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Wu H, Wang X, Li H, Li C, Zhu J, Hu J, Zhang C, Zhou X. Thyroid hormone ameliorates ursodeoxycholic acid-induced heart damage in zebrafish embryos. Life Sci 2025:123716. [PMID: 40389024 DOI: 10.1016/j.lfs.2025.123716] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2025] [Revised: 05/08/2025] [Accepted: 05/15/2025] [Indexed: 05/21/2025]
Abstract
Ursodeoxycholic acid (UDCA) is the most commonly prescribed treatment for intrahepatic cholestasis of pregnancy (ICP) worldwide. Clinical studies show that UDCA helps alleviate maternal pruritus and lowers serum bile acid levels. However, despite treatment, women with ICP still experience unpredictable fetal deaths and other serious pregnancy complications. In this study, we hypothesize that while UDCA improves maternal symptoms, it may have harmful effects on the fetus due to its placental barrier crossing, potentially leading to negative pregnancy outcomes. We found that UDCA concentrations above 150 mg/L can exert toxic effects on zebrafish embryos, including increased mortality, slower heart rates, and pericardial edema. At these concentrations, UDCA also triggered apoptosis and elevated oxidative stress in embryonic cardiomyocytes. Importantly, the thyroid hormone T4 was able to partially mitigate these toxic effects. These findings suggest that adverse pregnancy outcomes in ICP may be related to fetal heart damage caused by UDCA's effects on circulation, providing a possible explanation for fetal death in clinical settings. This also underscores the need to optimize UDCA dosing in clinical practice and explore the use of thyroid hormones as a potential protective therapy for the fetus in ICP cases.
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Affiliation(s)
- Haoran Wu
- Department of Cardiology, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China; Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Institute of Metabolic Diseases, Luzhou, Sichuan 646000, China
| | - Xueqin Wang
- Department of Thyroid Surgery, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Honghao Li
- Department of Thyroid Surgery, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Chunhong Li
- Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646000, China
| | - Jinshun Zhu
- Department of Thyroid Breast Vascular Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, People's Republic of China
| | - Jian Hu
- Department of Cardiology, Suining First People's Hospital, Suining, Sichuan 629000, China
| | - Chunxiang Zhang
- Department of Cardiology, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China; Key Laboratory of Medical Electrophysiology, Ministry of Education, Institute of Cardiovascular Research, Institute of Metabolic Diseases, Luzhou, Sichuan 646000, China.
| | - Xiangyu Zhou
- Department of Thyroid Surgery, Affiliated Hospital, Southwest Medical University, Luzhou, Sichuan 646000, China; Basic Medicine Research Innovation Center for Cardiometabolic Diseases, Ministry of Education, Southwest Medical University, Luzhou, Sichuan 646000, China.
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You P, Ding M, Li X, Shao Y, Jiang T, Jia Y, Wang Y, Zhang X. Determining Urinary Bile Acid Profiles to Predict Maternal and Neonatal Outcomes in Patients with Intrahepatic Cholestasis of Pregnancy. Diagnostics (Basel) 2025; 15:657. [PMID: 40150000 PMCID: PMC11941055 DOI: 10.3390/diagnostics15060657] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2025] [Revised: 02/28/2025] [Accepted: 03/06/2025] [Indexed: 03/29/2025] Open
Abstract
Objective: Intrahepatic cholestasis of pregnancy (ICP) is associated with an elevated risk of adverse perinatal outcomes, including perinatal morbidity and mortality. The objectives of this study were to evaluate the bile acid (BA) metabolism profiles in the urine of patients with ICP and to investigate the association between specific BAs and maternal and neonatal outcomes in patients with ICP. Methods: A total of 127 Chinese women with ICP and 55 healthy pregnant women were enrolled in our retrospective study. Spot urine samples and clinical data were collected from pregnant women from January 2019 to December 2022 at the First Affiliated Hospital of Chongqing Medical University, Chongqing. Based on total bile acid (TBA) levels, the ICP group was subdivided into mild (10-40 μmol/L) and severe (≥40 μmol/L) ICP groups. Patients in the ICP group were further divided into two categories according to neonatal outcomes: an ICP with adverse pregnancy outcomes group and an ICP with non-adverse pregnancy outcomes group. Metabolites from maternal urine were collected and analyzed using ultra-high-performance liquid chromatography-triple quadrupole time-of-flight mass spectroscopy (UPLC-triple TOF-MS). Results: Significant differences were observed between the mild and severe ICP groups in the onset time of symptoms, gestational weeks at time of ICP diagnosis, the duration of using ursodeoxycholic acid (UDCA) drugs during pregnancy, gestational age at delivery, premature delivery, and cesarean delivery. The expression levels of the composition of different urinary bile acids including THCA, TCA, T-ω-MCA, TCA-3-S, TCDCA-3-S, TDCA-3-S, GCDCA-3-S, DCA-3-G and GDCA-3-G were remarkably higher in the ICP with adverse pregnancy outcomes group than those in the ICP with non-adverse pregnancy outcomes group and the control group. The single-parameter model used to predict adverse pregnancy outcomes in ICP had similar areas under the curve (AUCs) of the receiver operating characteristic (ROC), ranging from 0.755 to 0.869. However, an AUC of 0.886 and 95% CI were obtained by the index of combined urinary bile acids in multiple prediction models (95% CI 0.790 to 0.983, p < 0.05). TCA-3-S in the urinary bile acids had a strong positive correlation with the aspartate aminotransferase (AST) level (r = 0.617, p < 0.05). Furthermore, TCDCA-3-S and GCDCA-3-S in the urinary bile acids had a strong positive correlation with the alanine aminotransferase (ALT) level (r = 0.607, p < 0.05; r = 0.611, p < 0.05) and AST level (r = 0.629, p < 0.05; r = 0.619, p < 0.05). Conclusions: Maternal urinary bile acid profiles were prominent for the prognosis of maternal and neonatal outcomes of ICP. Elevated levels of TCA-3-S, TCDCA-3-S, and GCDCA-3-S in urine might be important predictors for indicating adverse pregnancy outcomes in ICP.
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Affiliation(s)
- Ping You
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
| | - Min Ding
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
| | - Xue Li
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
| | - Yong Shao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;
| | - Tingting Jiang
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
| | - Yuanyuan Jia
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
| | - Yuxuan Wang
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
| | - Xiaoqing Zhang
- Key Laboratory of Clinical Laboratory Diagnostics (Ministry of Education of China), School of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, China; (P.Y.); (M.D.); (X.L.); (T.J.); (Y.J.); (Y.W.)
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Nie L, Zhang Z, Yao Q, Chen H, Xu C, Chen L, Liu C, Tu L, Yi Y, Huang T, Zeng X, Yu L. The new era of risk assessment for hypertension in pregnancy: From clinical to biochemical markers in a comprehensive predictive model. Taiwan J Obstet Gynecol 2025; 64:253-264. [PMID: 40049809 DOI: 10.1016/j.tjog.2024.10.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/09/2024] [Indexed: 05/13/2025] Open
Abstract
OBJECTIVE This study aims to develop and validate a model based on the weighted random forest (WRF) algorithm to predict early-onset preeclampsia (PE) and to assess the importance of various clinical and biochemical markers in early risk identification. MATERIALS AND METHODS This study was conducted at the Jiangxi Maternal and Child Health Hospital and involved 12,699 pregnant women from January 2019 to June 2022. Extensive clinical and biochemical markers were collected through prenatal care data, which were used to construct a predictive model for early-onset PE. The model was developed using the WRF and Logistic regression methods, and multivariable analysis was employed to identify markers significantly associated with the risk of PE. RESULTS The relative importance of various markers was evaluated using the random forest (RF) model in a sample of 1200 patients diagnosed with PE. Blood pressure and pre-pregnancy body mass index (BMI) were identified as the most critical variables affecting the accuracy of the PE prediction model. The WRF model demonstrated higher predictive accuracy (AUC = 0.9614) than the Logistic regression model (AUC = 0.9138), highlighting its superiority in early risk identification for PE. CONCLUSION The WRF-based predictive model developed in this study effectively predicts the risk of early-onset PE, with blood pressure and BMI as vital predictive factors. These findings underscore the importance of employing a comprehensive predictive model for risk assessment in early pregnancy, facilitating early intervention and improving health outcomes for pregnant women and their newborns.
