OBJECTIVE: To examine the effect of intrahepatic cholestasis of pregnancy (ICP) on fetal heart morphology.
METHODS: This case-control study was conducted with 40 women with ICP and 54 pregnant controls. Fetal heart quantification based on speckle tracking technology was used to assess the morphology of the fetal right and left ventricles. Routine ventricular size parameters, global and 24-segment spherical indices (SIs) were measured and compared between groups.
RESULTS: The routine fetal cardiac parameters, global and right-ventricular SIs did not differ between the ICP and control groups. The left-ventricular apical (segments 16-24) SIs were lower in the ICP group than in the control group (P < .05), with no significant difference in the other left-ventricular segments.
CONCLUSIONS: Subclinical morphological changes were observed in the left ventricular apical segments of the fetal hearts in women with ICP, which indicates an intrauterine environment with high bile acid concentrations. Twenty-four-segment SIs can be used to effectively evaluate these changes.

Intrahepatic cholestasis of pregnancy is one of the most common liver diseases during the second and third trimesters of pregnancy, but its pathogenesis remains unclear. Intrahepatic cholestasis of pregnancy is associated with elevations of maternal bile acids, serum aminotransferases, and adverse fetal outcomes. Besides direct cytotoxic liver injury by bile acids, it has been suggested that bile acid-induced oxidative stress and mitochondrial injury lead to a cascade of inflammatory responses. Here, we demonstrate that the extended elevation of serum aminotransferases after normalization of bile acid levels coincides with an extended increase of the chemokine CXCL10 and inflammatory cytokines.

BACKGROUND: The pregnant women with intrahepatic cholestasis were at high risk of fetal distress, preterm birth and unexpected stillbirth. Intrahepatic cholestasis of pregnancy (ICP) was mainly caused by disorder of bile acid metabolism, whereas the specific mechanism was obscure.
METHODS: We performed proteomics analysis of 10 ICP specimens and 10 placenta specimens from patients without ICP through data-independent acquisition (DIA) technique to disclose differentially expressed proteins. We executed metabolomic analysis of 30 ICP specimens and 30 placenta specimens from patients without ICP through UPLC-MS/MS to identify differentially expressed metabolites. Enrichment and correlation analysis was used to obtain the direct molecular insights of ICP development. The ICP rat models were constructed to validate pathological features.
RESULTS: The heatmap of proteomics analysis showed the top 30 up-regulated and 30 down-regulated proteins. The metabolomic analysis revealed 20 richer and 4 less abundant metabolites in ICP samples compared with placenta specimens from patients without ICP, and enrichment pathways by these metabolites included primary bile acid biosynthesis, cholesterol metabolism, bile secretion, nicotinate and nicotinamide metabolism, purine metabolism and metabolic pathways. Combined analysis of multiple omics results demonstrated that bile acids such as Glycohyocholic acid, Glycine deoxycholic acid, beta-Muricholic acid, Noncholic acid, cholic acid, Gamma-Mercholic Acid, alpha-Muricholic acid and Glycochenodeoxycholic Aicd were significantly associated with the expression of GLRX3, MYL1, MYH7, PGGT1B, ACTG1, SP3, LACTB2, C2CD5, APBB2, IPO9, MYH2, PPP3CC, PIN1, BLOC1S1, DNAJC7, RASAL2 and ATCN3 etc. The core protein ACAT2 was involved in lipid metabolic process and animal model showed that ACAT2 was up-regulated in placenta and liver of pregnant rats and fetal rats. The neonates had low birth weight and Safranin O-Fast green FCF staining of animal models showed that poor osteogenic and chondrogenic differentiation of fetal rats.
CONCLUSIONS: Multiple metabolites-alpha-Muricholic acid, beta-Muricholic acid, Glycine deoxycholic acid and Glycochenodeoxycholic Acid etc. were perfect biomarkers to predict occurrence of ICP. Bile acids were significantly associated with varieties of protein expression and these proteins were differentially expressed in ICP samples. Our study provided several biomarkers for ICP detection and potential therapeutic targets for ICP development.

[This corrects the article DOI: 10.3389/fphys.2024.1276722.].

[This corrects the article DOI: 10.3389/fcvm.2024.1401010.].

