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Wang X, Xu C, Wang H, Du B, Wang Q, Li Z, Xu Z, Wang Z, Wang B, Ouyang F, Wang J, Sun K. Association of Maternal Whole Blood Selenium with Cardiac Structure at 4 years of Age:a prospective birth cohort study. J Nutr 2025:S0022-3166(25)00284-6. [PMID: 40368297 DOI: 10.1016/j.tjnut.2025.05.002] [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: 11/03/2024] [Revised: 03/18/2025] [Accepted: 05/07/2025] [Indexed: 05/16/2025] Open
Abstract
BACKGROUND Currently, little is known about the relationship between maternal blood selenium levels and offspring cardiac structure. OBJECTIVES This study aimed to evaluate the association of maternal whole blood selenium levels during early pregnancy with children's cardiac structure at 4 years of age. METHODS Using data from the Shanghai Birth Cohort, this study analyzed the data from 956 mother-child pairs. Multiple linear or logistic regressions and restricted cubic spline were used to explore the association of maternal whole blood selenium levels with offspring cardiac structure. RESULTS Low maternal selenium levels were associated with increased left ventricular posterior wall thickness at systole (LVPWs) (β = 0.29, 95%CI: 0.06, 0.53), left ventricular posterior wall thickness at diastole (LVPWd) (β = 0.17, 95%CI: 0.01, 0.31), and relative wall thickness (RWT) (β = 0.011, 95%CI: 0.003, 0.019) in male offspring. Moreover, maternal selenium showed a U-shape curve with left ventricular mass index (LVMI) (P for nonlinearity = 0.002), LVPWd (P for nonlinearity = 0.035), IVSd (P for nonlinearity = 0.006) and RWT (P for nonlinearity = 0.013) in male offspring. However, no significant association of structural changes was found in female offspring. Compared with offspring with medium maternal selenium levels, the increased risk of left ventricular hypertrophy (LVH) (OR = 4.14; 95% CI: 1.81, 9.45) was only found in male offspring with lower maternal selenium levels. CONCLUSIONS Low maternal selenium levels were associated with cardiac structural changes and higher LVH risk in preschool male offspring, while no correlation was found in female offspring.
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Affiliation(s)
- Xiaowen Wang
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Caifang Xu
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hualin Wang
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bowen Du
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qianchuo Wang
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhuoyan Li
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhikang Xu
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Zhi Wang
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Bo Wang
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fengxiu Ouyang
- Ministry of Education and Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jian Wang
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
| | - Kun Sun
- Department of Pediatric Cardiology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute for Developmental and Regenerative Cardiovascular Medicine, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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You Y, Qian Z, Jiang Y, Chen L, Wu D, Liu L, Zhang F, Ning X, Zhang Y, Xiao J. Insights into the pathogenesis of gestational and hepatic diseases: the impact of ferroptosis. Front Cell Dev Biol 2024; 12:1482838. [PMID: 39600338 PMCID: PMC11588751 DOI: 10.3389/fcell.2024.1482838] [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: 08/20/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
Ferroptosis, a distinct form of non-apoptotic cell death characterized by iron dependency and lipid peroxidation, is increasingly linked to various pathological conditions in pregnancy and liver diseases. It plays a critical role throughout pregnancy, influencing processes such as embryogenesis, implantation, and the maintenance of gestation. A growing body of evidence indicates that disruptions in these processes can precipitate pregnancy-related disorders, including pre-eclampsia (PE), gestational diabetes mellitus (GDM), and intrahepatic cholestasis of pregnancy (ICP). Notably, while ICP is primarily associated with elevated maternal serum bile acid levels, its precise etiology remains elusive. Oxidative stress induced by bile acid accumulation is believed to be a significant factor in ICP pathogenesis. Similarly, the liver's susceptibility to oxidative damage underscores the importance of lipid metabolism dysregulation and impaired iron homeostasis in the progression of liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), cholestatic liver injury, autoimmune hepatitis (AIH), acute liver injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). This review discusses the shared signaling mechanisms of ferroptosis in gestational and hepatic diseases, and explores recent advances in understanding the mechanisms of ferroptosis and its potential role in the pathogenesis of gestational and hepatic disorders, with the aim of identifying viable therapeutic targets.
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Affiliation(s)
- Yilan You
- Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Zhiwen Qian
- Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Ying Jiang
- Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, China
| | - Lingyan Chen
- Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Danping Wu
- Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, China
| | - Lu Liu
- Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, China
| | - Feng Zhang
- Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
| | - Xin Ning
- Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, China
| | - Yan Zhang
- Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
- Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, China
| | - Jianping Xiao
- Departments of Obstetrics and Gynecology, Wuxi Maternal and Child Healthcare Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, China
- Departments of Obstetrics and Gynecology, Wuxi Maternity and Child Healthcare Hospital, Women’s Hospital of Jiangnan University, Jiangnan University, Wuxi, China
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Ye X, Baker PN, Tong C. The updated understanding of advanced maternal age. FUNDAMENTAL RESEARCH 2024; 4:1719-1728. [PMID: 39734537 PMCID: PMC11670706 DOI: 10.1016/j.fmre.2023.09.013] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2023] [Revised: 06/29/2023] [Accepted: 09/21/2023] [Indexed: 12/31/2024] Open
Abstract
The rising rates of pregnancies associated with advanced maternal age (AMA) have created unique challenges for healthcare systems worldwide. The elevated risk of poor maternal outcomes among AMA pregnancies is only partially understood and hotly debated. Specifically, AMA is associated with reduced fertility and an increased incidence of pregnancy complications. Finding a balance between global fertility policy, socioeconomic development and health care optimization ultimately depends on female fertility. Therefore, there is an urgent need to develop technologies and identify effective interventions. Support strategies should include prepregnancy screening, intervention and postpartum maintenance. Although some reviews have considered the relationship between AMA and adverse pregnancy outcomes, no previous work has comprehensively considered the long-term health effects of AMA on mothers. In this review, we will begin by presenting the current knowledge of global health issues associated with AMA and the effects of advanced age on the female reproductive system, endocrine metabolism, and placental function. We will then discuss physiological alterations, pregnancy complications, and long-term health problems caused by AMA.
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Affiliation(s)
- Xuan Ye
- National Clinical Research Center for Child Health and Disorder, Children's Hospital of Chongqing Medical University, Chongqing 401122, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
| | - Philip N. Baker
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
- College of Life Sciences, University of Leicester, Leicester LE1 7RH, UK
| | - Chao Tong
- National Clinical Research Center for Child Health and Disorder, Children's Hospital of Chongqing Medical University, Chongqing 401122, China
- State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China
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Hague WB, Williamson C, Beuers U. Intrahepatic cholestasis of pregnancy: Introduction and overview 2024. Obstet Med 2024; 17:138-143. [PMID: 39262909 PMCID: PMC11384812 DOI: 10.1177/1753495x241265772] [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: 03/07/2024] [Accepted: 06/04/2024] [Indexed: 09/13/2024] Open
Abstract
Considerable progress has been made to explain the aetiology of intrahepatic cholestasis of pregnancy (ICP) and of the adverse pregnancy outcomes associated with high maternal total serum bile acids (TSBAs). The reported thresholds for non-fasting TSBA associated with the risk of stillbirth and spontaneous preterm birth can be used to identify pregnancies at risk of these adverse outcomes to decide on appropriate interventions and to give reassurance to women with lower concentrations of TSBA. Data also support the use of ursodeoxycholic acid to protect against the risk of spontaneous preterm birth. A previous history of ICP may be associated with higher rates of subsequent hepatobiliary disease: if there is a suspicion of underlying susceptibility, clinicians caring for women with ICP should screen for associated disorders or for genetic susceptibility and, where appropriate, refer for ongoing hepatology review.
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Affiliation(s)
- Wm Bill Hague
- Robinson Research Institute, The University of Adelaide, North Adelaide, Australia
| | | | - Ulrich Beuers
- Department of Gastroenterology and Hepatology and Tytgat Institute for Liver and Intestinal Research, Amsterdam University Medical Centres, Amsterdam, Netherlands
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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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Shan D, Chen Q, Xie Y, Dai S, Hu Y. Current understanding of essential trace elements in intrahepatic cholestasis of pregnancy. Biometals 2024; 37:943-953. [PMID: 38367126 DOI: 10.1007/s10534-024-00586-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2023] [Accepted: 01/19/2024] [Indexed: 02/19/2024]
Abstract
Trace elements are important components in the body and have fundamental roles in maintaining a healthy and balanced pregnancy process. Either deficiency or excess of trace elements, including selenium, iron, zinc, copper, and magnesium can lead to pregnancy complications. As a rare disorder during pregnancy of unknown aetiology, intrahepatic cholestasis of pregnancy (ICP) poses a significant risk to the fetus of perinatal mortality. ICP is a multifactorial complication of which the pathogenesis is still an enigma. Epidemiological studies have demonstrated the association of ICP with some trace elements. Evidence from retrospective studies in humans further revealed the possible contributing roles of trace elements in the pathogenesis of ICP. The published literature on the association of trace elements with ICP was reviewed. Recent advances in molecular biological techniques from animal studies have helped to elucidate the possible mechanisms by how these trace elements function in regulating oxidative reactions, inflammatory reactions and immune balance in the maternal-fetal interface, as well as the influence on hepato-intestinal circulation of bile acid. The scenario regarding the role of trace elements in the pathogenesis of ICP is still developing. The administration or depletion of these trace elements may have promising effects in alleviating the symptoms and improving the pregnancy outcomes of ICP.
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Affiliation(s)
- Dan Shan
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, South Renmin Road, Section 3, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Qian Chen
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, South Renmin Road, Section 3, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Yupei Xie
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, South Renmin Road, Section 3, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Siyu Dai
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, South Renmin Road, Section 3, Chengdu, 610041, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China
| | - Yayi Hu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, No. 20, South Renmin Road, Section 3, Chengdu, 610041, China.
- Key Laboratory of Birth Defects and Related Diseases of Women and Children, Ministry of Education, Sichuan University, Chengdu, 610041, China.
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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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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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Liu LW, Chen Y, Zhu LJ, Xu QX, Xu S, Ding Y, Yin B. A study on the relationship between gut microbiota and intrahepatic cholestasis of pregnancy. Heliyon 2024; 10:e25861. [PMID: 38384504 PMCID: PMC10878930 DOI: 10.1016/j.heliyon.2024.e25861] [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: 10/30/2023] [Revised: 02/04/2024] [Accepted: 02/05/2024] [Indexed: 02/23/2024] Open
Abstract
Objective Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with a high incidence of complications in the mid and late stages of gestation. This study investigates differences in the composition of intestinal flora among pregnant women diagnosed with ICP, employing Illumina MiSeq high-throughput sequencing technology. Methods This case-control study obtained patient data from the hospital information system (HIS) and the laboratory information system (LIS). Fecal samples were collected from 25 pregnant women who did not undergo intestinal preparation before delivery between December 2020 and March 2021. Whole-genome analysis was performed. PCR was used to amplify the 16S rRNA V3-V4 variable region, which was then sequenced. Alpha and beta diversity were computed, and the maternal intestinal flora's abundance and composition characteristics were analyzed. Differences in intestinal flora between the two sample groups were examined. Results Bacteroides and Proteobacteria exhibited positive correlations with TBIL and IBIL. Betaproteobacteria, Gammaproteobacteria, and Erysipeiotrichi showed positive correlations with TBIL, IBIL, and DBIL, while Lactobacillus, Delftia, and Odoribacter demonstrated positive correlations with ALT. Conclusion The ICP group displayed significantly higher levels of total bile acid and ALT compared to the control group. The intestinal flora composition comprised four primary phyla: Firmicutes, Actinobacteria, Bacteroidetes, and Proteobacteria. ICP patients exhibited a lower relative abundance of intestinal flora across different levels of community composition when compared to the control group. Specific correlations between certain intestinal flora and clinical liver parameters were identified.
