\u003c/p\u003e \u003cp\u003e3) Availability of blood pressure monitoring data after 20 weeks of gestation;\u003c/p\u003e \u003cp\u003e4) Agreement to participate in the study and provision of signed informed consent.\u003c/p\u003e \u003cp\u003eExclusion criteria (meeting any of the following conditions):\u003c/p\u003e \u003cp\u003e1) Preexisting essential hypertension;\u003c/p\u003e \u003cp\u003e2) Systolic blood pressure (SBP)\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg or diastolic blood pressure (DBP)\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg detected before 20 weeks of gestation;\u003c/p\u003e \u003cp\u003e3) History of hyperthyroidism, hypothyroidism, subclinical hypothyroidism, positive thyroid antibodies, or other thyroid disorders requiring medication;\u003c/p\u003e \u003cp\u003e4) Pprepregnancy diagnosis of anxiety disorders, phobias, obsessive‒compulsive disorder, depression, or a history of psychotropic medication use;\u003c/p\u003e \u003cp\u003e5) Threatened abortion or miscarriage;\u003c/p\u003e \u003cp\u003e6) Fetal malformation or abnormal development;\u003c/p\u003e \u003cp\u003e7) Twin or multiple pregnancies;\u003c/p\u003e \u003cp\u003e8) Malignancies, syphilis, HIV, liver or kidney diseases, or the use of assisted reproductive technologies;\u003c/p\u003e \u003cp\u003e9) Lack of thyroid function indicators during the first and second trimesters;\u003c/p\u003e \u003cp\u003e10) Inability to comprehend questionnaire content due to cognitive or educational limitations.\u003c/p\u003e \u003cp\u003e11) Participants who had already been diagnosed with hypertensive disorders of pregnancy before thyroid function and lipid testing (exclusion criteria for the case group in the mediation analysis).\u003c/p\u003e\n\u003ch3\u003eCollection of epidemiological data\u003c/h3\u003e\n\u003cp\u003eBaseline Survey\u003c/p\u003e \u003cp\u003eTrained research assistants conducted face‒to-face interviews via questionnaires to collect general sociodemographic information (e.g., age, education level, occupation, marital status), lifestyle behaviors (e.g., smoking, alcohol consumption), dietary habits (e.g., intake of fish, meat, eggs, dairy products, vegetables, and fruits), reproductive and obstetric history (e.g., age at menarche, menstrual history, number of pregnancies and deliveries), history of past diseases (e.g., uterine fibroids, ovarian tumors, diabetes, hypertension), and history of adverse pregnancy outcomes (e.g., miscarriage, stillbirth, and preterm birth).\u003c/p\u003e \u003cp\u003eFollow-up during the second and third trimesters\u003c/p\u003e \u003cp\u003eTrained research assistants performed face‒to-face interviews via epidemiological questionnaires to gather information on changes in lifestyle behaviors and nutritional status during pregnancy in the second and third trimesters.\u003c/p\u003e \u003cp\u003eThe information of ZPWC cohort and questionnaire used in our study has previously been published by Shao B et al[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e].\u003c/p\u003e\n\u003ch3\u003eSampling Blood Specimens\u003c/h3\u003e\n\u003cp\u003eOn the day of the questionnaire survey in pregnant women after an 8-hour fast during the first, second, and third trimesters of pregnancy, as well as at delivery, approximately 5 mL of peripheral venous blood was collected from the superficial veins of the elbow into vacuum blood collection tubes containing ethylenediaminetetraacetic acid (EDTA) as an anticoagulant. After collection, the tubes were gently inverted several times to ensure thorough mixing of the blood with the EDTA coating the tube walls. The blood samples were then centrifuged at 1500\u0026times;g for 10 minutes. Following centrifugation, the upper plasma layer and the intermediate leukocyte layer were carefully aliquoted into separate 2 mL cryovials. All the samples were stored in a freezer at -80\u0026deg;C.\u003c/p\u003e\n\u003ch3\u003eDefinition of Variables\u003c/h3\u003e\n\u003cp\u003eBlood Pressure Measurement\u003c/p\u003e \u003cp\u003eBlood pressure was measured via an electronic sphygmomanometer. After the pregnant woman had rested quietly for at least 5 minutes, she was instructed to sit upright with her back supported, her feet flat on the floor, and her limbs relaxed, ensuring that her arm was positioned at heart level. An appropriately sized cuff was selected. Initial measurements were taken on both arms, and the arm with the higher reading was selected for subsequent measurements. Two measurements were taken on the selected arm, with an interval of 1\u0026ndash;2 minutes between each. The average of the two readings was recorded. If the systolic blood pressure (SBP) or diastolic blood pressure (DBP) differed by more than 5 mmHg between the two measurements, an additional measurement was taken after further rest, and the average of all three readings was used. Blood pressure measurements were obtained at the following six time points throughout pregnancy: \u0026le;20 weeks, 20\u0026ndash;24 weeks, 24\u0026ndash;28 weeks, 28\u0026ndash;32 weeks, 32\u0026ndash;36 weeks, and \u0026ge;\u0026thinsp;36 weeks.\u003c/p\u003e \u003cp\u003eDefinition of HDP\u003c/p\u003e \u003cp\u003eMost international guidelines define gestational hypertension as a blood pressure (BP) reading of \u0026ge;\u0026thinsp;140/90 mmHg[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]. This study adopted the following criteria: SBP\u0026thinsp;\u0026ge;\u0026thinsp;140 mmHg and/or DBP\u0026thinsp;\u0026ge;\u0026thinsp;90 mmHg after 20 weeks of gestation was used to diagnose HDP. This study focused exclusively on women who developed new-onset hypertension after 20 weeks of gestation.\u003c/p\u003e \u003cp\u003eThyroid hormone testing\u003c/p\u003e \u003cp\u003eThyroid hormone levels were routinely measured during pregnancy in the study participants. The thyroid function data used in this study were obtained from the electronic medical records system of Zhoushan Maternal and Child Health Hospital. Venous blood samples were collected from pregnant women after an 8-hour fast. The concentrations of thyroid hormones\u0026mdash;including TSH, FT3, and FT4\u0026mdash;were measured via a Beckman Coulter UniCel Dxl 800 Access immunoassay analyzer and its corresponding reagents. Measurements were taken at two time points: during the first trimester (before 14 weeks of gestation) and during the second trimester (20\u0026ndash;24 weeks of gestation).\u003c/p\u003e \u003cp\u003eThyroid hormone sensitivity indices\u003c/p\u003e \u003cp\u003eThyroid hormone sensitivity was categorized into central and peripheral measures. Indicators used to assess central thyroid hormone sensitivity include the thyroid-stimulating hormone index (TSHI), the thyroid T4 resistance index (TT4RI), and the thyroid feedback quantile-based index (TFQI).\u003c/p\u003e \u003cp\u003eHigher values of TSHI and TT4RI indicate lower central thyroid hormone sensitivity[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e, \u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]. The specific formulas are as follows:\u003c/p\u003e \u003cp\u003eTSHI\u0026thinsp;=\u0026thinsp;ln(TSH)\u0026thinsp;+\u0026thinsp;0.1345\u0026times;FT4\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eTT4RI\u0026thinsp;=\u0026thinsp;FT4 \u0026times; TSH\u003c/h2\u003e \u003cp\u003eThe TFQI is calculated via the following formula:\u003c/p\u003e \u003cp\u003eTFQI\u0026thinsp;=\u0026thinsp;cdf(FT4) - [1 - cdf(TSH)]\u003c/p\u003e \u003cp\u003eThe TFQI values range from \u0026minus;\u0026thinsp;1 to 1. A negative value indicates greater pituitary sensitivity to thyroid hormones, whereas a positive value suggests reduced sensitivity[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e \u003cp\u003ePeripheral thyroid hormone sensitivity is evaluated via the FT3/FT4 ratio. A higher ratio of FT3 (the active form of thyroid hormone) to FT4 suggests increased peripheral metabolic activity and greater peripheral sensitivity to thyroid hormones.\u003c/p\u003e \u003cp\u003eFT3/FT4 ratio\u0026thinsp;=\u0026thinsp;FT3/FT4\u003c/p\u003e \u003cp\u003eUnits: TSH (mIU/L), FT3 (pmol/L), FT4 (pmol/L)\u003c/p\u003e \u003cp\u003eSerum lipid measurement\u003c/p\u003e \u003cp\u003eThe mid-pregnancy serum lipid data in this study were extracted from the biochemical database of the study hospital. For lipid profiling, venous blood samples were collected from pregnant women after an 8-hour fast. The concentrations of blood lipids were measured via a Beckman AU5800 biochemical analyzer and its corresponding reagents. The lipid indicators included in this analysis were total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGs). The lipid measurements were conducted during the second trimester, after the assessment of thyroid hormone levels and prior to blood pressure evaluation at 24\u0026ndash;28 weeks of gestation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eIn this study, descriptive statistics were performed for thyroid hormones and thyroid hormone sensitivity in the study population. The quantitative data are expressed as the means\u0026thinsp;\u0026plusmn;\u0026thinsp;SDs, and the categorical data are presented as numbers and percentages. For continuous variables with a normal distribution, an independent samples t test was used for comparisons between two groups, and one-way analysis of variance (ANOVA) was applied for comparisons among multiple groups. For continuous variables with an abnormal distribution, the Kruskal‒Wallis test was used for intergroup comparisons. For categorical data, the chi-square test was employed for intergroup comparisons; in special cases, Fisher\u0026rsquo;s exact test or nonparametric tests were used instead.\u003c/p\u003e \u003cp\u003eConsidering that blood pressure monitoring during pregnancy involves longitudinal repeated measurements, a generalized estimating equation (GEE) regression model was subsequently used to analyze the associations between thyroid hormone/thyroid hormone sensitivity and longitudinal changes in blood pressure throughout pregnancy. Specifically, when the impact of second-trimester thyroid hormone sensitivity on longitudinal blood pressure was explored, only the four blood pressure measurements taken after the second-trimester thyroid hormone test were analyzed.\u003c/p\u003e \u003cp\u003eNext, a restricted cubic spline (RCS) method was applied, with three knots set at the 25th, 50th, and 75th percentiles, to assess whether there was a potential nonlinear association between thyroid hormone sensitivity and HDP. This process was performed via the \"plotRCS\" package in R software.\u003c/p\u003e \u003cp\u003eFurthermore, on the basis of the results of the RCS analysis, an unconditional logistic regression model was used to investigate the associations between different thyroid hormone sensitivity indices and the risk of developing HDP. Similarly, when the associations between second-trimester thyroid hormone sensitivity indices and HDP were analyzed, 5 participants who developed HDP before second-trimester thyroid hormone testing were excluded.\u003c/p\u003e \u003cp\u003eConsidering the substantial amount of missing lipid profile data among subjects during the second trimester, a nested case‒control study design was employed to further explore the mediating role of serum lipids. The matching criteria were as follows: age within \u0026plusmn;\u0026thinsp;1 year, obesity status, and primiparity. Patients and controls were matched at a 1:2 ratio. Patients were defined as women with mid-pregnancy lipid profiles who developed HDP after lipid measurement. The data of thyroid hormone sensitivity indices in the first trimester, TG in the second trimester and HDP occurring after TG measurement were used for mediating effect analysis. The mediating effect of serum lipids was analyzed via R software (with the \"Mediation\" package, version 4.5.0), and the random seed number was set to 123456.\u003c/p\u003e \u003cp\u003eOn the basis of previous reports, all multivariate models above were adjusted for maternal age (continuous variable), parity, BMI, educational level, smoking, alcohol consumption, and gestational weight gain. Statistical analyses were performed via R software, and a two-tailed test with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\n \u003ch2\u003eAssociations between thyroid sensitivity and HDP\u003c/h2\u003e\n \u003cp\u003eCharacteristics of the Study Population\u003c/p\u003e\n \u003cp\u003eThe detailed flow chart of the subjects is shown in Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The characteristics of the final 4,041 pregnant women are presented in Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was 28.0 years (IQR: 26.0\u0026ndash;32.0 years), and the median BMI was 21.08 kg/m\u0026sup2; (IQR: 19.31\u0026ndash;23.07 kg/m\u0026sup2;). A total of 126 patients were prepregnant obese, accounting for 3.1% of the sample. A total of 2,326 cases were primiparas, accounting for 57.6% of the total. Few of the subjects reported smoking (including passive smoking) or drinking, with 22 (0.5%) and 41 (1.0%) cases, respectively.