Establishment of an accurate prediction system for gestational diabetes mellitus based on the characteristics of metabolic kinetics in early pregnancy: a prospective two-center cohort study in population according to IOM criteria.

ObjectiveThis two-center prospective cohort study aimed to evaluate the predictive value of the Metabolic Score for Insulin Resistance (METS-IR) for gestational diabetes mellitus (GDM) in Chinese women during early pregnancy and compare its performance with conventional insulin resistance (IR) indices.MethodsThis prospective investigation evaluated 1450 Chinese gravidas (<12 gestational weeks) without pregestational diabetes from two obstetrical institutions. Baseline clinical-biochemical profiling occurred during the first trimester (6–12 weeks), with GDM confirmation via standardized 75g oral glucose tolerance testing at 24–28 weeks’ gestation. Analytical methodologies incorporated multivariable regression modeling and ROC curve optimization to quantify the predictive validity of five metabolic indices (METS-IR, TyG index, TG/HDL-C ratio, HOMA-IR, TyG-BMI) for GDM risk stratification.ResultsAmong participants, 378 (26.1%) developed GDM. The GDM group (n=378, 26.1%) was older (median age 31.0 vs 30.0 years, p<0.0001) and had higher prepregnancy BMI (22.62 vs 21.32 kg/m², p<0.0001), fasting glucose (4.7 vs 4.5 mmol/L, p<0.0001) compared to NGT. The GDM group exhibited significantly higher METS-IR (31.14 vs 29.03, p <0.001) and other IR indices (p <0.001). In unadjusted models, METS-IR quartile 4 (Q4) was strongly associated with GDM (OR=3.33, 95% CI:2.38–4.70), but this association attenuated after adjusting for age, weight gain, lipids, and insulin (adjusted OR=1.56, 95% CI:1.04–2.35). Comparatively, the TyG index (adjusted OR=3.06, 95% CI:2.03–4.66) and TG/HDL-C ratio (adjusted OR=2.02, 95% CI:1.38–2.99) retained robust predictive power. ROC analysis revealed a moderate discriminative capacity for METS-IR (AUC=0.629 unadjusted; 0.676 fully adjusted), outperformed by HOMA-IR (AUC=0.699) and TyG (AUC=0.699). METS-IR demonstrated high specificity (76.2%) in unadjusted screening but showed dependency on metabolic confounders in adjusted models.ConclusionMETS-IR shows promise for early GDM screening and is outperformed by TyG and HOMA-IR in predictive value. METS-IR in early pregnancy reflects metabolic dysregulation linked to GDM risk, yet its predictive utility is partially mediated by lipid and insulin abnormalities. While METS-IR offers clinical feasibility through routine measurements, TyG and HOMA-IR exhibit superior independent predictive value. These findings highlight the importance of context-specific IR indices for early GDM risk stratification and underscore METS-IR’s role as a composite marker of metabolically unhealthy obesity in pregnancy.

Background/Objective: Early identification of and intervention for pregnant persons with a high risk of developing gestational diabetes mellitus (GDM) may lead to better health outcomes for both mother and infant. We aimed to assess both biomarkers and clinical predictors in early and late pregnancy to aid in the future development of an early pregnancy predictive model for GDM. Methods: This project is part of the Hoosier Moms Cohort, a prospective, longitudinal cohort study of pregnant women followed from early pregnancy through the postpartum period. Blood samples were taken in early and late pregnancy to discover clinical laboratory biomarkers which could be used for GDM risk prediction. Other pertinent medical history and findings were collected through patient surveys and chart abstraction. Data analysis included general descriptive statistics, Pearson’s correlation, and nonparametric tests. Results: 409 participants’ data were analyzed. Many biomarkers weakly correlated with maternal age and BMI in early and late pregnancy. Early pregnancy HbA1c was moderately correlated with BMI (0.32, p&lt;0.001), and fructosamine was moderately negatively correlated with BMI (-0.43, p&lt;0.001). Total cholesterol (TC), fructosamine, HDL, LDL, and triglycerides (TG) were weakly correlated with maternal age in early pregnancy. Blood glucose (BG) and TG were weakly correlated with BMI, and HDL was weakly negatively correlated with BMI in early pregnancy. Similar correlations were found with the biomarkers later in pregnancy with maternal age and BMI. White women had significantly lower HbA1c and higher TC and HDL levels when compared to Black/African American and “other race/ethnicity” women. Black/African American women had significantly lower fructosamine levels. LDL and TG were significantly lower and higher in “other race/ethnicity” women, respectively. Conclusion: BMI and race/ethnicity have significant relationships with biomarkers in early pregnancy that must be adjusted for in the development of a GDM predictive model.