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Affiliation(s)
- Li-wen Liu
- Department of Anesthesia, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning City, 530000, China
| | - Yan Chen
- Department of Obstetrical, Guangzhou Women and Children's Hospital Liuzhou Hospital, Liuzhou City, 545000, China
| | - Liu-jing Zhu
- Department of Obstetrical, Guangzhou Women and Children's Hospital Liuzhou Hospital, Liuzhou City, 545000, China
| | - Qun-xiang Xu
- Department of Breast, Guangzhou Women and Children's Hospital Liuzhou Hospital, Liuzhou City, 545000, China
| | - Shaolin Xu
- Department of Laboratory, Guangzhou Women and Children's Hospital Liuzhou Hospital, Liuzhou City, 545000, China
| | - Yanling Ding
- Department of Laboratory, Guangzhou Women and Children's Hospital Liuzhou Hospital, Liuzhou City, 545000, China
| | - Biao Yin
- Department of Eugenic Genetics, The Reproductive Hospital of Guangxi Zhuang Autonomous Region, Nanning City, 530000, China
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Guan L, Wang Y, Lin L, Zou Y, Qiu L. Variations in Blood Copper and Possible Mechanisms During Pregnancy. Biol Trace Elem Res 2024; 202:429-441. [PMID: 37777692 DOI: 10.1007/s12011-023-03716-x] [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: 04/09/2023] [Accepted: 05/24/2023] [Indexed: 10/02/2023]
Abstract
Copper (Cu), an essential trace element, is crucial for both the mother and fetus. Currently, an increasing number of studies have focused on blood copper levels during pregnancy. Studies have found that blood copper levels in pregnant women are higher than those in reproductive-age women, but the trend, mainly in the 2nd and 3rd trimester, is still controversial. Most studies showed that blood copper levels gradually increased during pregnancy, while some studies found that blood copper levels remained stable or even decreased in the 3rd trimester. The possible mechanisms of variations in blood copper during pregnancy include the influence of estrogen (hepatic uptake and excretion, ceruloplasmin synthesis, maternal-fetal transport, etc.), the interaction of other trace elements (Fe, Zn, etc.) and other factors. Among them, maternal-fetal copper transport caused by elevated estrogen may be the main reason for the inconsistencies observed in the 2nd and 3rd trimester during pregnancy. However, there are some mechanisms require further investigation. In the future, the trend and mechanisms of blood copper during pregnancy should be explored more deeply to help doctors better monitor copper status and detect copper abnormalities in time.
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Affiliation(s)
- Lihua Guan
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Yifei Wang
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Liling Lin
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Yutong Zou
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China
| | - Ling Qiu
- Department of Laboratory Medicine, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China.
- State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Peking Union Medical College & Chinese Academy of Medical Science, Beijing, 100730, People's Republic of China.
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11
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Yin N, Jiang X, Yu M, Yang Y, Ge H, Han TL, Qi H. The maternal hair metabolome is capable of discriminating intrahepatic cholestasis of pregnancy from uncomplicated pregnancy. Front Endocrinol (Lausanne) 2024; 14:1280833. [PMID: 38260149 PMCID: PMC10801165 DOI: 10.3389/fendo.2023.1280833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/21/2023] [Accepted: 12/18/2023] [Indexed: 01/24/2024] Open
Abstract
Introduction Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disease associated with elevated bile acids in the blood. Diagnosis typically only occurs after the manifestation of clinical symptoms and the metabolic mechanisms underlying its development remain unclear. The aim of this study was to investigate potential specific metabolites and the underlying metabolic changes occurring during the development of ICP in the maternal plasma and hair metabolomes of women diagnosed with either ICP or having a healthy pregnancy. Methods A total of 35 Chinese women with ICP and 42 healthy pregnancies were enrolled in our study. Plasma and hair samples, total bile acid levels (TBA), alanine transaminase levels (ALT), aspartate aminotransferase levels (AST), and additional clinical information were collected during the third trimester. Metabolites from maternal plasma and hair segments collected pre-conception and analyzed using gas chromatography-mass spectrometry (GC-MS). Results Three plasma metabolites (p < 0.05, q < 0.38) and 21 hair metabolites (p < 0.05, q < 0.05) were significantly different between ICP and healthy pregnancies. A combination of the eight most significant hair metabolites in a multivariate receiver operating characteristic curve model showed the best area under the curve (AUC) was 0.885, whereas the highest AUC using metabolites from plasma samples was only 0.74. Metabolic pathway analysis revealed 32 pathways were significantly (p and q values < 0.05) affected in the hair samples of patients with ICP. Pathways associated with glutathione metabolism and ABC transporters were affected. No metabolic pathways were significantly affected in plasma. Discussion Overall, this study showed that the hair metabolome could be more useful than the plasma metabolome for distinguishing ICP from normal pregnancy.
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Affiliation(s)
- Nanlin Yin
- Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- Center for Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Xiuping Jiang
- Center for Reproductive Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Muhua Yu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yang Yang
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Huisheng Ge
- Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
| | - Ting-Li Han
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
| | - Hongbo Qi
- Department of Obstetrics and Gynecology, Women and Children’s Hospital of Chongqing Medical University, Chongqing, China
- Joint International Research Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, China
- Chongqing Key Laboratory of Maternal and Fetal Medicine, Chongqing Medical University, Chongqing, China
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12
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Kaviani R, Chahal D, Chung MH, Yoshida EM. Prolonged and Recurrent Intrahepatic Cholestasis of Pregnancy. ACG Case Rep J 2023; 10:e01182. [PMID: 38025842 PMCID: PMC10651348 DOI: 10.14309/crj.0000000000001182] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2023] [Accepted: 09/19/2023] [Indexed: 12/01/2023] Open
Abstract
Intrahepatic cholestasis of pregnancy is one of the most common disorders of pregnancy, which typically resolves in the postpartum period. Intrahepatic cholestasis is characterized by elevated bile acid levels that present as pruritus. The maternal clinical significance of recurrent and prolonged cholestasis is unknown. We discuss the longest reported case of postpartum cholestasis of 125 weeks.
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Affiliation(s)
- Rojin Kaviani
- Division of Gastroenterology, University of Alberta, Alberta, Canada
| | - Daljeet Chahal
- Division of Gastroenterology, Division of Liver Transplant, Vancouver Coastal Health, Vancouver, British Columbia, Canada
| | - Michelle Ho Chung
- Department of Pharmacy, Vancouver Coastal Health, Vancouver, British Columbia, Canada
| | - Eric M. Yoshida
- Division of Gastroenterology, Division of Liver Transplant, Vancouver Coastal Health, Vancouver, British Columbia, Canada
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13
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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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14
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Li J, Chen J, Lee PMY, Zhang J, Li F, Ren T. Familial clustering of intrahepatic cholestasis of pregnancy: A nationwide population-based study in Denmark. Hepatology 2023; 78:389-396. [PMID: 36815353 DOI: 10.1097/hep.0000000000000328] [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: 08/05/2022] [Accepted: 01/12/2023] [Indexed: 02/24/2023]
Abstract
BACKGROUND AND AIMS Genetics plays a role in the pathogenesis of intrahepatic cholestasis of pregnancy (ICP); however, empirical evidence on familial clustering of ICP is scarce. We aimed to assess the extent of familial recurrence of ICP. APPROACH AND RESULTS This population-based cohort study included all 668,461 primiparous women who gave birth between 1995 and 2018 in Denmark. Women diagnosed with ICP were included to the index cohort. Kinship with index women was determined with the Danish Civil Registration System. Log-binomial regression was used to calculate the relative recurrence risk (RRR) of ICP in relatives of index women. A total of 6722 (1.0%) primiparous women were diagnosed with ICP. In co-twins (n=57), first-degree (n=2279), second-degree (n=1373), and third-degree (n=1758) relatives of the index women, the incidence of ICP reached 5.3%, 2.6%, 0.7%, and 1.4%, respectively, corresponding to adjusted RRRs of 4.82 (95% CI, 1.60-14.48), 2.54 (1.98-3.26), 0.81 (0.44-1.51), and 1.15 (0.77-1.71), respectively. The first-degree relatives of women who had recurrent ICP or first-trimester ICP seemed to be at higher risks [RRR, 4.30 (2.85-6.48), 3.04 (1.93-4.77), respectively]. A minor increased risk was observed in nonbiological relatives [RRR, 1.35 (1.05-1.73); n=4274, including women's full-brothers' partner and women's husbands' full sisters]. CONCLUSIONS Co-twins and first-degree relatives of ICP patients were at ~5- and ~2.5-fold increased risk of ICP, respectively. No increased risk was observed in second-degree and third-degree relatives. Recurrent ICP and first-trimester ICP might indicate a higher degree of family clustering. Further investigation is needed to investigate the increased risk of ICP in nonbiological relatives.
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Affiliation(s)
- Jiong Li
- State Key Laboratory of Reproductive Medicine, Department of Epidemiology, Nanjing Medical University, Nanjing, China
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Jiawen Chen
- Department of Dermatology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Priscilla Ming Yi Lee
- Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
- Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Jun Zhang
- Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Fei Li
- Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Developmental and Behavioural Paediatric & Child Primary Care, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Tai Ren
- Ministry of Education - Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
- Department of Developmental and Behavioural Paediatric & Child Primary Care, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
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15
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Xie S, Wei S, Ma X, Wang R, He T, Zhang Z, Yang J, Wang J, Chang L, Jing M, Li H, Zhou X, Zhao Y. Genetic alterations and molecular mechanisms underlying hereditary intrahepatic cholestasis. Front Pharmacol 2023; 14:1173542. [PMID: 37324459 PMCID: PMC10264785 DOI: 10.3389/fphar.2023.1173542] [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: 03/03/2023] [Accepted: 05/16/2023] [Indexed: 06/17/2023] Open
Abstract
Hereditary cholestatic liver disease caused by a class of autosomal gene mutations results in jaundice, which involves the abnormality of the synthesis, secretion, and other disorders of bile acids metabolism. Due to the existence of a variety of gene mutations, the clinical manifestations of children are also diverse. There is no unified standard for diagnosis and single detection method, which seriously hinders the development of clinical treatment. Therefore, the mutated genes of hereditary intrahepatic cholestasis were systematically described in this review.