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Affiliation(s)
- Liju Nie
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China
| | - Ziyu Zhang
- Department of Pathology, Jiangxi Maternal and Child Health Hospital, Nanchang, China
| | - Qinglan Yao
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China
| | - Huayan Chen
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China
| | - Chao Xu
- Fujian Normal University, Fuzhou 350007, China
| | - Lin Chen
- Fujian Normal University, Fuzhou 350007, China
| | - Chengcheng Liu
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China
| | - Lantao Tu
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China
| | - Yuping Yi
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China
| | | | - Xiaoming Zeng
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China.
| | - Lamei Yu
- Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, China; Department of Obstetrics, Maternal and Child Health Hospital of Nanchang Medical College, Nanchang, China.
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Agaoglu Z, Tanacan A, Toptas GR, Akgun Aktas B, Gulen Yildiz E, Kara O, Sahin D. Ultrasonographic assessment of the fetal heart in intrahepatic cholestasis of pregnancy: Pulsed wave Doppler, M-mode, and tissue Doppler imaging prospective study. Int J Gynaecol Obstet 2025; 168:753-761. [PMID: 39258467 DOI: 10.1002/ijgo.15910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/23/2024] [Accepted: 08/28/2024] [Indexed: 09/12/2024]
Abstract
OBJECTIVES To investigate the fetal heart using pulsed wave Doppler, M-mode, and tissue Doppler imaging (TDI) in cases of intrahepatic cholestasis of pregnancy (ICP). METHODS This prospective study was conducted at a single tertiary center and included 35 patients with ICP and 70 healthy pregnant women at 28-36 weeks of pregnancy. Among the patients with ICP, 26 had serum bile acid (SBA) levels less than 40 μmol/L and nine had SBA levels of 40 μmol/L or greater. Pulsed wave Doppler, M-mode, and TDI evaluations were performed on the patients to assess fetal cardiac function. RESULTS The ICP group exhibited significantly higher myocardial performance index (MPI) and isovolumetric relaxation time (IRT), but similar isovolumetric contraction time (ICT). The tricuspid and mitral valve E, A, and E/A ratios were significantly reduced in the ICP group. The TDI parameters showed significantly reduced tricuspid and mitral valve E'/A' ratios in the ICP group compared with the control group (P < 0.001). The E/E' ratio was significantly increased in the ICP group (P < 0.001). According to the M-mode Doppler findings, tricuspid and mitral annular plane systolic excursion values were significantly decreased in the ICP group (P = 0.005 and P = 0.001, respectively). In the subgroup analysis, MPI and IRT were significantly higher in the severe ICP group. CONCLUSION ICP might induce changes in the fetal heart during the early systolic and diastolic phases. The detection of these early changes using M-mode and TDI during the antenatal period can provide valuable insights into the condition of the fetus.
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Affiliation(s)
- Zahid Agaoglu
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, Türkiye
| | - Atakan Tanacan
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, University of Health Sciences, Ankara, Türkiye
| | - Gulnihal Reyhan Toptas
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, Türkiye
| | - Betul Akgun Aktas
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, Türkiye
| | - Esra Gulen Yildiz
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, Türkiye
| | - Ozgur Kara
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, Ankara, Türkiye
| | - Dilek Sahin
- Department of Obstetrics and Gynecology, Ministry of Health, Ankara City Hospital, University of Health Sciences, Ankara, Türkiye
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Pan X, Chu R, Qiao X, Zhang X, Li L, Zhang W. Association of Adverse Perinatal Outcomes with Blood Components Transfusion in Patients with Acute Fatty Liver of Pregnancy. Int J Womens Health 2025; 17:21-32. [PMID: 39802922 PMCID: PMC11720634 DOI: 10.2147/ijwh.s477944] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2024] [Accepted: 11/21/2024] [Indexed: 01/16/2025] Open
Abstract
Purpose To investigate the rare obstetric emergency with no specific treatments called acute fatty liver of pregnancy. The primary objective was to evaluate association of adverse perinatal outcomes with blood components transfusion. While the secondary objective focused on further establishing the predictive risk factors for adverse perinatal outcomes. Participants and Methods This retrospective cohort study included patients, who diagnosed with acute fatty liver of pregnancy without hepatic/malignant diseases in Qilu Hospital of Shandong University over 12-year period (collected 2007-2019, aged 20-41years). Chi-square test was used to explore the relevance between blood transfusion therapy and adverse perinatal outcomes. Meanwhile, logistic regression analysis was performed to identify predictive risk factors. Results Of 146 patients, 26 (26/146, 17.8%) received prenatal blood transfusions. These patients had reduced gestational ages and exhibited more severe clinical symptoms. The association between blood transfusion and adverse maternal outcomes yielded a P value of 0.044, while the association with fetal outcomes was highly significant (P<0.001). Multivariate logistic regression analysis identified seven high-risk factors for maternal outcomes and six for fetal outcomes, all demonstrating strong discriminatory capacity. Conclusion Blood component transfusion may serve as a marker of disease severity. Prompt identification of patients with high-risk factors is crucial to improve maternal and fetal outcomes.
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Affiliation(s)
- Xiyu Pan
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China
| | - Ran Chu
- Department of Obstetrics and Gynecology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong Province, People’s Republic of China
| | - Xu Qiao
- Institute of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong Province, People’s Republic of China
| | - Xianru Zhang
- Institute of Biomedical Engineering, School of Control Science and Engineering, Shandong University, Jinan, Shandong Province, People’s Republic of China
| | - Li Li
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China
| | - Wenxia Zhang
- Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan, Shandong Province, People’s Republic of China
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Chen Z, Zhu M, Ni W, Wu B, Liu T, Lin B, Lai L, Jing Y, Jiang L, Ouyang Z, Hu J, Zheng H, Peng W, Yu X, Fan J. Association of PM 2.5 exposure in early pregnancy and maternal liver function: A retrospective cohort study in Shenzhen, China. ENVIRONMENTAL RESEARCH 2024; 263:119934. [PMID: 39276834 DOI: 10.1016/j.envres.2024.119934] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 09/02/2024] [Accepted: 09/03/2024] [Indexed: 09/17/2024]
Abstract
OBJECTIVE Studies have shown that fine particulate matter (PM2.5) has adverse effects on the liver function, but epidemiological evidence is limited, especially regarding pregnant women. This study aims to investigate the association between PM2.5 exposure in early pregnancy and maternal liver function during pregnancy. METHODS This retrospective cohort study included 13,342 pregnant participants. PM2.5 and Ozone (O3) exposure level, mean temperature, and relative humidity for each participant were assessed according to their residential address. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were measured during the second and third trimesters. Data on PM2.5 and O3 exposure level were sourced from Tracking Air Pollution in China (TAP), while the mean temperature and relative humidity were obtained from the ERA5 dataset. The Generalized Additive Model (GAM) was used to analyze the associations between PM2.5 exposure and maternal liver function during pregnancy, adjusting for potential confounding factors. RESULTS According to the results, each 10 μg/m3 increase in PM2.5 was associated with an increase of 3.57% (95% CI: 0.29%, 6.96%) in ALT and 4.25% (95% CI: 2.33%, 6.21%) in TBIL during the second trimester and 4.51% (95% CI: 2.59%, 6.47%) in TBIL during the third trimester, respectively. After adjusting for O3, these associations remained significant, and the effect of PM2.5 on ALT during the second trimester was further strengthened. No significant association observed between PM2.5 and AST. CONCLUSIONS PM2.5 exposure in early pregnancy is associated with increasement of maternal ALT and TBIL, suggesting that PM2.5 exposure may have an adverse effect on maternal liver function. Although this finding indicates an association between PM2.5 exposure and maternal liver function, more research is needed to confirm our findings and explore the underlying biological mechanisms.