This study aimed to evaluate the association between gestational diabetes mellitus (GDM) and circulating folate metabolites, folic acid (FA) intake, and the methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) genotype. A prospective pregnancy cohort study was conducted in Beijing, China, from 2022 to 2023. Circulating folate metabolites, including red blood cell (RBC) 5-methyltetrahydrofolate (5-MTHF), 5, 10-methylene-tetrahydrofolate (5,10-CH2-THF), 5- formyltetrahydrofolate (5-CHO-THF), and unmetabolised folic acid (UMFA), and plasma homocysteine (HCY), 5-MTHF, and methylmalonic acid (MMA), were determined at 6-17weeks and 20-26weeks of gestation. FA intake and the MTHFR and MTRR genotype were also examined. GDM was diagnosed between 24 and 28weeks of pregnancy by a 75-g oral glucose tolerance test (OGTT). The association between the folate status and GDM was ascertained using multivariate generalised linear models, logistic regression models, and restricted cubic spline regression, adjusting for potential confounders. The study included 2032 pregnant women, of whom 392 (19.29%) developed GDM. UMFA above the 75th percentile (≥P75) [adjusted OR (aOR) (95% confidence interval [CI])=1.36 (1.01-1.84)], UMFA≥P90 [aOR (95% CI)=1.82 (1.23-2.69)], and HCY≥P75 [aOR (95% CI)=1.40 (1.04-1.88)] in early pregnancy, and RBC 5-MTHF [aOR (95% CI)=1.48 (1.10-2.00)], RBC 5,10-CH2-THF [aOR (95% CI)=1.55 (1.15-2.10)], and plasma 5-MTHF [aOR (95% CI)=1.36 (1.00-1.86)] in mid-pregnancy≥P75 are associated with GDM. Higher UMFA levels in early pregnancy show positive associations with the 1-h and 2-h glucose levels during the OGTT, and higher HCY levels are associated with increased fasting glucose levels during the OGTT. In comparison, RBC 5- MTHF and 5,10-CH2-THF, and plasma 5- MTHF in mid-pregnancy are positively associated with the 1-h glucose level (p<0.05). The MTHFR and MTRR genotype and FA intake are not associated with GDM. Elevated levels of UMFA and HCY during early pregnancy, along with elevated RBC 5-MTHF and 5,10-CH2-THF and plasma 5-MTHF during mid-pregnancy, are associated with GDM. These findings indicate distinct connections between different folate metabolites and the occurrence of GDM.

Objective To assesment the effect of risk factors at gestational diabetes mellitus (GDM).Methods We collected 427 pregnant women who had done 75 g oral glucose tolerance test (OGTT) between September 1st,2012 and April 19th,2013 in Peking University First Hospital,including 74 pregnant women diagnosed as GDM (GDM group) and 353 pregnant women undiagnosed (non-GDM group).Then we conducted a multiple logistic regression to analyze the clinical datas collected from two groups,which included age,pre-pregnancy body weight and body mass index (BMI),body weight during 11-12 weeks pregnancy,body weight during 23-24 weeks pregnancy; and fasting plasma glucose(FPG),triglyceride (TG),total cholesterol (TCH),high density lipoprotein (H DL),low density lipoprotein (LDL),fasting insulin (FINS),homeostasis model assessment of insulin resistance (HOMA-IR) during early pregnancy; and family history of diabetes mellitus.Results (1)There were significant difference in age,pre-pregnancy BMI,and FPG,TG,FINS,HOMA-IR during early pregnancy,and family history of diabetes mellitus between two groups (P ＜ 0.05).(2) The risk factors of GDM that have statistical significance included FPG during early pregnancy (OR:4.03,95 ％ CI:1.62-10.02),family history of diabetes mellitus (OR:3.15,95 ％ CI:1.66-5.99),TG during early pregnancy (OR:2.13,95 ％ CI:1.17-3.87),BMI before pregnancy (OR:1.36,95 ％ CI:1.08-1.70),age ≥ 35 years (OR:1.15,95 ％ CI:1.05-1.26),early pregnancy weight gain (OR:1.20,95％ CI:1.06-1.35),mid pregnancy weight gain (OR:1.28,95％ CI:1.12-1.47),FINS during early pregancy (OR:1.09,95％ CI:1.01-1.17).Conclusions FPG,TG and FINS during early pregnancy,BMI before pregnancy,early and mid pregnancy weight gain,family history of diabetes mellitus and age≥35 years are the indepadent risk factors for GDM.We should pay more attention to FPG and TG during early pregnancy,and put weight management into practise since early pregnancy and try to control pregnancy weight gain within reasonable limits. Key words: Diabetes,gestational ; Weight gain ; Risk factors ;