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Affiliation(s)
- Shuying Xie
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Shizhang Wei
- Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Health Science Center, Peking University, Beijing, China
| | - Xiao Ma
- Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ruilin Wang
- Department of Pharmacy, 5th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Tingting He
- Department of Pharmacy, 5th Medical Center of Chinese PLA General Hospital, Beijing, China
| | - Zhao Zhang
- Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Ju Yang
- Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jiawei Wang
- Pharmacy College, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Lei Chang
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
| | - Manyi Jing
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Haotian Li
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Xuelin Zhou
- Department of Pharmacology, School of Basic Medical Sciences, Capital Medical University, Beijing, China
| | - Yanling Zhao
- School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
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16
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Xu J, Zhou F, Wang X, Mo C. Role of ferroptosis in pregnancy related diseases and its therapeutic potential. Front Cell Dev Biol 2023; 11:1083838. [PMID: 36968201 PMCID: PMC10031498 DOI: 10.3389/fcell.2023.1083838] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2022] [Accepted: 02/20/2023] [Indexed: 03/11/2023] Open
Abstract
Ferroptosis is a form of regulated cell death characterized by iron overload, overwhelming lipid peroxidation, and disruption of antioxidant systems. Emerging evidence suggests that ferroptosis is associated with pregnancy related diseases, such as spontaneous abortion, pre-eclampsia, gestational diabetes mellitus, intrahepatic cholestasis of pregnancy, and spontaneous preterm birth. According to these findings, inhibiting ferroptosis might be a potential option to treat pregnancy related diseases. This review summarizes the mechanisms and advances of ferroptosis, the pathogenic role of ferroptosis in pregnancy related diseases and the potential medicines for its treatment.
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Affiliation(s)
- Jinfeng Xu
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- West China School of Medicine, Sichuan University, Chengdu, China
| | - Fan Zhou
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
| | - Xiaodong Wang
- Department of Obstetrics and Gynecology, West China Second University Hospital, Sichuan University, Chengdu, China
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
- *Correspondence: Chunheng Mo, ; Xiaodong Wang,
| | - Chunheng Mo
- Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, West China Second University Hospital, Sichuan University, Chengdu, China
- *Correspondence: Chunheng Mo, ; Xiaodong Wang,
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17
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Li C, Yu JL, Xu JJ, He YC, Qin KZ, Chen L, Huang HF, Wu YT. Interactive effects of ambient air pollution and sunshine duration on the risk of intrahepatic cholestasis of pregnancy. ENVIRONMENTAL RESEARCH 2022; 215:114345. [PMID: 36116502 DOI: 10.1016/j.envres.2022.114345] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Revised: 09/10/2022] [Accepted: 09/12/2022] [Indexed: 06/15/2023]
Abstract
INTRODUCTION While the associations among ambient pollutants and various pregnancy complications are well documented, the effect of ambient pollutants on intrahepatic cholestasis of pregnancy (ICP) has not been examined. This study aimed to explore the effects of ambient pollutants and sunshine duration on ICP. METHODS The study enrolled 169,971 pregnant women who delivered between 2015 and 2020 in two hospitals. The associations between ICP and exposure to ambient pollutants and sunshine duration, averaged throughout different periods (including the 3 months before conception, 1st trimester and 2nd trimester), were estimated using a generalized linear model. The interaction effects of ambient pollutants and sunshine duration on ICP were estimated. RESULTS The fitted curves for ICP incidence were similar to the temporal trends of PM2.5, PM10, SO2, CO and NO2 but not that of O3. The risk of ICP was significantly elevated following a 10-μg/m3 increase in PM2.5 (aOR [adjusted odds ratio] = 1.057, 95% CI [confidence interval]: 1.017-1.099) and PM10 (aOR = 1.043, 95% CI: 1.013-1.074) and a 1-h decrease in sunshine duration (aOR = 1.039, 95% CI: 1.011-1.068) during the 3 months before conception. In the second trimester, a 1-μg/m3 increase in the concentration of SO2 was associated with an increased risk of ICP (aOR = 1.011, 95% CI: 1.001-1.021). Increased concentrations of PM2.5 and PM10 had interactive effects with reduced sunshine duration during the 3 months before conception on increasing the risk of ICP. CONCLUSIONS Exposure to PM2.5 and PM10 during the 3 months before conception and exposure to SO2 in the second trimester were associated with an increased ICP risk. Reduced sunshine duration had an interactive effect with increased concentrations of PM2.5 and PM10 during the 3 months before conception on the occurrence of ICP.
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Affiliation(s)
- Cheng Li
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Jia-Le Yu
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - Jing-Jing Xu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Yi-Chen He
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Kai-Zhou Qin
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China
| | - Lei Chen
- International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
| | - He-Feng Huang
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China; International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
| | - Yan-Ting Wu
- Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
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18
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Abdelhafez MMA, Ahmed KAM, Than WW, Baharuddin DMP, Kadir F, Jeffree S, Hayati MF, Daud MNBM, Eldiastey AM, Tay KX. Intrahepatic cholestasis of pregnancy: from an obstetrician point of view. J OBSTET GYNAECOL 2022; 42:2550-2557. [PMID: 35666947 DOI: 10.1080/01443615.2022.2081801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is the commonest among the specific dermatoses of pregnancy. The disease is characterised by intense pruritus and specifically by elevated bile acid levels and owing to the rarity of data published in this context, the disease carries a great challenge in both diagnosis and management. The disease is associated with significant maternal as well as perinatal adverse effects, hence, this article aims at improving the knowledge of the women's health carers with the up-to-date and evidence-based, whenever possible, recommendations while managing patients with ICP.
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Affiliation(s)
- Mohsen M A Abdelhafez
- Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | - Karim A M Ahmed
- Department of Dermatology, Helios Saint Johannes Klinikum, Duisburg, Germany
| | - Win Win Than
- Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | - Dg Marshitah Pg Baharuddin
- Department of Obstetrics and Gynaecology, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | - Fairrul Kadir
- Department of Emergency Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | - Saffree Jeffree
- Department of Public Health Medicine, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | - Mohammad Firdaus Hayati
- Department of Surgery, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | - Mohd Nazri Bin Mohd Daud
- Department of Public Health Medicine, Faculty of Medicine and Health Sciences, Family Medicine Unit, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
| | | | - Kai Xin Tay
- Faculty of Business, Economic, and Accountancy, Universiti Malaysia Sabah, Kota Kinabalu, Malaysia
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19
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Dixon PH, Levine AP, Cebola I, Chan MMY, Amin AS, Aich A, Mozere M, Maude H, Mitchell AL, Zhang J, Chambers J, Syngelaki A, Donnelly J, Cooley S, Geary M, Nicolaides K, Thorsell M, Hague WM, Estiu MC, Marschall HU, Gale DP, Williamson C. GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements. Nat Commun 2022; 13:4840. [PMID: 35977952 PMCID: PMC9385867 DOI: 10.1038/s41467-022-29931-z] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2020] [Accepted: 04/08/2022] [Indexed: 12/15/2022] Open
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5-2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility.
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Affiliation(s)
- Peter H Dixon
- Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK
| | - Adam P Levine
- Department of Renal Medicine, University College London, London, UK
- Research Department of Pathology, University College London, London, UK
| | - Inês Cebola
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Melanie M Y Chan
- Department of Renal Medicine, University College London, London, UK
| | - Aliya S Amin
- Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK
| | - Anshul Aich
- Department of Renal Medicine, University College London, London, UK
| | - Monika Mozere
- Department of Renal Medicine, University College London, London, UK
| | - Hannah Maude
- Section of Genetics and Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Alice L Mitchell
- Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK
| | - Jun Zhang
- Department of Renal Medicine, University College London, London, UK
- Division of Nephrology, Department of Medicine, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China
| | - Jenny Chambers
- ICP Support, 69 Mere Green Road, Sutton Coldfield, UK
- Women's Health Research Centre, Imperial College London, London, UK
| | - Argyro Syngelaki
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
| | | | | | | | - Kypros Nicolaides
- Harris Birthright Research Centre for Fetal Medicine, King's College Hospital, London, UK
| | | | - William M Hague
- Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
| | | | - Hanns-Ulrich Marschall
- Department of Molecular and Clinical Medicine/Wallenberg Laboratory, University of Gothenburg, Gothenburg, Sweden
| | - Daniel P Gale
- Department of Renal Medicine, University College London, London, UK
| | - Catherine Williamson
- Department of Women and Children's Health, School of Life Course Sciences, King's College London, London, UK.
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20
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Liu W, Wang Q, Chang J, Bhetuwal A, Bhattarai N, Ni X. Circulatory Metabolomics Reveals the Association of the Metabolites With Clinical Features in the Patients With Intrahepatic Cholestasis of Pregnancy. Front Physiol 2022; 13:848508. [PMID: 35899031 PMCID: PMC9309339 DOI: 10.3389/fphys.2022.848508] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 06/08/2022] [Indexed: 11/13/2022] Open
Abstract
Objective: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse pregnancy to the mother and fetus. As yet, the metabolic profiles and the association of the clinical features remain obscure. Methods: Fifty-seven healthy pregnant women and 52 patients with ICP were recruited in this study. Plasma samples were collected from pregnancies who received prenatal care between 30 and 36 weeks. Untargeted metabolomics to portray the metabolic profiles were performed by LC/MS. Multivariate combined with the univariate analysis was performed to screen out differential metabolites between the ICP and control groups. A de-biased sparse partial correlation (DSPC) network analysis of differential metabolites was conducted to explore the potential mutual regulation among metabolites on the basis of de-sparsified graphical lasso modeling. The pathway analysis was carried out using MetaboAnalyst. Linear regression and Pearson correlation analysis was applied to analyze correlations of bile acid levels, metabolites, newborn weights, and pregnancy outcomes in ICP patients. Results: Conspicuous metabolic changes and choreographed metabolic profiles were disclosed: 125 annotated metabolites and 18 metabolic pathways were disturbed in ICP patients. DSPC networks indicated dense interactions among amino acids and their derivatives, bile acids, carbohydrates, and organic acids. The levels of total bile acid (TBA) were increased in ICP patients with meconium-stained amniotic fluid (MSAF) compared with those without MSAF. An abnormal tryptophan metabolism, elevated long chain saturated fatty acids and estrone sulfate levels, and a low-antioxidant capacity were relevant to increased bile acid levels. Newborn weights were significantly associated with the levels of bile acids and some metabolites of amino acids. Conclusion: Our study revealed the metabolomic profiles in circulation and the correlation of the metabolites with clinical features in ICP patients. Our data suggest that disturbances in metabolic pathways might be associated with adverse pregnancy outcomes.
