Diagnosis Of Intrahepatic Cholestasis Of Pregnancy Research Articles

The effect of twin pregnancy in intrahepatic cholestasis of pregnancy: A case control study.

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. 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. 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). 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.

Is the Risk of Intrahepatic Cholestasis Increased with Supplemental Progesterone?

This study aimed to evaluate the relationship between supplemental progesterone use during pregnancy and the development of intrahepatic cholestasis of pregnancy (ICP). A retrospective, matched case-control study was conducted among a population of women who delivered at George Washington University Hospital (GW) between 2012 and 2022. Women diagnosed with ICP (cases) were identified using International Statistical Classification of Diseases (ICD) codes, and data were collected via chart abstraction. Descriptive data included patient demographics, pregnancy characteristics, and medical history. Laboratory values related to ICP were collected. Cases were matched on a 1:3 ratio by maternal age, body mass index, and gravidarum to women who delivered at GW during the same month and did not carry a diagnosis of ICP (controls). A univariate logistic regression model was created to assess the use of supplemental progesterone between groups, adjusting for the use of assisted reproductive technology in the current pregnancy, and a history of liver disease. One hundred and twenty women who delivered during the study period were confirmed to have a diagnosis of ICP. Cases were matched with 360 controls and measures compared between the two groups. Cases were significantly more likely to have a history of liver disease (5.9 vs. 1.7%, p = 0.0021), multiple gestation (10.0 vs. 3.3%, p < 0.0001), a history of ICP in a previous pregnancy (10.0 vs. 0%, p < 0.0001), and to have delivered at an earlier gestational age (mean 37.1 vs. 38.6 weeks, p < 0.0001) as compared with controls. No differences were seen in the odds of supplemental progesterone use in both unadjusted and adjusted models (OR 1.14, 95% CI 0.30-4.34; adjusted Odds Ratio [aOR] 0.98 0.24-3.94). Contrary to recent evidence, no association was seen with the use of supplemental progesterone. It is possible that the associated risk with supplemental progesterone is dependent on medication formulation or route of administration. · Supplemental progesterone use in pregnancy may increase the risk of developing ICP.. · Previous investigations of progesterone and ICP have demonstrated mixed results.. · The association may be dependent on the route of administration and formulation of progesterone..

Characteristics and diagnostic value of serum bile acids profile in pregnant women with intrahepatic cholestasis of pregnancy and asymptomatic hypercholanemia of pregnancy

Objective: To analyze serum bile acid profiles in pregnant women with normal pregnancy, intrahepatic cholestasis of pregnancy (ICP) and asymptomatic hypercholanemia of pregnancy (AHP), and to evaluate the application value of serum bile acid profiles in the diagnosis of ICP and AHP. Methods: The clinical data of 122 pregnant women who underwent prenatal examination in Xuzhou Maternal and Child Health Care Hospital from June 2022 to May 2023 were collected, including 54 cases of normal pregnancy group, 28 cases of ICP group and 40 cases of AHP group. Ultraperformance liquid chromatography-tandem mass spectrometry was used to measure the levels of 15 serum bile acids in each group, including cholic acid (CA), chenodeoxycholic acid (CDCA), deoxycholic acid (DCA), lithocholic acid (LCA), ursodeoxycholic acid (UDCA), glycolcholic acid (GCA), glycochenodeoxycholic acid (GCDCA), glycodeoxycholic acid (GDCA), glycolithocholic acid (GLCA), glycoursodeoxycholic acid (GUDCA), taurocholic acid (TCA), taurochenodeoxycholic acid (TCDCA), taurodeoxycholic acid (TDCA), taurolithocholic acid (TLCA) and tauroursodeoxycholic acid (TUDCA). Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to screen differential bile acids. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of differential bile acids and combined indicators between groups. Results: (1) Compared with normal pregnancy group, the serum levels of LCA, GCA, GCDCA, GDCA, GLCA, UDCA, TCA, TCDCA, TDCA, TLCA, GUDCA and TUDCA in ICP group were significantly different (all P<0.05), while the levels of LCA, DCA, GCA, GCDCA, GDCA, GLCA, TCA, TCDCA, TDCA, TLCA, GUDCA and TUDCA in AHP group were significantly different (all P<0.05). Compared with ICP group, the serum levels of CDCA, DCA, UDCA, TDCA, GUDCA and TUDCA in AHP group were significantly different (all P<0.05). (2) In the OPLS-DA model, the differential bile acids between ICP group and AHP group were TUDCA, TCA, UDCA, GUDCA and GCA, and their variable importance in projection (VIP) were 1.489, 1.345, 1.344, 1.184 and 1.111, respectively. TCA, GCDCA, GCA, TDCA, GDCA and TCDCA were the differentially expressed bile acids between AHP group and normal pregnancy group, and their VIP values were 1.236, 1.229, 1.197, 1.145, 1.139 and 1.138, respectively. (3) ROC analysis showed that the area under the curve (AUC) of TUDCA, TCA, UDCA, GUDCA and GCA in the differential diagnosis of ICP and AHP was 0.860, and the sensitivity and specificity were 67.9% and 95.0%, respectively. The AUC of TCA, GCDCA, GCA, TDCA, GDCA and TCDCA in the diagnosis of AHP was 0.964, and the sensitivity and specificity were 95.0% and 93.1%, respectively. Conclusions: There are differences in serum bile acid profiles among normal pregnant women, ICP and AHP. The serum bile acid profiles of pregnant women have potential application value in the differential diagnosis of ICP and AHP and the diagnosis of AHP.