Promotion of a healthy pregnancy is dependent on a coordinated immune response that minimizes inflammation at the maternal-fetal interface. Few studies investigated the effect of fetal sex on proinflammatory biomarkers during pregnancy and whether maternal race could impact this association. We aimed to examine whether fetal sex could, independently of maternal race/ethnicity and the condition of pregnancy (normal vs. complicated), impact inflammatory markers (C-reactive protein [CRP] and interleukin-8 [IL-8] levels) in early and late pregnancy. This study was a cohort analysis using prospectively collected data from pregnant women who participated in the Vitamin Antenatal Asthma Reduction Trial (VDAART, N=816). Maternal serum CRP and IL-8 levels were measured in early and late pregnancy (10-18 and 32-38weeks of gestation, respectively). Five hundred and twenty-eight out of 816 pregnant women who participated in the trial had available CRP and IL-8 measurements at both study time points. We examined the association of fetal sex with early and late CRP and IL-8 levels and their paired sample difference. We further investigated whether maternal race/ethnicity, pregnancy complications (i.e., preeclampsia and gestational diabetes), and early pregnancy body mass index (BMI) could affect the association between these two biomarkers and fetal sex adjusting for potential confounders. For this purpose, we used generalized linear and logistic regression models on log-normalized early and late CRP and IL-8 levels as well as their split at median to form high and low groups. Women pregnant with male fetuses (266/528=56.5%) had higher CRP levels in early to mid-pregnancy (β=.18: 95% confidence interval [CI]: CI=0.03-0.32; p=.02). Twenty-seven percent (143/528) of the study subjects were Hispanic. Hispanic African American [AA] women and women of races other than White and AA had higher levels of CRP at early to mid-pregnancy compared with White women (β=.57; 95% CI: 0.17-0.97; p<.01 and β=.27; 95% CI: 0.05-0.48; p=.02, respectively). IL-8 levels were not associated with fetal sex in early and late pregnancy (p's>.05). Other factors such as gestational diabetes and early pregnancy BMI were associated with higher CRP levels and higher CRP and IL-8 levels, respectively. Dichotomizing log-normalized cytokine levels at the median in a sensitivity analysis, women with male fetuses had lower odds of high (above-median) IL-8 levels at early pregnancy. Also, women with races other than AA and White carrying male fetuses had higher odds of having high (above-median) late-pregnancy CRP and early-pregnancy IL-8 levels (adjusted odds ratio [aOR]=3.80, 95% CI: 0.24-1.23; p=.02 and aOR=3.57; 95% CI: 0.23-1.03; p=.02, respectively). Of the pregnancy complications, women with gestational diabetes mellitus had a higher paired difference of early and late pregnancy CRP levels (β=.38; 95% CI: 0.09-0.68; p=.01), but no difference in IL-8 levels (p's>.05). No associations between the inflammatory markers and preeclampsia were found. Fetal sex is associated with CRP in early pregnancy and an association with IL-8 in early pregnancy is implied. Our study further indicates that maternal race/ethnicity could be a contributing factor in the relationship between fetal sex and inflammatory responses during pregnancy. However, the specificity and level of the contribution might vary by type of cytokine, pregnancy stage, and other confounding factors such as BMI that may impact these associations.