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Affiliation(s)
- Zhijian Chen
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China; Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China
| | - Minting Zhu
- School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - Weigui Ni
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China
| | - Bo Wu
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China
| | - Tao Liu
- China Greater Bay Area Research Center of Environmental Health, School of Medicine, Jinan University, Guangzhou 510632, China; Key Laboratory of Viral Pathogenesis & Infection Prevention and Control, Jinan University, Ministry of Education, Guangzhou 510632, China
| | - Bingyi Lin
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China
| | - Lijuan Lai
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China
| | - Yi Jing
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China
| | - Long Jiang
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China
| | - Zhongai Ouyang
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China; School of Public Health, Southern Medical University, Guangzhou 510515, China
| | - Jianxiong Hu
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Haoqu Zheng
- Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China
| | - Wan Peng
- Department of Public Health and Preventive Medicine, School of Medicine, Jinan University, Guangzhou 510632, China
| | - Xi Yu
- Faculty of Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau, China.
| | - Jingjie Fan
- Department of Preventive Healthcare, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen 518028, China.
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Zhang B, Zhan Z, Zhang F, Xi S, Yuan X, Shi Z. Serum triglyceride to high density lipoprotein cholesterol ratio in late pregnancy as a potential predictor of adverse birth outcomes: an analysis of real-world data. Diabetol Metab Syndr 2024; 16:262. [PMID: 39497103 PMCID: PMC11536801 DOI: 10.1186/s13098-024-01503-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 10/29/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND The association between serum triglyceride to high density lipoprotein cholesterol ratio (THR) in late pregnancy and adverse birth outcomes (ABO) remains controversial because of inconsistent results. The present study assessed the association between maternal serum THR and incidence of ABO [preterm birth (PTB), small and large for gestational age (SGA/LGA), low birth weight (LBW) and macrosomia] in a Chinese population. METHODS A total of 11,553 consecutive participants from a real-world database with data on lipid profiles and birth outcomes were included. Logistic regression models were applied to assess the association between THR and incident ABO. Mediation analysis was performed to investigate the contribution of pregnancy complications [gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP) and pre-eclampsia (PE)] to this association. RESULTS Approximately 6.6% (762/11,553), 8.9% (1023/11,553), 15.5% (1792/11,553), 4.3% (494/11,553), and 7.4% (851/11,553) of individuals developed PTB, SGA, LGA, LBW and macrosomia, respectively. Significant trends across the quintiles of THR toward decreasing incidence of SGA and LBW and increasing incidence of LGA and macrosomia were observed. The multivariate-adjusted odds ratios (OR) in the top quintile of serum THR (> 3.16) versus the bottom quintile (< 1.44) were 0.52 for PTB, 0.48 for SGA, 0.64 for LBW, 2.80 for LGA and 3.80 for macrosomia, respectively. A 1-standard deviation (SD) increase in serum THR was associated with decreased risk of PTB [OR = 0.84, 95% confidence interval (CI): 0.76-0.93), SGA (OR = 0.71, 95% CI:0.65-0.78) and LBW (OR = 0.76, 95% CI:0.65-0.90) and increased risk of LGA (OR = 1.40, 95% CI:1.32-1.49) and macrosomia (OR = 1.49, 95% CI:1.38-1.62). In mediation analyses, PE mediated - 19.8%, -10.6% and - 24.6% of THR-associated PTB, SGA and LBW, respectively, GDM accounted for - 3.7%, 6.8% and 4.3% of THR-associated PTB, LGA and macrosomia, respectively, and ICP explained - 1.9% and - 2.1% of THR-associated PTB and LBW, respectively. In addition, incorporating THR to ABO predictive models significantly improved the area under the curve for SGA (0.743 vs. 0.753, P < 0.001), LGA (0.734 vs. 0.745, P < 0.001) and macrosomia (0.786 vs. 0.800, P < 0.001). CONCLUSION Real-world data showed an association between serum THR in late pregnancy and ABO risk, and this association may be partially mediated by prevalent pregnancy complications (PE/GDM/ICP), suggesting a potential role of THR in predicting ABO (SGA/LGA/macrosomia).
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Affiliation(s)
- Bin Zhang
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Zhaolong Zhan
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Feng Zhang
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Sijie Xi
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China
| | - Xiaosong Yuan
- Department of Medical Genetics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
| | - Zhonghua Shi
- Department of Obstetrics, Changzhou Maternal and Child Health Care Hospital, Changzhou Medical Center, Nanjing Medical University, Changzhou, China.
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de Vera SA, Brecht-Doscher A, Fejzo MS, Brecht ML, Kwon IM, MacGibbon KW. Risk Factors for Infusions, Emergency Room Visits and Hospitalizations for Hyperemesis Gravidarum: New Data and Literature Review. Int J Womens Health 2024; 16:1789-1802. [PMID: 39493662 PMCID: PMC11531718 DOI: 10.2147/ijwh.s371458] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/02/2024] [Accepted: 10/17/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose Few factors have been identified that increase the risk of visits (hospital emergency room or inpatient stays) due to hyperemesis gravidarum (HG). The purpose of this study is to understand trends in HG management and identify variables increasing visit frequency so that strategies may be developed to reduce hospital utilization. Study Design An online survey was posted on the Hyperemesis Education and Research Foundation website and social media between June 2022 and May 2023. Participants had previous or current severe pregnancy nausea and vomiting. Respondents were asked about themselves and their HG experience, including weight loss, medications, infusion care, and visit frequency. Odds ratios, p-values, and 95% confidence intervals were calculated via MedCalc to analyze the significance of each factor, and Spearman rank correlations were analyzed via SPSS for associations of ondansetron usage with visits and weight loss. Microsoft Excel and SPSS were used to calculate treatment and visit frequencies. Results Survey data from 1220 respondents who reported a current or prior pregnancy with HG were included in this study. Respondents were primarily White, from the US, and had at least one visit due to HG. Participants with a visit were significantly more likely to be a person of color (POC), unable to work, have no children, and lose over 15 pounds (6.8 kg). Those who took medications as prescribed had fewer visits. No medication combination or dose was found to be significantly more effective in preventing weight loss or repeat hospital visits. Conclusion Risk factors predicting visits included POC, not having children, being too sick to work, and having extreme weight loss. Utilization of medication and nutritional therapies is inconsistent and inadequate in this population, which may increase visit frequency.