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe characteristics of the 4041 finally included pregnant women\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal subjects\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-HDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;4041\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;3949\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;92\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.0(26.0,32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28.0(26.0, 32.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e29.0(27.0, 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.007\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eParity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirstborn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2326 (57.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2270 (57.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e56 (60.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.793\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-firstborn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1497 (37.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1466 (37.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e31 (33.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e218 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e213 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e5 (5.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeight, cm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e160.0(158.0,164.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e160.0(158.0,164.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e160.0(158.0,165.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.781\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight, kg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e55.0(50.0, 60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e54.8(50.0, 60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e59.5(53.9, 69.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-pregnancy BMI, kg/m\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.08(19.31,23.07)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e21.04(19.29,23.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e23.39(21.05,26.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eObesity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3914 (96.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3836 (97.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e78 (84.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e126(3.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e112 (2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e14 (15.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJunior high school or below\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e716 (17.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e696 (17.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e20 (21.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.439\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e699 (17.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e681 (17.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e18 (19.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJunior college or above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2267 (56.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e2223 (56.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e44 (47.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e359 (8.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e349 (8.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e10 (10.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3995 (98.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3903 (98.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e92 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.582\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e22 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e24 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrinking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3972 (98.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e3881 (98.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e91 (98.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.719\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e41 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e40 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e1 (1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e28 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAmong the 4,041 pregnant women, 92 (2.3%) developed HDP. In the HDP group, the median age and BMI were 29.0 years (IQR: 27.0\u0026ndash;33.0 years) and 23.39 kg/m\u0026sup2; (IQR: 21.05\u0026ndash;26.46 kg/m\u0026sup2;), respectively. Compared with those of non-HDP subjects, the age, weight, and prepregnancy BMI of HDP patients were significantly greater (all \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In addition, obesity in the HDP group was also significantly greater than that in the non-HDP group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). No significant differences were found in parity, height, educational level, smoking status or drinking status between the two groups.\u003c/p\u003e\n \u003cp\u003eDistribution of thyroid hormone sensitivity\u003c/p\u003e\n \u003cp\u003eAs shown in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, in the first trimester of pregnancy, the levels of FT3/FT4, TT4RI, TSHI, and TFQI were 0.44 (0.39, 0.49), 11.80 (6.41, 18.15), 1.55 (0.95, 1.98), and \u0026minus;\u0026thinsp;0.01 (-0.22, 0.21), respectively. The FT3/FT4 ratio was significantly greater in the HDP group than in the non-HDP group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In the second trimester, the median levels of FT3/FT4, TT4RI, TSHI, and TFQI were 0.52 (0.46, 0.58), 13.85 (9.96, 18.87), 1.64 (1.31, 1.95), and \u0026minus;\u0026thinsp;0.01 (-0.27, 0.28), respectively. The FT3/FT4 ratio was significantly greater, and the TT4RI, TSHI, and TFQI were significantly lower in the HDP group than in the non-HDP group (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe distribution of thyroid hormone and thyroid hormone sensitivity\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-HDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eFirst-trimester\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eTotal\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;3949\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eN\u0026thinsp;=\u0026thinsp;92\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3, pmol/L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.89 (4.53, 5.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.88 (4.53, 5.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5.02 (4.68, 5.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT4, pmol/L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.03 (10.09, 12.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.04 (10.10, 12.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10.50 (9.66, 11.90)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.018\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSH, mIU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08 (0.59, 1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.08 (0.58, 1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.15 (0.72, 1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.577\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3/F4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.39, 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.44 (0.39, 0.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.47 (0.42, 0.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.80 (6.41, 18.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11.80 (6.41, 18.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.24 (6.64, 16.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.824\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.55 (0.95, 1.98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.55 (0.94, 1.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.61 (1.01, 1.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.931\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.01 (-0.22, 0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.01 (-0.22, 0.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.05 (-0.24, 0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.104\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond-trimester\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTotal\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u0026thinsp;=\u0026thinsp;3949\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eN\u0026thinsp;=\u0026thinsp;87\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3, pmol/L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.41 (4.09, 4.73)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.40 (4.09, 4.72)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4.50 (4.22, 4.86)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT4, pmol/L\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.48 (7.76, 9.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.49 (7.77, 9.30)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8.02 (7.35, 8.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSH, mIU\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.18, 2.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.19, 2.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.59 (1.16, 2.04)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.284\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3/F4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.46, 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.52 (0.46, 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.56 (0.50, 0.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.85 (9.96, 18.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.88 (9.97, 18.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.38 (9.13, 16.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.31, 1.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64 (1.31, 1.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.53 (1.21, 1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e0.021\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.01 (-0.27, 0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.00 (-0.26, 0.28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.21 (-0.42, 0.14)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"char\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eAssociations between thyroid hormone sensitivity and longitudinal changes in blood pressure during pregnancy\u003c/p\u003e\n \u003cp\u003eIn the first trimester, the multivariate GEE model analysis indicated that an increase in the FT3/FT4 ratio was positively associated with longitudinal SBP and DBP (SBP: \u0026beta;\u0026thinsp;=\u0026thinsp;14.78, SE\u0026thinsp;=\u0026thinsp;1.61, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; DBP: \u0026beta;\u0026thinsp;=\u0026thinsp;6.76, SE\u0026thinsp;=\u0026thinsp;1.23, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001), whereas an increase in the TFQI was negatively associated with a longitudinal change in SBP (\u0026beta;= -1.05, SE\u0026thinsp;=\u0026thinsp;0.36, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003) (Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e3.1\u003c/span\u003e).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003c/div\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"577\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" valign=\"bottom\" style=\"width: 577px;\"\u003e\n \u003cp\u003eTable 3.1. Association between thyroid hormone sensitivity and longitudinal changes in blood pressure during first-trimester pregnancy(GEE model)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 95px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 56px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (se)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (se)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 577px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eUnivariate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3/FT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e14.68(1.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6.64(1.