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Affiliation(s)
- Wenhu Liu
- Department of Gynecology and Obstetrics, International Collaborative Research Center for Medical Metabolomics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, China
- School of Pharmacy, School of Basic Medical Sciences and Forensic Medical, North Sichuan Medical College, Nanchong, China
| | - Qiang Wang
- Department of Laboratory Medicine, Translational Medicine Research Center, North Sichuan Medical College, Nanchong, China
- Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jinxia Chang
- School of Pharmacy, School of Basic Medical Sciences and Forensic Medical, North Sichuan Medical College, Nanchong, China
| | - Anup Bhetuwal
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Nisha Bhattarai
- Department of Radiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Xin Ni
- Department of Gynecology and Obstetrics, International Collaborative Research Center for Medical Metabolomics, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital Central South University, Changsha, China
- *Correspondence: Xin Ni,
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21
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Liu ZZ, Sun JH, Wang WJ. Gut microbiota in gastrointestinal diseases during pregnancy. World J Clin Cases 2022; 10:2976-2989. [PMID: 35647135 PMCID: PMC9082698 DOI: 10.12998/wjcc.v10.i10.2976] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Revised: 07/18/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Gut microbiota (GM) is a micro-ecosystem composed of all microorganisms in the human intestine. The interaction between GM and the host plays an important role in maintaining normal physiological functions in the host. Dysbiosis of the GM may cause various diseases. GM has been demonstrated to be associated with human health and disease, and changes during individual development and disease. Pregnancy is a complicated physiological process. Hormones, the immune system, metabolism, and GM undergo drastic changes during pregnancy. Gastrointestinal diseases during pregnancy, such as hepatitis, intrahepatic cholestasis of pregnancy, and pre-eclampsia, can affect both maternal and fetal health. The dysregulation of GM during pregnancy may lead to a variety of diseases, including gastrointestinal diseases. Herein, we review recent research articles on GM in pregnancy-related gastrointestinal diseases, discuss the interaction of the GM with the host under normal physiological conditions, gastrointestinal diseases, and pregnancy-specific disorders. As more attention is paid to reproductive health, the pathogenic mechanism of GM in gastrointestinal diseases during pregnancy will be further studied to provide a theoretical basis for the use of probiotics to treat these diseases.
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Affiliation(s)
- Zhong-Zhen Liu
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
| | - Jing-Hua Sun
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
- College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China
| | - Wen-Jing Wang
- BGI-Shenzhen, Shenzhen 518083, Guangdong Province, China
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Huri M, Seravalli V, Lippi C, Tofani L, Galli A, Petraglia F, Di Tommaso M. Intrahepatic cholestasis of pregnancy - Time to redefine the reference range of total serum bile acids: A cross-sectional study. BJOG 2022; 129:1887-1896. [PMID: 35373886 PMCID: PMC9543426 DOI: 10.1111/1471-0528.17174] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Revised: 03/21/2022] [Accepted: 03/28/2022] [Indexed: 12/02/2022]
Abstract
Objective To establish pregnancy‐specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations. Design Cross‐sectional study. Setting Tertiary‐care university hospital. Population Healthy pregnant women at term admitted to the Obstetrics Department over a period of 1 year. Exclusion criteria were an established diagnosis of intrahepatic cholestasis of pregnancy (ICP) or any coexisting condition of increased risk for ICP. Methods Both fasting (after 8–14 h of fasting) and postprandial (2 h after meal) TSBA concentrations were measured in 612 women (with 528 fasting samples and 377 postprandial samples) by automated enzymatic spectrophotometric assay. Main outcome measures Fasting and postprandial TSBA concentrations in 612 women. Results Reference intervals of 4.4–14.1 μmol/L for fasting TSBA and 4.7–20.2 μmol/L for postprandial TSBA were established. The postprandial values were significantly higher than the fasting values, with a median increase of 1.0 μmol/L (p < 0.0001). A correlation between fasting TSBA concentrations and postprandial concentrations was found, as well as correlations with fetal sex, parity and assisted reproductive technologies. A seasonal pattern was noticed for both fasting and postprandial TSBA, with the highest values measured in the winter season (p < 0.01 and 0.02, respectively) Conclusions Normal pregnancy is associated with mild hypercholanaemia, and therefore a higher threshold should be considered for the diagnosis of ICP. We suggest using the upper reference limits observed in our healthy pregnant population (14 μmol/L for fasting TSBA and 20 μmol/L for postprandial TSBA). As the fasting measurement is more specific for the diagnosis, and the postprandial measurement is essential for the assessment of severity, it is recommended to measure both values rather than use random sampling. Tweetable abstract Normal pregnancy is associated with mild hypercholanaemia, a higher threshold should be considered for the diagnosis of ICP. Normal pregnancy is associated with mild hypercholanaemia, a higher threshold should be considered for the diagnosis of ICP. Linked article: This article is commented on by Ovadia et al., pp. 1897–1898. in this issue. To view this minicommentary visit https://doi.org/10.1111/1471‐0528.17171
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Affiliation(s)
- Mor Huri
- Obstetrics and Gynaecology Unit, Department of Health Sciences, University of Florence, Florence, Italy
| | - Viola Seravalli
- Obstetrics and Gynaecology Unit, Department of Health Sciences, University of Florence, Florence, Italy
| | - Camilla Lippi
- Obstetrics and Gynaecology Unit, Department of Health Sciences, University of Florence, Florence, Italy
| | - Lorenzo Tofani
- Department of Statistics, Computer Science, Applications, University of Florence, Florence, Italy
| | - Andrea Galli
- Gastroenterology Unit, Department of Experimental and Clinical Biochemical Sciences, University of Florence, Florence, Italy
| | - Felice Petraglia
- Obstetrics and Gynaecology Unit, Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
| | - Mariarosaria Di Tommaso
- Obstetrics and Gynaecology Unit, Department of Health Sciences, University of Florence, Florence, Italy
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Zu Y, Yang J, Zhang C, Liu D. The Pathological Mechanisms of Estrogen-Induced Cholestasis: Current Perspectives. Front Pharmacol 2021; 12:761255. [PMID: 34819862 PMCID: PMC8606790 DOI: 10.3389/fphar.2021.761255] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Accepted: 10/26/2021] [Indexed: 12/31/2022] Open
Abstract
Estrogens are steroid hormones with a wide range of biological activities. The excess of estrogens can lead to decreased bile flow, toxic bile acid (BA) accumulation, subsequently causing intrahepatic cholestasis. Estrogen-induced cholestasis (EIC) may have increased incidence during pregnancy, and within women taking oral contraception and postmenopausal hormone replacement therapy, and result in liver injury, preterm birth, meconium-stained amniotic fluid, and intrauterine fetal death in pregnant women. The main pathogenic mechanisms of EIC may include deregulation of BA synthetic or metabolic enzymes, and BA transporters. In addition, impaired cell membrane fluidity, inflammatory responses and change of hepatocyte tight junctions are also involved in the pathogenesis of EIC. In this article, we review the role of estrogens in intrahepatic cholestasis, and outlined the mechanisms of EIC, providing a greater understanding of this disease.
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Affiliation(s)
- Yue Zu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Jinyu Yang
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Chengliang Zhang
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Dong Liu
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Islam S, Bhowmik S, Hossain MK, Nordin N, Rahman M, Ahmmed MK, Parvin A, Hossain MA. Tilapia from Most of the Sources in Bangladesh are Safe for Human Consumption: A Hazard Index (HI) Based Study on Heavy Metals. JOURNAL OF AQUATIC FOOD PRODUCT TECHNOLOGY 2021. [DOI: 10.1080/10498850.2021.1963377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Shabiha Islam
- Department of Fisheries and Marine Science, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Shuva Bhowmik
- Department of Fisheries and Marine Science, Noakhali Science and Technology University, Noakhali, Bangladesh
| | - Md. Kamal Hossain
- Soil and Environment Research Section, Biological Research Division, BCSIR Laboratories, Bangladesh Council of Scientific and Industrial Research, Dhaka, Bangladesh
| | - Noordiana Nordin
- Laboratory of Food Safety and Food Integrity, Institute of Tropical Agriculture and Food Security, Universiti Putra Malaysia, Serdang, Malaysia
| | - Mahabubur Rahman
- Department of Fisheries and Marine Science, Noakhali Science and Technology University, Noakhali, Bangladesh
- School of Veterinary and Life Sciences, Murdoch University, Perth, Australia
| | - Mirja Kaizer Ahmmed
- Department of Food Science, University of Otago, Dunedin, New Zealand
- Department of Fishing and Post-harvest Technology, Faculty of Fisheries, Chittagong Veterinary and Animal Sciences University, Chittagong, Bangladesh
| | - Afroza Parvin
- Soil and Environment Research Section, Biological Research Division, BCSIR Laboratories, Bangladesh Council of Scientific and Industrial Research, Dhaka, Bangladesh
| | - Md. Abul Hossain
- Department of Fisheries and Marine Science, Noakhali Science and Technology University, Noakhali, Bangladesh
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Gijbels E, Pieters A, De Muynck K, Vinken M, Devisscher L. Rodent models of cholestatic liver disease: A practical guide for translational research. Liver Int 2021; 41:656-682. [PMID: 33486884 PMCID: PMC8048655 DOI: 10.1111/liv.14800] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 01/08/2021] [Accepted: 01/15/2021] [Indexed: 12/12/2022]
Abstract
Cholestatic liver disease denotes any situation associated with impaired bile flow concomitant with a noxious bile acid accumulation in the liver and/or systemic circulation. Cholestatic liver disease can be subdivided into different types according to its clinical phenotype, such as biliary atresia, drug-induced cholestasis, gallstone liver disease, intrahepatic cholestasis of pregnancy, primary biliary cholangitis and primary sclerosing cholangitis. Considerable effort has been devoted to elucidating underlying mechanisms of cholestatic liver injuries and explore novel therapeutic and diagnostic strategies using animal models. Animal models employed according to their appropriate applicability domain herein play a crucial role. This review provides an overview of currently available in vivo animal models, fit-for-purpose in modelling different types of cholestatic liver diseases. Moreover, a practical guide and workflow is provided which can be used for translational research purposes, including all advantages and disadvantages of currently available in vivo animal models.
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Affiliation(s)
- Eva Gijbels
- Department of In Vitro Toxicology and Dermato‐CosmetologyVrije Universiteit BrusselBrusselsBelgium,Gut‐Liver Immunopharmacology Unit, Basic and Applied Medical SciencesLiver Research Center GhentFaculty of Medicine and Health SciencesGhent UniversityGhentBelgium
| | - Alanah Pieters
- Department of In Vitro Toxicology and Dermato‐CosmetologyVrije Universiteit BrusselBrusselsBelgium
| | - Kevin De Muynck
- Gut‐Liver Immunopharmacology Unit, Basic and Applied Medical SciencesLiver Research Center GhentFaculty of Medicine and Health SciencesGhent UniversityGhentBelgium,Hepatology Research UnitInternal Medicine and PaediatricsLiver Research Center GhentFaculty of Medicine and Health SciencesGhent UniversityGhentBelgium
| | - Mathieu Vinken
- Department of In Vitro Toxicology and Dermato‐CosmetologyVrije Universiteit BrusselBrusselsBelgium
| | - Lindsey Devisscher
- Gut‐Liver Immunopharmacology Unit, Basic and Applied Medical SciencesLiver Research Center GhentFaculty of Medicine and Health SciencesGhent UniversityGhentBelgium
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26
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Li R, Chen X, Liu Z, Chen Y, Liu C, Ye L, Xiao L, Yang Z, He J, Wang WJ, Qi H. Characterization of gut microbiota associated with clinical parameters in intrahepatic cholestasis of pregnancy. BMC Gastroenterol 2020; 20:395. [PMID: 33225888 PMCID: PMC7682054 DOI: 10.1186/s12876-020-01510-w] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2019] [Accepted: 10/21/2020] [Indexed: 12/20/2022] Open
Abstract
Background Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that specifically occurs in pregnancy. Elevated levels of liver transaminases aspartate aminotransferase, alanine aminotransferase and serum bilirubin levels are common biochemical characteristics in ICP. The disorder is associated with an increased risk of premature delivery and stillbirth. The characterization of the potential microbiota in ICP could go a long way in the prevention and treatment of this pregnancy disease. Methods A total of 58 patients were recruited for our study: 27 ICP patients and 31 healthy pregnant subjects with no ICP. The V3 and V4 regions of the 16S rDNA collected from fecal samples of both diseased and control groups were amplified. 16S rRNA gene amplicon sequencing was then performed on gut microbiota. Sequencing data were analyzed and the correlation between components of microbiota and patient ICP status was found. Related metabolic pathways, relative abundance and significantly different operational taxonomic units (OTUs) between ICP and controls were also identified. Results Elevated levels of total bile acid, ALT, AST, Dbil and Tbil were recorded or observed in ICP subjects as compared to the control. Gut microbiota in pregnant women was dominated by four major phyla and 27 core genera. PCoA analysis results indicated that there was no significant clustering in Bray–Curtis distance matrices. Our results showed that there was a correlation between specific OTUs and measured clinical parameters of pregnant women. Comparison at the different taxonomy levels revealed high levels of abundance of Blautia and Citrobacter in ICP patients. At the family level, Enterobacteriaceae and Leuconostocaceae were higher in ICP patients. 638 KEGG Orthologs and 138 pathways significantly differed in the two groups. PLS-DA model with VIP plots indicated a total of eight genera and seven species were key taxa in ICP and control groups. Conclusions Our research indicated that although there was no significant clustering by PCoA analysis, patients with ICP have increased rare bacteria at different phylogenetic levels. Our results also illustrated that all 638 KEGG Orthologs and 136 in 138 KEGG pathways were less abundant in ICP patients compared to the controls.
