Significance of Levothyroxine Treatment on Serum Lipid in Pregnant Women With Subclinical Hypothyroidism

Significance of Levothyroxine Treatment on Serum Lipid in Pregnant Women With Subclinical Hypothyroidism | 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 Significance of Levothyroxine Treatment on Serum Lipid in Pregnant Women With Subclinical Hypothyroidism Yuxi Yang, Huabing Yuan, Xueran Wang, Zheng Zhang, Ruixia Liu, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1175883/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract Background There is no consensus reference range for serum lipid levels during pregnancy. The benefit of levothyroxine (L-T4) on serum lipid levels are unclear among pregnant women with subclinical hypothyroidism (SCH). Objective To determine the recommended reference ranges for serum lipid concentrations during pregnancy and effects of L-T4 treatment on serum lipids in pregnant women with SCH. Design cohort study. Methods A analysis of 20365 women in the first trimester was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University during 2018–2020. After excluding women with adverse pregnancy outcomes, we determined the reference range of serum lipid in the first and third trimesters of pregnancy by using median and quartile to determine appropriate percentiles. Next, we divided into three groups as follows: SCH L-T4 treatment group (n=319), SCH non-intervention group (n=103) and the control group(n=9598). Results The recommended reference range for serum lipids in the first trimester of pregnancy should be: TC < 5.33 mmol/L, TG < 1.73 mmol/L, LDL-C 1.1 mmol/L, and in third trimester of pregnancy should be: TC < 8.47 mmol/L, TG < 4.86 mmol/L, LDL-C 1.34 mmol/L. There are significant differences in TC and LDL-C levels between SCH treatment group and SCH non-intervention Group (P=0.043, P=0.046; respectively). Conclusions We determine the recommended reference ranges for serum lipid concentrations during pregnancy. TC and LDL-C levels in pregnant women with SCH could improve after L-T4 treatment. Maternal & Fetal Medicine levothyroxine treatment serum lipid subclinical hypothyroidism Figures Figure 1 Introduction Subclinical hypothyroidism (SCH) is defined as the co-presentation of a thyroid-stimulating hormone (TSH) level above the normal range (4.0–10.0 mIU/L) and a serum free thyroxine (FT4) level within the normal range. It is common among women of childbearing age and because of its asymptomatic nature and insidious clinical symptoms, it can be easily missed in clinical practice. The prevalence of SCH during pregnancy is approximately 2%–3% [1] . SCH usually linked to some adverse pregnancy outcomes, such as preterm birth, miscarriage, gestational diabetes mellitus (GDM), and l ow birth weight [2] - [3] [4] [5] . Elevated TSH concentrations in SCH may alter the synthesis and degradation of lipids as well as the function of various enzymes in the lipid metabolism pathway [6] . Key effects of elevated TSH include down-regulation of low-density lipoprotein cholesterol (LDL-C) receptor expression and increased proprotein convertase subtilsin-kexin type 9 (PCSK-9), which together result in higher total cholesterol (TC), LDL-C, and triglyceride (TG), and lower high-density lipoprotein cholesterol (HDL-C) [7] - [8] [9] . Previous study has indicated that non-gestational SCH leads to elevated blood lipid levels with TSH concentrations elevation [10] . Studies had also shown that L-T4 treatment of SCH can improve serum lipid levels, while the research object were all adults, not pregnant women [11] - [12] [13] . However, there is no consensus reference range for maternal TC, TG, LDL-C, HDL-C levels during gestation. Given the lack of trimester-specific reference values cut-off points, the aim of the present cohort study was to discuss recommended reference ranges for serum lipid concentrations in the first and third trimester s of pregnancy and effects of L-T4 treatment on serum lipid levels in pregnant women with SCH. Material And Methods Study design and participants This cohort study recruited pregnant women in their first trimester who visited the Beijing Obstetrics and Gynecology Hospital, Capital Medical University between January 2018 and May 2020. All participants answered a questionnaire during early pregnancy(6-13 ＋ 6 weeks of gestation) about demographic and obstetric characteristics (age, weight, parity, and history of adverse pregnancy outcomes), history of thyroid disease before pregnancy, history of hypertension, and history of diabetes. Written consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used. We continued to follow up these women through the middle and third trimesters of pregnancy until delivery. A total of 20365 women who had complete thyroid examination data and lipid data in the first and third trimesters of pregnancy( 6-13 ＋ 6 weeks of gestation and 28-33 ＋ 6 weeks of gestation) respectively were enrolled in this study. We excluded pregnant women with TSH levels < 0.59 mIU/L (n = 3001), mild TSH elevation(TSH concentration between 2.5 and 4.0 mIU/L, n = 2414) and those who had thyroid disease before pregnancy (including thyroid cancer , thyroid nodule , and H ashimoto thyroiditis ; n = 328). When all the women had given birth, we also excluded those who had twin or multiple pregnancies (n = 541). Thus, ultimately, 14081 pregnant women were included in this cohort study (Figure 1). We grouped the women as follows: SCH treatment group (treatment begin at 6-13 ＋ 6 weeks of gestation, n = 319), SCH non-intervention group (n = 103) and normal thyroid function group (n = 13659). Ethical considerations Our study protocol was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Review approval number: 2018-KY-003-01). Definitions SCH was defined as a normal FT4 level with TSH elevation (4.0–10 mIU/L). The reference values for the normal FT4 range during the first trimester were 11.8–18.4 pmol/L, and these values were determined using Roche Modular Analytics E170 (Roche Diagnostics, Mannheim, Germany). Electrochemiluminescence immunoassays (ADVIA Centaur XP, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) were used to measure the serum FT4 and TSH concentrations. The methods and kits used for the FT4, TSH, and TPOAb tests in our hospital remained the same throughout the study period. Serum lipids measurement All pregnant women collected venous blood samples after overnight fasting. The concentrations of TC, TG, HDL-C and LDL-C were determined for each sample. Automatic biochemical analyser (AU5400, Beckman, US) were used to measure TC, TG, HDL-C and LDL-C detection kits (Beckman, US). All measurements were measured using continuous monitoring methods with appropriate quality control prior to measurement. Adverse pregnancy outcomes Adverse pregnancy outcomes included preterm delivery (defined as birth before 37 weeks of gestation), , gestational diabetes mellitus (screened for at 24–28 weeks, and diagnosed according to the criteria of the International Association of Diabetes and Pregnancy Study Groups, which require a 75-g oral glucose tolerance test and cut-off values of >5.1 mmol/L, >10.0 mmol/L, and >8.5 mmol/L for fasting blood glucose, blood glucose at 1 h after sugar intake, and blood glucose at 2 h after sugar intake, respectively), gestational hypertension and macrosomia (≥4000 g). Statistical analysis All statistical analyses were performed using the SPSS, version 24.0 (SPSS Inc., Chicago, IL, USA). In order to observe the normal trend of serum lipid levels during the first and third trimesters of pregnancy, we excluded those pregnant women with overweight/obesity, gestational hypertension, GDM, preterm birth and macrosomia. Then, using appropriate percentiles and median to descriptive analyses of TC, TG, LDL-C and HDL-C levels for this group (excluded adverse pregnancy outcomes) in first and third trimester of pregnancy. Finally, to establish the lipid reference ranges suitable for the first and third trimester s of pregnancy. Categorical variables were presented as frequency (percentage), and continuous variables were presented as mean (standard deviation [SD]) or median (interquartile range), as appropriate. Analysis of variance was used for normally distributed continuous variables in the multiple subgroup analyses. The Kruskal-Wallis test was used to evaluate continuous variables with non-normal distributions. To compare categorical variables, we used the chi square test or Fisher exact test. The Bonferroni correction was applied for pairwise comparisons. To evaluate the effect of L-T4 treatment on SCH with hyperlipidemia, we used generalized estimation equation. A P value < 0.05 or a P value < 0.05/n in the Bonferroni corrections was considered statistically significant. Results Reference range of serum lipid in the first and third trimesters of pregnancy In total, 20365 pregnant women were included in our study. After excluded GDM (n=3038), overweight/obesity (n=2040), gestational hypertension (n=806), preterm birth (n=867), macrosomia (n=1305), 12309 pregnant women remained. Table 1 presents the median (interquartile range) concentrations and appropriate percentiles for TC, TG, LDL-C and HDL-C in both first and third trimesters of pregnancy. Serum concentrations of TC, TG, LDL-C and HDL-C in the third trimester were significantly higher than those in the first trimester of pregnancy, especially the level of TG increased 2.81 times in the third trimester of pregnancy. The level of TC, TG, LDL-C and HDL-C had 1.57, 2.81, 1.70 and 1.22-fold elevations from the first to third trimester, respectively. Reference range for serum TC, TG and LDL-C in the first and third trimesters of pregnancy ought to less than the 95th percentile and that of HDL-C ought to greater than the 5th percentile [18] . Specifically, the recommended reference range for serum lipids in the first trimester of pregnancy should be: TC < 5.33 mmol/L, TG < 1.73 