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e-0.89(0.35)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.01\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e-0.08(0.27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.774\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e-0.004(0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.761\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e-0.002(0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.982\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e0.13(0.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.346\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e-0.002(0.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e0.988\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 577px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMultivariate*\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3/FT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e14.78(1.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e6.76(1.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e-1.05(0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e0.003\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 152px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 95px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 47px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 56px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 577px;\"\u003e\n \u003cp\u003e*:Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eSimilarly, we also analyzed the relationship in the second trimester. This analysis included only the four blood pressure measurements taken after the second-trimester thyroid hormone assessment (Table 3.2). Multivariate GEE regression analysis revealed that an increased FT3/FT4 ratio was significantly associated with increases in both SBP and DBP (SBP: \u0026beta;\u0026thinsp;=\u0026thinsp;14.74, SE\u0026thinsp;=\u0026thinsp;1.51, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; DBP: \u0026beta;\u0026thinsp;=\u0026thinsp;7.71, SE\u0026thinsp;=\u0026thinsp;1.13, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Conversely, increases in the TFQI, TT4RI, and TSHI were significantly associated with decreases in SBP (TFQI: \u0026beta;=-1.96, SE\u0026thinsp;=\u0026thinsp;0.34, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; TT4RI: \u0026beta;=-0.07, SE\u0026thinsp;=\u0026thinsp;0.02, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; TSHI: \u0026beta;=-1.07, SE\u0026thinsp;=\u0026thinsp;0.26, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Furthermore, increased TFQI was also associated with a decrease in DBP (\u0026beta;=-0.86, SE\u0026thinsp;=\u0026thinsp;0.26, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001).\u003c/p\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"577\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\" style=\"width: 572px;\"\u003e\n \u003cp\u003eTable 3.2. Association between thyroid hormone sensitivity and longitudinal changes in blood pressure during second-trimester pregnancy(GEE model)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 4px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" style=\"width: 91px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" rowspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (se)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (se)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 577px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eUnivariate\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3/FT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e15.29(1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e7.89(1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e-1.87(0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e-0.79(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e-0.06(0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e-0.02(0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e-0.93(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e-0.38(0.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 577px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eMultivariate*\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3/FT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e14.74(1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e7.71(1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e-1.96(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e-0.86(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e-0.07(0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 113px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 153px;\"\u003e\n \u003cp\u003e-1.07(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 91px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 30px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 125px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\" style=\"width: 64px;\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"7\" style=\"width: 577px;\"\u003e\n \u003cp\u003e*:Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cp\u003eAssociations between thyroid hormone sensitivity and HDP\u003c/p\u003e\n \u003cp\u003eAs shown in Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, the RCS results revealed significant nonlinear associations between each thyroid hormone sensitivity index and HDP risk (all \u003cem\u003eP\u003c/em\u003e values for nonlinearity\u0026thinsp;\u0026gt;\u0026thinsp;0.05). As shown in Table \u003cspan class=\"InternalRef\"\u003e4\u003c/span\u003e, multivariate logistic regression analysis revealed that a higher FT3/FT4 ratio was significantly associated with an increased risk of HDP (OR\u0026thinsp;=\u0026thinsp;27.23, 95% CI: 1.83\u0026ndash;406.26, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.017) after adjusting for covariates. Additionally, in the second trimester, the analysis was conducted after five subjects who developed HDP prior to the second-trimester thyroid hormone measurement were excluded. A similar association was found between the FT3/FT4 ratio and HDP (OR\u0026thinsp;=\u0026thinsp;38.93, 95% CI: 4.26\u0026ndash;355.49; \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001). Interestingly, increases in three central thyroid sensitivity indices were associated with a reduced risk of HDP (TT4RI: OR\u0026thinsp;=\u0026thinsp;0.96, 95% CI: 0.93\u0026ndash;1.00, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.038; TSHI: OR\u0026thinsp;=\u0026thinsp;0.65, 95% CI: 0.43\u0026ndash;0.99, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.047; TFQI: OR\u0026thinsp;=\u0026thinsp;0.48, 95% CI: 0.27\u0026ndash;0.85,\u0026nbsp;\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.012).\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab4\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation between thyroid hormone sensitivity and HDP\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"6\"\u003e\n \u003cp\u003eTable\u0026nbsp;3.2. Association between thyroid hormone sensitivity and longitudinal changes in blood pressure during second-trimester pregnancy(GEE model)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariables\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDBP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eP\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (se)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026beta; (se)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003e\u003cstrong\u003eUnivariate\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3/FT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15.29(1.50)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.89(1.11)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.87(0.33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.79(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.06(0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.02(0.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.132\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.93(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.38(0.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"8\"\u003e\n \u003cp\u003e\u003cstrong\u003eMultivariate*\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eFT3/FT4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.74(1.51)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7.71(1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.96(0.34)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.86(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.07(0.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-1.07(0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"8\"\u003e*:Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\n \u003ch2\u003eMediating effect of blood lipids on the association between thyroid hormone sensitivity and HDP\u003c/h2\u003e\n \u003cp\u003eFinally, a total of 201 women, comprising 67 cases with HDP and 134 controls, were matched at a 1:2 ratio. The sociodemographic characteristics of the two groups were comparable, as shown in Table \u003cspan class=\"InternalRef\"\u003e5\u003c/span\u003e. Interestingly, only the TG level was significantly elevated in the cases compared with the controls (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.0114). No statistically significant differences in TC, HDL-C, or LDL-C levels were detected between the two groups (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05, Table \u003cspan class=\"InternalRef\"\u003e6\u003c/span\u003e). The necessary conditions for the mediation analysis of TG in the FT3/FT4-HDP and TFQI-HDP associations are all satisfied; the details are shown in Fig. \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan class=\"InternalRef\"\u003e7\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv class=\"gridtable\"\u003e\u0026nbsp;\u003ctable id=\"Tab5\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe characteristics of subjects in nested case-control study\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR(95%CI)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eOR(95%CI)*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cem\u003eFirst-trimester\u003c/em\u003e\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3/F4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e185.76 (15.18-2272.63)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e27.23 (1.83-406.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00 (0.97\u0026ndash;1.02)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.906\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.09 (0.85\u0026ndash;1.39)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.495\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.60 (0.32\u0026ndash;1.13)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.111\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e/\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\" colspan=\"5\"\u003e\n \u003cp\u003e\u003cstrong\u003eSecond-trimester\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eF3/F4\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e176.40 (23.23-1339.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e38.93 (4.26-355.49)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTT4RI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96 (0.93-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.025\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.96 (0.93-1.00)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTSHI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.64 (0.43\u0026ndash;0.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.65 (0.43\u0026ndash;0.99)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.047\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eTFQI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.38 (0.22\u0026ndash;0.65)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.48 (0.27\u0026ndash;0.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.012\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003e*: Adjusting for age, education, smoking, drinking, Parity, Pre-pregnancy BMI, Weight gain\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab6\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 6\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe distribution of thyroid hormone sensitivity and serum lipid of subjects in nested case-control study (second-trimester)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-HDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;201\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;134\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;67\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\u0026nbsp;\u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge, years\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.0(27.0, 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.0(27.0, 33.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e29.0(27.0, 33.