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Affiliation(s)
- Rong Li
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People's Republic of China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, People's Republic of China.,International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Xuehai Chen
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People's Republic of China.,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, People's Republic of China.,International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China
| | - Zhongzhen Liu
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China
| | - Yan Chen
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China
| | - Chuan Liu
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China
| | - Lingfei Ye
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China
| | - Liang Xiao
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China
| | - Zhenjun Yang
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China.,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China
| | - Jian He
- BGI-Chongqing Clinical Laboratory, BGI-Shenzhen, Chongqing, 401120, People's Republic of China
| | - Wen-Jing Wang
- BGI-Shenzhen, Build 11, Beishan Industrial Zone, Yantian District, Shenzhen, 518000, People's Republic of China. .,China National GeneBank, BGI-Shenzhen, Shenzhen, 518000, People's Republic of China.
| | - Hongbo Qi
- Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, People's Republic of China. .,State Key Laboratory of Maternal and Fetal Medicine of Chongqing Municipality, Chongqing Medical University, Chongqing, 400016, People's Republic of China. .,International Collaborative Laboratory of Reproduction and Development of Chinese Ministry of Education, Chongqing Medical University, Chongqing, 400016, People's Republic of China.
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Wang R, Cheng N, Peng R, Yu Z, Nan M, Cao H. Oral herbal medicine for women with intrahepatic cholestasis in pregnancy: a systematic review of randomized controlled trials. BMC Complement Med Ther 2020; 20:303. [PMID: 33028282 PMCID: PMC7542867 DOI: 10.1186/s12906-020-03097-x] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2020] [Accepted: 09/28/2020] [Indexed: 01/17/2023] Open
Abstract
Background Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy complication whose range has been calculated to be between 0.01 and 15.6% all around the world. We wanted to systematically evaluate the effect and safety of oral herbal medicine on treatment for ICP. Methods Details of the methods could be found in the registered protocol on PROSPERO (CRD42018096013). Trials assessing the effectiveness of herbal medicine for ICP were searched from seven electronic databases from inception to 28th February 2020. RevMan 5.3 software was used to perform all statistical analysis. Meta-analysis, additional analysis, Trial Sequential Analysis (TSA) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) were conducted if data permitted. Results Totally 43 randomized controlled trials with 3556 patients were included. Meta-analysis showed potential good adjunctive effect of herbal medicine on decreasing the pruritus scores (MD -0.58, 95% CI − 0.79 to − 0.36), the serum TBA scores (MD − 3.99 μmol/L, 95% CI − 4.24 to − 3.74) on the basis with Ursodesoxycholic acid. Compared to the medicine alone, significantly lower incidence of fetal distress (RR 0.41, 95% CI 0.32 to 0.51), asphyxia neonatorum (RR 0.35, 95%CI 0.25 to 0.49), cesarean section (RR 0.73, 95% CI 0.63 to 0.85), postpartum hemorrhage (RR 0.45, 95% CI 0.28 to 0.72) were observed in the combination group. But the comparison between herbal medicine and medicine showed inconsistent results among trials. Insufficient information could be used to evaluate the safety of herbal medicine for ICP. Conclusion This review found the current evidence may support the effectiveness of combination of herbal medicine and conventional medicine for decreasing the maternal pruritus scores, the serum TBA, and the number of fetal distress, or asphyxia neonatorum events related to this condition (which was supported by TSA results). Since there were obvious statistical and clinical heterogeneity among trials, and the methodological quality of the included studies was poor, the level of the evidence could only be defined as “very low” according to the GRADE criteria. Further high quality studies are still needed to testify the effectiveness and safety of herbal medicine for ICP.
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Affiliation(s)
- Ruiting Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Nuo Cheng
- Beijing University of Chinese Medicine, Beijing, China
| | - Rongyan Peng
- Beijing University of Chinese Medicine, Beijing, China
| | - Zeyu Yu
- Centre for Evidence Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Mengdie Nan
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Huijuan Cao
- Centre for Evidence Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, China.
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Wang JQ, Gao H, Sheng J, Tao XY, Huang K, Zhang YW, Mao LJ, Zhou SS, Jin ZX, Tao FB. Urinary concentrations of phthalate metabolites during gestation and intrahepatic cholestasis of pregnancy: a population-based birth cohort study. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2020; 27:11714-11723. [PMID: 31975012 DOI: 10.1007/s11356-020-07675-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/24/2019] [Accepted: 01/07/2020] [Indexed: 06/10/2023]
Abstract
Phthalates, a class of widely used endocrine-disrupting chemicals (EDCs), are toxic to various organ systems in animals and humans. Intrahepatic cholestasis of pregnancy (ICP) is a reversible liver dysfunction causing cholestasis in late pregnancy. Evidence on the associations between exposure to phthalates and ICP is still lacking. In the present study, we investigated the relationships between urinary concentrations of phthalate metabolites and the risk of ICP in a Chinese population-based birth cohort. Pregnant women participated in the Ma'anshan Birth Cohort (MABC) study in China. Seven phthalate metabolites were detected in a urine sample in early pregnancy. Chemical concentrations were grouped by quartiles, and associations with outcomes were examined using logistic regression with adjustment for urine creatinine, race, education, poverty status, smoking status, alcohol consumption, maternal age, prepregnancy body mass index (BMI), parity, twin pregnancy, and pregnancy-related liver complications. Of 3474 women recruited into the Ma'anshan Birth Cohort, 2760 met the inclusion criteria and contributed to further analysis and biomonitoring data. Elevated odds ratios (ORs) of ICP were observed in the highest quartiles of monomethyl phthalate (MMP) exposure (OR = 1.59, 95% confidence intervals (CI) = 1.01-2.51) and monobutyl phthalate (MBP) exposure (OR = 1.82, 95% CI = 1.16-2.85) in the adjusted analyses. Our findings add to the evidence that supports the role of maternal phthalate exposure in the first trimester of gestation as a risk factor for ICP.
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Affiliation(s)
- Jian-Qing Wang
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei, 230032, Anhui, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
- The Fourth Affiliated Hospital, Anhui Medical University, Hefei, 230022, Anhui, China
| | - Hui Gao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Jie Sheng
- MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Xing-Yong Tao
- MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Kun Huang
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
- MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei, 230032, Anhui, China
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Yun-Wei Zhang
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Lei-Jing Mao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Shan-Shan Zhou
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Zhong-Xiu Jin
- MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei, 230032, Anhui, China
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China
| | - Fang-Biao Tao
- Department of Maternal, Child and Adolescent Health, School of Public Health, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.
- MOE Key Laboratory of Population Health Across Life Cycle, No 81 Meishan Road, Hefei, 230032, Anhui, China.
- NHC Key Laboratory of Study on Abnormal Gametes and Reproductive Tract, No 81 Meishan Road, Hefei, 230032, Anhui, China.
- Anhui Provincial Key Laboratory of Population Health and Aristogenics, Anhui Medical University, No 81 Meishan Road, Hefei, 230032, Anhui, China.
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Manzotti C, Casazza G, Stimac T, Nikolova D, Gluud C, Cochrane Hepato‐Biliary Group. Total serum bile acids or serum bile acid profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev 2019; 7:CD012546. [PMID: 31283001 PMCID: PMC6613619 DOI: 10.1002/14651858.cd012546.pub2] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Intrahepatic cholestasis of pregnancy is a pregnancy-specific liver disorder, possibly associated with an increased risk of severe fetal adverse events. Total serum bile acids (TSBA) concentration, alone or in combination with serum aminotransferases, have been the most often used biomarkers for the diagnosis of intrahepatic cholestasis of pregnancy in clinical practice. Serum bile acid profile, composed of primary or secondary, conjugated or non-conjugated bile acids, may provide more specific disease information. OBJECTIVES To assess and compare, independently or in combination, the diagnostic accuracy of total serum bile acids or serum bile acids profile, or both, for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women, presenting with pruritus. To define the optimal cut-off values for components of serum bile acid profile; to investigate possible sources of heterogeneity. SEARCH METHODS We searched the Cochrane Hepato-Biliary Group Controlled Trials Register, the Cochrane Hepato-Biliary Group Diagnostic Test Accuracy Studies Register, the Cochrane Library, MEDLINE Ovid, Embase Ovid, Science Citation Index Expanded, Conference Proceedings Citation Index - Science, BIOSIS, CINAHL, two Chinese databases (CKNI, VIP), Latin American and Caribbean Health Sciences Literature (LILACS), Scientific Electronic Library Online (SciELO), Evidence Search: Health and Social Care by the National Institute for Health and Care Excellence (NICE), the World Health Organization (WHO) Reproductive Health Library (RHL), and the Turning Research into Practice database (TRIP). The most recent date of search was 6 May 2019. We identified additional references by handsearching the references of articles, meta-analyses, and evidence-based guidelines retrieved from the computerised databases, on-line trial registries, and grey literature through OpenSIGLE, National Technical Information Service (NTIS), ProQuest Dissertations & Thesis Database, and Index to Theses in Great Britain and Ireland. SELECTION CRITERIA Prospective or retrospective diagnostic case-control or cross-sectional studies, irrespective of publication date, format, and language, which evaluated the diagnostic accuracy of total serum bile acids (TSBA) or components of serum bile acid profile for the diagnosis of intrahepatic cholestasis of pregnancy in pregnant women of any age or ethnicity, in any clinical setting, symptomatic for pruritus. DATA COLLECTION AND ANALYSIS We selected studies by reading titles, abstracts, or full texts, and assessing their fulfilment of our inclusion criteria. We emailed primary authors to request missing data or individual participant data. Having extracted data from each included study, we built the two-by-two tables for each primary study and for all the index tests considered. We estimated sensitivity and specificity with their 95% confidence intervals (CI). We presented data in coupled forest plots, showing sensitivities and specificities of each study, and we plotted the studies in the Receiver Operating Characteristic (ROC) space. We performed meta-analyses adopting the hierarchical summary ROC model (HSROC) or the bivariate model to meta-analyse the data. We made indirect comparisons of the considered index tests by adding the index tests as covariates to the bivariate or HSROC models. We performed heterogeneity analysis and sensitivity analysis on studies assessing TSBA accuracy. We used Review Manager 5 (RevMan 5) and SAS statistical software, release 9.4 (SAS Institute Inc., Cary, NC, USA), to perform all statistical analyses. We used QUADAS-2 domains to assess the risk of bias of the included studies. MAIN RESULTS Our search yielded 5073 references, but at the end of our selection process, only 16 studies fulfilled the review inclusion criteria. Nine of these provided individual participant data. We analysed only data concerning TSBA, cholic acid (CA), glycocholic acid (GCA), chenodeoxycholic acid (CDCA), and CA/CDCA because the remaining planned index tests were assessed in few studies. Only one study had low risk of bias in all four QUADAS-2 domains. The most biased domains were the patient sampling and the reference standard domains. When considering all studies with a cut-off of 10 μmol/L, TSBA overall sensitivity ranged from 0.72 to 0.98 and specificity ranged from 0.81 to 0.97. After a sensitivity analysis excluding case-control studies, TSBA sensitivity ranged from 0.48 to 0.66 and specificity from 0.52 to 0.99. After a sensitivity analysis excluding studies in which TSBA was part of the reference standard, TSBA sensitivity ranged from 0.49 to 0.65 and specificity from 0.53 to 0.99. We found the estimates of the overall accuracy for some serum bile acid components (CA, GCA, CDCA, and CA/CDCA) to be imprecise, with the CI for sensitivity and specificity very wide or impossible to calculate. Indirect comparisons between serum bile acid profile components and TSBA were not statistically significant. None of the heterogeneity analysis performed was statistically significant, except for the timing of assessment of TSBA (onset of symptoms, peak value among multiple assessments, delivery) but without clinically relevant results. We could not analyse the diagnostic accuracy of combinations of index tests because none of the included studies carried them out, and because of the small number of included studies. AUTHORS' CONCLUSIONS The overall high risk of bias, the existing concern regarding applicability of the results in clinical practice, and the great heterogeneity of the results in the included studies prevents us from making recommendations and reaching definitive conclusions at the present time. Thus, we do not find any compelling evidence to recommend or refute the routine use of any of these tests in clinical practice. So far, the diagnostic accuracy of TSBA for intrahepatic cholestasis of pregnancy might have been overestimated. There were too few studies to permit a precise estimate of the accuracy of serum bile acid profile components. Further primary clinical research is mandatory. We need both further phase II and phase III diagnostic studies.