mmol/L, LDL-C 1.1 mmol/L, and in third trimester of pregnancy should be: TC < 8.47 mmol/L, TG < 4.86 mmol/L, LDL-C 1.34 mmol/L. Baseline characteristics of SCH pregnant women and control Group The baseline characteristics of the patients in the L-T4 treatment group (n=319), non-intervention group (n=103) and the control group are shown in Table 2. Control group was defined as normal thyroid function and serum lipid(n=9598). Of all pregnant women with SCH, 348(82.5%) were tested for TSH concentration during the second trimester(20-23 ＋ 6 weeks of gestation) and 304(72.0%) were tested for TSH concentration during the third trimester(28-33 ＋ 6 weeks of gestation). No significant differences in BMI, gestational age (GA) at delivery, neonatal birth weight, history of adverse pregnancy outcomes, histories of hypertension, and rate of cesarean section were found among the three groups. The median (interquartile range) age significantly differed between L-T4 treatment group (30 years; 28-33 years), non-intervention group (31.84years; 3.83), and the control group (30years; 28-33years; P = 0.014). The TSH concentration was significantly higher in the L-T4 treatment group and non-intervention group than in the control group ( P < 0.001). In contrast, the FT4 value was significantly higher in the control group than in the other two groups ( P < 0.001), though the FT4 value was within the normal range in all three groups. Serum lipid levels of SCH pregnant women after L-T4 treatment Serum concentrations of TC, TG, LDL-C and HDL-C in SCH pregnant women with hyperlipidemia treatment group(n=319) and non-intervention group (n=103) in the first and third trimester of pregnancy are shown in Table 3. Table 4 shows the effects of L-T4 on pregnant women with SCH who did or did not receive treatment. There are significant differences in TC and LDL-C levels between SCH treatment group and SCH non-intervention Group ( P =0.017, P =0.011; respectively), which indicated that L-T4 treatment could reduce TC and LDL-C levels in pregnant women with SCH. No significant difference in TG and HDL-C concentration between pregnant women with SCH and non-intervention group after L-T4 treatment ( P ＞0.05).L-T4 treatment had a significant interaction with age and BMI. Treatment could not directly reduce TG level, but the interaction between treatment and age reduced TG level ( P =0.022). Identically, treatment could not directly reduce TG and HDL-C levels, but the interaction between treatment and BMI reduced TG and HDL-C levels( P <0.001). There are no significant interaction in L-T4 treatment and TSH, FT4 levels( P ＞0.05). Discussion The current cohort study was performed to evaluate the recommended reference ranges for serum lipid concentrations in the first and third trimester s of pregnancy and effects of L-T4 treatment on serum lipid levels in pregnant women with SCH. Wang et al. [14] recommend that the reference values of serum TC, TG and LDL-C in early and middle pregnancy should be less than the 95th percentiles and the reference value of HDL-C should be greater than the 5th percentile. So using the same method, we found that the recommended reference range for serum lipids in the first trimester of pregnancy should be: TC < 5.33 mmol/L, TG < 1.73 mmol/L, LDL-C 1.1 mmol/L, and in third trimester of pregnancy should be: TC < 8.47 mmol/L, TG < 4.86 mmol/L, LDL-C 1.34 mmol/L, which is appropriated for Beijing area. We also found that L-T4 treatment reduced the level of TC and LDL-C in SCH pregnant women. To date, there are no unified reference ranges evaluate serum lipid in women during pregnancy, our recommended reference range of serum lipid during the various periods of pregnancy is suitable for pregnant women in Beijing area. Furthermore, we also found serum concentrations of TC, TG, LDL-C and HDL-C were significantly higher in pregnant women in the third trimester than they were in the first trimester, especially 2.81-fold TG elevation in third trimester of pregnancy. Previous studies revealed that from the 12 th week of pregnancy, TC, TG, LDL-C and HDL-C gradually increase, especially in the second and third trimesters, which consisted with our study [15] - [16] [17] [18] [19] [20] . The main finding of our study was that pregnant women with SCH who received L-T4 treatment could improve TC and LDL-C levels compared to non-intervention group ( P =0.043, P =0.046; respectively). As is well-known, SCH patients often present lipid abnormalities, especially elevated TC and LDL-C [21] . Amsterdam Born Children and Their Development cohort study reported that high TG in late pregnancy was independently associated with increased risk of GDM, preeclampsia and premature delivery [22] . Thus, the control of serum lipids may benefit SCH patients. However, pregnant women shall not take statins during pregnancy to reduce serum lipid. Most current studies have focused on the reduction of serum lipid in adults with SCH after L-T4 treatment [23] . To date, clinical trials have not consistently shown the benefit of L-T4 treatment in improving lipid levels in SCH patients. Kong et al. [24] found that L-T4 treatment had no effect on serum lipids and other metabolic indicators in a 6-month randomized trial of female with SCH. Our study is the first in China to report effects of L-T4 therapy on SCH pregnant women with hyperlipidemia. Strengths and limitations of this study A strength of this study is that all study participants completed a comprehensive questionnaire, which included a detailed review of their medical history, serum lipid tests (including TC, TG, LDL-C and HDL-C) and the results of thyroid function tests (including T4and TSH). We also continued to follow up the patients through the middle and third trimesters of pregnancy until delivery. Nevertheless, our study has several limitations. The main limitation of our study was that the study population was small for some subgroups. Therefore, prospective collection of data from multiple centers is needed to verify the results of this study. In addition, our study was a non-randomized controlled trial, and the quality of evidence for the results was not as good as that of a randomized controlled trial. In conclusion, the levels of TC, TG, LDL-C and HDL-C have been changing dynamically during pregnancy. Therefore, we determine the recommended reference ranges for serum lipid concentrations in the first and third trimesters of pregnancy. Furthermore, we found that L-T4 treatment could reduce TC and LDL-C levels in pregnant women with SCH. These findings may provide more evidence to support lipid screening during pregnancy, further guidance on the treatment of thyroid disease in pregnant women and inform the development of future guidelines. Trial registration: Chinese Clinical Trial Register, ChiCTR2100047394. Registered 16 June 2021 - Retrospectively registered, http://www.chictr.org.cn. Declarations Consent to participate statement Written Informed consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used. Ethics approval Our study protocol was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Review approval number: 2018-KY-003-01). All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication Written consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used. Availability of data and materials The datasets generated and/or analysed during the current study are available in the ResMan repository, www.medresman.org.cn . Competing interests The authors have no conflicts of interest to declare. Funding This work was financially supported by the N ational Key Research and Development Program of China (No.2016YFC1000101) Authors' contributions Yuxi Yang and Huabing Yuan design of the work, interpretation of data and are the major contributor in writing the manuscript. Xueran Wang and Zheng Zhang analyze data of the work; Ruixia Liu and Chenghong Yin substantively revised the manuscript. Acknowledgements Not applicable References van den Boogaard, E., Vissenberg, R., Land, J.A., van Wely, M., van der Post, J.A.M., Goddijn, M., Bisschop, P.H., 2011. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum.Reprod. Update 17, 605–619. DOI:10.1093/humupd/dmr024. 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Serum lipid levels of pregnant women in the first and third trimester s of pregnancy Serum lipid levels Trimester median (interquartile range) Percentile (n=12309) 2.5% 5% 10% 25% 50% 75% 90% 95% 97.5% TC (mmol/L) First 4.11(3.72-4.56) 3.03 3.19 3.38 3.72 4.11 4.56 5.02 5.33 5.64 Third 6.46(5.78-7.22) 4.58 4.85 5.20 5.78 6.46 7.22 7.98 8.47 8.92 TG (mmol/L) First 0.92(0.73-1.17) 0.50 0.54 0.61 0.73 0.92 1.17 1.49 1.73 2.00 Third 2.76(2.25-3.44) 1.54 1.68 1.88 2.25 2.76 3.44 4.23 4.87 5.57 LDL-C (mmol/L) First 2.11(1.77-2.48) 1.20 1.35 1.50 1.77 2.11 2.48 2.85 3.12 3.41 Third 3.54(2.91-4.20) 1.85 2.09 2.39 2.91 3.54 4.20 4.86 5.30 5.72 HDL-C(mmol/L) First 1.51(1.34-1.71) 1.03 1.10 1.19 1.34 1.51 1.71 1.91 2.04 2.16 Third 1.85(1.62-2.09) 1.25 1.34 1.44 1.62 1.85 2.09 2.34 2.50 2.66 Abbreviations: TC : total cholesterol, TG : triglycerides, LDL-C low-density lipid cholesterol, HDL-C : high-density lipid cholesterol. Table 2. Characteristics of pregnant women with SCH who did or did not receive treatment and control subjects Characteristic SCH non-intervention Group (n = 103) SCH treatment Group (n = 319) Control group (n =9598) P value Age (years) 31.84(3.83) 30(28-33) 30(28-33) 0.014 BMI (kg/m 2 ) 22.70(3.77) 21.56(19.61-24.01) 21.48(19.83-23.44) 0.115 TSH (mIU/L) 4.56(4.22-5.22) 4.75(4.33-5.59) 1.34(0.96-1.79) <0.001 FT4 (pmol/L) 14.73(1.43) 14.76(1.47) 15.92(14.77-16.91) <0.001 GA at delivery (wks) 39 (38–40) 38 (38–40) 39 (38–40) 0.695 Neonatal weight (g) 3349.08(399.47) 3307.07(483.43) 3350 (3085–3620) 0.249 History of adverse pregnancy outcomes, n (%) 3 (2.91) 3 (0.94) 159(1.66) 0.294 History of hypertension, n (%) 1 (0.97) 3（0.94） 40(0.42) 0.532 History of diabetes, n (%) 0 0 31 (0.32) Cesarean