Intrahepatic Cholestasis of Pregnancy during COVID-19 Pandemic.

Background and Objectives: Intrahepatic cholestasis of pregnancy (ICP) stands as one of the most prevalent concerns in maternal-fetal medicine, presenting a significant risk to fetal health and often associated with liver dysfunction. Concurrently, the coronavirus-19 (COVID-19) infection can lead to hepatic cell injury through both direct and indirect pathways. Hypothetically, these two conditions may coincide, influencing each other. This study aimed to comparatively assess the incidence and severity of ICP before and during the COVID-19 pandemic. Methods: A retrospective cohort study was conducted, comparing the incidence and severity of ICP between January 2018 and February 2020 (pre-COVID-19 period) and March 2020 to March 2022 (COVID-19 period) across two hospitals, encompassing 7799 deliveries. The diagnosis of ICP was established using the ICD-10 code and defined as total bile acids (BA) levels ≥ 10 μmol/L. Statistical analysis included descriptive statistics, Chi-square and Mann-Whitney U tests, as well as multiple or logistic regression analysis. Results: A total of 226 cases of ICP were identified. The incidence of mild cholestasis (BA < 40 μmol/L) was lower during the pandemic compared to before (3% before versus 2%, p < 0.05), while the incidence of moderate and severe ICP remained unchanged (0.6% before vs. 0.4%, p = 0.2). Overall, the total incidence of ICP was lower during the pandemic (3.6% before versus 2.4%, p = 0.01). No significant differences were observed in severity (as defined by BA and liver function test levels), rates of caesarean section, or neonatal birth weights. Conclusions: During the COVID-19 pandemic, the total incidence of ICP appeared to be lower. However, this reduction was primarily observed in cases of mild ICP, potentially indicating challenges in detection or reduced access to medical services during this period. The incidence of moderate and severe ICP remained unchanged, suggesting that these forms of the condition were unaffected by the pandemic's circumstances.

Metabolomic profiling of serum and tongue coating of pregnant women with intrahepatic cholestasis in pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of cesarean section and adverse fetal outcomes. Currently, ICP diagnosis depends largely on serum levels of bile acids and lacks sensitivity and specificity for accurate diagnosis. Tongue diagnosis is an important diagnostic tool in traditional Chinese medicine (TCM) and is used in our clinic as complementary treatment and personalized medicine for ICP. However, the molecular basis of the manifestation of greasy white tongue coatings in ICP remains unknown. In this study, we performed untargeted metabolomic profiling of the serum, tongue coating, and saliva of 66 pregnant women, including 22 with ICP. The metabolomic profiles of the serum and tongue coatings showed marked differences between the two clinical groups. Forty-six differentially abundant metabolites were identified, and their relative concentrations correlated with total bile acid levels. These differential metabolites included bile acids, lipids, microbiota- and diet-related metabolites, and exposomes. Conventional biochemical markers, including serum aminotransferases and bilirubin, were not significantly increased in the ICP group, whereas the total cholesterol and triglyceride levels were significantly increased as early as the first trimester. Our data provide insights into the pathophysiology of ICP and implicate the gut-liver axis and environmental exposure. Tongue coating has the potential to be a non-invasive diagnostic approach. Further studies are required to validate the clinical utility of these findings.