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Affiliation(s)
- Cristina Manzotti
- Fondazione IRCCS Ca' Granda ‐ Ospedale Maggiore Policlinico, Università degli Studi di MilanoObstetrics and Gynecology DepartmentVia Commenda 12 ‐ Clinica Mangiagalli, piano terraMilanMilanItaly20122
- Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention ResearchCopenhagenDenmark
- Fondazione IRCCS Ca' Granda ‐ Ospedale Maggiore Policlinico, Università degli Studi di MilanoGastro‐Intestinal UnitVia Commenda 12 ‐ Clinica Mangiagalli, 1° piano, scala AMilanMilanItaly20122
| | - Giovanni Casazza
- Università degli Studi di MilanoDipartimento di Scienze Biomediche e Cliniche "L. Sacco"via GB Grassi 74MilanItaly20157
| | - Tea Stimac
- Clinical Hospital Centre RijekaObstetrics and GynecologyCambierieva 17RijekaCroatia51000
| | - Dimitrinka Nikolova
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
| | - Christian Gluud
- Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Rigshospitalet, Copenhagen University HospitalCochrane Hepato‐Biliary GroupBlegdamsvej 9CopenhagenDenmarkDK‐2100
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Pieczyńska J, Płaczkowska S, Sozański R, Orywal K, Mroczko B, Grajeta H. Is maternal dietary selenium intake related to antioxidant status and the occurrence of pregnancy complications? J Trace Elem Med Biol 2019; 54:110-117. [PMID: 31109600 DOI: 10.1016/j.jtemb.2019.04.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2018] [Revised: 04/02/2019] [Accepted: 04/18/2019] [Indexed: 10/27/2022]
Abstract
Selenium (Se) is a trace element essential for the appropriate course of vital processes in the human body. It is also a constituent of the active center of glutathione peroxidase and other antioxidant compounds which play an important role in red-ox processes. Associations between lower blood selenium concentration and obstetric complications has been reported in many studies. The aim of this study was to determine the dietary selenium intake and serum selenium content in pregnant Polish women and relate this to antioxidant status as whole blood glutathione peroxidase (GPX) activity, serum uric acid (UA) content and serum total antioxidant status (TAS) and pregnancy complications occurrence. Ninety-four pregnant women at a mean age 30.6 ± 5.4 years from the Lower Silesia region of Poland were recruited to the study, 37% of studied group had pregnancy complications. The mean reported Se intake and serum selenium content for Polish pregnant women was in the first trimester - 53.99 μg/day and 44.36 μg/l, the second trimester - 58.93 μg/day and 43.16 μg/l and the third trimester - 62.89 μg/day and 40.97 μg/l, respectively. Selenium intake below or above recommended value hadn't significant effect on GPX activity, TAS and UA levels. There were no statistical differences in selenium intake, serum selenium content, GPX activity and TAS and UA level between physiological and complicated pregnancy, but a positive correlation between Se intake and serum selenium content was observed during all period of gestation as well as in the second trimester of pregnancy between Se intake and GPX activity in group with physiological pregnancy where selenium intake was below the recommended level. Selenium intake above the recommended level was positively correlated also with serum UA level in first and second trimester of pregnancy. Despite weak, positive correlations in the first two trimesters of pregnancy between selenium supply and GPX activity and UA concentration we concluded that selenium intake does not significantly affect during pregnancy, both: markers of the antioxidant status of pregnant women and the occurrence of pregnancy complications.
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Affiliation(s)
- Joanna Pieczyńska
- Department of Food Science and Dietetics, Wroclaw Medical University, Borowska 211, 50-556, Wroclaw, Poland.
| | - Sylwia Płaczkowska
- Diagnostics Laboratory for Teaching and Research, Wroclaw Medical University, Borowska 211a, 50-556, Wroclaw, Poland
| | - Rafał Sozański
- 1st Department and Clinic of Gynaecology and Obstetrics, Wroclaw Medical University, T. Chałubińskiego 3, 50-368, Wroclaw, Poland
| | - Karolina Orywal
- Department of Biochemical Diagnostics, Medical University of Białystok, Waszyngtona 15A, 15-269, Bialystok, Poland
| | - Barbara Mroczko
- Department of Biochemical Diagnostics, Medical University of Białystok, Waszyngtona 15A, 15-269, Bialystok, Poland; Department of Neurodegeneration Diagnostics, Medical University of Białystok, Waszyngtona 15A, 15-269, Bialystok, Poland
| | - Halina Grajeta
- Department of Food Science and Dietetics, Wroclaw Medical University, Borowska 211, 50-556, Wroclaw, Poland
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Hämäläinen ST, Turunen K, Mattila KJ, Kosunen E, Sumanen M. Long-term survival after intrahepatic cholestasis of pregnancy: A follow-up of 571 mothers. Eur J Obstet Gynecol Reprod Biol 2019; 240:109-112. [PMID: 31247486 DOI: 10.1016/j.ejogrb.2019.06.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2019] [Accepted: 06/11/2019] [Indexed: 02/07/2023]
Abstract
OBJECTIVE Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder during pregnancy. ICP has been associated with morbidity but little is known about women's long-term survival. Our aim was to determine whether ICP is associated with mothers' long-term survival. STUDY DESIGN The study population comprised 571 women with ICP in at least one pregnancy seen at Tampere University Hospital in Finland between 1969‒1988. The reference group comprised 1333 women: the previous and the following participant in the maternity ward diary. The data were obtained from Statistics Finland in March 2017 containing deaths among the study participants between 1971‒2015. The follow-up time of the cohort was 27-46 years. The Kaplan-Meier method was used. RESULTS Totally, 39 of the mothers with ICP (6.8%) and 111 of the reference group (8.3%) had died by the end of 2015 (p = 0.267). The mean survival time of ICP women was 77.4 years and of the reference group 79.2 years (p = 0.288). The mean survival time from labour in the ICP group was 45.0 years and in the reference group 44.8 years (p = 0.259). CONCLUSIONS Based on this study ICP does not seem to be associated with women's survival. There is no need to follow-up ICP mothers' health because of the nonexistent risk of premature death.
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Affiliation(s)
- Suvi-Tuulia Hämäläinen
- Department of General Practice, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland; Janakkala Health Centre, Tapailanpiha 13 B, 14200 Turenki, Finland; Science Center, Tampere University Hospital, 33521 Tampere, Finland; Centre for General Practice, Pirkanmaa Hospital District, 33521 Tampere, Finland.
| | - Kaisa Turunen
- Department of General Practice, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland
| | - Kari J Mattila
- Department of General Practice, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland
| | - Elise Kosunen
- Department of General Practice, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland; Science Center, Tampere University Hospital, 33521 Tampere, Finland; Centre for General Practice, Pirkanmaa Hospital District, 33521 Tampere, Finland
| | - Markku Sumanen
- Department of General Practice, Faculty of Medicine and Health Technology, Tampere University, Arvo Ylpön katu 34, 33520 Tampere, Finland
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Yildirim S, Ozkan C, Huyut Z, Çınar A. Detection of Se, Vit. E, Vit. A, MDA, 8-OHdG, and CoQ10 Levels and Histopathological Changes in Heart Tissue in Sheep with White Muscle Disease. Biol Trace Elem Res 2019; 188:419-423. [PMID: 30054878 DOI: 10.1007/s12011-018-1434-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2018] [Accepted: 07/04/2018] [Indexed: 10/28/2022]
Abstract
This study was carried out to determine vit. E, Se, vit. A, malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and ubiquinone-10 (CoQ10) levels and histopathological changes in sheep with white muscle disease (WMD). A total of 30 sheep were used; 20 sheep with WMD were brought to our clinic for diagnosis and treatment at various times, and 10 healthy sheep were in the control group. The Se, vit. E, vit. A, MDA, 8-OHdG, and CoQ10 values of the healthy and WMD sheep were as follows: 0.917 ± 0.037, 0.790 ± 0.067; 1.190 ± 0.011, 1.090 ± 0.021; 5.400 ± 0.275, 5.200 ± 0.173; 1.602 ± 0.264, 2.636 ± 0.576; 0.656 ± 0.197, 1.485 ± 0.271; and 0.280 ± 0.044, 1.753 ± 0.551 respectively (p < 0.05). According to histopathological and immunohistochemical findings in the WMD group, hyaline degeneration, Zenker's necrosis, and dystrophic calcification were observed in the muscle fibers. Immunohistochemically, 8-OHdG staining of the heart tissue determined a severe 8-OHdG expression in the WMD group. The findings of this study suggest that MDA, 8-OHdG, and CoQ10 values could be used as diagnostic and prognostic biomarkers in sheep affected with WMD.