section rate, n (%) 41 (39.81) 117(36.68) 3374(35.15) 0.154 Abbreviations:TSH: thyroid-stimulating hormone; FT4: free thyroxine; GA: gestational age; BMI: body mass index. The Kruskal-Wallis test was used to compare non-normally distributed continuous variables. The chi-square test or Fisher exact test was used to compare categorical variables among the three groups. Table 3. Serum lipid levels of pregnant women with SCH who did or did not receive treatment Serum lipid levels SCH non-intervention Group (n = 103) SCH treatment Group (n = 319) TC (mmol/L) first trimester of pregnancy 4.37(0.77) 4.29(3.80-4.81) third trimester of pregnancy 6.61(1.29) 6.42(5.62-7.05) TG (mmol/L) first trimester of pregnancy 1.06(0.85-1.47) 1.07(0.81-1.44) third trimester of pregnancy 2.99(2.49-3.74) 2.81(2.32-3.52) LDL-C(mmol/L) first trimester of pregnancy 2.28(0.61) 2.20(1.77-2.61) third trimester of pregnancy 3.64(1.10) 3.41(2.70-4.09) HDL-C(mmol/L) first trimester of pregnancy 1.55(1.34-1.77) 1.55(1.35-1.75) third trimester of pregnancy 1.80(1.61-1.97) 1.84(0.36) Abbreviations: TC : total cholesterol, TG : triglycerides, LDL-C low-density lipid cholesterol, HDL-C : high-density lipid cholesterol. continuous variables were presented as mean (standard deviation [SD]) or median (interquartile range) Table 4. Effects of L-T4 on pregnant women with SCH who did or did not receive treatment Serum lipid levels group group*age group*BMI group*TSH group*TSH wald x 2 P value wald x 2 P value wald x 2 P value wald x 2 P value wald x 2 P value TC (mmol/L) 5.700 0.017 10.233 0.006 2.627 0.269 1.127 0.569 2.420 0.298 TG (mmol/L) 0.274 0.600 7.608 .022 21.548 <0.001 2.192 0.334 0.519 0.771 HDL-C (mmol/L) 2.466 0.116 1.227 0.541 28.795 <0.001 0.164 0.921 1.616 0.771 LDL-C (mmol/L) 6.430 0.011 5.800 0.055 0.115 0.944 0.020 0.990 2.816 0.245 Abbreviations: TC : total cholesterol, TG : triglycerides, LDL-C low-density lipid cholesterol, HDL-C : high-density lipid cholesterol. The generalized estimation equation was used to compare categorical variables among the two groups. Dependent variable：TC, TG, HDL-C and LDL-C. Model：（intercept）, group, group * age, group * BMI, group * TSH, group * FT4. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 25 May, 2022 Reviews received at journal 13 Apr, 2022 Reviewers agreed at journal 08 Apr, 2022 Reviewers invited by journal 21 Feb, 2022 Editor assigned by journal 21 Jan, 2022 Editor invited by journal 06 Jan, 2022 Submission checks completed at journal 06 Jan, 2022 First submitted to journal 15 Dec, 2021 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-1175883","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":74632866,"identity":"fab58406-5c0e-4053-8ac5-ca4b8fd30c46","order_by":0,"name":"Yuxi Yang","email":"","orcid":"","institution":"Beijing Obstetrics and Gynecology Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yuxi","middleName":"","lastName":"Yang","suffix":""},{"id":74632867,"identity":"9ef214c1-153b-4a05-bc3f-e1b095317df0","order_by":1,"name":"Huabing Yuan","email":"","orcid":"","institution":"Hebei General Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Huabing","middleName":"","lastName":"Yuan","suffix":""},{"id":74632868,"identity":"f74c8210-06e3-41f8-9b01-f6cde908e4d4","order_by":2,"name":"Xueran Wang","email":"","orcid":"","institution":"Beijing Obstetrics and Gynecology Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Xueran","middleName":"","lastName":"Wang","suffix":""},{"id":74632869,"identity":"ec6cde2b-cc96-4c8b-a727-280e9f99af44","order_by":3,"name":"Zheng Zhang","email":"","orcid":"","institution":"Beijing Obstetrics and Gynecology Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Zheng","middleName":"","lastName":"Zhang","suffix":""},{"id":74632870,"identity":"8bd56805-8e02-4c58-aaf2-76da5d4a381e","order_by":4,"name":"Ruixia Liu","email":"","orcid":"","institution":"Beijing Obstetrics and Gynecology Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ruixia","middleName":"","lastName":"Liu","suffix":""},{"id":74632871,"identity":"5448aaf9-2362-4484-bd04-0374aae9f692","order_by":5,"name":"Chenghong Yin","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAuklEQVRIiWNgGAWjYDACZiBibLCB8tiI15JGihYGsJbDJGgxOM578HPhjvPy/NPOGDB8KDvMwD+7gYCWw3zJ0jPP3DaccTvHgHHGucMMEncOENLCY8bM23Y7wUA6xwDIOMxgIJFAlJZzEC1/SdByAKKFkRgtkod5jKV525KBfkkrONhzLp1H4gYBLXznzxh+5m2zk+efnbzxwY8yazn+GQS0KBxA4oDYPPjVA4F8A0Elo2AUjIJRMOIBAOG1PSjYq68IAAAAAElFTkSuQmCC","orcid":"","institution":"Beijing Obstetrics and Gynecology Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Chenghong","middleName":"","lastName":"Yin","suffix":""}],"badges":[],"createdAt":"2021-12-16 03:29:02","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1175883/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1175883/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":17100058,"identity":"210a2b7b-06fe-4e12-9932-0cbf9ad78300","added_by":"auto","created_at":"2022-01-07 14:34:29","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":99715,"visible":true,"origin":"","legend":"\u003cp\u003eFlow chart of patient inclusion\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1175883/v1/2c6ceedcbe78f79a7c86d959.jpg"},{"id":17100059,"identity":"b29b26c5-3934-4b25-bd4c-926c95ded3b7","added_by":"auto","created_at":"2022-01-07 14:34:31","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":489872,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1175883/v1/810add87-3254-4325-b6fa-c12e7b4c5438.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSignificance of Levothyroxine Treatment on Serum Lipid in Pregnant Women With Subclinical Hypothyroidism\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eSubclinical hypothyroidism (SCH)\u0026nbsp;is\u0026nbsp;defined as the co-presentation of a thyroid-stimulating hormone (TSH) level\u0026nbsp;above the normal range (4.0\u0026ndash;10.0 mIU/L) and a serum free thyroxine (FT4) level within the normal range.\u0026nbsp;It\u0026nbsp;is\u0026nbsp;common among women of\u0026nbsp;childbearing\u0026nbsp;age\u0026nbsp;and because of its asymptomatic nature and insidious clinical symptoms,\u0026nbsp;it can be\u0026nbsp;easily missed in clinical practice. The prevalence of SCH during pregnancy\u0026nbsp;is\u0026nbsp;approximately 2%\u0026ndash;3%\u003csup\u003e[1]\u003c/sup\u003e. SCH usually linked to some adverse pregnancy outcomes, such as preterm birth, miscarriage,\u0026nbsp;gestational diabetes mellitus\u0026nbsp;(GDM), and l\u003ca href=\"javascript%3A;\"\u003eow\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003ebirth\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003eweight\u003c/a\u003e\u003csup\u003e[2]\u003c/sup\u003e\u003csup\u003e-\u003c/sup\u003e\u003csup\u003e[3]\u003c/sup\u003e\u003csup\u003e[4]\u003c/sup\u003e\u003csup\u003e[5]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eElevated TSH concentrations in SCH may alter the synthesis and degradation of lipids as well as the function of various enzymes in the lipid metabolism pathway\u003csup\u003e[6]\u003c/sup\u003e.\u0026nbsp;Key effects of\u0026nbsp;elevated TSH\u0026nbsp;include down-regulation of\u0026nbsp;low-density lipoprotein cholesterol (LDL-C)\u0026nbsp;receptor expression\u0026nbsp;and increased proprotein convertase subtilsin-kexin type 9 (PCSK-9), which together result in higher total cholesterol (TC), LDL-C,\u0026nbsp;and triglyceride (TG), and lower high-density lipoprotein cholesterol (HDL-C)\u003csup\u003e[7]\u003c/sup\u003e\u003csup\u003e-\u003c/sup\u003e\u003csup\u003e[8]\u003c/sup\u003e\u003csup\u003e[9]\u003c/sup\u003e.\u0026nbsp;Previous study has indicated that non-gestational SCH leads to elevated blood lipid levels with TSH concentrations elevation\u003csup\u003e[10]\u003c/sup\u003e.\u0026nbsp;Studies had also shown that L-T4 treatment of SCH can improve serum lipid levels, while\u0026nbsp;the research object were all\u0026nbsp;adults, not pregnant women\u003csup\u003e[11]\u003c/sup\u003e\u003csup\u003e-\u003c/sup\u003e\u003csup\u003e[12]\u003c/sup\u003e\u003csup\u003e[13]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eHowever, there is no consensus reference range for maternal TC, TG, LDL-C, HDL-C levels during gestation. Given the lack of trimester-specific reference values cut-off points,\u0026nbsp;the aim of the present cohort\u0026nbsp;study was\u0026nbsp;to discuss recommended reference ranges for serum lipid concentrations in the first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003es of pregnancy and effects of L-T4 treatment on serum lipid levels in pregnant women with SCH.\u003c/p\u003e"},{"header":"Material And Methods","content":"\u003cp\u003e\u003cem\u003eStudy design and participants\u003c/em\u003e\u003c/p\u003e\n\u003cp skip=\"true\"\u003eThis cohort study recruited pregnant women in their first trimester who visited the Beijing Obstetrics and Gynecology Hospital, Capital Medical University between \u003ca href=\"javascript%3A;\"\u003eJanuary\u003c/a\u003e 2018 and May 2020. All participants answered a questionnaire during early pregnancy(6-13\u003csup\u003e＋\u003c/sup\u003e\u003csup\u003e6 \u003c/sup\u003eweeks of gestation) about demographic and obstetric characteristics (age, weight, parity, and history of adverse pregnancy outcomes), history of thyroid disease before pregnancy, history of hypertension, and history of diabetes. Written consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used. We continued to follow up these women through the middle and third trimesters of pregnancy until delivery. A total of 20365 women who had complete thyroid examination data and lipid data in the first and \u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimesters of pregnancy( 6-13\u003csup\u003e＋\u003c/sup\u003e\u003csup\u003e6 \u003c/sup\u003eweeks of gestation and 28-33\u003csup\u003e＋\u003c/sup\u003e\u003csup\u003e6\u003c/sup\u003e weeks of gestation) respectively were enrolled in this study. \u003c/p\u003e\n\u003cp\u003eWe\u0026nbsp;excluded\u0026nbsp;pregnant women with\u0026nbsp;TSH levels \u0026lt; 0.59\u0026nbsp;mIU/L (n = 3001), mild TSH\u0026nbsp;elevation(TSH concentration between 2.5 and 4.0\u0026nbsp;mIU/L,\u0026nbsp;n = 2414) and those who had thyroid disease before pregnancy (including\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethyroid\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003ecancer\u003c/a\u003e,\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethyroid\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003enodule\u003c/a\u003e,\u0026nbsp;and H\u003ca href=\"javascript%3A;\"\u003eashimoto\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003ethyroiditis\u003c/a\u003e; n = 328). When all the women had given birth, we also excluded those who had\u0026nbsp;twin or multiple pregnancies (n = 541). Thus, ultimately, 14081 pregnant women were included in this\u0026nbsp;cohort study (Figure 1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eWe grouped the women as follows:\u0026nbsp;SCH\u0026nbsp;treatment group\u0026nbsp;(treatment begin at 6-13\u003csup\u003e＋\u003c/sup\u003e\u003csup\u003e6\u0026nbsp;\u003c/sup\u003eweeks of gestation,\u0026nbsp;n\u0026nbsp;= 319), SCH non-intervention\u0026nbsp;group (n = 103) and\u0026nbsp;normal thyroid function group\u0026nbsp;(n = 13659).