Exosomes from Intrahepatic Cholestasis of Pregnancy Induce Cell Apoptosis Through the miRNA-6891-5p/YWHAE Pathway.

Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse pregnancy outcomes; however, the underlying mechanisms are not fully understood. This study aimed to determine the role of exosomal miR-6891-5p in placental trophoblast dysfunction in ICP and identify new biomarkers for ICP diagnosis. Serum samples were collected from ICP patients and healthy pregnant women, and serum exosomes were extracted and identified. Fluorescent dye labeling of exosomes and cell-verified cell phagocytosis were performed. In vitro experiments were conducted by adding taurocholic acid to simulate the ICP environment. Cell proliferation and apoptosis levels were detected using flow cytometry and the cell counting kit-8 assay. Mimics were constructed to overexpress miR-6891-5p in cells, and the binding site between miR-6891-5p and YWHAE was verified using luciferase reporter genes. miR-6891-5p expression was significantly decreased in serum exosomes of ICP patients. Co-culturing with exosomes derived from ICP patients' serum (ICP-Exos) decreased HTR-8/SVeno cell proliferation and increased apoptosis levels. miR-6891-5p upregulation in HTR-8/SVeno cells significantly increased cell viability and reduced cell apoptosis levels, as determined by the cell counting kit-8 assay and flow cytometry. A double luciferase assay confirmed that miR-6891-5p affected the expression of the downstream YWHAE protein. This study indicates that serum exosomes from ICP patients can impact the apoptosis of placental trophoblast HTR-8/SVeno cells through the miR-6891-5P/YWHAE pathway and can serve as specific molecular markers for ICP diagnosis.

An omics review and perspective of researches on intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is one of the common pregnancy complications that may threaten the health of both pregnant women and their fetuses. Hence, it is of vital importance to identify key moleculars and the associated functional pathways of ICP, which will help us to better understand the pathological mechanisms as well as to develop precise clinical biomarkers. The emerging and developing of multiple omics approaches enable comprehensive studies of the genome, transcriptome, proteome and metabolome of clinical samples. The present review collected and summarized the omics based studies of ICP, aiming to provide an overview of the current progress, limitations and future directions. Briefly, these studies covered a broad range of research contents by the comparing of different experimental groups including ICP patients, ICP subtypes, ICP fetuses, ICP models and other complications. Correspondingly, the studied samples contain various types of clinical samples, in vitro cultured tissues, cell lines and the samples from animal models. According to the main research objectives, we further categorized these studies into two groups: pathogenesis and diagnosis analyses. The pathogenesis studies identified tens of functional pathways that may represent the key regulatory events for the occurrence, progression, treatment and fetal effects of ICP. On the other hand, the diagnosis studies tested more than 40 potential models for the early-prediction, diagnosis, grading, prognosis or differential diagnosis of ICP. Apart from these achievements, we also evaluated the limitations of current studies, and emphasized that many aspects of clinical characteristics, sample processing, and analytical method can greatly affect the reliability and repeatability of omics results. Finally, we also pointed out several new directions for the omics based analyses of ICP and other perinatal associated conditions in the future.

Systemic Inflammation Response Index as a diagnostic and prognostic predictor of intrahepatic cholestasis of pregnancy: A case-control study from a tertiary center.

To investigate the diagnostic and prognostic value of the Systemic Inflammation Response Index (SIRI) in intrahepatic cholestasis of pregnancy (ICP). The present case-control study comprised 386 participants, including 192 women with ICP and 194 gestational age-matched pregnant women. Increased fasting biliary acid (FBA) levels (≥10 μmol/L) were accepted as ICP criteria. SIRI values were calculated for the first trimester (SIRI 1), time of diagnosis (SIRI 2), and time of delivery (SIRI 3). The ICP and control groups were compared based on SIRI values, and on obstetrical and neonatal outcomes. The ICP subgroups based on FBA levels (severe ICP [FBA ≥40 μmol/L] and mild ICP [FBA <40 μmol/L]) were also compared for SIRI and pregnancy outcomes. Adverse outcomes were significantly higher in the ICP group (P < 0.001). SIRI 2 and SIRI 3 showed negative significant differences between the ICP and control groups, with P values of 0.001 and 0.009, respectively. A significant difference in ICP severity subgroups (P = 0.046) was observed for SIRI 3. In receiver operating characteristics curve analyses, optimal cut-off values for the prediction of ICP were found to be 2.01 and 2.08 for SIRI 2 and SIRI 3, respectively. A cut-off value 1.74 was determined to predict the disease severity for SIRI 3. SIRI has clinical significance in accordance with the inflammatory etiology of ICP. SIRI might be used with other clinical and laboratory findings for ICP diagnosis and prediction.