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Affiliation(s)
- Serkan Yildirim
- Department of Pathology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey
| | - Cumali Ozkan
- Department of Internal Diseases, Faculty of Veterinary Medicine, Van Yuzuncu Yil University, Van, Turkey
| | - Zubeyir Huyut
- Department of Biochemistry, Faculty of Medicine, Van Yuzuncu Yil University, Van, Turkey
| | - Ali Çınar
- Department of Physiology, Faculty of Veterinary Medicine, Ataturk University, Erzurum, Turkey.
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Parisi F, di Bartolo I, Savasi VM, Cetin I. Micronutrient supplementation in pregnancy: Who, what and how much? Obstet Med 2019; 12:5-13. [PMID: 30891086 PMCID: PMC6416688 DOI: 10.1177/1753495x18769213] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 03/05/2018] [Indexed: 12/22/2022] Open
Abstract
Pregnancy represents a period of major physiological and metabolic change, aiming to ensure proper fetal growth and development, as well as maternal preservation. This review focuses on maternal nutrition, and particularly on micronutrient deficiencies and supplementation during pregnancy. Nutrient deficiencies and consequences in pregnant women are presented, with an overview of current recommendations for dietary supplementation in pregnancy, even considering the risk of micronutrient overload. Appropriate universal supplementation and prophylaxis/treatment of nutritional needs currently appear to be the most cost-effective goal in low-income countries, thus ensuring adequate intake of key elements including folate, iron, calcium, vitamin D and A. In high-income countries, a proper nutritional assessment and counselling should be mandatory in obstetric care in order to normalize pregestational body mass index, choose a healthy dietary pattern and evaluate the risk of deficiencies.
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Affiliation(s)
- F Parisi
- Center for Fetal Research Giorgio Pardi, Department
of Biomedical and Clinical Sciences, Università degli Studi di Milano, Hospital
Luigi Sacco, Unit of Obstetrics and Gynecology, Milan, Italy
| | - I di Bartolo
- Center for Fetal Research Giorgio Pardi, Department
of Biomedical and Clinical Sciences, Università degli Studi di Milano, Hospital
Luigi Sacco, Unit of Obstetrics and Gynecology, Milan, Italy
| | - VM Savasi
- Center for Fetal Research Giorgio Pardi, Department
of Biomedical and Clinical Sciences, Università degli Studi di Milano, Hospital
Luigi Sacco, Unit of Obstetrics and Gynecology, Milan, Italy
| | - I Cetin
- Center for Fetal Research Giorgio Pardi, Department
of Biomedical and Clinical Sciences, Università degli Studi di Milano, Hospital
Luigi Sacco, Unit of Obstetrics and Gynecology, Milan, Italy
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Li P, Yin J, Zhu Y, Li S, Chen S, Sun T, Shan Z, Wang J, Shang Q, Li X, Yang W, Liu L. Association between plasma concentration of copper and gestational diabetes mellitus. Clin Nutr 2019; 38:2922-2927. [PMID: 30661907 DOI: 10.1016/j.clnu.2018.12.032] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Revised: 11/26/2018] [Accepted: 12/26/2018] [Indexed: 12/28/2022]
Abstract
BACKGROUND & AIMS Emerging findings have raised concerns about significant associations between excessive copper (Cu) and abnormal glucose metabolism. Nevertheless, related researches on the relationship of Cu concentration and gestational diabetes mellitus (GDM) are limited. The objective of this study was to determine whether plasma Cu concentration is associated with GDM. METHODS A case-control study of 248 cases of GDM and 248 age-, parity- and gestational age-matched controls was conducted in Wuhan, China between August 2012 and April 2015. Fasting blood samples of participants were collected at the time of GDM screening (≥24 weeks of gestation). Plasma Cu concentrations were detected by inductively coupled plasma mass spectrometry. The strength of the association of plasma Cu with GDM odds was evaluated by odds ratios (ORs) with 95% confidence intervals (CIs) from conditional logistic regression. Partial Spearman or Pearson correlation coefficients were calculated to estimate the interrelationship between plasma Cu and the risk factors of GDM. RESULTS Plasma Cu concentrations in the GDM group (mean ± SD: 1960.24 ± 391.98 μg/L) were higher than in the control group (mean ± SD: 1842.43 ± 387.09 μg/L) (P = 0.001). After adjustment for possible confounders, the ORs (95% CIs) of GDM across increasing quartiles of plasma Cu levels were 1.00 (referent), 1.79 (0.90-3.55), 2.72 (1.35-5.48) and 2.91 (1.48-5.75), respectively; the OR (95% CI) of GDM was 1.33 (1.06-1.67) for each standard deviation increment of plasma Cu. Moreover, Cu concentrations were positively associated with fasting plasma glucose, 1-h post-glucose load and 2-h post-glucose load (all P < 0.05). CONCLUSIONS The present study indicated a significantly increased odds of GDM in association with higher concentrations of plasma Cu. Prospective cohort studies in other populations are needed to confirm our findings.
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Affiliation(s)
- Peiyun Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Jiawei Yin
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Yalun Zhu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Shuzhen Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Sijing Chen
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Taoping Sun
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Zhilei Shan
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Jiawei Wang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Qianqian Shang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Xiaoqin Li
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China
| | - Wei Yang
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
| | - Liegang Liu
- Department of Nutrition and Food Hygiene, Hubei Key Laboratory of Food Nutrition and Safety, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China; Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, PR China.
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Maglie R, Quintarelli L, Verdelli A, Fabbri P, Antiga E, Caproni M. Specific dermatoses of pregnancy other than pemphigoid gestationis. GIORN ITAL DERMAT V 2018; 154:286-298. [PMID: 30375214 DOI: 10.23736/s0392-0488.18.06159-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Specific dermatoses of pregnancy are skin disorders that occur specifically during or immediately after pregnancy and cannot be found in non-pregnant patients. According to the current consensus, they include atopic eruption of pregnancy (AEP), polymorphic eruption of pregnancy (PEP), pemphigoid gestationis (PG), and intrahepatic cholestasis of pregnancy (ICP). The diagnosis of specific dermatoses of pregnancy can be challenging due to their variation in clinical presentation; moreover, the tests currently available do not always provide the clue for the diagnosis. However, some distinctive features may be helpful to differentiate between such entities. Accordingly, the knowledge of specific dermatoses of pregnancy and of their management is critical, since their early recognition may allow to provide care for the mother and prevent potential increased fetal risk. In fact, while AEP and PEP do not affect maternal and fetal prognosis, PG and, mainly, ICP are associated to maternal complications as well as the risk of fetal loss. In this paper, the epidemiology, pathogenesis, clinical features as well as management of AEP and PEP are reviewed in detail, while PG is described in another article of this issue. Moreover, the main features of ICP, which cannot be considered a primarily skin disease but may be managed first by dermatologists, are reported.
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Affiliation(s)
- Roberto Maglie
- Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Lavinia Quintarelli
- Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Alice Verdelli
- Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Paolo Fabbri
- Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
| | - Emiliano Antiga
- Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy -
| | - Marzia Caproni
- Section of Dermatology, Department of Surgery and Translational Medicine, University of Florence, Florence, Italy
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Demir N, Başaranoğlu M, Huyut Z, Değer İ, Karaman K, Şekeroğlu MR, Tuncer O. The relationship between mother and infant plasma trace element and heavy metal levels and the risk of neural tube defect in infants. J Matern Fetal Neonatal Med 2017; 32:1433-1440. [DOI: 10.1080/14767058.2017.1408064] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Nihat Demir
- Department of Pediatrics, Division of Neonatology, Yuzuncu Yil University School of Medicine, Van, Turkey
| | - Murat Başaranoğlu
- Department of Pediatrics, Division of Neonatology, Yuzuncu Yil University School of Medicine, Van, Turkey
| | - Zübeyir Huyut
- Department of Medical Biochemistry, Yuzuncu Yil University School of Medicine, Van, Turkey
| | - İbrahim Değer
- Department of Pediatrics, Division of Neonatology, Yuzuncu Yil University School of Medicine, Van, Turkey
| | - Kamuran Karaman
- Department of Pediatrics, Division of Neonatology, Yuzuncu Yil University School of Medicine, Van, Turkey
| | - M. Ramazan Şekeroğlu
- Department of Medical Biochemistry, Yuzuncu Yil University School of Medicine, Van, Turkey
| | - Oğuz Tuncer
- Department of Pediatrics, Division of Neonatology, Yuzuncu Yil University School of Medicine, Van, Turkey
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Mishra N, Panigrahy S, Behera AA. FOETOMATERNAL OUTCOME OF OBSTETRIC CHOLESTASIS. ACTA ACUST UNITED AC 2017. [DOI: 10.18410/jebmh/2017/705] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Review: Effects of maternal micronutrient supplementation on placental function. Placenta 2017; 54:38-44. [DOI: 10.1016/j.placenta.2016.12.022] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2016] [Revised: 12/14/2016] [Accepted: 12/18/2016] [Indexed: 01/07/2023]
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Choi R, Sun J, Yoo H, Kim S, Cho YY, Kim HJ, Kim SW, Chung JH, Oh SY, Lee SY. A Prospective Study of Serum Trace Elements in Healthy Korean Pregnant Women. Nutrients 2016; 8:749. [PMID: 27886083 PMCID: PMC5133131 DOI: 10.3390/nu8110749] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2016] [Revised: 11/16/2016] [Accepted: 11/17/2016] [Indexed: 01/22/2023] Open
Abstract
This prospective study sought to investigate serum levels of trace elements (cobalt, copper, zinc, and selenium) and to assess their effects on pregnancy and neonatal outcomes. Serum levels of trace elements in 245 Korean pregnant women (median gestational age at delivery was 39 + 4 weeks and interquartile range was 38 + 4-40 + 1 weeks) were compared with those of 527 general adults and those of previous studies in other ethnic groups. Pregnancy and neonatal outcomes including gestational diabetes, preeclampsia, neonatal birth weight, and congenital abnormalities were assessed. The median serum trace element concentrations of all pregnant women were: cobalt: 0.39 μg/L (interquartile range, IQR 0.29-0.53), copper: 165.0 μg/dL (IQR 144.0-187.0), zinc: 57.0 μg/dL (IQR 50.0-64.0), and selenium: 94.0 μg/L (IQR 87.0-101.0). Serum cobalt and copper concentrations were higher in pregnant women than in the general population, whereas zinc and selenium levels were lower (p < 0.01). Concentrations of all four trace elements varied significantly during the three trimesters (p < 0.05), and seasonal variation was found in copper, zinc, and selenium, but was not observed for cobalt. The prevalence of preeclampsia was significantly lower with high copper (p = 0.03). Trace element levels varied by pregnancy trimester and season, and alteration in copper status during pregnancy might influence pregnancy outcomes such as preeclampsia.
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Affiliation(s)
- Rihwa Choi
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Jiyu Sun
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Heejin Yoo
- Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Seonwoo Kim
- Statistics and Dater Center, Samsung Biomedical Research Institute, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Yoon Young Cho
- Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Hye Jeong Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Sun Wook Kim
- Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Jae Hoon Chung
- Division of Endocrinology and Metabolism, Department of Medicine, Thyroid Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Soo-Young Oh
- Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
| | - Soo-Youn Lee
- Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
- Department of Clinical Pharmacology & Therapeutics, Samsung Medical Center, 81 Irwon-Ro, Gangnam-Gu, Seoul 06351, Korea.