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eEthical considerations\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eOur study protocol was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Review approval number: 2018-KY-003-01).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eDefinitions\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eSCH was defined as a normal FT4 level with\u0026nbsp;TSH elevation\u0026nbsp;(4.0\u0026ndash;10 mIU/L).\u0026nbsp;The reference values for the normal FT4 range during\u0026nbsp;the first trimester were 11.8\u0026ndash;18.4 pmol/L, and these\u0026nbsp;values were determined using Roche\u0026nbsp;Modular Analytics E170 (Roche Diagnostics,\u0026nbsp;Mannheim, Germany).\u0026nbsp;Electrochemiluminescence immunoassays (ADVIA Centaur XP, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) were used to measure the serum FT4 and TSH concentrations.\u0026nbsp;The methods and kits used for the FT4, TSH, and TPOAb tests in our hospital remained the same throughout the study period.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eSerum lipids measurement\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll pregnant women collected venous blood samples after overnight fasting. The concentrations of TC, TG, HDL-C and LDL-C were determined for each sample. Automatic biochemical analyser (AU5400, Beckman, US) were used to measure TC, TG, HDL-C and LDL-C detection kits (Beckman, US). All measurements were measured using continuous monitoring methods with appropriate quality control prior to measurement.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAdverse pregnancy outcomes\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAdverse pregnancy outcomes included\u0026nbsp;preterm delivery (defined as birth before 37 weeks of gestation),\u0026nbsp;, gestational diabetes mellitus (screened for at 24\u0026ndash;28 weeks, and diagnosed according to the criteria of the\u0026nbsp;International Association of Diabetes and Pregnancy Study Groups, which require a 75-g\u0026nbsp;oral glucose tolerance test\u0026nbsp;and cut-off values of \u0026gt;5.1 mmol/L, \u0026gt;10.0 mmol/L, and \u0026gt;8.5 mmol/L for fasting blood glucose, blood glucose at 1 h after sugar intake, and blood glucose at 2 h after sugar intake, respectively),\u0026nbsp;gestational hypertension\u0026nbsp;and\u0026nbsp;macrosomia (\u0026ge;4000 g).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eStatistical analysis\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eAll statistical analyses were performed using the SPSS, version 24.0 (SPSS Inc., Chicago, IL, USA). In order to observe the normal trend of serum lipid levels during the first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimesters of pregnancy, we excluded those pregnant women with overweight/obesity, gestational hypertension, GDM, preterm birth and macrosomia. Then, using appropriate percentiles and median to descriptive analyses of TC, TG, LDL-C and HDL-C levels for this group (excluded adverse pregnancy outcomes) in first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of pregnancy. Finally, to establish the lipid reference ranges suitable for the first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003es of pregnancy.\u0026nbsp;Categorical variables were presented as frequency (percentage), and continuous variables were presented as mean (standard deviation [SD]) or median (interquartile range), as appropriate.\u0026nbsp;Analysis of variance was\u0026nbsp;used\u0026nbsp;for normally distributed continuous variables\u0026nbsp;in\u0026nbsp;the multiple subgroup\u0026nbsp;analyses. The\u0026nbsp;Kruskal-Wallis test was\u0026nbsp;used to evaluate\u0026nbsp;continuous variables\u0026nbsp;with\u0026nbsp;non-normal distributions.\u0026nbsp;To\u0026nbsp;compare\u0026nbsp;categorical variables, we used the chi square test or Fisher exact test.\u0026nbsp;The\u0026nbsp;Bonferroni correction was applied for pairwise comparisons.\u0026nbsp;To evaluate the effect of L-T4 treatment on SCH with hyperlipidemia, we used generalized estimation equation.\u0026nbsp;A\u0026nbsp;\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue \u0026lt; 0.05 or a\u0026nbsp;\u003cem\u003eP\u0026nbsp;\u003c/em\u003evalue \u0026lt; 0.05/n in the Bonferroni corrections was considered statistically significant.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cstrong\u003eReference range of serum lipid in the first and\u0026nbsp;\u003c/strong\u003e\u003ca href=\"javascript%3A;\"\u003e\u003cstrong\u003ethird\u003c/strong\u003e\u003c/a\u003e\u003cstrong\u003e\u0026nbsp;trimesters of pregnancy\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn total,\u0026nbsp;20365\u0026nbsp;pregnant women were included in our study. After excluded GDM (n=3038), overweight/obesity (n=2040),\u0026nbsp;gestational hypertension (n=806), preterm birth (n=867), macrosomia (n=1305), 12309 pregnant women remained. Table\u0026nbsp;\u003ca href=\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6211477/table/Tab2/\" target=\"table\"\u003e1\u003c/a\u003e presents\u0026nbsp;the median (interquartile range) concentrations and appropriate percentiles for TC, TG, LDL-C and HDL-C in both first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimesters of pregnancy. Serum concentrations of TC, TG, LDL-C and HDL-C in the third trimester were significantly higher than those in the first trimester of pregnancy, especially\u0026nbsp;the level of\u0026nbsp;TG increased 2.81 times in the third trimester of pregnancy. The level of TC, TG, LDL-C and HDL-C had 1.57, 2.81, 1.70 and 1.22-fold elevations from the first to third trimester, respectively. Reference range for serum TC, TG and LDL-C in the first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimesters of pregnancy ought to less than the 95th percentile and that of HDL-C ought to greater than the 5th percentile\u003csup\u003e[18]\u003c/sup\u003e. Specifically, the recommended reference range for serum lipids in the\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003efirst\u003c/a\u003e trimester of pregnancy should be: TC \u0026lt;\u0026thinsp;5.33 mmol/L, TG \u0026lt;\u0026thinsp;1.73 mmol/L, LDL-C\u0026thinsp;\u0026lt;\u0026thinsp;3.12 mmol/L and HDL-C\u0026gt;\u0026thinsp;1.1 mmol/L, and in\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimester of pregnancy should be: TC \u0026lt;\u0026thinsp;8.47 mmol/L, TG \u0026lt;\u0026thinsp;4.86 mmol/L, LDL-C\u0026thinsp;\u0026lt;\u0026thinsp;5.3 mmol/L and HDL-C\u0026thinsp;\u0026gt;1.34 mmol/L.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eBaseline characteristics\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eof SCH pregnant women and control Group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;baseline\u0026nbsp;characteristics of the patients in the L-T4 treatment group (n=319), non-intervention\u0026nbsp;group\u0026nbsp;(n=103)\u0026nbsp;and the control group\u0026nbsp;are shown in Table 2. Control group was defined as\u0026nbsp;normal thyroid function and\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eserum lipid(n=9598).\u003c/p\u003e\n\u003cp\u003eOf all pregnant women with SCH, 348(82.5%) were tested for TSH concentration during the second trimester(20-23\u003csup\u003e＋\u003c/sup\u003e\u003csup\u003e6\u003c/sup\u003e weeks of gestation) and 304(72.0%) were tested for TSH concentration during the third trimester(28-33\u003csup\u003e＋\u003c/sup\u003e\u003csup\u003e6\u003c/sup\u003e weeks of gestation).\u0026nbsp;No significant differences in BMI, gestational age (GA) at delivery, neonatal birth weight, history of adverse pregnancy outcomes, histories of hypertension, and rate of\u0026nbsp;cesarean section were found among the three groups.\u0026nbsp;The median (interquartile range) age significantly differed between\u0026nbsp;L-T4 treatment group\u0026nbsp;(30 years; 28-33 years),\u0026nbsp;non-intervention\u0026nbsp;group (31.84years; 3.83), and the control group (30years; 28-33years; \u003cem\u003eP\u0026nbsp;\u003c/em\u003e= 0.014).\u0026nbsp;The TSH concentration was significantly higher in the L-T4 treatment group and non-intervention group than in the control group (\u003cem\u003eP \u0026lt;\u003c/em\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e0.001). In contrast, the FT4 value was significantly higher in the control group than in the other two groups (\u003cem\u003eP \u0026lt;\u0026nbsp;\u003c/em\u003e0.001), though the\u0026nbsp;FT4 value\u0026nbsp;was within the normal range\u0026nbsp;in all three groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSerum lipid levels of SCH pregnant women after L-T4 treatment\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum concentrations of TC, TG, LDL-C and HDL-C\u0026nbsp;in SCH pregnant women with\u0026nbsp;hyperlipidemia treatment group(n=319) and\u0026nbsp;non-intervention\u0026nbsp;group\u0026nbsp;(n=103) in the first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy are shown in Table 3.