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.932\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eParity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirstborn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e126 (62.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e84 (62.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (62.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.911\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon-firstborn\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62 (30.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e42 (31.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (29.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (6.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5 (7.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eHeight, cm\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160.0(158.0, 164.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160.5(158.0, 164.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e160.0(158.0, 165.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.458\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eWeight, kg\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e56.0 (51.0, 62.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e55.7 (50.0, 60.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58.0 (53.5, 66.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.015\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003ePre-pregnancy BMI, kg/m\u003c/strong\u003e\u003csup\u003e\u003cstrong\u003e2\u003c/strong\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.64 (19.81,24.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21.05 (19.41,23.41)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e22.83 (20.54,25.21)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.009\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eObesity\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e180 (89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e120 (89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e60 (89.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e21 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7 (10.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eEducation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJunior high school\u003c/p\u003e\n \u003cp\u003eor below\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e39 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e26 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13 (19.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.695\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigh school\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e30 (14.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18 (13.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 (17.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ejunior college or above\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e112 (55.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e78 (58.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e34 (50.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20 (10.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12 ( 9.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8 (11.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eSmoking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e197 (98.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e130 (97.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.360\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3 (2.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cstrong\u003eDrinking\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e198 (98.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e131 (97.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67 (100.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.467\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1 (0.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0 (0.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\u0026nbsp;\u003ctable id=\"Tab7\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 7\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eAssociation between thyroid sensitivity, TG and HDP of subjects in nested case-control study (second-trimester)\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eVariables\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTotal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eNon-HDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eHDP\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;201\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;134\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eN\u0026thinsp;=\u0026thinsp;67\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFT3/FT4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.54(0.48, 0.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.53(0.46, 0.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.55(0.50, 0.62)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTT4RI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13.94(10.14, 18.84)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14.57(10.99, 21.23)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12.67(9.16, 16.46)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.027\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTSHI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.64(1.34, 1.95)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.69(1.40, 2.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.54(1.21, 1.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.023\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTFQI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.01(-0.31, 0.26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.04(-0.25, 0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-0.18(-0.39, 0.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCholesterol, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.07(5.41, 6.76)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.08(5.38, 6.85)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6.01(5.44, 6.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.615\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHDL-C, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.80(1.52, 2.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.81(1.59, 2.18)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1.75(1.47, 2.03)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.081\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLDL-C, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.20(2.47, 3.87)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.30(2.48, 3.96)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3.16(2.45, 3.58)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTG, mmol/L\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.32(1.85, 2.92)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.27(1.80,2.78)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2.48(2.05, 3.24)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cp\u003eWe subsequently employed a mediation analysis. Regarding the mediating effect of TG on the FT3/FT4-HDP association (Table \u003cspan class=\"InternalRef\"\u003e8.1\u003c/span\u003e), the average causal mediating effect (ACME) was 0.153 (95% CI: 0.018\u0026ndash;0.390, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008). The proportion of mediation was 18.7% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.030). The overall relationships among TG, FT3/FT4 and HDP are shown in Fig. \u003cspan class=\"InternalRef\"\u003e4.1\u003c/span\u003e. Furthermore, the mediating effect of TG on the TFQI-HDP association is shown in Table \u003cspan class=\"InternalRef\"\u003e8.2\u003c/span\u003e. The ACME was \u0026minus;\u0026thinsp;0.031 (95% CI: -0.068\u0026ndash;0.000, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026), and the proportion of mediation was 15.4% (\u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.028). The mediating relationships among TG, the TFQI, and HDP are visually summarized in Fig. \u003cspan class=\"InternalRef\"\u003e4.2\u003c/span\u003e.\u003c/p\u003e\n \u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTable 8.1. The mediating effect of TG in the association between FT3/FT4 and HDP in second-trimester.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndicators of mediating effects\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 21px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95%CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003evalue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eACME (control) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.096\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.005 ~ 0.340\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eACME (case) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.210\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.029 ~ 0.470\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eADE (control) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.492\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.056 ~ 0.880\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eADE (case) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.607\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.083 ~ 0.930\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eTotal Effect \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.703\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.155 ~ 0.940\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.022\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eProp. Mediated (control)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.002 ~ 0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eProp. Mediated (case)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.287\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.018 ~ 1.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eACME (average) \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.018 ~ 0.390\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eADE (average) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.550\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.066 ~ 0.900\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.072\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 40px;\"\u003e\n \u003cp\u003eProp. Mediated (average)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 21px;\"\u003e\n \u003cp\u003e0.187\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e0.010 ~ 0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 14px;\"\u003e\n \u003cp\u003e0.030\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003eACME (control)：The average causal mediating effect in control group.\u003c/p\u003e\n \u003cp\u003eACME (case)：The average causal mediating effect in case group.\u003c/p\u003e\n \u003cp\u003eADE (control)：The average causal direct effect in control group.\u003c/p\u003e\n \u003cp\u003eADE (case)：The average causal direct effect in case group.\u003c/p\u003e\n \u003cp\u003eProp. Mediated (control)：The proportion of the mediating effect in control group to the total effect。\u003c/p\u003e\n \u003cp\u003eProp. Mediated (case)：The proportion of the mediating effect in case group to the total effect.\u003c/p\u003e\n \u003cp\u003eACME (average)：Average causal mediating effect.\u003c/p\u003e\n \u003cp\u003eADE (average)：Average causal direct effect.\u003c/p\u003e\n \u003cp\u003eProp. Mediated (average)：The proportion of the average mediating effect to the total effect.\u003c/p\u003e\n \u003cp\u003eAdjusting for pregnant woman\u0026apos;s age, BMI, parity, educational level, and weight gain(considering the stability of the model, smoking and drinking were not included, for there are 0 categories in each variable).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"center\"\u003e\n \u003ctable border=\"0\" cellspacing=\"0\" cellpadding=\"0\" width=\"100%\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003eTable 8.2 The mediating effect of TG in the association between TFQI and HDP in second-trimester.