Pregnancy outcomes following antenatal screening for intrahepatic cholestasis of pregnancy (ICP)

ObjectiveTo evaluate the maternal and perinatal outcomes following antenatal screening for ICP using a retrospective approach. Materials and methodsA retrospective study was conducted at the second affiliated hospital of Chongqing Medical University, Chongqing, China, from 2012 to 2017. Pregnant women registered for antenatal in our hospital were screened for ICP. The pregnant women with detailed delivery record and presenting with the diagnosis of ICP based on TBA level ≥10 mmol/L and abnormal liver enzymes were included in the study. MethodThe pregnant women with detailed delivery records presenting with the diagnosis of ICP based on TBA level ≥10 mmol/L and abnormal liver enzymes were included in the study. 1410 pregnant women were enrolled in this study. We selected 940 pregnant women without the diagnosis of ICP as our control and 470 pregnant women diagnosed with ICP as our case study. Data collection and sampling in the control group was done using microsoft excel (version 16.61) random number generator. ResultsThe mean age of the pregnant women and the gestational age at the time of diagnosis of ICP were 29.01 ± 4.3 years and 31.90 ± 8.83 weeks, respectively. It was found that a significant number of patients with ICP had a preterm birth and low birth weight (LBW), n = 151 (32.5%) P < 0.001 and n = 70 (14.9%) P < 0.001, respectively. A significant number of patients in the case group had a history of liver disease and gall bladder disease, p < 0.001 and p = 0.005, respectively, and a higher rate of GDM p < 0.001. Despite treatment, high TBA titer among ICP patients was associated with preterm delivery. ConclusionICP in pregnancy leads to complications and poor perinatal outcomes. Fetal outcomes depend on the TBA levels; therefore, early diagnosis of ICP through routine screening followed by treatment is recommended in high-risk persons/areas.

Could real-time sonoelastography-measured placental strain ratio (PSR) value be a soft marker for the diagnosis of intrahepatic cholestasis of pregnancy?: A case-control study and short reviews.

Diagnosis of intrahepatic cholestasis of pregnancy (ICP) is often decided upon with typical pruritus supported by elevated serum bile acid levels. However, there is confusion regarding the absolute reference range for serum bile acid . To confirm the utility of Placental Strain Ratio (PSR) measurement as a marker for the diagnosis of ICP and to reveal the extent to which it is correlated with serum bile acid concentration. A case-control study was conducted. The case group included 29 patients who were admitted to our hospital in the second or third trimester of pregnancy with typical itching and were clinically diagnosed with ICP with >10 mmol/L serum bile acid. The first 45 pregnant women were assigned to a control group. Real-time tissue elastography software was used for ultrasound assessment of all pregnant placentas. Software was used to estimate the SR values. Biochemical liver function parameters, hemograms, serum bile acid levels, and SR values were compared between these groups. PSR was found to predict the development of cholestasis with poor discrimination (area under the curve [AUC] = 0.524; 95% CI = 0.399-0.646). The optimal threshold value with the best sensitivity and specificity rates was calculated to be 0.46 PSR. ICP developed significantly more frequently in the low PSR group than in the high PSR group (60% vs 29.3%, P = .05, odds ratios [OR] = 0.276, 95% CI = 0.069-1.105). No correlation was found between the PSR and bile acid levels (rho = -0.029, P = .816). PSR values can support the diagnosis of ICP, predict serum bile acid levels, and can be used as soft markers.

Maternal and Neonatal Outcomes in Intrahepatic Cholestasis of Pregnancy.