\u0026nbsp;Table 4 shows the\u0026nbsp;effects of L-T4 on\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003epregnant women with SCH\u0026nbsp;who did\u0026nbsp;or did not receive treatment.\u0026nbsp;There are significant differences in TC and LDL-C levels between SCH treatment group and\u0026nbsp;SCH\u0026nbsp;non-intervention\u0026nbsp;Group (\u003cem\u003eP\u003c/em\u003e=0.017,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e=0.011;\u0026nbsp;respectively), which indicated that L-T4 treatment could reduce TC and LDL-C levels in pregnant women with SCH. No significant difference in TG and HDL-C concentration between pregnant women with SCH and\u0026nbsp;non-intervention\u0026nbsp;group\u0026nbsp;after L-T4 treatment (\u003cem\u003eP\u003c/em\u003e＞0.05).L-T4 treatment had a significant interaction with age and BMI. Treatment could not directly reduce TG level, but the interaction between treatment and age reduced TG level (\u003cem\u003eP\u003c/em\u003e=0.022). Identically, treatment could not directly reduce TG and HDL-C levels, but the interaction between treatment and BMI reduced TG and HDL-C levels(\u003cem\u003eP\u003c/em\u003e\u0026lt;0.001). There are no significant interaction in L-T4 treatment and TSH, FT4 levels(\u003cem\u003eP\u003c/em\u003e＞0.05).\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current\u0026nbsp;cohort study\u0026nbsp;was performed to evaluate the\u0026nbsp;recommended reference ranges for serum lipid concentrations in the first and\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003es\u0026nbsp;of\u0026nbsp;pregnancy and effects of L-T4 treatment on serum lipid levels in pregnant women with SCH. Wang et al.\u003csup\u003e[14]\u003c/sup\u003e recommend that the reference values of serum TC, TG and LDL-C in early and middle pregnancy should be less than the 95th percentiles and the reference value of HDL-C should be greater than the 5th percentile. So\u0026nbsp;using the same method, we\u0026nbsp;found that the recommended reference range for serum lipids in the\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003efirst\u003c/a\u003e trimester of pregnancy should be: TC \u0026lt;\u0026thinsp;5.33 mmol/L, TG \u0026lt;\u0026thinsp;1.73 mmol/L, LDL-C\u0026thinsp;\u0026lt;\u0026thinsp;3.12 mmol/L and HDL-C\u0026gt;\u0026thinsp;1.1 mmol/L, and in\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimester of pregnancy should be: TC \u0026lt;\u0026thinsp;8.47 mmol/L, TG \u0026lt;\u0026thinsp;4.86 mmol/L, LDL-C\u0026thinsp;\u0026lt;\u0026thinsp;5.3 mmol/L and HDL-C\u0026thinsp;\u0026gt;1.34 mmol/L, which is\u0026nbsp;appropriated for Beijing area. We also found that\u0026nbsp;L-T4 treatment reduced the level of TC and LDL-C\u0026nbsp;in SCH pregnant women.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTo date, there are no unified reference ranges evaluate serum lipid in women during pregnancy, our recommended reference range of serum lipid during the various periods of pregnancy is suitable for pregnant women in Beijing area.\u0026nbsp;Furthermore, we also found serum concentrations of TC, TG, LDL-C and HDL-C were significantly higher in pregnant women in the third trimester than they were in the first trimester, especially 2.81-fold TG elevation in\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e trimester of pregnancy.\u0026nbsp;Previous studies revealed that from the 12\u003csup\u003eth\u003c/sup\u003e week of pregnancy, TC, TG, LDL-C and HDL-C gradually increase, especially in the second and third trimesters, which consisted with our study\u003csup\u003e[15]\u003c/sup\u003e\u003csup\u003e-\u003c/sup\u003e\u003csup\u003e[16]\u003c/sup\u003e\u003csup\u003e[17]\u003c/sup\u003e\u003csup\u003e[18]\u003c/sup\u003e\u003csup\u003e[19]\u003c/sup\u003e\u003csup\u003e[20]\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe main\u0026nbsp;finding of our study\u0026nbsp;was that\u0026nbsp;pregnant women\u0026nbsp;with\u0026nbsp;SCH who received L-T4 treatment could improve TC and LDL-C levels compared to non-intervention group\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(\u003cem\u003eP\u003c/em\u003e=0.043,\u003cem\u003e\u0026nbsp;P\u003c/em\u003e=0.046;\u0026nbsp;respectively).\u0026nbsp;As is well-known, SCH patients often present lipid abnormalities, especially elevated TC and LDL-C\u003csup\u003e[21]\u003c/sup\u003e\u003csup\u003e.\u003c/sup\u003e \u0026nbsp;Amsterdam Born Children and Their Development cohort study\u003csup\u003e\u0026nbsp;\u003c/sup\u003ereported that high TG in late pregnancy was independently associated with increased risk of GDM, preeclampsia and\u0026nbsp;premature delivery\u003csup\u003e[22]\u003c/sup\u003e.\u0026nbsp;Thus, the control of serum lipids may benefit SCH patients. However, pregnant women shall not take statins during pregnancy to reduce serum lipid. Most current studies have focused on the reduction of serum lipid in adults with SCH after L-T4 treatment\u003csup\u003e[23]\u003c/sup\u003e.\u0026nbsp;To date, clinical trials have not consistently shown the benefit of L-T4 treatment in improving lipid levels in SCH patients. Kong\u003cem\u003e\u0026nbsp;et al.\u003c/em\u003e\u003csup\u003e[24]\u003c/sup\u003e\u003csup\u003e\u0026nbsp;\u003c/sup\u003efound that L-T4 treatment had no effect on serum lipids and other metabolic indicators in a 6-month randomized trial of\u0026nbsp;female with SCH. Our study is the first in China to report effects of L-T4 therapy on SCH pregnant women with hyperlipidemia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStrengths and limitations of this study\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA strength of this study is that all\u0026nbsp;study participants completed a comprehensive questionnaire, which included a detailed review of their medical history, serum lipid tests (including TC, TG, LDL-C and HDL-C) and the results of thyroid function tests (including T4and TSH).\u0026nbsp;We also continued to follow up the patients through the middle and third trimesters of pregnancy until delivery.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eNevertheless, our study has several limitations. The main limitation of our study was that the study population was small for some subgroups. Therefore, prospective collection of data from multiple centers is needed to verify the results of this study.\u0026nbsp;In addition,\u0026nbsp;our study was a non-randomized controlled trial, and the quality of evidence for the results was not as good as that of a randomized controlled trial.\u003c/p\u003e\n\u003cp\u003eIn conclusion, the levels of TC, TG, LDL-C and HDL-C have been changing dynamically during pregnancy. Therefore, we determine the recommended reference ranges for serum lipid concentrations in the \u003ca href=\"javascript%3A;\"\u003efirst\u003c/a\u003e and third trimesters of pregnancy. Furthermore, we found that L-T4 treatment could reduce TC and LDL-C levels in pregnant women with SCH. These findings may provide more evidence to support lipid screening during pregnancy, further guidance on the treatment of thyroid disease in pregnant women and inform the development of future guidelines.\u003c/p\u003e\n\u003cp\u003eTrial registration: Chinese Clinical Trial Register, ChiCTR2100047394. Registered 16 June 2021 - Retrospectively registered, http://www.chictr.org.cn.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConsent to participate statement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWritten Informed consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used.\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOur study protocol was approved by the Ethics Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (Review approval number: 2018-KY-003-01).\u0026nbsp;All methods were performed in accordance with the relevant guidelines and regulations.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten consent has been obtained from each patient or subject after full explanation of the purpose and nature of all procedures used.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analysed during the current study are available in the ResMan repository,\u0026nbsp;\u003ca href=\"http://www.medresman.org.cn/\" target=\"_blank\"\u003ewww.medresman.org.cn\u003c/a\u003e.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eThis work was financially supported\u003cem\u003e\u0026nbsp;by\u003c/em\u003e\u003cem\u003e\u0026nbsp;the\u0026nbsp;\u003c/em\u003e\u003cem\u003eN\u003c/em\u003eational Key Research and Development Program of China\u0026nbsp;(No.2016YFC1000101)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eYuxi Yang and Huabing Yuan design of the work, interpretation of data and are the major contributor in writing the manuscript.\u0026nbsp;Xueran Wang and Zheng Zhang analyze data of the work; Ruixia Liu and Chenghong Yin substantively revised the manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003evan den Boogaard, E., Vissenberg, R., Land, J.A., van Wely, M., van der Post, J.A.M., Goddijn, M., Bisschop, P.H., 2011. Significance of (sub)clinical thyroid dysfunction and thyroid autoimmunity before conception and in early pregnancy: a systematic review. Hum.Reprod. Update 17, 605\u0026ndash;619. DOI:10.1093/humupd/dmr024.\u003c/li\u003e\n \u003cli\u003eCasey BM, Dashe JS, Wells CE, McIntire DD, Byrd W, Leveno KJ, Cunningham FG. Subclinical hypothyroidism and pregnancy outcomes. Obstet Gynecol. 2005;105(2):239\u0026ndash;245.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAbalovich M, Gutierrez S, Alcaraz G, Maccallini G, Garcia A, Levalle O. Overt and subclinical hypothyroidism complicating pregnancy. Thyroid. 2002;12(1):63\u0026ndash;68.