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eIndicators of mediating effects\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 26px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eEstimated value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 23px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e95%CI\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 15px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\u003c/em\u003e\u003c/strong\u003e\u003cstrong\u003e值\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eACME (control) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.038\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.082\u0026nbsp;～\u0026nbsp;0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eACME (case) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.024\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.057\u0026nbsp;～\u0026nbsp;0.000\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eADE (control) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.164\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.251\u0026nbsp;～\u0026nbsp;-0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eADE (case) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.150\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.234\u0026nbsp;～\u0026nbsp;-0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eTotal Effect \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.188\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.268\u0026nbsp;～\u0026nbsp;-0.090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.002\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eProp. Mediated (control)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e0.197\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.013\u0026nbsp;～\u0026nbsp;0.520\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eProp. Mediated (case)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e0.112\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.006\u0026nbsp;～\u0026nbsp;0.440\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eACME (average) \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.031\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.068\u0026nbsp;～\u0026nbsp;0.000\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.026\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eADE (average) \u0026nbsp; \u0026nbsp; \u0026nbsp; \u0026nbsp;\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e-0.157\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e-0.240\u0026nbsp;～\u0026nbsp;-0.050\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.008\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 34px;\"\u003e\n \u003cp\u003eProp. Mediated (average)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 26px;\"\u003e\n \u003cp\u003e0.154\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 23px;\"\u003e\n \u003cp\u003e0.010\u0026nbsp;～\u0026nbsp;0.480\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 15px;\"\u003e\n \u003cp\u003e0.028\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"4\" style=\"width: 100px;\"\u003e\n \u003cp\u003eACME (control)：The average causal mediating effect in control group.\u003c/p\u003e\n \u003cp\u003eACME (case)：The average causal mediating effect in case group.\u003c/p\u003e\n \u003cp\u003eADE (control)：The average causal direct effect in control group.\u003c/p\u003e\n \u003cp\u003eADE (case)：The average causal direct effect in case group.\u003c/p\u003e\n \u003cp\u003eProp. Mediated (control)：The proportion of the mediating effect in control group to the total effect。\u003c/p\u003e\n \u003cp\u003eProp. Mediated (case)：The proportion of the mediating effect in case group to the total effect.\u003c/p\u003e\n \u003cp\u003eACME (average)：Average causal mediating effect.\u003c/p\u003e\n \u003cp\u003eADE (average)：Average causal direct effect.\u003c/p\u003e\n \u003cp\u003eProp. Mediated (average)：The proportion of the average mediating effect to the total effect.\u003c/p\u003e\n \u003cp\u003eAdjusting for pregnant woman\u0026apos;s age, BMI, parity, educational level, and weight gain(considering the stability of the model, smoking and drinking were not included, for there are 0 categories in each variable).\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n \u003c/div\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this study, increased FT3/FT4 in the first trimester was positively associated with longitudinal changes in both SBP and DBP, whereas the TFQI was negatively correlated with SBP. Similar results were observed in the second trimester. Furthermore, higher FT3/FT4 ratios in the first trimester were significantly associated with an increased risk of HDP, and similar results were observed in the second trimester. However, increased levels of three central thyroid hormone sensitivity indices in the second trimester were associated with a reduced risk of HDP. Furthermore, our analysis revealed that TG had a mediating effect on approximately 15% of the associations between both FT3/FT4 and the TFQI with HDPs.\u003c/p\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003eLevels of thyroid hormone sensitivity during pregnancy\u003c/h2\u003e \u003cp\u003eIn the present study, the median FT3 and FT4 levels during the first trimester were 4.89 (IQR: 4.53, 5.28) pmol/L and 11.03 (IQR: 10.09, 12.17) pmol/L, respectively. The first-trimester FT3 level was similar to that reported in the Belgian cohort of 597 pregnant women (5.0\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8 pmol/L). However, their FT4 level was notably higher than that in our study (14.9\u0026thinsp;\u0026plusmn;\u0026thinsp;2.4 pmol/L). Consequently, the value of the FT3/FT4 ratio was lower than our result (0.34\u0026thinsp;\u0026plusmn;\u0026thinsp;0.06 vs 0.44, 0.39\u0026ndash;0.49). Similar differences were found in the second trimester[\u003cspan citationid=\"CR44\" class=\"CitationRef\"\u003e44\u003c/span\u003e]. Additionally, the FT3/FT4 ratio of a Chinese cohort study by Wang was 2.75 (IQR: 2.44, 3.15), which was also lower than our result[\u003cspan citationid=\"CR45\" class=\"CitationRef\"\u003e45\u003c/span\u003e]. The subjects of the above two cohorts were from the general pregnant population, including individuals with thyroid dysfunction, which may limit comparability. However, in 2023, a study conducted by Zhao among euthyroid pregnant women also reported a lower FT3/FT4 ratio than previously reported[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e]. This pattern may be related to physiological thyroid enlargement during pregnancy, which increases hormone production capacity by approximately 40% to meet gestational demands. This adaptation is accompanied by alterations in FT3 and FT4 secretion and an overall increase in metabolic activity. The FT3/FT4 ratio reflects the conversion rate of T4 to T3, indicating peripheral tissue responsiveness to thyroid hormones[\u003cspan citationid=\"CR47\" class=\"CitationRef\"\u003e47\u003c/span\u003e]. A higher ratio suggests increased peripheral metabolic activity and heightened sensitivity to thyroid hormones, which has been associated with conditions such as insulin resistance[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], metabolic syndrome[\u003cspan citationid=\"CR49\" class=\"CitationRef\"\u003e49\u003c/span\u003e], and cardiometabolic dysfunction[\u003cspan citationid=\"CR50\" class=\"CitationRef\"\u003e50\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe TFQI is a novel resistance index derived from the empirical joint distribution of FT4 and TSH. It is increasingly used to assess central thyroid hormone sensitivity in relation to conditions such as diabetes, obesity, and metabolic syndrome[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. The TFQI values range from \u0026minus;\u0026thinsp;1 to 1, with negative values indicating increased pituitary sensitivity to thyroid hormones and positive values indicating reduced sensitivity. A key advantage of the TFQI is its robustness against extreme values, offering greater stability than other central sensitivity indices, such as the TT4RI and TSHI. In our study, the median TFQI values were \u0026minus;\u0026thinsp;0.01 (IQR: -0.22, 0.21) and \u0026minus;\u0026thinsp;0.01 (IQR:-0.27, 0.28) in the first trimester and second trimester, respectively, which were similar to the findings of Zhao in a euthyroid pregnant population[\u003cspan citationid=\"CR46\" class=\"CitationRef\"\u003e46\u003c/span\u003e] but were slightly lower than those reported in Chinese euthyroid women[\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e] and the euthyroid general population[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR51\" class=\"CitationRef\"\u003e51\u003c/span\u003e]. In addition, a study of 1,075 Greek singleton pregnancies in 2024 reported a mean TFQI of -0.06 during pregnancy, which was lower than our findings[\u003cspan citationid=\"CR52\" class=\"CitationRef\"\u003e52\u003c/span\u003e]. Our results indicated that central thyroid hormone sensitivity in euthyroid pregnant individuals may be slightly greater than that in the general Chinese population but may be lower than that in the European population.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eThyroid Hormone Sensitivity and Blood Pressure/Hypertension during Pregnancy\u003c/h2\u003e \u003cp\u003ePrevious studies have typically focused on the relationships between individual thyroid hormone indicators and blood pressure and have rarely focused on the associations between thyroid hormone sensitivity and blood pressure in pregnant women[\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan additionalcitationids=\"CR20\" citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Our study revealed that an elevated FT3/FT4 ratio was positively correlated with longitudinal increases in SBP and DBP and an increased risk of HDP. To our knowledge, this is the first study to report such an association in euthyroid pregnant women. However, to date, several studies in other populations have been reported. In 2024, Chen[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e] reported a similar positive association among 107,301 Chinese euthyroid type 2 diabetes mellitus patients who were overweight or obese. Conversely, Samet reported no significant difference in FT3/FT4 between hypertensive and nonhypertensive obese subjects[\u003cspan citationid=\"CR54\" class=\"CitationRef\"\u003e54\u003c/span\u003e], and Birck[\u003cspan citationid=\"CR55\" class=\"CitationRef\"\u003e55\u003c/span\u003e], Yuan[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e] and Xu[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e] reported no significant associations. These discrepant results may be attributed to variations in the study populations, including differences in health status, age, and ethnicity, especially in the pregnant population, whose hormonal status differs substantially from that of the general population. The FT3/FT4 ratio reflects the peripheral conversion of T4 to T3 and is considered an indicator of peripheral thyroid hormone sensitivity. An elevated ratio may result from increased type 2 deiodinase (DIO2) activity in response to adverse metabolic conditions[\u003cspan citationid=\"CR48\" class=\"CitationRef\"\u003e48\u003c/span\u003e], serving as an early marker of metabolic alterations[\u003cspan citationid=\"CR57\" class=\"CitationRef\"\u003e57\u003c/span\u003e] and a predictor of cardiovascular mortality[\u003cspan citationid=\"CR58\" class=\"CitationRef\"\u003e58\u003c/span\u003e]. This may explain the association between higher FT3/FT4 ratios and increased HDP risk. Moreover, the FT3/FT4 ratio may be a more precise and clinically feasible indicator of thyroid hormone metabolic variability than FT3 or FT4 alone[\u003cspan citationid=\"CR56\" class=\"CitationRef\"\u003e56\u003c/span\u003e, \u003cspan citationid=\"CR59\" class=\"CitationRef\"\u003e59\u003c/span\u003e, \u003cspan citationid=\"CR60\" class=\"CitationRef\"\u003e60\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe TFQI is a recently developed index for assessing central thyroid hormone sensitivity [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]. Previous studies have reported positive associations between the TFQI and BP or HDP risk. Mehran[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e] reported that a higher TFQI was associated with greater BP in an Iranian community-based population (OR\u0026thinsp;=\u0026thinsp;1.14, 95% CI: 1.06\u0026ndash;1.23). Similarly, Yang[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] reported that the TFQI was positively correlated with both SBP (β\u0026thinsp;=\u0026thinsp;3.22) and DBP (β\u0026thinsp;=\u0026thinsp;2.32), and high TFQI levels were associated with increased HDP risk (OR\u0026thinsp;=\u0026thinsp;1.27, 95% CI: 1.07\u0026ndash;1.51). In contrast, our study revealed that the first-trimester TFQI was negatively correlated with longitudinal changes in SBP, and a higher second-trimester TFQI was associated with a reduced risk of HDP. Our results were consistent with findings in Chinese [\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e] and Latin American middle-aged and older adults[\u003cspan citationid=\"CR62\" class=\"CitationRef\"\u003e62\u003c/span\u003e]. Moreover, one study of 5,124 adults from the Tehran Thyroid Study revealed that both TSHI (OR\u0026thinsp;=\u0026thinsp;1.22, 95% CI: 1.08\u0026ndash;1.38) and TT4RI (OR\u0026thinsp;=\u0026thinsp;1.08, 95% CI: 1.01\u0026ndash;1.16) were associated with increased HDP risk[\u003cspan citationid=\"CR61\" class=\"CitationRef\"\u003e61\u003c/span\u003e]. Conversely, a study of 34,310 participants reported negative associations between these indices and HDP risk[\u003cspan citationid=\"CR53\" class=\"CitationRef\"\u003e53\u003c/span\u003e]. Another study of 1,789 adults from a Spanish subcohort also reported a trend toward a negative association [\u003cspan citationid=\"CR63\" class=\"CitationRef\"\u003e63\u003c/span\u003e]. Similarly, our study revealed that higher TT4RI and TSHI in the second trimester were associated with a reduced risk of HDP. These results suggest that reduced central thyroid hormone sensitivity may be protective against HDP; in other words, increased sensitivity may increase HDP risk. This may be due to links between central sensitivity and metabolic disorders and dyslipidemia[\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR64\" class=\"CitationRef\"\u003e64\u003c/span\u003e]. The current evidence remains controversial, and many more large-scale prospective studies are needed to clarify these relationships.