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Affiliation(s)
- Summer A de Vera
- Hyperemesis Education and Research Foundation, Clackamas, OR, USA
| | | | - Marlena S Fejzo
- Center for Genetic Epidemiology, Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA
| | - Mary-Lynn Brecht
- School of Nursing, University of Southern California, Los Angeles, CA, USA
| | - Irene M Kwon
- Hyperemesis Education and Research Foundation, Clackamas, OR, USA
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Ozkavak OO, Tanacan A, Haksever M, Sahin R, Serbetci H, Okutucu G, Aldemir E, Sahin D. The utility of albumin-bilirubin score in patients with intrahepatic cholestasis of pregnancy: a retrospective comparative study. REVISTA DA ASSOCIACAO MEDICA BRASILEIRA (1992) 2024; 70:e20240860. [PMID: 39475920 PMCID: PMC11509178 DOI: 10.1590/1806-9282.20240860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/01/2024] [Accepted: 08/11/2024] [Indexed: 11/02/2024]
Abstract
OBJECTIVE The aim of this study was to examine the utility of the albumin-bilirubin score in cases of intrahepatic cholestasis of pregnancy. METHODS A total of 413 patients (182 intrahepatic cholestasis of pregnancy, 50 suspected intrahepatic cholestasis of pregnancy, 181 healthy controls) enrolled in this study. Patients with typical pruritus and bile acid levels >10 μmol/L are defined as the intrahepatic cholestasis of pregnancy group. Patients with pruritus have the same pattern as intrahepatic cholestasis of pregnancy, but who are ultimately diagnosed with other dermatoses of pregnancy are defined as suspected intrahepatic cholestasis of pregnancy. Demographic data, laboratory parameters, and albumin-bilirubin scores were compared between three groups. Correlation analysis was performed on the albumin-bilirubin score and bile acid levels. Also, receiver operating curve analyses were performed to evaluate the predictive performance of the albumin-bilirubin score for intrahepatic cholestasis of pregnancy diagnosis. RESULTS The albumin-bilirubin score of the intrahepatic cholestasis of pregnancy group was significantly higher than the other groups. A positive, weak correlation was found between the albumin-bilirubin score and bile acid levels in the intrahepatic cholestasis of pregnancy group. The receiver operating curve curve analyses showed albumin-bilirubin score has significant performance for the prediction of intrahepatic cholestasis of pregnancy in all subjects (area under the curve: 0.726, 95%CI 0.679-0.774, p<0.001) (sensitivity: 69%, specificity: 64%). The detection rate for albumin-bilirubin score was calculated as 67.3%. The positive predictive value was 3.95% (CI 2.9-5.3%), and the negative predictive value was 98.9% (CI 98.6-99.2%). CONCLUSION This study indicated higher albumin-bilirubin score levels in the intrahepatic cholestasis of pregnancy group and a positive relationship between serum bile acid levels and albumin-bilirubin score. Therefore, albumin-bilirubin score could be a cost-effective liver function test for pregnant women with intrahepatic cholestasis of pregnancy.
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Affiliation(s)
- Osman Onur Ozkavak
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
| | - Atakan Tanacan
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
- University of Health Sciences, Ankara Bilkent City Hospital, Department of Obstetrics and Gynaecology – Ankara, Turkey
| | - Murat Haksever
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
| | - Refaettin Sahin
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
| | - Hakki Serbetci
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
| | - Gulcan Okutucu
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
| | - Eda Aldemir
- Ankara Bilkent City Hospital, Department of Obstetrics and Gynaecology – Ankara, Turkey
| | - Dilek Sahin
- Ankara Bilkent City Hospital, Department of Perinatology – Ankara, Turkey
- University of Health Sciences, Ankara Bilkent City Hospital, Department of Obstetrics and Gynaecology – Ankara, Turkey
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Kothari S, Afshar Y, Friedman LS, Ahn J. AGA Clinical Practice Update on Pregnancy-Related Gastrointestinal and Liver Disease: Expert Review. Gastroenterology 2024; 167:1033-1045. [PMID: 39140906 DOI: 10.1053/j.gastro.2024.06.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/13/2023] [Revised: 06/19/2024] [Accepted: 06/20/2024] [Indexed: 08/15/2024]
Abstract
DESCRIPTION The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with pregnancy-related gastrointestinal and liver disease. METHODS This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Gastroenterology. This article provides practical advice for the management of pregnant patients with gastrointestinal and liver disease based on the best available published evidence. The Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: To optimize gastrointestinal and liver disease before pregnancy, preconception and contraceptive care counseling by a multidisciplinary team should be encouraged for reproductive-aged persons who desire to become pregnant. BEST PRACTICE ADVICE 2: Procedures, medications, and other interventions to optimize maternal health should not be withheld solely because a patient is pregnant and should be individualized after an assessment of the risks and benefits. BEST PRACTICE ADVICE 3: Coordination of birth for a pregnant patient with complex inflammatory bowel disease, advanced cirrhosis, or a liver transplant should be managed by a multidisciplinary team, preferably in a tertiary care center. BEST PRACTICE ADVICE 4: Early treatment of nausea and vomiting of pregnancy may reduce progression to hyperemesis gravidarum. In addition to standard diet and lifestyle measures, stepwise treatment consists of symptom control with vitamin B6 and doxylamine, hydration, and adequate nutrition; ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids may be required in moderate to severe cases. BEST PRACTICE ADVICE 5: Constipation in pregnant persons may result from hormonal, medication-related, and physiological changes. Treatment options include dietary fiber, lactulose, and polyethylene glycol-based laxatives. BEST PRACTICE ADVICE 6: Elective endoscopic procedures should be deferred until the postpartum period, whereas nonemergent but necessary procedures should ideally be performed in the second trimester. Pregnant patients with cirrhosis should undergo evaluation for, and treatment of, esophageal varices; upper endoscopy is suggested in the second trimester (if not performed within 1 year before conception) to guide consideration of nonselective β-blocker therapy or endoscopic variceal ligation. BEST PRACTICE ADVICE 7: In patients with inflammatory bowel disease, clinical remission before conception, during pregnancy, and in the postpartum period is essential for improving outcomes of pregnancy. Biologic agents should be continued throughout pregnancy and the postpartum period; use of methotrexate, thalidomide, and ozanimod must be stopped at least 6 months before conception. BEST PRACTICE ADVICE 8: Endoscopic retrograde cholangiopancreatography during pregnancy may be performed for urgent indications, such as choledocholithiasis, cholangitis, and some cases of gallstone pancreatitis. Ideally, endoscopic retrograde cholangiopancreatography should be performed during the second trimester, but if deferring the procedure may be detrimental to the health of the patient and fetus, a multidisciplinary team should be convened to decide on the advisability of endoscopic retrograde cholangiopancreatography. BEST PRACTICE ADVICE 9: Cholecystectomy is safe during pregnancy; a laparoscopic approach is the standard of care regardless of trimester, but ideally in the second trimester. BEST PRACTICE ADVICE 10: The diagnosis of intrahepatic cholestasis of pregnancy is based on a serum bile acid level >10 μmol/L in the setting of pruritus, typically during the second or third trimester. Treatment should be offered with oral ursodeoxycholic acid in a total daily dose of 10-15 mg/kg. BEST PRACTICE ADVICE 11: Management of liver diseases unique to pregnancy, such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy requires planning for delivery and timely evaluation for possible liver transplantation. Daily aspirin prophylaxis for patients at risk for pre-eclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome is advised beginning at week 12 of gestation. BEST PRACTICE ADVICE 12: In patients with chronic hepatitis B virus infection, serum hepatitis B virus DNA and liver biochemical test levels should be ordered. Patients not on treatment but with a serum hepatitis B virus DNA level >200,000 IU/mL during the third trimester of pregnancy should be considered for treatment with tenofovir disoproxil fumarate. BEST PRACTICE ADVICE 13: In patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should be continued at the lowest effective dose during pregnancy. Mycophenolate mofetil should not be administered during pregnancy.
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Affiliation(s)
- Shivangi Kothari
- Division of Gastroenterology and Hepatology, University of Rochester, Rochester, New York.
| | - Yalda Afshar
- Division of Maternal Fetal Medicine, University of California Los Angeles, Los Angeles, California
| | - Lawrence S Friedman
- Department of Medicine, Newton-Wellesley Hospital, Boston, Massachusetts; Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts; Department of Medicine, Harvard Medical School, Boston, Massachusetts; Department of Medicine, Tufts University School of Medicine, Boston, Massachusetts
| | - Joseph Ahn
- Division of Gastroenterology and Hepatology, Oregon Health and Science University, Portland, Oregon
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Hobson SR, Cohen ER, Gandhi S, Jain V, Niles KM, Roy-Lacroix MÈ, Wo BL. Guideline No. 452: Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2024; 46:102618. [PMID: 39089469 DOI: 10.1016/j.jogc.2024.102618] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
OBJECTIVE To summarize the current evidence and to make recommendations for the diagnosis and management of intrahepatic cholestasis of pregnancy. TARGET POPULATION Pregnant people with intrahepatic cholestasis of pregnancy. OPTIONS Diagnosing the condition using fasting or non-fasting bile acids, classifying disease severity, determining what treatment to offer, establishing how to monitor for antenatal fetal wellbeing, identifying when to perform elective birth. BENEFITS, HARMS, AND COSTS Individuals with intrahepatic cholestasis of pregnancy are at increased risk of adverse perinatal outcomes including preterm birth, neonatal respiratory distress and admission to a neonatal intensive care unit, with an increased risk of stillbirth when bile acid levels are ≥100 μmol/L. There is inequity in bile acid testing availability and timely access to results, along with uncertainly of how to treat, monitor. and ultimately deliver these pregnancies. Optimization of diagnostic and management protocols can improve maternal and fetal postnatal outcomes. EVIDENCE Medline, PubMed, Embase, and the Cochrane Library were searched from inception to March 2023, using medical subject headings (MeSH) and keywords related to pregnancy, intrahepatic cholestasis of pregnancy, bile acids, pruritis, ursodeoxycholic acid, and stillbirth. This document presents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations). INTENDED AUDIENCE Obstetric care providers, including obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, and radiologists. SOCIAL MEDIA ABSTRACT Intrahepatic cholestasis of pregnancy requires adequate diagnosis with non-fasting bile acid levels which guide optimal management and delivery timing. SUMMARY STATEMENTS RECOMMENDATIONS.