\u003c/li\u003e\n \u003cli\u003eSharmeen M, Shamsunnahar PA, Laita TR, Chowdhury SB. Overt and subclinical hypothyroidism among Bangladeshi pregnant women and its effect on fetomaternal outcome. Bangladesh Medical Research Council bulletin. 2014;40(2):52-57.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eAlexander EK, Pearce EN, Brent GA, Brown RS, Chen H, Dosiou C, Grobman WA, Laurberg P, Lazarus JH, Mandel SJ, Peeters RP, Sullivan S. 2017 Guidelines of the American Thyroid Association for the diagnosis and management of thyroid disease during pregnancy and the postpartum. Thyroid. 2017; 27(3):315\u0026ndash;389.\u003c/li\u003e\n \u003cli\u003eGagnon A, Antunes TT, Ly T, Pongsuwan P, Gavin C, Lochnan HA, et al. Thyroid-stimulating hormone stimulates lipolysis in adipocytes in culture and raises serum free fatty acid levels in vivo. Metabolism 2010;59(4):547\u003c/li\u003e\n \u003cli\u003eMa S, Jing F, Xu C, Zhou L, Song Y, Yu C, Jiang D, Gao L, Li Y, Guan Q, Zhao J.\u0026nbsp;Thyrotropin and obesity: increased adipose triglyceride content through glycerol-3-phosphate acyltransferase 3.\u0026nbsp;Sci Rep. 2015 Jan 6;5:7633. doi: 10.1038/srep07633. PMID: 25559747; PMCID: PMC4284501.\u003c/li\u003e\n \u003cli\u003eKwakernaak AJ, Lambert G, Muller Kobold AC, et al.Adiposity blunts the positive relationship of thyrotropinwith proprotein convertase subtilisin-kexin type 9 levelsin euthyroid subjects [J]. Thyroid, 2013, 23(2): 166-172.\u003c/li\u003e\n \u003cli\u003eZhou L, Wu K, Zhang L, Gao L, Chen S. Liver-specific deletion of TSHR inhibits hepatic lipid accumulation in mice. Biochem Biophys Res Commun. 2018 Feb 26;497(1):39-45. doi: 10.1016/j.bbrc.2018.01.187. Epub 2018 Feb 6. PMID: 29421660.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Zhao M, Yang T, Chen L, et al. Subclinical hypothyroidism might worsen the effects of aging on serum lipid profiles: a population-based case-control study. Thyroid. 2015 May;25(5):485-93. Doi: 10.1089/thy.2014.0219.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Abreu IM, Lau E, de Sousa Pinto B, et al. Subclinical hypothyroidism: to treat or not to treat, that is the question! A systematic review with meta-analysis on lipid profile. Endocr Connect. 2017 Apr;6(3):188-199. Doi: 10.1530/EC-17-0028.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eCaraccio N, Ferrannini E, Monzani F. Lipoprotein profile in subclinical hypothyroidism: response to levothyroxine replacement, a randomized placebo-controlled study. J Clin Endocrinol Metab. 2002 Apr;87(4):1533-8. Doi: 10.1210/jcem.87.4.8378.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Kotwal A, Cortes T, Genere N, Hamidi O, Jasim S, Newman CB, Prokop LJ, Murad MH, Alahdab F. Treatment of Thyroid Dysfunction and Serum Lipids: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2020 Dec 1;105(12):dgaa672. doi: 10.1210/clinem/dgaa672.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Wang C, Kong L, Yang Y,\u0026nbsp;et al. Recommended reference values for serum lipids during early and middle pregnancy: a retrospective study from China.\u0026nbsp;[J]. Lipids Health Dis. 2018 Oct 31;17(1):246. Doi: 10.1186/s12944-018-0885-3. PMID: 30382875; PMCID: PMC6211477.\u003c/li\u003e\n \u003cli\u003eBartels \u0026Auml;, Egan N, Broadhurst DI, Khashan AS, Joyce C, Stapleton M, et al. Maternal serum cholesterol levels are elevated from the 1st trimester of pregnancy: A cross-sectional study.\u0026nbsp;\u003cem\u003eJ Obstet Gynaecol.\u0026nbsp;\u003c/em\u003e2012;32(8):747\u0026ndash;52. Doi:\u0026nbsp;10.3109/01443615.2012.714017.\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Brizzi P, Tonolo G, Esposito F, Puddu L, Dessole S, Maioli M, Milia S. Lipoprotein metabolism during normal pregnancy.\u0026nbsp;\u003cem\u003eAm J Obstet Gynecol.\u0026nbsp;\u003c/em\u003e1999;\u003cstrong\u003e181\u003c/strong\u003e(2):430\u0026ndash;4. doi:\u0026nbsp;10.1016/S0002-9378(99)70574-0.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Piechota W, Staszewski A. Reference ranges of lipids and apolipoproteins in pregnancy.\u0026nbsp;\u003cem\u003eEur J Obstet Gynecol Reprod Biol.\u0026nbsp;\u003c/em\u003e1992;\u003cstrong\u003e45\u003c/strong\u003e(1):27\u0026ndash;35. doi:\u0026nbsp;10.1016/0028-2243(92)90190-A.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Lippi G, Albiero A, Montagnana M, Salvagno GL, Scevarolli S, Franchi M, Guidi GC. Lipid and lipoprotein profile in physiological pregnancy.\u0026nbsp;\u003cem\u003eClin Lab.\u0026nbsp;\u003c/em\u003e2007;\u003cstrong\u003e53\u003c/strong\u003e(3\u0026ndash;4):173\u0026ndash;7.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Husain F, Latif S, Uddin M, Nessa A. Lipid profile changes in second trimester of pregnancy.\u0026nbsp;\u003cem\u003eMymensingh Med J.\u0026nbsp;\u003c/em\u003e2008;\u003cstrong\u003e17\u003c/strong\u003e(1):17\u0026ndash;21.\u0026nbsp;PMID：18285725\u0026nbsp;\u003c/li\u003e\n \u003cli\u003e\u0026nbsp;Ghio A, Bertolotto A, Resi V, Volpe L, Di Cianni G. Triglyceride metabolism in pregnancy.\u0026nbsp;\u003cem\u003eAdv Clin Chem.\u0026nbsp;\u003c/em\u003e2011;\u003cstrong\u003e55\u003c/strong\u003e:133\u0026ndash;53. doi:\u0026nbsp;10.1016/B978-0-12-387042-1.00007-1.\u003c/li\u003e\n \u003cli\u003eZhao M, Tang X, Yang T,\u0026nbsp;et al.\u0026nbsp;Lipotoxicity, a potential risk factor for the increasing prevalence of subclinical hypothyroidism? J Clin Endocrinol Metab. 2015 May;100(5):1887-94. Doi: 10.1210/jc.2014-3987.\u0026nbsp;\u003c/li\u003e\n \u003cli\u003eVrijkotte TG, Krukziener N, Hutten BA, et al. Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study. J Clin Endocrinol Metab. 2012 Nov;97(11):3917-25. Doi: 10.1210/jc.2012-1295. Epub 2012 Aug 29. PMID: 22933545.\u003c/li\u003e\n \u003cli\u003eLi X, Wang Y, Guan Q, Zhao J, Gao L. The lipid-lowering effect of levothyroxine in patients with subclinical hypothyroidism: A systematic review and meta-analysis of randomized controlled trials. Clin Endocrinol (Oxf). 2017 Jul;87(1):1-9. doi: 10.1111/cen.13338. Epub 2017 Apr 24. PMID: 28342184.\u003c/li\u003e\n \u003cli\u003eKong WM, Sheikh MH, Lumb PJ, Naoumova RP, Freedman DB, Crook M, Dor\u0026eacute; CJ, Finer N. A 6-month randomized trial of thyroxine treatment in women with mild subclinical hypothyroidism. Am J Med. 2002 Apr 1;112(5):348-54. Doi: 10.1016/s0002-9343(02)01022-7.\u0026nbsp;\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Serum lipid levels of pregnant women in the first and \u003ca href=\"javascript%3A;\"\u003ethird\u003c/a\u003e \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003es of pregnancy\u003c/strong\u003e\u003c/p\u003e\n\u003ctable align=\"left\" border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.884476534296029%\"\u003e\n \u003cp\u003eSerum lipid levels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"10.22864019253911%\"\u003e\n \u003cp\u003e\u003ca href=\"javascript%3A;\"\u003eTrimester\u003c/a\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"20.45728038507822%\"\u003e\n \u003cp\u003emedian (interquartile range)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"9\" valign=\"top\" width=\"53.42960288808664%\"\u003e\n \u003cp\u003ePercentile (n=12309)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.866817155756207%\"\u003e\n \u003cp\u003e2.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e5%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e10%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e25%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e50%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e75%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e90%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.609480812641083%\"\u003e\n \u003cp\u003e95%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"12.866817155756207%\"\u003e\n \u003cp\u003e97.5%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.903614457831326%\"\u003e\n \u003cp\u003eTC\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.240963855421686%\"\u003e\n \u003cp\u003eFirst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.481927710843372%\"\u003e\n \u003cp\u003e4.11(3.72-4.56)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e3.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e3.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e3.38\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e3.72\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e4.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e4.56\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e5.02\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e5.33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e5.64\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.177650429799426%\"\u003e\n \u003cp\u003eThird\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.355300859598852%\"\u003e\n \u003cp\u003e6.46(5.78-7.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e4.58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e4.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e5.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e5.78\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e6.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e7.22\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e7.98\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e8.47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e8.92\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.903614457831326%\"\u003e\n \u003cp\u003eTG\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.240963855421686%\"\u003e\n \u003cp\u003eFirst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.481927710843372%\"\u003e\n \u003cp\u003e0.92(0.73-1.17)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e0.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e0.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e0.61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e0.