\u003c/p\u003e \u003cp\u003eIn summary, our findings indicate that high thyroid hormone sensitivity (both central and peripheral) may be associated with elevated BP and a greater risk of HDP in euthyroid pregnant women. Potential mechanisms may include the following: ①Thyroid hormones influence cardiac contractility, heart rate, peripheral vascular resistance, endothelial function, and renin synthesis and secretion, thereby modulating BP through multiple pathways[\u003cspan additionalcitationids=\"CR66\" citationid=\"CR65\" class=\"CitationRef\"\u003e65\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR67\" class=\"CitationRef\"\u003e67\u003c/span\u003e]. Altered thyroid hormone sensitivity may affect hormone activity and vascular function. ② Type 2 iodothyronine deiodinase (DIO2), which plays a key role in thyroid feedback regulation, has been linked to increased hypertension risk[\u003cspan additionalcitationids=\"CR69\" citationid=\"CR68\" class=\"CitationRef\"\u003e68\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR70\" class=\"CitationRef\"\u003e70\u003c/span\u003e]. Increased thyroid hormone sensitivity may affect hypertension development through changes in DIO2 activity. Further research is needed to elucidate the regulatory mechanisms underlying these associations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eMediating Role of TG in the Association between FT3/FT4, TFQI, and HDP\u003c/h2\u003e \u003cp\u003eThe present study revealed that TG significantly mediated the association between FT3/FT4 and HDP, with 10.5% of the total effect. Similarly, the relationship between the TFQI and HDP (12.1% of the total effect) was investigated. These results suggested that TG mediates approximately 10% of the association between both peripheral and central thyroid hormone sensitivity and HDP, and the dominant effect remains the direct influence of thyroid hormone sensitivity on HDP.\u003c/p\u003e \u003cp\u003eThyroid hormones modulate cardiovascular function through genomic and nongenomic mechanisms, primarily affecting vascular smooth muscle and endothelial cells. Potential pathways include ion channel activation (Na⁺, K⁺, Ca\u0026sup2;⁺) and the regulation of specific signaling cascades. Among these pathways, the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) pathway plays a central role. Its activation promotes endothelial nitric oxide (NO) production, thereby reducing systemic vascular resistance through effects on vascular smooth muscle cells[\u003cspan citationid=\"CR71\" class=\"CitationRef\"\u003e71\u003c/span\u003e, \u003cspan citationid=\"CR72\" class=\"CitationRef\"\u003e72\u003c/span\u003e]. These mechanisms have been corroborated by multiple interventional studies[\u003cspan additionalcitationids=\"CR74\" citationid=\"CR73\" class=\"CitationRef\"\u003e73\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR75\" class=\"CitationRef\"\u003e75\u003c/span\u003e]. T3 is recognized as an inotropic vasodilator that is particularly effective in treating diastolic dysfunction because of its unique pharmacological profile[\u003cspan citationid=\"CR76\" class=\"CitationRef\"\u003e76\u003c/span\u003e]. Additionally, thyroid hormones regulate lipid metabolism by stimulating hepatic lipid mobilization, degradation, and de novo fatty acid synthesis[\u003cspan citationid=\"CR77\" class=\"CitationRef\"\u003e77\u003c/span\u003e, \u003cspan citationid=\"CR78\" class=\"CitationRef\"\u003e78\u003c/span\u003e]. Notably, recent evidence highlights the critical role of free fatty acids (FFAs), which are key metabolites of TG, in endothelial function. As Garc\u0026iacute;a-Prieto[\u003cspan citationid=\"CR79\" class=\"CitationRef\"\u003e79\u003c/span\u003e] demonstrated, a high-fat diet downregulates the AMPK-PI3K-Akt-eNOS pathway in endothelial cells, leading to endothelial dysfunction, which is correlated with elevated plasma FFAs and TG levels. FFAs may impair insulin-mediated NO production and peripheral blood flow via two primary mechanisms: reducing tyrosine phosphorylation of IRS-1/2 (insulin receptor substrate-1/2) and inhibiting the PI3K/Akt signaling pathway, which regulates eNOS-derived NO synthesis in endothelial cells[\u003cspan citationid=\"CR80\" class=\"CitationRef\"\u003e80\u003c/span\u003e, \u003cspan citationid=\"CR81\" class=\"CitationRef\"\u003e81\u003c/span\u003e]. Thus, the PI3K/Akt pathway appears to be a key mechanistic link underlying the partial mediating effect of TG on the relationship between thyroid hormone sensitivity and HDP. However, further biological investigations are warranted to elucidate more detailed mechanisms involved.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section2\"\u003e \u003ch2\u003eStrengths and Limitations\u003c/h2\u003e \u003cp\u003eThis is a prospective cohort study with longitudinal blood pressure measurements at six time points, enhancing the reliability of causal inference and providing a comprehensive assessment of blood pressure changes throughout pregnancy. This approach also allows for more accurate and timely identification of HDPs. Furthermore, the study exclusively enrolled pregnant women with normal thyroid function, thereby minimizing the potential confounding effects of thyroid dysfunction. Additional exclusions included women with preexisting hypertension, those with other serious pregnancy complications, and those diagnosed with abnormal liver or kidney function during pregnancy, which may significantly reduce the influence of potential confounders on the relationship between thyroid hormone sensitivity and blood pressure changes or HDP. Unlike previous studies that focused on individual thyroid hormones, our study employed composite indices to assess thyroid hormone sensitivity, which provides more stable and robust results. In addition, we are the first to evaluate the mediating role of TG in the relationship between thyroid hormone sensitivity (both peripheral and central) and HDP, offering new insights and evidence for potential mechanisms modulating thyroid hormone sensitivity and HDP risk. Nevertheless, this study has several limitations. First, a substantial proportion of the original cohort was excluded because of missing thyroid function tests or blood pressure measurements, which may affect the generalizability of the findings. Second, although the proportion of missing data at various time points was less than 5%, this minor missingness could still reduce the statistical power and introduce potential selection bias. Finally, the relatively small number of HDP cases in the cohort resulted in a wide confidence interval in the regression models. However, we conducted a nested case‒control study to further validate our findings.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusions","content":"\u003cp\u003eIn conclusion, we found that thyroid hormone sensitivity is greater in pregnant women than in the general population. Our results suggest that increased thyroid hormone sensitivity may be associated with a greater risk of HDP. Interestingly, we further revealed the mediating role of TG in the associations of both FT3/FT4 and the TFQI with HDPs. These findings provide important clues and a foundation for further investigations into the potential mechanisms of HDP.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eHDP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehypertensive disorders of pregnancy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eGEE\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003egeneralized estimating equation\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eSBP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003esystolic blood pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eDBP\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ediastolic blood pressure\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTSHI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethyroid-stimulating hormone index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTT4RI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe thyroid T4 resistance index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTFQI\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ethe thyroid feedback quantile-based index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eCVD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ecardiovascular disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eASCVD\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eatherosclerotic cardiovascular disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eEDTA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eethylenediaminetetraacetic acid\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTC\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etotal cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eHDL-C\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ehigh-density lipoprotein cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eLDL-C\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003elow-density lipoprotein cholesterol\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eTG\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003etriglycerides\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eANOVA\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eone-way analysis of variance\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eRCS\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erestricted cubic spline\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003e\u003cb\u003eACME\u003c/b\u003e\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eaverage causal mediating effect\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u003c/strong\u003e This study was approved by the Ethics Committee of the Zhejiang University School of Medicine. Signed informed consent forms were obtained from all participants prior to the survey.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u003c/strong\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e Data that underlie the results reported in this article (text, tables, figures, and appendices) will be made available upon request following publication, with no end date, to anyone who wishes to access the data for any purpose. Proposals should be directed to the corresponding author to gain access.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors report that there are no competing interests to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThis work was supported by the National Key R\u0026amp;D Program of China [grant numbers 2022YFC2703505 and 2021YFC2701901].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eZexin Chen and Yunxian Yu had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.\u003c/p\u003e\n\u003cp\u003eConcept and design: Zexin Chen and Yunxian Yu.\u003c/p\u003e\n\u003cp\u003eAcquisition, analysis, or interpretation of data: Zexin Chen, Xialidan Alifu, Wanli Li, Yunxian Yu.\u003c/p\u003e\n\u003cp\u003eDrafting of the manuscript: Zexin Chen.\u003c/p\u003e\n\u003cp\u003eCritical review of the manuscript: Yunxian Yu.\u003c/p\u003e\n\u003cp\u003eStatistical analysis: Zexin Chen, Xialidan\u0026nbsp;Alifu.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e Not applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSay L, Chou D, Gemmill A, Tuncalp O, Moller AB, Daniels J, Gulmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Global health. 2014;2(6):e323\u0026ndash;333.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhuang C, Gao J, Liu J, Wang X, He J, Sun J, Liu X, Liao S. Risk factors and potential protective factors of pregnancy-induced hypertension in China: A cross-sectional study. J Clin Hypertens. 