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Hobson SR, Cohen ER, Gandhi S, Jain V, Niles KM, Roy-Lacroix MÈ, Wo BL. Directive clinique n o 452 : Diagnostic et prise en charge de la cholestase intrahépatique de la grossesse. JOURNAL OF OBSTETRICS AND GYNAECOLOGY CANADA 2024; 46:102619. [PMID: 39089470 DOI: 10.1016/j.jogc.2024.102619] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
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Jalil S, Elfeki MA, Kiefer MK, Kuo YF, Singal AK. Waitlist and posttransplant outcomes of pregnancy-related acute liver failure in the United States. Liver Transpl 2024; 30:573-581. [PMID: 38108820 DOI: 10.1097/lvt.0000000000000319] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 12/08/2023] [Indexed: 12/19/2023]
Abstract
Data on the liver transplant (LT) outcomes of women with acute liver failure (ALF) due to liver diseases unique to pregnancy (P-ALF) are limited. Using United Network of Organ Sharing (UNOS) data (1987-2021), we analyzed waitlist and post-LT outcomes of ALF in women of childbearing age comparing P-ALF versus ALF due to liver diseases not unique to pregnancy. Baseline characteristics were compared between groups at the time of listing for LT. Of 3542 females aged 16-43 years and listed for LT for ALF, 84 (2%) listed for P-ALF were less likely to be Black (11 vs. 21%, p =0.033), have lower international normalized ratio (2.74 vs. 4.53 p <0.002), but more likely to have respiratory failure (56% vs. 41%, p <0.005), be on pressors (58% vs. 43%, p <0.005), and require dialysis (23% vs. 10%, p <0.001). The cumulative 90-day waitlist mortality (WLM) was lower in P-ALF vs. ALF due to liver diseases not unique to pregnancy (7.4 vs. 16.6%, p <0.001). Posttransplant survival rates at 5 years were similar (82% vs. 79%, p =0.89). In a Fine and Gray regression model controlled for listing year and Model for End-Stage Liver Disease score, 90-day WLM was lower in P-ALF with a sub-HR of 0.42 (95% CI: 0.19-0.94, p =0.035). Of 84 women with P-ALF and listed for LT, 45 listed for hemolysis-elevated liver enzymes-low platelets (HELLP) versus 39 for acute fatty liver of pregnancy had higher 90-day WLM (19.3% vs. 5.7% p <0.005). The 90-day WLM was about 10-fold higher in HELLP versus acute fatty liver of pregnancy with a sub-HR of 9.97 (95% CI: 1.64-60.55, p =0.013). In this UNOS database analysis of ALF among women of childbearing age, the waitlist outcome is better in women with P-ALF compared to women with ALF due to liver diseases not unique to pregnancy. Among women with P-ALF, the 90-day WLM is worse for HELLP versus acute fatty liver of pregnancy. Further studies are needed to improve the management of HELLP and prevent the development of ALF in this subgroup population.
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Affiliation(s)
- Sajid Jalil
- Department of Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Mohamed A Elfeki
- Department of Medicine, University of South Dakota Sanford School of Medicine, Sioux Falls, South Dakota, USA
- Department of Medicine, Avera McKennan University Hospital and Transplant Institute, Sioux Falls, Sioux Falls, SD, USA
| | - Miranda K Kiefer
- Department of Medicine, Maternal Fetal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio, USA
| | - Yong-Fang Kuo
- Department of Biostatistics, University of Texas Medical Branch, Galveston, Texas, USA
| | - Ashwani K Singal
- Department of Medicine, University of Louisville, Louisville, KY, USA
- Department of Medicine, Trager Transplant Center, Jewish Hospital, Louisville, Kentucky, USA
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Cui J, Zhai Q, Chen M, Yang Z. Genetically predicted lipids mediate the association between intrahepatic cholestasis of pregnancy and cardiovascular disease. Front Cardiovasc Med 2024; 11:1401010. [PMID: 38745758 PMCID: PMC11091286 DOI: 10.3389/fcvm.2024.1401010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2024] [Accepted: 04/18/2024] [Indexed: 05/16/2024] Open
Abstract
Introduction Intrahepatic cholestasis of pregnancy (ICP), the most prevalent liver disorder specific to pregnancy, affects approximately 1.5%-4% of pregnancies. However, the influence of ICP on cardiovascular disease (CVD), including hypertension (HTN) and coronary artery disease (CAD), has not been thoroughly investigated. Methods This study explores the causal relationship between ICP and CVD (HTN, CAD) using Mendelian Randomization (MR). Utilizing summary-level data from Genome-Wide Association Studies (GWAS), we applied the inverse-variance weighted (IVW) method, supplemented by sensitivity and reverse MR analyses, to ascertain robustness. Results Our findings reveal significant causal links, indicating ICP notably increases the risk of CVD (P = 0.001), hypertension (HTN, P = 0.024), and coronary artery disease (CAD, P = 0.039). A two-step MR analysis highlighted the mediation role of lipid profiles, with LDL, TC, and Apo-B contributing to increased CVD risk by 25.5%, 12.2%, and 21.3%, respectively. Additionally, HTN was identified as a mediator in the ICP-CAD association, accounting for a 14.5% mediation effect. Discussion The results underscore the genetic predisposition of ICP to elevate CVD risk and the critical mediating role of lipid levels, emphasizing the need for vigilant lipid monitoring and early intervention in individuals with ICP.
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Affiliation(s)
- Ji Cui
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qilong Zhai
- Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Mengjie Chen
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Zhu Yang
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
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Ren SJ, Feng JT, Xiang T, Liao CL, Zhou YP, Xuan RR. Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy. World J Hepatol 2024; 16:601-611. [PMID: 38689740 PMCID: PMC11056904 DOI: 10.4254/wjh.v16.i4.601] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 02/04/2024] [Accepted: 03/07/2024] [Indexed: 04/24/2024] Open
Abstract
BACKGROUND Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. AIM To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. METHODS Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. RESULTS Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). CONCLUSION Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.
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Affiliation(s)
- Shuai-Jun Ren
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo 315100, Zhejiang Province, China
| | - Jia-Ting Feng
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo 315100, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Ting Xiang
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo 315100, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Cai-Lian Liao
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo 315100, Zhejiang Province, China
- Health Science Center, Ningbo University, Ningbo 315211, Zhejiang Province, China
| | - Yu-Ping Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Ningbo University, Ningbo 315211, Zhejiang Province, China
- Institute of Digestive Disease, Ningbo University, Ningbo 315020, Zhejiang Province, China
| | - Rong-Rong Xuan
- Department of Obstetrics and Gynecology, The First Affiliated Hospital of Ningbo University, Ningbo 315100, Zhejiang Province, China.