To develop a predictive model using machine learning for levothyroxine (L-T4) dose selection in patients with differentiated thyroid cancer (DTC) after resection and radioactive iodine (RAI) therapy and to prospectively validate the accuracy of the model in two institutions. A total of 266 DTC patients who received RAI therapy after thyroidectomy and achieved target thyroid stimulating hormone (TSH) level were included in this retrospective study. Sixteen clinical and biochemical characteristics that could potentially influence the L-T4 dose were collected; Significant features correlated with L-T4 dose were selected using machine learning random forest method, and a total of eight regression models were established to assess their performance in prediction of L-T4 dose after RAI therapy; The optimal model was validated through a two-center prospective study (n=263). Six significant clinical and biochemical features were selected, including body surface area (BSA), weight, hemoglobin (HB), height, body mass index (BMI), and age. Cross-validation showed that the support vector regression (SVR) model was with the highest accuracy (53.4%) for prediction of L-T4 dose among the established eight models. In the two-center prospective validation study, a total of 263 patients were included. The TSH targeting rate based on constructed SVR model were dramatically higher than that based on empirical administration (Rate 1 (first rate): 52.09% (137/263) vs 10.53% (28/266); Rate 2 (cumulative rate): 85.55% (225/263) vs 53.38% (142/266)). Furthermore, the model significantly shortens the time (days) to achieve target TSH level (62.61 ± 58.78 vs 115.50 ± 71.40). The constructed SVR model can effectively predict the L-T4 dose for postoperative DTC after RAI therapy, thus shortening the time to achieve TSH target level and improving the quality of life for DTC patients.

Purpose Transforaminal lumbar interbody fusion (TLIF) is a widely accepted surgical procedure for degenerative disk disease. While numerous studies have analyzed complication rates and risk factors this study investigates the extent to which complications after TLIF spondylodesis alter the clinical outcome regarding pain and physical function.Methods A prospective clinical two-center study was conducted, including 157 patients undergoing TLIF spondylodesis with 12-month follow-up (FU). Our study classified complications into three subgroups: none (I), minor (IIa), and major complications (IIb). Complications were considered “major” if revision surgery was required or new permanent physical impairment ensued. Clinical outcome was assessed using visual analog scales for back (VAS-B) and leg pain (VAS-L), and Oswestry Disability Index (ODI).Results Thirty-nine of 157 patients (24.8%) had at least one complication during follow-up. At FU, significant improvement was seen for group I (n = 118) in VAS-B (–50%), VAS-L (–54%), and ODI (–48%) and for group IIa (n = 27) in VAS-B (–40%), VAS-L (–64%), and ODI (–47%). In group IIb (n = 12), VAS-B (–22%, P = 0.089) and ODI (–33%, P = 0.056) improved not significantly, while VAS-L dropped significantly less (–32%, P = 0.013) compared to both other groups.Conclusion Our results suggest that major complications with need of revision surgery after TLIF spondylodesis lead to a significantly worse clinical outcome (VAS-B, VAS-L, and ODI) compared to no or minor complications. It is therefore vitally important to raise the surgeon´s awareness of consequences of major complications, and the topic should be given high priority in clinical work.

Nissen fundoplication in children with and without neurological impairment: A prospective cohort study

Oxidative stress is linked to the development of gestational diabetes mellitus (GDM). Maternal antioxidant vitamins in early pregnancy may play a role in GDM occurrence. We aimed to investigate the associations of vitamins A and E in early pregnancy with the risk of GDM and to explore whether these antioxidant vitamins can be biomarkers for the early prediction of GDM. We carried out a prospective cohort study conducted in Beijing and enrolled pregnant women (n = 667) with vitamins A and E measurements at 9 weeks (IQR 8-10) of gestation and having one-step GDM screened with a 75-g oral glucose tolerance test between 24 and 28 weeks of gestation. The vitamin A levels in early pregnancy were significantly higher in women with GDM than in those without GDM (p < 0.0001) and positively correlated with fasting blood glucose. In multivariate models, vitamin A levels were significantly associated with GDM (OR, 1.46; 95% CI: 1.14-1.88; p = 0.0032) per SD. A significant trend of risk effect on GDM risk across quartiles of vitamin A was observed (ptrend = 0.016). No significant association of serum vitamin E with GDM was observed overall. However, a noted trend of protective effect on GDM risk across quartiles of vitamin E/cholesterol ratio was observed (ptrend = 0.043). In ROC analysis, the multivariate model consisting of vitamin A and other risk factors showed the best predictive performance (AUC: 0.760; 95% CI: 0.705-0.815; p < 0.001). Higher levels of vitamin A in early pregnancy were significantly associated with an increased risk of GDM. Vitamin A has the potential to be a biomarker indicating pathogenesis of GDM.