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e0.92\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.73\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e2.00\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.177650429799426%\"\u003e\n \u003cp\u003eThird\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.355300859598852%\"\u003e\n \u003cp\u003e2.76(2.25-3.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e1.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e1.68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e1.88\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.76\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e3.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e4.23\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e4.87\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e5.57\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.903614457831326%\"\u003e\n \u003cp\u003eLDL-C\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.240963855421686%\"\u003e\n \u003cp\u003eFirst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.481927710843372%\"\u003e\n \u003cp\u003e2.11(1.77-2.48)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e1.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.35\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.77\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e2.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e2.48\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e2.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e3.12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e3.41\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.177650429799426%\"\u003e\n \u003cp\u003eThird\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.355300859598852%\"\u003e\n \u003cp\u003e3.54(2.91-4.20)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e3.54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e4.20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e4.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e5.30\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e5.72\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.903614457831326%\"\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"10.240963855421686%\"\u003e\n \u003cp\u003eFirst\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"20.481927710843372%\"\u003e\n \u003cp\u003e1.51(1.34-1.71)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.51\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e1.91\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"5.662650602409639%\"\u003e\n \u003cp\u003e2.04\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.867469879518072%\"\u003e\n \u003cp\u003e2.16\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"12.177650429799426%\"\u003e\n \u003cp\u003eThird\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"24.355300859598852%\"\u003e\n \u003cp\u003e1.85(1.62-2.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e1.25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e1.44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e1.62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e1.85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.09\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"6.73352435530086%\"\u003e\n \u003cp\u003e2.50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"8.166189111747851%\"\u003e\n \u003cp\u003e2.66\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: \u003cem\u003eTC\u003c/em\u003e: total cholesterol, \u003cem\u003eTG\u003c/em\u003e: triglycerides, \u003cem\u003eLDL-C\u003c/em\u003e low-density lipid cholesterol, \u003cem\u003eHDL-C\u003c/em\u003e: high-density lipid cholesterol.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Characteristics of pregnant women with SCH who did or did not receive treatment and control subjects\u003c/strong\u003e\u003c/p\u003e\n\u003ctable\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003e\u003cstrong\u003eCharacteristic\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCH\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003enon-intervention\u003c/strong\u003e \u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 103)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCH treatment Group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 319)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e\u003cstrong\u003eControl group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n =9598)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eP\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 valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eAge (years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e31.84(3.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e30(28-33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e30(28-33)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e22.70(3.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e21.56(19.61-24.01)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e21.48(19.83-23.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eTSH (mIU/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e4.56(4.22-5.22)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e4.75(4.33-5.59)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e1.34(0.96-1.79)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eFT4 (pmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e14.73(1.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e14.76(1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e15.92(14.77-16.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eGA at delivery (wks)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e39 (38\u0026ndash;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e38 (38\u0026ndash;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e39 (38\u0026ndash;40)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.695\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eNeonatal weight (g)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e3349.08(399.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e3307.07(483.43)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e3350 (3085\u0026ndash;3620)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.249\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eHistory of adverse pregnancy outcomes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e3 (2.91)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e3 (0.94)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e159(1.66)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.294\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eHistory of hypertension, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e1 (0.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e3（0.94）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e40(0.42)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.532\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eHistory of diabetes, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e31 (0.32)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"26.865671641791046%\"\u003e\n \u003cp\u003eCesarean section rate, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"23.066485753052916%\"\u003e\n \u003cp\u003e41 (39.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e117(36.68)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"19.26729986431479%\"\u003e\n \u003cp\u003e3374(35.15)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"11.533242876526458%\"\u003e\n \u003cp\u003e0.154\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations:TSH: thyroid-stimulating hormone; FT4: free thyroxine; GA: gestational age; BMI: body mass index.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe Kruskal-Wallis test was used to compare non-normally distributed continuous variables. The chi-square test or Fisher exact test was used to compare categorical variables among the three groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Serum lipid levels of pregnant women with SCH who did or did not receive treatment\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\" width=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"15.695600475624257%\"\u003e\n \u003cp\u003eSerum lipid levels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.061831153388823%\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.250891795481568%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCH\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003enon-intervention\u003c/strong\u003e \u003cstrong\u003eGroup\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 103)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.991676575505352%\"\u003e\n \u003cp\u003e\u003cstrong\u003eSCH treatment Group\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(n = 319)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.695600475624257%\"\u003e\n \u003cp\u003eTC\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.061831153388823%\"\u003e\n \u003cp\u003efirst \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.250891795481568%\"\u003e\n \u003cp\u003e4.37(0.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.991676575505352%\"\u003e\n \u003cp\u003e4.29(3.80-4.81)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.286318758815234%\"\u003e\n \u003cp\u003ethird\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.69675599435825%\"\u003e\n \u003cp\u003e6.61(1.29)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.01692524682652%\"\u003e\n \u003cp\u003e6.42(5.62-7.05)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.695600475624257%\"\u003e\n \u003cp\u003eTG\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.061831153388823%\"\u003e\n \u003cp\u003efirst \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.250891795481568%\"\u003e\n \u003cp\u003e1.06(0.85-1.47)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.991676575505352%\"\u003e\n \u003cp\u003e1.07(0.81-1.44)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.286318758815234%\"\u003e\n \u003cp\u003ethird\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.69675599435825%\"\u003e\n \u003cp\u003e2.99(2.49-3.74)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.01692524682652%\"\u003e\n \u003cp\u003e2.81(2.32-3.52)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.695600475624257%\"\u003e\n \u003cp\u003eLDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.061831153388823%\"\u003e\n \u003cp\u003efirst \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.250891795481568%\"\u003e\n \u003cp\u003e2.28(0.