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Venou TM, Vetsiou E, Varelas C, Daniilidis A, Psarras K, Koravou EE, Koutra M, Touloumenidou T, Tsolakidis V, Papalexandri A, Minti F, Mandala E, Dinas K, Vlachaki E, Gavriilaki E. Increased Complement Activation and Decreased ADAMTS13 Activity Are Associated with Genetic Susceptibility in Patients with Preeclampsia/HELLP Syndrome Compared to Healthy Pregnancies: An Observational Case-Controlled Study. J Pers Med 2024; 14:387. [PMID: 38673014 PMCID: PMC11051193 DOI: 10.3390/jpm14040387] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2024] [Revised: 03/13/2024] [Accepted: 04/02/2024] [Indexed: 04/28/2024] Open
Abstract
Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.
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Affiliation(s)
- Theodora-Maria Venou
- Hematological Laboratory, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece (E.V.); (V.T.)
| | - Evangelia Vetsiou
- Hematological Laboratory, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece (E.V.); (V.T.)
| | - Christos Varelas
- Hematology Department, Papanicolaou General Hospital, 57010 Thessaloniki, Greece; (C.V.); (E.-E.K.); (M.K.); (T.T.); (A.P.)
| | - Angelos Daniilidis
- 1st Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Papageorgiou General Hospital, 56429 Thessaloniki, Greece;
| | - Kyriakos Psarras
- 2nd Propedeutical Department of Surgery, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece;
| | - Evaggelia-Evdoxia Koravou
- Hematology Department, Papanicolaou General Hospital, 57010 Thessaloniki, Greece; (C.V.); (E.-E.K.); (M.K.); (T.T.); (A.P.)
| | - Maria Koutra
- Hematology Department, Papanicolaou General Hospital, 57010 Thessaloniki, Greece; (C.V.); (E.-E.K.); (M.K.); (T.T.); (A.P.)
| | - Tasoula Touloumenidou
- Hematology Department, Papanicolaou General Hospital, 57010 Thessaloniki, Greece; (C.V.); (E.-E.K.); (M.K.); (T.T.); (A.P.)
| | - Vasilis Tsolakidis
- Hematological Laboratory, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece (E.V.); (V.T.)
| | - Apostolia Papalexandri
- Hematology Department, Papanicolaou General Hospital, 57010 Thessaloniki, Greece; (C.V.); (E.-E.K.); (M.K.); (T.T.); (A.P.)
| | - Fani Minti
- Department of Medicine, School of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece;
| | - Evdokia Mandala
- 4th Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece;
| | - Konstantinos Dinas
- 2nd Department of Obstetrics and Gynecology, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece
| | - Efthymia Vlachaki
- Hematological Laboratory, 2nd Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece (E.V.); (V.T.)
| | - Eleni Gavriilaki
- 2nd Propedeutical Department of Internal Medicine, Aristotle University of Thessaloniki, Hippokration General Hospital, 54642 Thessaloniki, Greece;
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Fang ME, Peoples NA, Goulding AN, Tolcher MC. Hepatic encephalopathy precipitated by preeclampsia in the setting of cirrhosis: A case report. Case Rep Womens Health 2024; 41:e00587. [PMID: 38515998 PMCID: PMC10955193 DOI: 10.1016/j.crwh.2024.e00587] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Revised: 02/02/2024] [Accepted: 02/05/2024] [Indexed: 03/23/2024] Open
Abstract
Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications. A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved promptly post-delivery. Preeclampsia can trigger acute hepatic dysfunction, including hepatic encephalopathy, in the setting of previously compensated preexisting liver disease. Recognizing this association has important implications for management and treatment.
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Affiliation(s)
- Mary E. Fang
- Baylor College of Medicine, Houston, TX 77030, United States of America
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States of America
| | | | - Alison N. Goulding
- Baylor College of Medicine, Houston, TX 77030, United States of America
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States of America
| | - Mary C. Tolcher
- Baylor College of Medicine, Houston, TX 77030, United States of America
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, United States of America
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18
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Porrello G, Cannella R, Bernuau J, Agman A, Brancatelli G, Dioguardi Burgio M, Vilgrain V. Liver imaging and pregnancy: what to expect when your patient is expecting. Insights Imaging 2024; 15:66. [PMID: 38411871 PMCID: PMC10899155 DOI: 10.1186/s13244-024-01622-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Accepted: 01/07/2024] [Indexed: 02/28/2024] Open
Abstract
Liver diseases in pregnancy can be specific to gestation or only coincidental. In the latter case, the diagnosis can be difficult. Rapid diagnosis of maternal-fetal emergencies and situations requiring specialized interventions are crucial to preserve the maternal liver and guarantee materno-fetal survival. While detailed questioning of the patient and a clinical examination are highly important, imaging is often essential to reach a diagnosis of these liver diseases and lesions. Three groups of liver diseases may be observed during pregnancy: (1) diseases related to pregnancy: intrahepatic cholestasis of pregnancy, pre-eclampsia, eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, and acute fatty liver of pregnancy; (2) liver diseases that are more frequent during or exacerbated by pregnancy: acute herpes simplex hepatitis, Budd-Chiari syndrome, hemorrhagic hereditary telangiectasia, hepatocellular adenoma, portal vein thrombosis, and cholelithiasis; (3) coincidental conditions, including acute hepatitis, incidental focal liver lesions, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatocellular carcinoma, liver abscesses and parasitosis, and liver transplantation. Specific knowledge of the main imaging findings is required to reach an early diagnosis, for adequate follow-up, and to avoid adverse consequences in both the mother and the fetus.Critical relevance statement Pregnancy-related liver diseases are the most important cause of liver dysfunction in pregnant patients and, in pregnancy, even common liver conditions can have an unexpected turn. Fear of radiations should never delay necessary imaging studies in pregnancy.Key points• Pregnancy-related liver diseases are the most frequent cause of liver dysfunction during gestation.• Fear of radiation should never delay necessary imaging studies.• Liver imaging is important to assess liver emergencies and for the diagnosis and follow-up of any other liver diseases.• Common liver conditions and lesions may take an unexpected turn during pregnancy.• Pregnancy-specific diseases such as pre-eclampsia and HELLP syndrome must be rapidly identified. However, imaging should never delay delivery when it is considered to be urgent for maternal-fetal survival.
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Affiliation(s)
- Giorgia Porrello
- Service de Radiologie, AP-HP Nord, Hôpital Beaujon, Paris, Clichy, France.
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital "Paolo Giaccone", Palermo, Italy.
| | - Roberto Cannella
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital "Paolo Giaccone", Palermo, Italy
| | - Jacques Bernuau
- AP-HP Nord, Hôpital Beaujon, Service d'Hépatologie, Paris, Clichy, France
| | - Antoine Agman
- Service de Gynécologie obstétrique maternité, AP-HP Nord, Hôpital Beaujon, Paris, Clichy, France
| | - Giuseppe Brancatelli
- Department of Biomedicine, Neuroscience and Advanced Diagnostics (Bi.N.D.), University Hospital "Paolo Giaccone", Palermo, Italy
| | - Marco Dioguardi Burgio
- Service de Radiologie, AP-HP Nord, Hôpital Beaujon, Paris, Clichy, France
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, F-75018, Paris, France
| | - Valérie Vilgrain
- Service de Radiologie, AP-HP Nord, Hôpital Beaujon, Paris, Clichy, France
- Université Paris Cité, Inserm, Centre de recherche sur l'inflammation, F-75018, Paris, France
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19
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Beck CT. Survivors' Experiences of Hyperemesis Gravidarum. JOURNAL OF INFUSION NURSING 2023; 46:338-346. [PMID: 37920107 DOI: 10.1097/nan.0000000000000520] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2023]
Abstract
Hyperemesis gravidarum can result in life-threatening physical and psychological maternal morbidity, including severe dehydration, weight loss, electrolyte imbalance, depression, and suicidal ideation. The reported prevalence of hyperemesis gravidarum ranges from 0.3% to 3.6%. The purpose of this qualitative study was to investigate what blogs can tell us about women's experiences of hyperemesis gravidarum. Thirty-three blogs written by hyperemesis gravidarum survivors posted on Hyperemesis Australia's website were analyzed using Krippendorff's qualitative content analysis method. Clustering was used and yielded 6 themes: (1) debilitating physical and mental health problems: digging deep to persevere, (2) heartbreaking choices, (3) lack of understanding and dismissed, (4) so much guilt surrounding their unborn infant, (5) it takes a village to support women with hyperemesis gravidarum, and (6) warriors and survivors: giving back. Infusion nurses are in a perfect position to provide support and compassionate care for women who are repeatedly coming to the hospital for rehydration treatment. Infusion nurses can validate women's physical and emotional struggles with hyperemesis gravidarum and help to no longer make women feel stigmatized.