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Pařízek A, Dušková M, Vítek L, Šrámková M, Hill M, Adamcová K, Šimják P, Černý A, Kordová Z, Vráblíková H, Boudová B, Koucký M, Malíčková K, Stárka L. The role of steroid hormones in the development of intrahepatic cholestasis of pregnancy. Physiol Res 2016; 64:S203-9. [PMID: 26680481 DOI: 10.33549/physiolres.933117] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022] Open
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women.
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Affiliation(s)
- A Pařízek
- Department of Obstetrics and Gynecology of the First Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic, Institute of Endocrinology, Prague, Czech Republic.
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Huang GQ, Wang XD. New insights into diagnosis and treatment of intrahepatic cholestasis of pregnancy. Shijie Huaren Xiaohua Zazhi 2016; 24:3749-3756. [DOI: 10.11569/wcjd.v24.i26.3749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease, characterized by maternal pruritus and abnormal serum biochemistries in the late second and third trimester of pregnancy. The symptoms and abnormal biochemistries resolve rapidly after fetal delivery. As a diagnosis of exclusion, the diagnosis of ICP is based on unexplained pruritus with other causes and impaired liver function presenting with elevated serum liver transaminases and/or bile acids. It is considered as severe ICP when bile acid ≥ 40 μmol/L during pregnancy. The pathogenesis of ICP is still unclear. Adverse perinatal outcomes associated with ICP are focused on increased risk of preterm, meconium-stained amniotic fluid, and perinatal mortality. Unpredictable fetal hypoxia may result in intrauterine fetal death, fetal distress during birth and even stillbirth, and lead to an increase of iatrogenic preterm and cesarean section. The etiology and pathogenesis of fetal stress in ICP are not yet clarified, which may be associated with impaired infrastructure and decreased stress-compensatory in human utero-placental-fetal unit, and related with vascular constriction of chorionic veins and umbilical cord due to elevated bile acids in fetal serum and amniotic fluid. The essential measures of standard treatment of ICP include: (1) monitoring and evaluation of disease, uterine contraction and fetus; (2) prevention and treatment of uterine contraction; (3) treatment with ursodeoxycholic acid (500-1500 mg/d) alone or in combination with S-adenosylmehionine (800-1000 mg/d) or rifampicin (300-1200 mg/d) to promote drainage of bile acids; (4) promotion of fetal growth and lung development; (5) treatment with vitamin K1 before delivery to prevent maternal and fetal hemorrhage; (6) and timely termination of pregnancy. Gestational weeks, fetal condition and severity of disease need to be taken into account when obstetricians decide the time of termination. Elective early delivery is still an effective measure to avoid stillbirth during prolongation of gestational weeks.
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Marvin-Dowle K, Burley VJ, Soltani H. Nutrient intakes and nutritional biomarkers in pregnant adolescents: a systematic review of studies in developed countries. BMC Pregnancy Childbirth 2016; 16:268. [PMID: 27629406 PMCID: PMC5024513 DOI: 10.1186/s12884-016-1059-9] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2016] [Accepted: 09/06/2016] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Babies born to adolescent mothers have been shown to have poorer outcomes compared to those born to adults. Nutritional status may have an important role to play in improving the health of pregnant adolescents; however there is a lack of evidence regarding the adequacy of adolescent diets during pregnancy. This systematic review aims to examine what is known about the nutritional status of adolescent pregnant women. METHODS A systematic search of the literature identified 21 studies which met the inclusion criteria for the review. Primary research papers using any methods were included where they were published in English between January 1995 and May 2015 and included measurements of nutrient intakes or biological markers of nutritional status in pregnant women aged 11-19 years. Individual study data was first summarised narratively before study means were pooled to give an estimate of nutritional status in the population. RESULTS The results show that individual studies reported intakes of energy, fibre and a number of key micronutrients which were below recommended levels. Biological markers of iron and selenium status also showed cause for concern. Pooled analysis of individual means as a percentage of UK Dietary Reference Intakes showed intakes of vitamin D (34.8 % CI 0-83.1) to be significantly below recommendations (p = 0.05). Serum selenium levels were also found to be low (61.8 μg/L, CI 39-84). CONCLUSIONS This review has identified a number of areas where the nutritional status of pregnant adolescents is sub-optimal, which may have implications for the health of adolescent mothers and their babies. It was not however possible to examine the impact of supplement use or socio-demographic characteristics which limits the interpretation these results. Further work is needed to establish the characteristics of those most at risk within this population, how this differs from adult pregnant women and the role of supplementation in achieving adequate nutrition.
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Affiliation(s)
- Katie Marvin-Dowle
- Centre for Health and Social Care Research, Sheffield Hallam University, Collegiate Crescent, Sheffield, S10 2BP UK
| | | | - Hora Soltani
- Centre for Health and Social Care Research, Sheffield Hallam University, Collegiate Crescent, Sheffield, S10 2BP UK
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Abstract
Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease during pregnancy, characterized by otherwise unexplained pruritus in late second and third trimester of pregnancy and elevated bile acids and/or transaminases. ICP is associated with an increased risk of adverse perinatal outcomes for the fetus and the later development of hepatobiliary disease for the mother. Bile acids should be monitored throughout pregnancy since fetal risk is increased at serum bile acids >40 µmol/l. Management of ICP consists of treatment with ursodeoxycholic acid, which reduces pruritus. Early elective delivery is common practice but should be performed on an individualized basis as long as strong evidence supporting this practice is lacking. Mothers should be followed-up for normalization of liver function tests 6-12 weeks after delivery. Future research in large-scale studies is needed to address the impact of ursodeoxycholic acid and early elective delivery on fetal outcome.
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Affiliation(s)
- Hanns-Ulrich Marschall
- a Department of Molecular and Clinical Medicine, University of Gothenburg, Sahlgrenska Academy, Institute of Medicine, S-41345 Gothenburg, Sweden
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Abstract
Intrahepatic cholestasis of pregnancy, also known as obstetric cholestasis, is a pruritic condition of pregnancy characterized by an underlying elevation in circulating bile acids and liver derangement, and associated with adverse fetal outcomes, such as preterm labor and stillbirth. Limited understanding of the underlying pathophysiology and mechanisms involved in adverse outcomes has previously restricted treatment options and pregnancy management. Recent advances in these research fields provide tantalizing targets to improve the care of pregnant women affected by this condition.
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Affiliation(s)
- Caroline Ovadia
- Women's Health Academic Centre, King's College London, London, United Kingdom
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Abstract
Intrahepatic cholestasis of pregnancy (ICP) is characterized by maternal pruritus, and elevated serum transaminases and bile acids. Genetic defects in at least 6 canalicular transporters have been found. Association studies stress the variability of genotypes, different penetrance, and influence of environmental factors. Serum autotaxin is a sensitive, specific, and robust diagnostic marker. Elevated maternal bile acids correlate with fetal complications. Long-term sequelae for mothers include the gallstone risk and chronic liver disease. There is an association between ICP and hepatitis C. Current treatment is ursodeoxycholic acid, owing to benefits on pruritus, liver function, safety, and decreased rates of adverse effects.
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Affiliation(s)
- Annarosa Floreani
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Via Giustiniani, 2, Padova 35128, Italy.
| | - Maria Teresa Gervasi
- Department of Obstetrics and Gynecology, Azienda Ospedaliera, Via Giustiniani, 2, Padova 35128, Italy
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46
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Reyes H. What have we learned about intrahepatic cholestasis of pregnancy? Hepatology 2016; 63:4-8. [PMID: 26473339 DOI: 10.1002/hep.28295] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2015] [Revised: 10/09/2015] [Accepted: 10/11/2015] [Indexed: 12/27/2022]
Affiliation(s)
- Humberto Reyes
- Department of Medicine, Faculty of Medicine, University of Chile, Santiago de Chile
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47
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Kleszczewski T, Modzelewska B, Bal W, Sipowicz M, Kleszczewska E, Kostrzewska A. Cu(II) complexation does not affect oxytocin action on pregnant human myometrium in vitro. Reprod Toxicol 2016; 59:60-5. [DOI: 10.1016/j.reprotox.2015.11.004] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 11/03/2015] [Accepted: 11/10/2015] [Indexed: 12/14/2022]
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Dermatological Diseases Associated with Pregnancy: Pemphigoid Gestationis, Polymorphic Eruption of Pregnancy, Intrahepatic Cholestasis of Pregnancy, and Atopic Eruption of Pregnancy. Dermatol Res Pract 2015; 2015:979635. [PMID: 26609305 PMCID: PMC4644842 DOI: 10.1155/2015/979635] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2015] [Accepted: 10/11/2015] [Indexed: 12/16/2022] Open
Abstract
Dermatoses unique to pregnancy are important to recognize for the clinician as they carry considerable morbidity for pregnant mothers and in some instances constitute a risk to the fetus. These diseases include pemphigoid gestationis, polymorphic eruption of pregnancy, intrahepatic cholestasis of pregnancy, and atopic eruption of pregnancy. This review discusses the pathogenesis, clinical importance, and management of the dermatoses of pregnancy.
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49
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Shekhar S, Diddi G. Liver disease in pregnancy. Taiwan J Obstet Gynecol 2015; 54:475-82. [DOI: 10.1016/j.tjog.2015.01.004] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/16/2015] [Indexed: 12/17/2022] Open
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50
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Abstract
Pregnancy is associated with complex of endocrinological, immunological, metabolic, and vascular changes that may influence the skin and other organs in various ways. Pregnancy is a period in which more than 90% women have significant and complex skin changes that may have great impact on the woman's life. The dermatoses of pregnancy represent a heterogeneous group of skin diseases related to pregnancy and/or the postpartum period. The dermatoses of pregnancy can be classified into the following three groups: Physiologic skin changes in pregnancy, pre-existing dermatoses affected by pregnancy, and specific dermatoses of pregnancy. Though most of these skin dermatoses are benign and resolve in postpartum period, a few can risk fetal life and require antenatal surveillance. Most of the dermatoses of pregnancy can be treated conservatively but a few require intervention in the form of termination of pregnancy. Correct diagnosis is essential for the treatment of these disorders. This article discusses the current knowledge of various skin changes during pregnancy and the evaluation of the patient with pregnancy dermatoses with special emphasis on clinical features, diagnostic tests, maternal and fetal prognosis, therapy, and management.
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Affiliation(s)
- Rita V Vora
- Department of Skin and VD, Pramukhswami Medical College and Shree Krishna Hospital, Gujarat, India
| | - Rajat Gupta
- Department of Skin and VD, Pramukhswami Medical College and Shree Krishna Hospital, Gujarat, India
| | - Malay J Mehta
- Department of Skin and VD, Pramukhswami Medical College and Shree Krishna Hospital, Gujarat, India
| | - Arvind H Chaudhari
- Department of Skin and VD, Pramukhswami Medical College and Shree Krishna Hospital, Gujarat, India
| | - Abhishek P Pilani
- Department of Skin and VD, Pramukhswami Medical College and Shree Krishna Hospital, Gujarat, India
| | - Nidhi Patel
- Department of Skin and VD, Pramukhswami Medical College and Shree Krishna Hospital, Gujarat, India
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