The aims of our study were to evaluate the maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP). In this observational, retrospective case-control study, we included all pregnant women who gave birth with a diagnosis of ICP between January 2010 and December 2020 at the Unit of Obstetrics and Gynecology, University Hospital of Messina. The data were compared with those from a control group of pregnant women who did not have ICP. One hundred twenty-nine and eighty-five patients were included, respectively, in the study and in the control group. There was a significant difference between the two groups in the incidence of hypothyroidism, thrombophilia, gestational diabetes, gestational hypertension, postpartum hemorrhage, and preterm delivery, which were more frequent in the ICP patients. No neonatal adverse events were recorded, although a significant difference in the meconium-stained amniotic fluid condition was noted. After a 24-month follow-up, 48/129 patients with ICP accepted to be reassessed by liver ultrasound, elastographic examination, and liver function blood tests. No patient showed signs of chronic liver disease. This study confirmed a higher probability of adverse short-term maternal outcomes in ICP pregnant patients, but a lower probability of adverse short-term fetal outcomes and the absence of a long-term maternal risk of chronic liver disease.

Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy is associated with a 4- to 10-fold increase in the risk of stillbirth in the absence of intervention, leading to recommendations for antenatal assessment, ursodiol use, and often preterm or early term delivery. This study aimed to determine whether current management strategies for intrahepatic cholestasis of pregnancy mitigate the elevated risk of stillbirth at a population level. This was a retrospective cohort study using the 2015-2020 National Readmissions Database, an administrative database developed by the United States Agency for Healthcare Research and Quality. Our study identified delivery hospitalizations, gestational age at delivery, occurrence of intrahepatic cholestasis of pregnancy and stillbirth, and comorbid conditions using the International Classification of Diseases diagnosis and procedure codes. Moreover, this study compared the timing of delivery and stillbirth rates of pregnant patients with intrahepatic cholestasis of pregnancy vs those without intrahepatic cholestasis of pregnancy at the time of delivery hospitalization. This study identified a cohort of 9,987,705 delivery hospitalizations in the National Readmissions Database, corresponding to a weighted national estimate of 18,609,207 births. Of these births, 152,040 (0.8%) were noted to have an intrahepatic cholestasis of pregnancy diagnosis. Patients with an intrahepatic cholestasis of pregnancy diagnosis were older, with small differences in comorbidities, such as a higher rate of gestational diabetes mellitus, than patients without an intrahepatic cholestasis of pregnancy diagnosis at delivery hospitalization. The overall rates of stillbirth were lower among those with intrahepatic cholestasis of pregnancy than among those without intrahepatic cholestasis of pregnancy (252 vs 386 per 100,000 deliveries; risk difference, 133 fewer per 100,000 deliveries; 95% confidence interval, 98-170), a finding that persisted after adjustment for insurance status, socioeconomic factors, and comorbid conditions (risk difference, 160 fewer stillbirths per 100,000 deliveries; 95% confidence interval, 127-194). Furthermore, although patients with intrahepatic cholestasis of pregnancy were more likely to deliver before term than those without intrahepatic cholestasis of pregnancy (30.1% vs 9.3%; P<.001), increased rates of stillbirth were not noted at any point after stratification of the cohort by gestational age at delivery. Patients with intrahepatic cholestasis of pregnancy diagnosis codes delivered earlier than those without intrahepatic cholestasis of pregnancy diagnosis codes, but the percentage of births affected by stillbirth was lower, even when stratifying for gestational age at birth. These results may provide reassurance to patients receiving an intrahepatic cholestasis of pregnancy diagnosis that current management does mitigate stillbirth risk in intrahepatic cholestasis of pregnancy.

A comprehensive review of novel biomarkers in the diagnosis of intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a disease specific to pregnancy, featuring maternal itching and elevated serum bile acid levels. It leads to a series of adverse pregnancy outcomes as well as increased fetal mortality. Routine biochemical markers fail to fulfill the tremendous clinical requirements, thereby novel effective biomarkers are urgently desired. In our review, the potential novel biomarkers for ICP diagnosis are classified into four categories and elaborated in detail. The concrete diagnostic performances (sensitivity, specificityand area under the curve) of these biomarkers are demonstrated in tables. Moreover, the relationships between some biomarkers and ICP pathogenesis are briefly expounded. Nevertheless, only a few novel biomarkers are ideal, and their clinical applicability requires more evidence from larger multicenter trials.