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Affiliation(s)
- Cheryl Tatano Beck
- School of Nursing, University of Connecticut, 231 Glenbrook Rd, Storrs, CT
- Cheryl Tatano Beck, DNSc, CNM, FAAN, is a Distinguished Professor at the University of Connecticut School of Nursing. She also holds a joint appointment in the School of Medicine Department of Obstetrics and Gynecology. She is a fellow in the American Academy of Nursing and inducted into the Sigma Theta Tau International Nurse Researcher Hall of Fame. For over 35 years, her program of research has focused on postpartum depression and posttraumatic stress disorder due to traumatic childbirth. She developed the Postpartum Depression Screening Scale from her series of qualitative studies
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20
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White SW. Intrahepatic cholestasis of pregnancy: Contemporary management. Aust N Z J Obstet Gynaecol 2023; 63:623-624. [PMID: 37775914 DOI: 10.1111/ajo.13753] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2023] [Accepted: 09/09/2023] [Indexed: 10/01/2023]
Affiliation(s)
- Scott W White
- The Western Australian Centre for Health Research for Women and Babies, The University of Western Australia, Perth, Western Australia, Australia
- Division of Obstetrics and Gynaecology, The University of Western Australia, Perth, Western Australia, Australia
- Maternal Fetal Medicine Service, King Edward Memorial Hospital, Perth, Western Australia, Australia
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21
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Dajti E, Bruni A, Barbara G, Azzaroli F. Diagnostic Approach to Elevated Liver Function Tests during Pregnancy: A Pragmatic Narrative Review. J Pers Med 2023; 13:1388. [PMID: 37763154 PMCID: PMC10532949 DOI: 10.3390/jpm13091388] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2023] [Revised: 09/09/2023] [Accepted: 09/15/2023] [Indexed: 09/29/2023] Open
Abstract
Liver disease is not uncommon during pregnancy and is associated with increased maternal and fetal/neonatal morbidity and mortality. Physiological changes during pregnancy, including a hyperestrogenic state, increase in circulating plasma volume and/or reduction in splanchnic vascular resistance, and hemostatic imbalance, may mimic or worsen liver disease. For the clinician, it is important to distinguish among the first presentation or exacerbation of chronic liver disease, acute liver disease non-specific to pregnancy, and pregnancy-specific liver disease. This last group classically includes conditions such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, liver disorders associated with the pre-eclampsia spectrum, and an acute fatty liver of pregnancy. All of these disorders often share pathophysiological mechanisms, symptoms, and laboratory findings (such as elevated liver enzymes), but a prompt and correct diagnosis is fundamental to guide obstetric conduct, reduce morbidity and mortality, and inform upon the risk of recurrence or development of other chronic diseases later on in life. Finally, the cause of elevated liver enzymes during pregnancy is unclear in up to 30-40% of the cases, and yet, little is known on the causes and mechanisms underlying these alterations, or whether these findings are associated with worse maternal/fetal outcomes. In this narrative review, we aimed to summarize pragmatically the diagnostic work-up and the management of subjects with elevated liver enzymes during pregnancy.
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Affiliation(s)
- Elton Dajti
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), 40138 Bologna, Italy; (A.B.); (G.B.); (F.A.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy
| | - Angelo Bruni
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), 40138 Bologna, Italy; (A.B.); (G.B.); (F.A.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy
| | - Giovanni Barbara
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), 40138 Bologna, Italy; (A.B.); (G.B.); (F.A.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy
| | - Francesco Azzaroli
- IRCCS Azienda Ospedaliero-Universitaria di Bologna, European Reference Network on Hepatological Diseases (ERN RARE-LIVER), 40138 Bologna, Italy; (A.B.); (G.B.); (F.A.)
- Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40138 Bologna, Italy
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22
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Cai QY, Li X, Yang Y, Luo X, Luo SJ, Xiong J, He ZY, Chen Y, Mou YW, Hu JY, Yang S, Lan X, Liu TH. Rational use of drugs to alleviate adverse outcomes caused by COVID-19 quarantine in women with intrahepatic cholestasis of pregnancy. Front Med (Lausanne) 2023; 10:1122873. [PMID: 37608824 PMCID: PMC10441112 DOI: 10.3389/fmed.2023.1122873] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 07/21/2023] [Indexed: 08/24/2023] Open
Abstract
Purpose This study aimed to investigate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether the rational use of drugs will change these impacts. Methods This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period. Results A total of 3,161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2,345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, fetal growth restriction, pre-eclampsia, preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid. Conclusion COVID-19 quarantine would increase the incidence of ICP and lead to adverse pregnancy outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should enhance their management and life guidance for women with ICP and speed up developing home quarantine guidelines.
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Affiliation(s)
- Qin-Yu Cai
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Xia Li
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Yin Yang
- Department of Infection Controlling Section, Women and Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Xin Luo
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Shu-Juan Luo
- Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Jing Xiong
- Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Zong-Yan He
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Yuan Chen
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Yi-Wei Mou
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Ji-Yuan Hu
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Shu Yang
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
| | - Xia Lan
- Department of Obstetrics and Gynecology, Women and Children's Hospital of Chongqing Medical University, Chongqing, China
| | - Tai-Hang Liu
- Department of Bioinformatics, The School of Basic Medicine, Chongqing Medical University, Chongqing, China
- The Joint International Research Laboratory of Reproduction and Development, Ministry of Education, Chongqing, China
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23
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Yang L, Meng Y, Shi Y, Fang H, Zhang L. Maternal hepatic immunology during pregnancy. Front Immunol 2023; 14:1220323. [PMID: 37457700 PMCID: PMC10348424 DOI: 10.3389/fimmu.2023.1220323] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Accepted: 06/20/2023] [Indexed: 07/18/2023] Open
Abstract
The liver plays pivotal roles in immunologic responses, and correct hepatic adaptations in maternal immunology are required during pregnancy. In this review, we focus on anatomical and immunological maternal hepatic adaptations during pregnancy, including our recent reports in this area. Moreover, we summarize maternal pregnancy-associated liver diseases, including hyperemesis gravidarum; intrahepatic cholestasis of pregnancy; preeclampsia, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome; and acute fatty liver of pregnancy. In addition, the latest information about the factors that regulate hepatic immunology during pregnancy are reviewed for the first time, including human chorionic gonadotropin, estrogen, progesterone, growth hormone, insulin like growth factor 1, oxytocin, adrenocorticotropic hormone, adrenal hormone, prolactin, melatonin and prostaglandins. In summary, the latest progress on maternal hepatic anatomy and immunological adaptations, maternal pregnancy-associated diseases and the factors that regulate hepatic immunology during pregnancy are discussed, which may be used to prevent embryo loss and abortion, as well as pregnancy-associated liver diseases.