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is one of the most common hepatic disorders during pregnancy, and the etiology is thought to be multifactorial including both environmental and hormonal contributions. In twin pregnancies, the fetal and placental mass is generally greater than in singleton pregnancies, and is, theoretically, likely to have a greater influence upon the maternal hepatic metabolism compared to singleton pregnancy. The aim of this study was to compare ICP in twin and singleton pregnancies according to ICP characteristics, time of diagnosis, serum bile acid levels, pharmacological treatment, and pregnancy outcomes.
METHODS: This case control study was undertaken at Aarhus University Hospital, Denmark, from 2012 to 2019. The study comprised 51 women with twin pregnancies and ICP. These women were matched with 153 women with twin pregnancies without ICP and 153 women with singleton pregnancies with ICP, respectively. Three controls were matched per case, and data obtained from medical records and Danish obstetrical databases were compared.
RESULTS: We found a significantly lower gestational age at ICP diagnosis in twin pregnancies (227 vs. 242 days for singleton pregnancies; p = 0.002). Bile acids reached significantly higher maximum blood levels in twin pregnancies (32.9 vs. 22.2 μmol/L; p = 0.012), and at a lower gestational age (gestational age maximum bile acids: 235 vs. 250 days; p < 0.001). No difference in pharmacological treatment was observed between the groups. Twin pregnancies with and without ICP had comparable pregnancy outcomes; however, ICP pregnancies had a higher incidence of gestational diabetes mellitus (15.7% vs. 5.2%; p = 0.03). In repeat pregnancies, ICP was diagnosed earlier in the twin pregnancy (p = 0.006).
CONCLUSIONS: Compared to singleton pregnancies, twin pregnant women with ICP have an earlier diagnosis of ICP, and levels of bile acids are higher. Compared to twin pregnancies without ICP, the pregnancy outcomes are comparable.

BACKGROUND: Associated with adverse pregnancy outcomes, intrahepatic cholestasis of pregnancy is the most prevalent liver disease that women typically experience during pregnancy. This study aimed to evaluate prenatal comfort, sleep, and quality of life in pregnant women with cholestasis.
METHODS: This cross-sectional study was implemented between November 2022 and June 2023 at Mardin Training and Research Hospital with 150 pregnant women who received a diagnosis of pregnancy-induced intrahepatic cholestasis and agreed to participate. The following tools were utilized to collect data: A personal information form exploring socio-demographic and obstetric characteristics of participants, the Prenatal Comfort Scale (PCS), the Pittsburgh Sleep Quality Index (PSQI), and the World Health Organization Quality of Life-Brief Form (WHOQOL-BREF).
RESULTS: The mean age of participants was 27.79 ± 6.33 years. The mean PCS and PSQI scores were 61.20 ± 5.84 and 9.52 ± 3.02, respectively. The mean scores of \"physical health, psychological health, social relationships, and environmental health\" sub-dimensions in WHOQOL-BREF were 10.63 ± 2.18, 10.48 ± 2.10, 11.31 ± 3.28, and 11.27 ± 2.10, respectively. A significant difference was found for PSQI regarding hospitalization status and change in sleep quality variables (p = 0.025 and p = 0.035, respectively).
CONCLUSIONS: Cholestasis of pregnancy creates problems such as pruritus, body image changes, hospitalization, and poor sleep quality in women. This study showed that pregnant women with cholestasis had low levels of sleep quality and quality of life, implying that cholestasis affects their sleep quality, prenatal comfort levels, and quality of life in general. In addition, it is seen that women with this problem do not want to fall pregnant again.