Metabolic changes in bile acids with pregnancy progression and their correlation with perinatal complications in intrahepatic cholestasis of pregnant patients

Intrahepatic cholestasis of pregnancy (ICP) is a rare liver disease occurring during pregnancy that is characterized by disordered bile acid (BA) metabolism. It is related to adverse clinical outcomes in both the mother and fetus. Our aim was to evaluate the BA metabolism profiles in different types of ICP and investigate the association between specific BAs and perinatal complications in ICP patients. We consecutively evaluated 95 patients with ICP, in which 53 patients were diagnosed with early-onset ICP (EICP) and 42 patients were diagnosed with late-onset ICP (LICP). Concentrations of 15 BA components were detected using high-performance liquid chromatography tandem mass spectrometry. Clinical information was abstracted from the medical records. The percentage of conjugated bile acids increased in ICP patients. Specifically, taurocholic acid (TCA) accumulated in LICP patients, and glycocholic acid (GCA) predominated in EICP patients. A higher preterm birth incidence was observed among ICP patients. Albumin, total bile acids, total bilirubin and GCA percentage values at ICP diagnosis predicts 83.5% of preterm birth in EICP, and the percentage of TCA in total bile acids at ICP diagnosis predicts 93.2% of preterm birth in LICP. This analysis showed that the BA metabolism profiles of EICP and LICP were distinct. Increased hepatic load was positively correlated with preterm birth in EICP. An elevated TCA percentage in total bile acids provides a biomarker to predict preterm birth in LICP.

Placental exosomal level of alanine aminotransferase is more accurate predictive biomarker of intrahepatic cholestasis of pregnancy than total bile acid

Aims: As a serious liver abnormality, intrahepatic cholestasis of pregnancy (ICP) uniquely occurs in pregnant women. In the present study, we examined whether placental exosomes and their protein contents could serve as novel indicators to help early diagnosis of ICP.&#x0D; Methods: The current retrospective stratified study design included a 100 healthy pregnant females and a 100 patients with ICP. Plancental exosomes were isolated to determine the exosomal levels of alanine aminotransferase (ALT) and total bile acid (TBA). The predictive values of placental exosomal TBA and ALT were determined using receiver operating characteristic (ROC) curve analysis.&#x0D; Results: The placental exosomal TBA level did not exhibit any obvious differences between healthy and ICP pregnancies. Moreover, placental exosomal ALT level was significantly higher in ICP-affected pregnancy than healthy control. Analysis of the ROC curve further demonstrated that placental exosomal level of ALT yields better sensitivity and specificity to distinguish ICP patients from healthy individuals, than that of TBA.&#x0D; Conclusions: Placental exosomal ALT is a more accurate predictive biomarker of ICP than TBA and, therefore, can be employed with reliability as a characteristic abnormality in diagnosis of ICP.

Hematological Markers: Testing a new diagnostic modality for Intrahepatic Cholestasis of pregnancy

Background: Intrahepatic Cholestasis of pregnancy (ICP) is the most common pregnancy specific liver disorder presenting usually in the 3rd trimester with unexplained pruritis, elevated serum bile acids and/or raised liver enzymes. ICP is associated with adverse perinatal outcomes. Serum total bile acids (TBA) are considered as a gold standard for diagnosis of ICP but are time consuming, expensive and not readily available everywhere. Neutrophil to Lymphocyte ratio (NLR), Mean Platelet Volume (MPV) and Red cell Distribution Width (RDW) are haematological inflammatory markers and are routinely available on a simple complete blood count test when asked for. Aims: To study the role of haematological inflammatory markers in Intrahepatic Cholestasis of Pregnancy (ICP) and their association with the severity of the disease. Methods: This prospective case-control study was done in a tertiary care setting in New Delhi, from January 2021- August 2022(20 months) wherein 82 women with ICP were recruited after a written and informed consent. NLR, MPV, RDW and TBA levels were done. 82 healthy women with uncomplicated pregnancies served as the control group. Results: Both cases &amp; controls were comparable in terms of sociodemographic characteristics. Mean TBA levels were 22.85+/-7.82 in mild cases(60 subjects) &amp; 66.20+/-26.97 (22 severe cases). Cases delivered earlier between 37–38 weeks. Majority of women delivered vaginally &amp; was statistically significant. Cases developed more fetal distress(42.7% vs 9.8%) NLR and MPV were significantly raised (p&lt;0.05) while RDW was lower in cases. The cut off for NLR &amp; MPV were statistically significant. Conclusion: MPV can serve as a good screening tool, a high sensitivity (95.1%) while NLR can serve as a confirmatory test as it has high specificity (96.3%) to make diagnosis of ICP, although further exploration with larger multicentric studies is required.