2019;21(5):618\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWen SW, Tan H, Retnakaran R, Shen M, Zhou S, Xie RH, Smith GN, Davidge ST, Trasler J, Walker MC. Pre-gravid predictors of new onset hypertension in pregnancy - Results from a pre-conception cohort study in China. Eur J Obstet Gynecol Reprod Biol. 2017;214:140\u0026ndash;4.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi F, Qin J, Zhang S, Chen L. Prevalence of hypertensive disorders in pregnancy in China: A systematic review and meta-analysis. Pregnancy Hypertens. 2021;24:13\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbalos E, Cuesta C, Carroli G, Qureshi Z, Widmer M, Vogel JP, Souza JP. Maternal WHOMSo, Newborn Health Research N: Pre-eclampsia, eclampsia and adverse maternal and perinatal outcomes: a secondary analysis of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG: Int J Obstet Gynecol. 2014;121(Suppl 1):14\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVogel JP, Souza JP, Mori R, Morisaki N, Lumbiganon P, Laopaiboon M, Ortiz-Panozo E, Hernandez B, Perez-Cuevas R, Roy M, et al. Maternal complications and perinatal mortality: findings of the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG: Int J Obstet Gynecol. 2014;121(Suppl 1):76\u0026ndash;88.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown MC, Best KE, Pearce MS, Waugh J, Robson SC, Bell R. Cardiovascular disease risk in women with pre-eclampsia: systematic review and meta-analysis. Eur J Epidemiol. 2013;28(1):1\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeffert LR, Clancy CR, Bateman BT, Bryant AS, Kuklina EV. Hypertensive disorders and pregnancy-related stroke: frequency, trends, risk factors, and outcomes. Obstet Gynecol. 2015;125(1):124\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArthur JR, Beckett GJ. Thyroid function. Br Med Bull. 1999;55(3):658\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eColzani RM, Emdin M, Conforti F, Passino C, Scarlattini M, Iervasi G. Hyperthyroidism is associated with lengthening of ventricular repolarization. Clin Endocrinol. 2001;55(1):27\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodondi N, den Elzen WP, Bauer DC, Cappola AR, Razvi S, Walsh JP, Asvold BO, Iervasi G, Imaizumi M, Collet TH, et al. Subclinical hypothyroidism and the risk of coronary heart disease and mortality. JAMA. 2010;304(12):1365\u0026ndash;74.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTakamura N, Hayashida N, Maeda T. Risk of coronary heart disease and mortality for adults with subclinical hypothyroidism. JAMA. 2010;304(22):2481\u0026ndash;2. author reply 2482.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIglesias P, Diez JJ. Hyperthyroidism and cardiovascular risk factors: A nationwide study. Endocrinologia diabetes y nutricion. 2023;70(4):255\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePearce EN. Update in lipid alterations in subclinical hypothyroidism. J Clin Endocrinol Metab. 2012;97(2):326\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaito I, Ito K, Saruta T. Hypothyroidism as a cause of hypertension. Hypertension. 1983;5(1):112\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCappola AR, Ladenson PW. Hypothyroidism and atherosclerosis. J Clin Endocrinol Metab. 2003;88(6):2438\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlein I, Danzi S. Thyroid disease and the heart. Circulation. 2007;116(15):1725\u0026ndash;35.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKlein I, Ojamaa K. Thyroid hormone and the cardiovascular system. N Engl J Med. 2001;344(7):501\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang J, Huang C, Meng Z, Fan Y, Yang Q, Zhang W, Gao Y, Yang Z, Cai H, Bian B et al. Gender-Specific Differences on the Association of Hypertension with Subclinical Thyroid Dysfunction. \u003cem\u003eInternational journal of endocrinology\u003c/em\u003e 2019, 2019:6053068.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVolzke H, Ittermann T, Schmidt CO, Dorr M, John U, Wallaschofski H, Stricker BH, Felix SB, Rettig R. Subclinical hyperthyroidism and blood pressure in a population-based prospective cohort study. Eur J Endocrinol. 2009;161(4):615\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCai Y, Ren Y, Shi J. Blood pressure levels in patients with subclinical thyroid dysfunction: a meta-analysis of cross-sectional data. Hypertens research: official J Japanese Soc Hypertens. 2011;34(10):1098\u0026ndash;105.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlves Junior JM, Bernardo WM, Ward LS, Villagelin D. Effect of Hyperthyroidism Control During Pregnancy on Maternal and Fetal Outcome: A Systematic Review and Meta-Analysis. Front Endocrinol. 2022;13:800257.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCooper DS, Laurberg P. Hyperthyroidism in pregnancy. lancet Diabetes Endocrinol. 2013;1(3):238\u0026ndash;49.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eToloza FJK, Derakhshan A, Mannisto T, Bliddal S, Popova PV, Carty DM, Chen L, Taylor P, Mosso L, Oken E, et al. Association between maternal thyroid function and risk of gestational hypertension and pre-eclampsia: a systematic review and individual-participant data meta-analysis. lancet Diabetes Endocrinol. 2022;10(4):243\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLai H, Zhan ZY, Liu H. Association between thyroid hormone parameters during early pregnancy and gestational hypertension: a prospective cohort study. J Int Med Res. 2020;48(2):300060520904814.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMaraka S, Ospina NM, O'Keeffe DT, De Espinosa AE, Gionfriddo MR, Erwin PJ, Coddington CC 3rd, Stan MN, Murad MH, Montori VM. Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis. Thyroid: official J Am Thyroid Association. 2016;26(4):580\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eVella K, Vella S, Savona-Ventura C, Vassallo J. Thyroid dysfunction in pregnancy - a retrospective observational analysis of a Maltese cohort. BMC Pregnancy Childbirth. 2022;22(1):941.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi Y, Shan Z, Teng W, Thyroid Disorders IS, Diabetes Epidemiological Survey G. The Iodine Status and Prevalence of Thyroid Disorders Among Women of Childbearing Age in China: National Cross-sectional Study. Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2021;27(10):1028\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYang S, Wang Z, Li J, Fu J, Guan H, Wang W. Thyroid Feedback Quantile-Based Index Is Associated With Blood Pressure and Other Hemodynamic Measures: A Cross-sectional Study. Endocr practice: official J Am Coll Endocrinol Am Association Clin Endocrinologists. 2022;28(10):1055\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLaclaustra M, Moreno-Franco B, Lou-Bonafonte JM, Mateo-Gallego R, Casasnovas JA, Guallar-Castillon P, Cenarro A, Civeira F. Impaired Sensitivity to Thyroid Hormones Is Associated With Diabetes and Metabolic Syndrome. Diabetes Care. 2019;42(2):303\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhang X, Chen Y, Ye H, Luo Z, Li J, Chen Z, Zhang E, Li W. Correlation between thyroid function, sensitivity to thyroid hormones and metabolic dysfunction-associated fatty liver disease in euthyroid subjects with newly diagnosed type 2 diabetes. Endocrine. 2023;80(2):366\u0026ndash;79.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDing X, Wang Y, Liu J, Wang G. Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Homocysteine Levels in the Euthyroid Population. J Clin Endocrinol Metab. 2022;107(9):e3731\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWei Y, Li X, Cui R, Liu J, Wang G. Associations between sensitivity to thyroid hormones and insulin resistance in euthyroid adults with obesity. Front Endocrinol. 2024;15:1366830.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYe G, Zhang Y, Peng L, Yu Z, Bai Y, Wu M, Lu D, Ding C. Impaired sensitivity to thyroid hormones is associated with lower heart rate in the euthyroid population. Heart rhythm 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSoppert J, Lehrke M, Marx N, Jankowski J, Noels H. Lipoproteins and lipids in cardiovascular disease: from mechanistic insights to therapeutic targeting. Adv Drug Deliv Rev. 2020;159:4\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDamiano F, Rochira A, Gnoni A, Siculella L. Action of Thyroid Hormones, T3 and T2, on Hepatic Fatty Acids: Differences in Metabolic Effects and Molecular Mechanisms. Int J Mol Sci 2017, 18(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eObregon MJ. Adipose tissues and thyroid hormones. Front Physiol. 2014;5:479.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKatz LS, Xu S, Ge K, Scott DK, Gershengorn MC. T3 and Glucose Coordinately Stimulate ChREBP-Mediated Ucp1 Expression in Brown Adipocytes From Male Mice. Endocrinology. 2018;159(1):557\u0026ndash;69.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXu R, Huang F, Zhang S, Lv Y, Liu Q. Thyroid function, body mass index, and metabolic risk markers in euthyroid adults: a cohort study. BMC Endocr disorders. 2019;19(1):58.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShao B, Mo M, Xin X, Jiang W, Wu J, Huang M, Wang S, Muyiduli X, Si S, Shen Y, et al. The interaction between prepregnancy BMI and gestational vitamin D deficiency on the risk of gestational diabetes mellitus subtypes with elevated fasting blood glucose. Clin Nutr. 2020;39(7):2265\u0026ndash;73.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarovic VD, Dechend R, Easterling T, Karumanchi SA, McMurtry Baird S, Magee LA, Rana S, Vermunt JV, August P, American Heart Association Council on H. Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association. Hypertension. 2022;79(2):e21\u0026ndash;41.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCappelli C, Rotondi M, Pirola I, Agosti B, Gandossi E, Valentini U, De Martino E, Cimino A, Chiovato L, Agabiti-Rosei E, et al. TSH-lowering effect of metformin in type 2 diabetic patients: differences between euthyroid, untreated hypothyroid, and euthyroid on L-T4 therapy patients. Diabetes Care. 2009;32(9):1589\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYagi H, Pohlenz J, Hayashi Y, Sakurai A, Refetoff S. Resistance to thyroid hormone caused by two mutant thyroid hormone receptors beta, R243Q and R243W, with marked impairment of function that cannot be explained by altered in vitro 3,5,3'-triiodothyroinine binding affinity. J Clin Endocrinol Metab. 1997;82(5):1608\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRaets L, Minschart C, Van den Bruel A, Van den Bogaert E, Van Crombrugge P, Moyson C, Verhaeghe J, Vandeginste S, Verlaenen H, Vercammen C et al. Higher Thyroid fT3-to-fT4 Ratio Is Associated with Gestational Diabetes Mellitus and Adverse Pregnancy Outcomes. J Clin Med 2022, 11(17).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang Y, Sun F, Wu P, Huang Y, Ye Y, Yang X, Yuan J, Liu Y, Zeng H, Wen Y, et al. A Prospective Study of Early-pregnancy Thyroid Markers, Lipid Species, and Risk of Gestational Diabetes Mellitus. J Clin Endocrinol Metab. 2022;107(2):e804\u0026ndash;14.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao X, Sun J, Yuan N, Zhang X. Free triiodothyronine (FT3)-to-free thyroxine (FT4) ratio identified as a risk factor for gestational diabetes in euthyroid pregnant women: insights from a Chinese population cohort study. Front Endocrinol. 2023;14:1281285.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNie X, Ma X, Xu Y, Shen Y, Wang Y, Bao Y. Increased Serum Adipocyte Fatty Acid-Binding Protein Levels Are Associated with Decreased Sensitivity to Thyroid Hormones in the Euthyroid Population. Thyroid: official J Am Thyroid Association. 2020;30(12):1718\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePark SY, Park SE, Jung SW, Jin HS, Park IB, Ahn SV, Lee S. Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects. Clin Endocrinol. 2017;87(1):87\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWolffenbuttel BHR, Wouters H, Slagter SN, van Waateringe RP, Muller Kobold AC, van Vliet-Ostaptchouk JV, Links TP, van der Klauw MM. Thyroid function and metabolic syndrome in the population-based LifeLines cohort study. BMC Endocr disorders. 2017;17(1):65.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoef GL, Rietzschel ER, Van Daele CM, Taes YE, De Buyzere ML, Gillebert TC, Kaufman JM. Triiodothyronine and free thyroxine levels are differentially associated with metabolic profile and adiposity-related cardiovascular risk markers in euthyroid middle-aged subjects. Thyroid: official J Am Thyroid Association. 2014;24(2):223\u0026ndash;31.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu C, Hua L, Liu K, Xin Z. Impaired sensitivity to thyroid hormone correlates to osteoporosis and fractures in euthyroid individuals. J Endocrinol Investig. 2023;46(10):2017\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIlias I, Milionis C, Alexiou M, Michou E, Karavasili C, Venaki E, Markou K, Mamali I, Koukkou E. Changes in Central Sensitivity to Thyroid Hormones vs. Urine Iodine during Pregnancy. Med Sci 2024, 12(4).