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24
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Dalvi S. Spectrum of Liver: GI Disorders in Pregnancy. J Obstet Gynaecol India 2023; 73:102-106. [PMID: 37073229 PMCID: PMC10105798 DOI: 10.1007/s13224-023-01752-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2023] [Accepted: 03/10/2023] [Indexed: 04/20/2023] Open
Abstract
Pregnant women are affected by gastrointestinal and liver disorders. These may or may not be related to pregnancy. Unrelated conditions are pre-existent or coincidental during pregnancy. Pregnancy may promote symptoms/alter course of new or pre-existing disease resulting in complications only during pregnancy. This in turn can have adverse effect on clinical course affecting mother and fetus. The management remains same but its effect on mother and fetus needs to be kept in mind with pro-active treatment. Severe liver diseases though rare during pregnancy can occasionally be life threatening. Pregnancy after bariatric surgery/liver transplant is possible but with thorough counseling and needs multidisciplinary approach. Endoscopy for GI problems, if required can be carried out by gastroenterologist with special attention. Hence, this article, for quick reference to tackle GI and liver disorders in pregnancy.
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Affiliation(s)
- Sujata Dalvi
- Nowrosjee Wadia Maternity Hospital, Mumbai, India
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25
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Lin S, Ye MY, Fu QY, Pan CL, Liu YJ, Zheng LM, Hong Q, Chen YH. Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway. FASEB J 2023; 37:e22820. [PMID: 36801982 DOI: 10.1096/fj.202202126r] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/19/2023] [Accepted: 01/30/2023] [Indexed: 02/23/2023]
Abstract
Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11β-Hydroxysteroid dehydrogenase-2 (11β-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11β-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down-regulation of 11β-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis-induced placental dysfunction and subsequent FGR.
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Affiliation(s)
- Shuai Lin
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Meng-Ying Ye
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Qian-Yun Fu
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Chao-Lin Pan
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Ya-Jie Liu
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Li-Ming Zheng
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Qiang Hong
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China
| | - Yuan-Hua Chen
- School of Basic Medical Sciences, Anhui Medical University, Hefei, China.,Key Laboratory of Environmental Toxicology of Anhui Higher Education Institutes, Anhui Medical University, Hefei, China
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26
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Williamson C, Terrault N. Reply. Gastroenterology 2023; 164:311-312. [PMID: 36181836 DOI: 10.1053/j.gastro.2022.09.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2022] [Accepted: 09/21/2022] [Indexed: 01/31/2023]
Affiliation(s)
- Catherine Williamson
- Department of Women and Children's Health, King's College London, London, United Kingdom
| | - Norah Terrault
- Gastrointestinal and Liver Disease Division, University of Southern California, Los Angeles, California
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27
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Maringhini A, Maringhini M. Bile and Liver in Pregnancy: No One Split Apart What God Has Joined Together. Gastroenterology 2023; 164:310-311. [PMID: 35934063 DOI: 10.1053/j.gastro.2022.08.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2022] [Accepted: 08/02/2022] [Indexed: 01/31/2023]
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28
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Little SE, Catalano OA, Edlow AG, Shroff SG. Case 39-2022: A 31-Year-Old Woman with Postpartum Abdominal Pain and Fever. N Engl J Med 2022; 387:2367-2375. [PMID: 36546630 DOI: 10.1056/nejmcpc2211363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Affiliation(s)
- Sarah E Little
- From the Department of Obstetrics and Gynecology, Brigham and Women's Hospital (S.E.L.), the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (A.G.E.), and Pathology (S.G.S.), Massachusetts General Hospital, and the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (S.E.L., A.G.E.), and Pathology (S.G.S.), Harvard Medical School - all in Boston
| | - Onofrio A Catalano
- From the Department of Obstetrics and Gynecology, Brigham and Women's Hospital (S.E.L.), the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (A.G.E.), and Pathology (S.G.S.), Massachusetts General Hospital, and the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (S.E.L., A.G.E.), and Pathology (S.G.S.), Harvard Medical School - all in Boston
| | - Andrea G Edlow
- From the Department of Obstetrics and Gynecology, Brigham and Women's Hospital (S.E.L.), the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (A.G.E.), and Pathology (S.G.S.), Massachusetts General Hospital, and the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (S.E.L., A.G.E.), and Pathology (S.G.S.), Harvard Medical School - all in Boston
| | - Stuti G Shroff
- From the Department of Obstetrics and Gynecology, Brigham and Women's Hospital (S.E.L.), the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (A.G.E.), and Pathology (S.G.S.), Massachusetts General Hospital, and the Departments of Radiology (O.A.C.), Obstetrics and Gynecology (S.E.L., A.G.E.), and Pathology (S.G.S.), Harvard Medical School - all in Boston
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29
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Deng W, Zhang L, Du Q, Li Y, Chen J, Du L, Chen D. The association of serum total bile acid with new-onset hypertension during pregnancy. BMC Pregnancy Childbirth 2022; 22:879. [DOI: 10.1186/s12884-022-05211-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Accepted: 11/14/2022] [Indexed: 11/28/2022] Open
Abstract
Abstract
Background
There has been considerable interest in the interrelationship between the liver and hypertension. The relationship between serum total bile acid (TBA) and hypertension has been reported. Moreover, intrahepatic cholestasis of pregnancy was correlated to gestation hypertension. However, the association between maternal serum TBA level in the normal range and new-onset hypertension disorders during pregnancy remains unclear. The present study aimed to evaluate the relationship between maternal serum TBA level in the normal range and the risk, disease severity and adverse pregnancy outcomes of new-onset hypertension during pregnancy.
Method
Using the electronic medical records on all pregnant women from the Department of Obstetrics and Gynecology, Third Affiliated Hospital of Guangzhou Medical University, between 2014 and 2020, we conducted a retrospective cohort study of 2581 singleton pregnant women with maternal serum TBA levels in the normal range. Patients were grouped into the non-hypertension during pregnancy (1071), gestational hypertension (480) and preeclampsia (1030) groups.
Result
We found that maternal serum TBA levels were significantly higher in the preeclampsia and gestational hypertension groups than in the non-hypertension group (p < 0.01). Multiple logistic regression analysis showed that TBA level was independently and significantly associated with preeclampsia and gestational hypertension (odds ratio: 1.37, 95% confidence interval [CI]: 1.27–1.48, p = 0.001, odds ratio: 1.34, 95% confidence interval [CI]: 1.24–1.46, p = 0.005, respectively). Moreover, elevated TBA level was positively associated with the risk of severe PE and negatively with mild PE (p < 0.01). In addition, maternal serum TBA levels were negatively related to birth weight (p < 0.001).
Conclusions
These results suggest that maternal serum TBA in the normal range also might be a valuable biomarker for disease severity in preeclampsia and gestational hypertension. Additionally, our results also indicate associations of serum total bile acid levels in the normal range with an increased risk of fetal growth restriction and low birth weight among offspring. These results suggest that TBA could serve as a prognostic biomarker for new-onset hypertension during pregnancy.
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30
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Cooper KM, Colletta A, Asirwatham AM, Moore Simas TA, Devuni D. COVID-19 associated liver injury: A general review with special consideration of pregnancy and obstetric outcomes. World J Gastroenterol 2022; 28:6017-6033. [PMID: 36405386 PMCID: PMC9669825 DOI: 10.3748/wjg.v28.i42.6017] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2022] [Revised: 10/24/2022] [Accepted: 10/27/2022] [Indexed: 11/15/2022] Open
Abstract
Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Coronavirus disease 2019 (COVID-19) associated liver injury (COVALI) is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 infection. Despite profound clinical implications, its pathophysiology is poorly understood. Unfortunately, most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research, including pregnant individuals. This manuscript reviews: Clinical features of COVALI, leading theories of COVALI, and existing literature on COVALI during pregnancy, a topic not widely explored in the literature. Ultimately, we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome, and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.
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Affiliation(s)
- Katherine M. Cooper
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Alessandro Colletta
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Alison M. Asirwatham
- Department of Obstetrics and Gynecology, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Tiffany A. Moore Simas
- Department of Obstetrics and Gynecology, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
- Departments of Pediatrics, Psychiatry, and Population & Quantitative Health Sciences, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
| | - Deepika Devuni
- Department of Medicine, University of Massachusetts Chan Medical School, Worcester, MA 01605, United States
- Division of Gastroenterology and Hepatology, University of Massachusetts Chan Medical School, Worcester, MA 1605, United States
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