Objective To compare the postoperative binocular visual quality in six treatment protocols for bilateral age-related cataract surgery with presbyopia correction for clinical decisions. Materials and methods In this prospective two-center single-blinded cohort study, participants from North or South China who underwent bilateral phacoemulsification and intraocular lens implantation were divided into six protocols: monovision, diffractive bifocal, mixed, refractive bifocal, trifocal, and micro-monovision extended range of vision (EROV). Binocular visual quality was evaluated at 3 months postoperatively, including binocular uncorrected full-range visual acuity, binocular defocus curves (depth of focus [DoF] and area under the curve [AUC]), binocular visual function (fusion function and stereopsis), binocular subjective spectacle independence rates, visual analog scale (VAS) of overall satisfaction, 25-item visual function questionnaire (VFQ-25), and binocular dysphotopsia symptoms. Results Of the 300 enrolled patients, 272 (90.7%; 544 eyes) were analyzed. The trifocal protocol showed excellent binocular full-range visual acuity and the best performance for most DoFs and AUCs. The monovision protocol presented the worst binocular visual quality in most perspectives, especially in convergence, distance, and near stereopsis (p < 0.001). The full-range subjective spectacle independence rates were sorted from highest to lowest as follows: trifocal (84.8%), refractive bifocal (80.9%), EROV (80.0%), mixed (73.3%), diffractive bifocal (65.2%), and monovision (32.6%) protocols, with no statistically significant differences between the former five protocols (p > 0.05). The EROV protocol achieved the highest VAS and VFQ-25 scores. The incidence of postoperative binocular dysphotopsia symptoms was comparable in all protocols. Conclusions The trifocal protocol showed the best performance, and the monovision protocol presented the worst performance in most perspectives of binocular visual quality for presbyopia correction. The refractive bifocal, mixed, or EROV protocols can provide an approximate performance as a trifocal protocol. Ophthalmologists can customize therapies using different protocols.

Objective: To investigate the association of lipoprotein a (Lpa) in early pregnancy with gestational diabetes mellitus (GDM) risk. Methods: A total of 445 pregnant women in 12-14 gestational weeks from "Maternal Key Nutritional Factors and Offspring's Atopic Dermatitis" cohort were included in this study. The demographic characteristics of participants were collected by using questionnaires, and the fasting glucose and lipids levels in early pregnancy were measured. The results of oral glucose tolerance test (OGTT) between 24-28 gestational weeks were recorded. Multivariate logistic regression model was applied to analyze the association of Lpa with GDM by calculating the OR and 95%CI after adjustment for covariates. Results: The incidence number of GDM was 78 (17.5%). The Lpa level in pregnant women with GDM was significantly higher than that in pregnant women without GDM [105.5 (92.0, 122.0) vs. 97.0 (87.0, 109.0) mg/L], P<0.05. Lpa was significantly associated with GDM risk [OR (95%CI) =1.21(1.08-1.36) per 10 mg/L], P<0.05. The association was still significant after adjustment for covariates including age, gestational weeks et al, the adjusted OR was 1.14 (95%CI: 1.01-1.30), P=0.03. Conclusions: The elevation of Lpa in early pregnancy is one of risk factor for GDM. Maintaining normal Lpa level during early pregnancy can benefit early prevention of GDM and offspring health.

The association between serum uric acid (UA) and gestational diabetes mellitus (GDM) was still unclear. Serum UA levels in pregnancy differed from that in non-pregnancy. This study aimed to investigate the changes of serum UA in early pregnancy, and to explore the association of serum UA with the risk of GDM. A prospective double-center study including 873 singleton pregnant women was conducted in Beijing, China since 2019 (clinical trial number: NCT03246295). Seventy-eight healthy non-pregnant women were selected to compare the changes of biomarkers in pregnancy. Spearman correlation and logistic regression analysis were performed to measure the relationship between serum UA in early pregnancy and GDM. The incidence of GDM in our cohort was 20.27%(177/873). Compared with non-pregnant women, serum UA and creatinine decreased significantly during early pregnancy. Serum UA concentration in early pregnancy was significantly higher in GDM women than that in normal glucose tolerance (NGT) women [217.0(192.9, 272.0) μmol/l vs. 201.9(176.0, 232.0) μmol/l, p < 0.001]. After adjusted for confounding factors, elevated serum UA remained as an independent risk factor for GDM. The risk of GDM increased when serum UA was above 240 μmol/l (adjusted OR 1.964, 95% CI 1.296-2.977, p < 0.001), and stronger relationships between serum UA and GDM were observed in pregnant women aged over 35 years old and preBMI ≥ 24 kg/m2. The normal range of serum UA and creatinine in pregnant women were lower than those in non-pregnant women. It is essential to monitor serum UA concentrations since early pregnancy to alert and prevent GDM, especially in older and heavier pregnant women. NCT03246295.