Fibrinogen Levels and Total Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy.

To determine the role of complete blood count and coagulation function factors as inflammatory markers in intrahepatic cholestasis of pregnancy (ICP). Descriptive, analytical study. Department of Obstetrics and Gynecology, Bursa Yüksek İhtisas Training and Research Hospital, Bursa, Turkey, between January 2018 and 2021. This study was conducted with a total of 200 pregnant women, 80 with ICP and 120 control healthy pregnant women. The diagnosis of ICP was made based on elevated liver enzymes and bile acids (≥10 μmol/L) and pruritis. Routine complete blood count parameters and coagulation function tests were compared between both groups. ROC analyses were used to analyse the predictive value of fibrinogen levels in ICP. Spearman's rank correlation analysis assessed the correlation between fasting bile acid value and complete blood count and coagulation parameters. Neutrophil-lymphocyte ratio (NLR), Platelet count, and Platecrit levels were significantly higher in the ICP group, and red blood cell distribution width (RDW) was lower than in the healthy group (p <0.05). The median plasma fibrinogen value was 571 mg/dl which was significantly higher in pregnant women with cholestasis (p <0.001). The prothrombin time and international normalized ratio (INR) values were also significantly different in each group (p <0.001 and 0.013, respectively). In addition, platelet distribution width (PDW), plasma fibrinogen, and prothrombin time (PT) showed significant association with the bile acid values (p values=0.007, 0.03, and 0.04 respectively). Each 1-unit elevation of the fibrinogen increased the risk of cholestasis by 1.02 times. There was a positive correlation of 0.24-fold between the plasma fibrinogen value and acids. The plasma fibrinogen value was the highest predictor of cholestasis diagnosis by analyzing blood parameters. Elevated fibrinogen levels correlated with bile acid levels, can potentially detect ICP. Bile acids, Cholestasis, Coagulation function parameters, Fibrinogen levels, Inflammation.

Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022.

Intrahepatic cholestasis of pregnancy: Green-top Guideline No. 43 June 2022.

The alcohol dehydrogenase isoenzyme (ADH I) as a marker of intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is an important pregnancy liver disorder. The alterations of different enzymes activity in the hepatocytes in the course of liver diseases are reflected in an increase in the activity of the corresponding enzymes in the blood. In present study we assayed the activity of alcohol dehydrogenase (ADH) and its isoenzyme in the serum of patients with ICP. Serum were collected from 100 pregnancies with ICP in the second or third trimester of pregnancy. Serum samples were also taken from 100 healthy pregnant women. The activity of ADH I was measured by spectrofluorometric method, ADH total was measured by photometric method. There was significant increase in the activity of ADH I (2.79 mU/l vs. 1.72 mU/l) and total ADH activity (1103 mU/l vs. 682 mU/l) in the sera of women with ICP compared to the healthy pregnant women. Importantly, the sensitivity and specificity of ADH I for diagnosis of ICP were 85% and 91%, respectively. Area under the Receiver Operating Curve for ADH I in ICP was 0.81. The activity of ADH I in the sera of women with ICP is statistically significantly increased, which may have a diagnostic significance for ICP patients.

Intrahepatic cholestasis of pregnancy - Time to redefine the reference range of total serum bile acids: A cross-sectional study.

ObjectiveTo establish pregnancy‐specific reference ranges for fasting and postprandial total serum bile acid (TSBA) concentrations.DesignCross‐sectional study.SettingTertiary‐care university hospital.PopulationHealthy 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.MethodsBoth 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 measuresFasting and postprandial TSBA concentrations in 612 women.ResultsReference 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)ConclusionsNormal 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 abstractNormal pregnancy is associated with mild hypercholanaemia, a higher threshold should be considered for the diagnosis of ICP.