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.991676575505352%\"\u003e\n \u003cp\u003e2.20(1.77-2.61)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.286318758815234%\"\u003e\n \u003cp\u003ethird\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.69675599435825%\"\u003e\n \u003cp\u003e3.64(1.10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.01692524682652%\"\u003e\n \u003cp\u003e3.41(2.70-4.09)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" valign=\"top\" width=\"15.695600475624257%\"\u003e\n \u003cp\u003eHDL-C(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"28.061831153388823%\"\u003e\n \u003cp\u003efirst \u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"29.250891795481568%\"\u003e\n \u003cp\u003e1.55(1.34-1.77)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"26.991676575505352%\"\u003e\n \u003cp\u003e1.55(1.35-1.75)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" width=\"33.286318758815234%\"\u003e\n \u003cp\u003ethird\u0026nbsp;\u003ca href=\"javascript%3A;\"\u003etrimester\u003c/a\u003e of\u0026nbsp;pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"34.69675599435825%\"\u003e\n \u003cp\u003e1.80(1.61-1.97)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" width=\"32.01692524682652%\"\u003e\n \u003cp\u003e1.84(0.36)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: \u003cem\u003eTC\u003c/em\u003e: total cholesterol, \u003cem\u003eTG\u003c/em\u003e: triglycerides, \u003cem\u003eLDL-C\u003c/em\u003e low-density lipid cholesterol, \u003cem\u003eHDL-C\u003c/em\u003e: high-density lipid cholesterol.\u003c/p\u003e\n\u003cp\u003econtinuous variables were presented as mean (standard deviation [SD]) or median (interquartile range)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 4. Effects of L-T4 on pregnant women with SCH who did or did not receive treatment\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellpadding=\"0\" cellspacing=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eSerum lipid levels\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003egroup\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003egroup*age\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\"\u003e\n \u003cp\u003egroup*BMI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003egroup*TSH\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003egroup*TSH\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ewald x\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ewald x\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ewald x\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ewald x\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003ewald x\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd\u003e\n \u003cp\u003e\u003cem\u003eP\u003c/em\u003e value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTC\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e10.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.006\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.627\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.127\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.569\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.420\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.298\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eTG\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.274\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.600\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e7.608\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e.022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e21.548\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.192\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.334\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.519\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.771\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eHDL-C\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.466\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.116\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.227\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.541\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e28.795\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.164\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.921\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e1.616\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.771\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd\u003e\n \u003cp\u003eLDL-C\u0026nbsp;(mmol/L)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e6.430\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.011\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e5.800\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.055\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.115\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.944\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.990\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e2.816\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\"\u003e\n \u003cp\u003e0.245\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003eAbbreviations: \u003cem\u003eTC\u003c/em\u003e: total cholesterol, \u003cem\u003eTG\u003c/em\u003e: triglycerides, \u003cem\u003eLDL-C\u003c/em\u003e low-density lipid cholesterol, \u003cem\u003eHDL-C\u003c/em\u003e: high-density lipid cholesterol.\u003c/p\u003e\n\u003cp\u003eThe generalized estimation equation was used to compare categorical variables among the two groups.\u003c/p\u003e\n\u003cp\u003eDependent variable：TC, TG, HDL-C and LDL-C.\u003c/p\u003e\n\u003cp\u003eModel：（intercept）, group, group * age, group * BMI, group * TSH, group * FT4.\u0026nbsp;\u003c/p\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"levothyroxine treatment, serum lipid, subclinical hypothyroidism","lastPublishedDoi":"10.21203/rs.3.rs-1175883/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1175883/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground\u003c/p\u003e\u003cp\u003eThere is no consensus reference range for serum lipid levels during pregnancy. The benefit of levothyroxine (L-T4) on serum lipid levels are unclear among pregnant women with subclinical hypothyroidism (SCH).\u003c/p\u003e\u003cp\u003eObjective\u003c/p\u003e\u003cp\u003eTo determine the recommended reference ranges for serum lipid concentrations during pregnancy and effects of L-T4 treatment on serum lipids in pregnant women with SCH. \u003c/p\u003e\u003cp\u003eDesign\u003c/p\u003e\u003cp\u003ecohort study.\u003c/p\u003e\u003cp\u003eMethods\u003c/p\u003e\u003cp\u003eA analysis of 20365 women in the first trimester was conducted at Beijing Obstetrics and Gynecology Hospital, Capital Medical University during 2018–2020.\u0026nbsp;After excluding women with adverse pregnancy outcomes, we determined the reference range of serum lipid in the first and third trimesters of pregnancy by using median and quartile to determine appropriate percentiles. Next, we divided into three groups as follows: SCH L-T4 treatment group (n=319), SCH non-intervention group (n=103) and the control group(n=9598).\u003c/p\u003e\u003cp\u003eResults\u003c/p\u003e\u003cp\u003eThe recommended reference range for serum lipids in the first trimester of pregnancy should be: TC \u0026lt; 5.33\u0026nbsp;mmol/L, TG \u0026lt; 1.73\u0026nbsp;mmol/L, LDL-C \u0026lt; 3.12\u0026nbsp;mmol/L and HDL-C\u0026gt; 1.1\u0026nbsp;mmol/L, and in third trimester of pregnancy should be: TC \u0026lt; 8.47\u0026nbsp;mmol/L, TG \u0026lt; 4.86\u0026nbsp;mmol/L, LDL-C \u0026lt; 5.3\u0026nbsp;mmol/L and HDL-C \u0026gt;1.34\u0026nbsp;mmol/L.\u003c/p\u003e\u003cp\u003eThere are significant differences in TC and LDL-C levels between SCH treatment group and SCH non-intervention Group (P=0.043, P=0.046; respectively).\u003c/p\u003e\u003cp\u003eConclusions\u003c/p\u003e\u003cp\u003eWe determine the recommended reference ranges for serum lipid concentrations during pregnancy. TC and LDL-C levels in pregnant women with SCH could improve after L-T4 treatment.\u003c/p\u003e","manuscriptTitle":"Significance of Levothyroxine Treatment on Serum Lipid in Pregnant Women With Subclinical Hypothyroidism","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-01-07 14:34:27","doi":"10.21203/rs.3.rs-1175883/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-05-25T09:21:33+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-04-13T19:51:14+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"1fc75458-3c62-4639-96e0-747310779a3f","date":"2022-04-08T20:30:10+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-02-21T17:27:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-01-21T12:15:45+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-01-06T07:44:32+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-01-06T07:30:52+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Pregnancy and Childbirth","date":"2021-12-16T03:20:59+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"a8b58818-c774-4521-b5f2-587550f071d3","owner":[],"postedDate":"January 7th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[{"id":9584148,"name":"Maternal \u0026 Fetal Medicine"}],"tags":[],"updatedAt":"2022-07-26T05:44:08+00:00","versionOfRecord":[],"versionCreatedAt":"2022-01-07 14:34:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1175883","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1175883","identity":"rs-1175883","version":["v1"]},"buildId":"WrCJVZZCHTDjtuVLN7oU0","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}