OBJECTIVETo investigate the association of folate and vitamin B12 in early pregnancy with gestational diabetes mellitus (GDM) risk.RESEARCH DESIGN AND METHODSThe data of this study were from a subcohort within the Shanghai Preconception Cohort Study. We included pregnancies with red blood cell (RBC) folate and vitamin B12 measurements at recruitment (between 9 and 13 gestational weeks) and those with three samples available for glucose measurements under an oral glucose tolerance test. GDM was diagnosed between 24 and 28 weeks’ gestation. Odds ratio (OR) and 95% CI of having GDM was used to quantify the association.RESULTSA total of 1,058 pregnant women were included, and GDM occurred in 180 (17.01%). RBC folate and vitamin B12 were significantly higher in pregnancies with GDM than those without GDM (P values were 0.045 and 0.002, respectively) and positively correlated with 1-h and 2-h serum glucose. Daily folic acid supplementation in early pregnancy increases the risk of GDM; OR (95% CI) was 1.73 (1.19–2.53) (P = 0.004). Compared with RBC folate <400 ng/mL, pregnancies with RBC folate ≥600 ng/mL were associated with ∼1.60-fold higher odds of GDM; the adjusted OR (95% CI) was 1.58 (1.03–2.41) (P = 0.033). A significant trend of risk effect on GDM risk across categories of RBC folate was observed (Ptrend = 0.021). Vitamin B12 was significantly associated with GDM risk (OR 1.14 per 100 pg/mL; P = 0.002). No significant association of serum folate and percentile ratio of RBC folate/vitamin B12 with GDM was observed.CONCLUSIONSHigher maternal RBC folate and vitamin B12 levels in early pregnancy are significantly associated with GDM risk, while the balance of folate/vitamin B12 is not significantly associated with GDM.

Environmental exposure to perfluoroalkyl substances in early pregnancy, maternal glucose homeostasis and the risk of gestational diabetes: A prospective cohort study.

Background: High bile acid concentration is associated with adverse perinatal outcomes (i.e., stillbirth and preterm birth) and experimental studies indicate that thyroid hormone regulates bile acid metabolism, but this has not yet been translated to clinical data in pregnant women. We aim to explore the association of thyroid function with bile acid concentrations and the risk of gestational hypercholanemia. Methods: This study comprised 68,016 singleton pregnancies without known thyroid or hepatobiliary diseases before pregnancy and thyroid medication based on a prospective cohort. Thyroid function and serum total bile acid (TBA) were routinely screened in both early (9-13 weeks) and late pregnancy (32-36 weeks). Hypercholanemia was defined as serum TBA concentration ≥10 μmol/L. Multiple linear regression models and multiple logistic regression models were performed. Results: A higher free thyroxine (fT4) during both early or late pregnancy was associated with a higher TBA concentration and a higher risk of hypercholanemia (all p < 0.01). A higher thyrotropin (TSH) in early pregnancy was associated with a higher TBA concentration in early pregnancy (p = 0.0155), but with a lower TBA concentration during later pregnancy (p < 0.0001), and there was no association of TSH with hypercholanemia. Overt hyperthyroidism in late pregnancy was associated with a 2.12-fold higher risk of hypercholanemia ([confidence interval; CI 1.12-4.03], p = 0.021) and subclinical hyperthyroidism during later pregnancy was associated with a 1.5-fold higher risk of hypercholanemia ([CI 1.14-1.97], p = 0.0034). Sensitivity analyses indicated that a high fT4 throughout pregnancy was associated with a higher risk of hypercholanemia rather than only in early or late pregnancy. Conclusions: A higher fT4 concentration during either early or late pregnancy, but not the TSH concentration, is associated with higher TBA and a higher risk of gestational hypercholanemia. Furthermore, hyperthyroidism during pregnancy could be a novel risk factor for hypercholanemia.