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen F, Chen R, Zhou J, Xu W, Zhou J, Chen X, Gong X, Chen Z. Impaired Sensitivity to Thyroid Hormones is Associated with Central Obesity in Euthyroid Type 2 Diabetes Mellitus Patients with Overweight and Obesity. Diabetes metabolic syndrome obesity: targets therapy. 2024;17:3379\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOzer S, Butun I, Sonmezgoz E, Yilmaz R, Demir O. Relationships among Thyroid Hormones and Obesity Severity, Metabolic Syndrome and Its Components in Turkish Children with Obesity. Nutr Hosp. 2015;32(2):645\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBirck MG, Janovsky C, Goulart AC, Meneghini V, Pititto BA, Sgarbi JA, Teixeira PFS, Bensenor IM. Associations of TSH, free T3, free T4, and conversion ratio with incident hypertension: results from the prospective Brazilian Longitudinal Study of Adult Health (ELSA-Brasil). Archives Endocrinol metabolism. 2024;68:e230301.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYuan D, Zhang C, Jia S, Liu Y, Jiang L, Xu L, Zhang Y, Xu J, Xu B, Hui R, et al. Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease. Nutr metabolism Cardiovasc diseases: NMCD. 2021;31(2):579\u0026ndash;86.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGokmen FY, Ahbab S, Ataoglu HE, Turker BC, Cetin F, Turker F, Mamac RY, Yenigun M. FT3/FT4 ratio predicts non-alcoholic fatty liver disease independent of metabolic parameters in patients with euthyroidism and hypothyroidism. Clinics. 2016;71(4):221\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYu T, Tian C, Song J, He D, Wu J, Wen Z, Sun Z, Sun Z. Value of the fT3/fT4 ratio and its combination with the GRACE risk score in predicting the prognosis in euthyroid patients with acute myocardial infarction undergoing percutaneous coronary intervention: a prospective cohort study. BMC Cardiovasc Disord. 2018;18(1):181.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLang X, Li Y, Zhang D, Zhang Y, Wu N, Zhang Y. FT3/FT4 ratio is correlated with all-cause mortality, cardiovascular mortality, and cardiovascular disease risk: NHANES 2007\u0026ndash;2012. Front Endocrinol. 2022;13:964822.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhao X, Sun J, Xin S, Zhang X. Predictive Effects of FT3/FT4 on Diabetic Kidney Disease: An Exploratory Study on Hospitalized Euthyroid Patients with T2DM in China. Biomedicines 2023, 11(8).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehran L, Delbari N, Amouzegar A, Hasheminia M, Tohidi M, Azizi F. Reduced Sensitivity to Thyroid Hormone Is Associated with Diabetes and Hypertension. J Clin Endocrinol Metab. 2022;107(1):167\u0026ndash;76.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSzili-Torok T, Xu Y, de Borst MH, Bakker SJL, Tietge UJF. Normal Fasting Triglyceride Levels and Incident Hypertension in Community-Dwelling Individuals Without Metabolic Syndrome. J Am Heart Association. 2023;12(16):e028372.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbasilim C, Persky V, Sargis RM, Argos M, Daviglus M, Freels S, Cai J, Tsintsifas K, Isasi CR, Peters BA, et al. Thyroid-related Hormones and Hypertension Incidence in Middle-Aged and Older Hispanic/Latino Adults: The HCHS/SOL Study. J Endocr Soc. 2024;8(6):bvae088.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLiu Y, Ma M, Li L, Liu F, Li Z, Yu L, Yang T, Wang Y, Gao S, Gao S, et al. Association between sensitivity to thyroid hormones and dyslipidemia in patients with coronary heart disease. Endocrine. 2023;79(3):459\u0026ndash;68.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRivas AM, Pena C, Kopel J, Dennis JA, Nugent K. Hypertension and Hyperthyroidism: Association and Pathogenesis. Am J Med Sci. 2021;361(1):3\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBerta E, Lengyel I, Halmi S, Zrinyi M, Erdei A, Harangi M, Pall D, Nagy EV, Bodor M. Hypertension in Thyroid Disorders. Front Endocrinol. 2019;10:482.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarvisi M, Balzarini L, Mancini C, Mouzakiti P. Thyroid gland and pulmonary hypertension. What's the link? Panminerva Med. 2013;55(1):93\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastagna MG, Dentice M, Cantara S, Ambrosio R, Maino F, Porcelli T, Marzocchi C, Garbi C, Pacini F, Salvatore D. DIO2 Thr92Ala Reduces Deiodinase-2 Activity and Serum-T3 Levels in Thyroid-Deficient Patients. J Clin Endocrinol Metab 2017, 102(5):1623\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGereben B, Zavacki AM, Ribich S, Kim BW, Huang SA, Simonides WS, Zeold A, Bianco AC. Cellular and molecular basis of deiodinase-regulated thyroid hormone signaling. Endocr Rev. 2008;29(7):898\u0026ndash;938.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGumieniak O, Perlstein TS, Williams JS, Hopkins PN, Brown NJ, Raby BA, Williams GH. Ala92 type 2 deiodinase allele increases risk for the development of hypertension. Hypertension. 2007;49(3):461\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJabbar A, Pingitore A, Pearce SH, Zaman A, Iervasi G, Razvi S. Thyroid hormones and cardiovascular disease. Nat reviews Cardiol. 2017;14(1):39\u0026ndash;55.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCarrillo-Sepulveda MA, Ceravolo GS, Fortes ZB, Carvalho MH, Tostes RC, Laurindo FR, Webb RC, Barreto-Chaves ML. Thyroid hormone stimulates NO production via activation of the PI3K/Akt pathway in vascular myocytes. Cardiovascular Res. 2010;85(3):560\u0026ndash;70.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePapaioannou GI, Lagasse M, Mather JF, Thompson PD. Treating hypothyroidism improves endothelial function. Metab Clin Exp. 2004;53(3):278\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTaddei S, Caraccio N, Virdis A, Dardano A, Versari D, Ghiadoni L, Salvetti A, Ferrannini E, Monzani F. Impaired endothelium-dependent vasodilatation in subclinical hypothyroidism: beneficial effect of levothyroxine therapy. J Clin Endocrinol Metab. 2003;88(8):3731\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRazvi S, Ingoe L, Keeka G, Oates C, McMillan C, Weaver JU. The beneficial effect of L-thyroxine on cardiovascular risk factors, endothelial function, and quality of life in subclinical hypothyroidism: randomized, crossover trial. J Clin Endocrinol Metab. 2007;92(5):1715\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRazvi S, Jabbar A, Pingitore A, Danzi S, Biondi B, Klein I, Peeters R, Zaman A, Iervasi G. Thyroid Hormones and Cardiovascular Function and Diseases. J Am Coll Cardiol. 2018;71(16):1781\u0026ndash;96.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarpey T, Kinateder KKJ. Clustering Functional Data. J Classif. 2003;20(1):093\u0026ndash;114.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRossi F, Conan-Guez B, Golli AE. Clustering functional data with the SOM algorithm. In: \u003cem\u003eEuropean Symposium on Artificial Neural Networks: 2004\u003c/em\u003e; 2004.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGarcia-Prieto CF, Hernandez-Nuno F, Rio DD, Ruiz-Hurtado G, Aranguez I, Ruiz-Gayo M, Somoza B, Fernandez-Alfonso MS. High-fat diet induces endothelial dysfunction through a down-regulation of the endothelial AMPK-PI3K-Akt-eNOS pathway. Mol Nutr Food Res. 2015;59(3):520\u0026ndash;32.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKosmas CE, Bousvarou MD, Kostara CE, Papakonstantinou EJ, Salamou E, Guzman E. Insulin resistance and cardiovascular disease. J Int Med Res. 2023;51(3):3000605231164548.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGhosh A, Gao L, Thakur A, Siu PM, Lai CWK. Role of free fatty acids in endothelial dysfunction. J Biomed Sci 2017, 24(1):50.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Thyroid hormone sensitivity, Hypertensive Disorders during Pregnancy, Triglycerides (TG), Serum lipid, mediated effect.","lastPublishedDoi":"10.21203/rs.3.rs-8051840/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8051840/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eFew studies have focused on the relationship between thyroid hormone sensitivity and hypertensive disorders of pregnancy (HDP) in euthyroid women. This study aimed to investigate this association among euthyroid pregnant women and the potential mediating effects of serum lipids.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis study was conducted at Zhoushan Maternal and Child Health Hospital, Zhejiang Province. The general sociodemographic characteristics and lifestyle behaviors of the participants were collected. Blood pressure was measured during pregnancy. Thyroid function data were extracted from medical records. GEE and logistic regression were applied to assess the associations of thyroid hormone sensitivity with longitudinal BP changes and HDP risk, respectively. A nested case‒control study was further adopted to validate the relationship and explore the mediating effects of serum lipids.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 4,041 pregnant women, 92 developed HDP. Early-pregnancy FT3/FT4 was positively associated with longitudinal increases in SBP (β\u0026thinsp;=\u0026thinsp;14.78, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DBP (β\u0026thinsp;=\u0026thinsp;6.76, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). The TFQI was negatively associated with SBP (β= -1.05, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.003). The mid-pregnancy FT3/FT4 ratio was strongly associated with SBP (β\u0026thinsp;=\u0026thinsp;14.74, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) and DBP (β\u0026thinsp;=\u0026thinsp;7.71, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). In contrast, higher mid-pregnancy TFQI, TT4RI, and TSHI were associated with decreased SBP (TFQI: β=-1.96, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; TT4RI: β=-0.07, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001; TSHI: β=-1.07, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Moreover, early-pregnancy FT3/FT4 was associated with increased HDP risk (OR\u0026thinsp;=\u0026thinsp;27.23, 95% CI: 1.83\u0026ndash;406.26). A similar association was found in mid-pregnancy (OR\u0026thinsp;=\u0026thinsp;38.93, 95% CI: 4.26\u0026ndash;355.49). Higher mid-pregnancy TT4RI, TSHI, and TFQI were associated with reduced HDP risk (TT4RI: OR\u0026thinsp;=\u0026thinsp;0.96, 95% CI: 0.93\u0026ndash;1.00; TSHI: OR\u0026thinsp;=\u0026thinsp;0.65, 95% CI: 0.43\u0026ndash;0.99; TFQI: OR\u0026thinsp;=\u0026thinsp;0.48, 95% CI: 0.27\u0026ndash;0.85). Mediation analysis indicated that TG mediated 18.7% of the FT3/FT4-HDP associations (β\u0026thinsp;=\u0026thinsp;0.153, 95% CI: 0.018\u0026ndash;0.390, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.008) and 15.4% of the TFQI-HDP associations (β=-0.031, 95% CI: -0.068\u0026ndash;0.000, \u003cem\u003eP\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.026).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eIn euthyroid pregnant women, high thyroid hormone sensitivity is associated with an increased risk of HDP. TGs mediate the associations between thyroid sensitivity (FT3/FT4 ratio and TFQI) and HDP.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003enot applicable\u003c/p\u003e","manuscriptTitle":"High thyroid hormone sensitivity is associated with the risk of hypertensive disorders during pregnancy in euthyroid women: the mediating role of triglycerides","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-22 09:02:04","doi":"10.21203/rs.3.rs-8051840/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2025-12-21T07:19:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"103716672861707646786625505843562918479","date":"2025-12-12T10:18:57+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-12-12T08:17:44+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-11-21T08:03:52+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-14T09:16:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-14T02:11:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Endocrine Disorders","date":"2025-11-14T02:07:42+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-endocrine-disorders","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bend","sideBox":"Learn more about [BMC Endocrine Disorders](http://bmcendocrdisord.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bend/default.aspx","title":"BMC Endocrine Disorders","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"535f272a-5501-4336-9a58-05375dfa1b05","owner":[],"postedDate":"December 22nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-12-22T09:02:04+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-22 09:02:04","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8051840","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8051840","identity":"rs-8051840","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}