UNASSIGNED: Research on intrahepatic cholestasis of pregnancy (ICP) has recently gained attention. However, no bibliometric analysis was performed in the ICP research field. Therefore, the present study aimed to use bibliometric analysis to analyze the current research hotspots and identify global research status in ICP to reference for future research directions.
UNASSIGNED: We comprehensively searched the Web of Science Core Collection (WoSCC) database from its inception to December 31, 2023. Articles and reviews related to ICP were downloaded as plain text file records. We used the VOSviewer and Citespace to perform the bibliometric analysis and visualization. The main bibliometric features were tabulated and calculated.
UNASSIGNED: A total of 1092 documents, including 921 original articles and 171 reviews, were identified in WoSCC. These publications were published in 395 journals by 4751 authors from 1250 institutions and 61 countries/regions. The global publication numbers exhibited a gradual upward trend. China, the United States, and the United Kingdom were top contributors to scientific research on ICP. King\'s College London, London Imperial Coll Sci Technol & Med, and Sichuan University were the most productive institutions. Catherine Williamson had published the most papers and received the most total citations. The most productive journal was Journal of Maternal-Fetal & Neonatal Medicine. The most cited paper was Beuers et al. in the Journal of Hepatology (2009). Citation burst terms showed that \"risk factors\" and \"perinatal outcomes\" were hotspots. \"Inflammation\", \"risk factors\", \"perinatal outcomes\", and \"bile acid\" have gained attention in more recent research.
UNASSIGNED: The present study comprehensively summarizes the global research status and research trends in ICP. Our study identifies hotspots, collaborative networks, and trends that will provide new insights and guidance for further research in the field.

Because of the pathological indication and the physiological functions, bile acids (BAs) have occupied the research hotspot in recent decades. Although extensive efforts have been paid onto BAs sub-metabolome characterization, as the subfamily, BA glucuronides (gluA-BAs) profile is seldom concerned. Here, we made efforts to develop a LC-MS/MS program enabling quantitative gluA-BAs sub-metabolome characterization and to explore the differential species in serum between intrahepatic cholestasis of pregnancy (ICP) patients and healthy subjects. To gain as many authentic gluA-BAs as possible, liver microsomes from humans, rats, and mice were deployed to conjugate glucuronyl group to authentic BAs through in vitro incubation. Eighty gluA-BAs were captured and subsequently served as authentic compounds to correlate MS/MS spectral behaviors to structural features using squared energy-resolved MS program. Optimal collision energy (OCE) of [M-H]->[M-H-176.1]- was jointly administrated by [M-H]- mass and glucuronidation site, and identical exciting energies corresponding to 50% survival rate of 1st-generation fragment ion (EE50) were observed merely when the aglycone of a gluA-BA was consistent with the suspected structure. Through integrating high-resolution m/z, OCE, and EE50 information to identify gluA-BAs in a BAs pool, 97 ones were found and identified, and further, quantitative program was built for all annotated gluA-BAs by assigning OCEs to [M-H]->[M-H-176.1]- ion transitions. Quantitative gluA-BAs sub-metabolome of ICP was different from that of the healthy group. More GCDCA-3-G, GDCA-3-G, TCDCA-7-G, TDCA-3-G, and T-β-MCA-3-G were distributed in the ICP group. Above all, this study not only offered a promising analytical tool for in-depth gluA-BAs sub-metabolome characterization, but also clarified gluA-BAs allowing the differentiation of ICP and healthy subjects.

OBJECTIVE: To evaluate the association of GDM and pre-eclampsia in women with obstetric cholestasis.
METHODS: Pregnant women with > 28 weeks gestation attending ANC, OPD and labor room of J.N.M.C.H, AMU, Aligarh UP (India) from 2020 to 2022 were included in the study after taking informed consent and ethical approval from the Institute. Women were divided into 2 groups, i.e. group 1 having 200 women with IHCP and group 2 having 200 healthy pregnant women; both the groups were followed up for the development of GDM and pre-eclampsia.
RESULTS: A statistically significant association was observed between IHCP and development of GDM [26.5% and odds ratio (OR) 1.64] and pre-eclampsia (17% and OR: 1.95) (p < 0.05), an also GDM and pre-eclampsia were found to be significantly associated with the severity of cholestasis (p < 0.05). Thus, on calculating OR, we found higher odds of developing GDM and pre-eclampsia in IHCP group with raised serum bile acid levels, maximum at 60 μmol/L level as compared to 10-40 μmol/L (GDM: OR: 8.647 and pre-eclampsia: OR: 6.303). Induction and cesarean rates were significantly higher in IHCP group (p < 0.05).
CONCLUSIONS: Our study concludes significant association of IHCP with GDM and pre-eclampsia as all three shares common pathogenetic pathways and greater risk of development at higher serum bile acid levels.