Cholestasis Of Pregnancy Research Articles

Systematic review and meta-analysis: Evaluating the influence of intrahepatic cholestasis of pregnancy on obstetric and neonatal outcomes.

Intrahepatic cholestasis of pregnancy (ICP) is a serious liver conditions that negatively impacts obstetric and neonatal outcomes. Elevated levels of bile acid, particularly glycine conjugate, may compromise blood flow and cause functional hypoxia-ischemia. This meta-analysis aims to assess the association between ICP and key pregnancy outcomes including emergency caesarian sections (C-sections), preeclampsia, hemorrhage, preterm birth, small for gestational age, admission rate to neonatal intensive care union (NICU), gestational age, and stillbirth. Literature search across five databases (PubMed, Embase, Web of Science) was done to detect relevant studies published up until June 2023. Meta-analysis of the identified studies was done using a random-effects model, and the results presented as Odds ratio (OR). A literature search identified 662 studies. Of them, 21 met the inclusion criteria. There was a significant association between ICP and odds of C-section (OR: 1.42, p <0.001), preeclampsia (OR: 2.64, p <0.001), NICU admission (OR: 2.1, p <0.001), and pre-term birth (OR: 2.64, p <0.001). ICP was not associated with postpartum hemmorhage (OR: 1.31, p = 0.13), small for gestational age (OR: 0.87, p = 0.07), stillbirth (OR: 1.49, p = 0.29). Our results confirm the adverse effects of ICP on co-existing pregnancy complications, obstetric and neonatal outcomes. ICP in associated with severe complications including increased rates of preeclampsia, emergency C-sections, preterm births, l gestational periods and higher rates of NICU admissions. These results may assist healthcare professionals in formulating comprehensive care guidelines for expectant mothers and newborns.

Association of gestational hepatitis B virus infection and antiviral therapy with pregnancy outcomes: A retrospective study.

To explore the relationships between gestational hepatitis B virus (HBV) infection, antiviral therapy, and pregnancy outcomes. We retrospectively selected hepatitis B surface antigen (HBsAg)-positive pregnant women hospitalized for delivery at Fujian Medical University Affiliated Hospital from October 1, 2016 to October 1, 2020. The control group included randomly selected healthy pregnant women hospitalized for delivery during the same time. Overall, 1115 participants were enrolled and grouped into control (n = 380) and HBsAg-positive groups (n = 735), which were further divided into groups I (n = 407; low viral load), II (n = 207; high viral load without antiviral therapy), and III (n = 121; high viral load with antiviral therapy). Pregnant women with HBV were positively correlated with the incidence of intrahepatic cholestasis of pregnancy (ICP) (adjusted odds ratio [aOR] 5.1, 95% confidence interval [CI] 2.62-9.92, P < 0.001), neonatal jaundice (aOR 10.56, 95% CI 4.49-24.83, P < 0.001), and neonatal asphyxia (aOR 5.03, 95% CI 1.46-17.27, P = 0.01). Aspartate aminotransferase (AST) greater than the upper limit of normal (ULN) was an independent risk factor for increased ICP incidence (aOR 3.49, 95% CI 1.26-9.67, P = 0.019). Antiviral therapy considerably reduced HBV DNA and improved liver function. High viral load and antiviral therapy did not correlate significantly with adverse pregnancy outcomes (P < 0.05). Pregnant women with HBV have significantly elevated incidence of ICP, neonatal jaundice, and neonatal asphyxia not significantly correlated with viral load. AST greater than ULN independently increases the risk of ICP. Antiviral therapy effectively reduces viral replication and improves liver function without increasing the risk of adverse outcomes.

LC-MS/MS untargeted lipidomics uncovers placenta lipid signatures from intrahepatic cholestasis of pregnancy.

Aims: Intrahepatic cholestasis of pregnancy (ICP) stands as the predominant liver disorder affecting pregnant women, with a prevalence ranging from 0.2% to 15.6%. While ICP is known to heighten the chances of perinatal mortality and morbidity, its pathogenesis remains elusive, and therapeutic options are limited. The objective of this study was to explore the characteristic lipid signature in placentas collected from normal pregnancies and those with mild and severe intrahepatic cholestasis of pregnancy. This research aims to clarify the pathogenesis and identify lipid biomarker for ICP through LC-MS/MS based lipidomic analysis. Methods and materials: Placenta samples were collected from 30 normal pregnancy women and 30 mild and severe ICP women respectively. Women with normal pregnancy and ICP were recruit from April 2021 to July 2022 in Chengdu, China. And LC-MS/MS based lipidomic analysis was used to explore the characteristic placental lipids in mild and severe ICP. Results: Fourty-four lipids were differentially expressed both in mild and severe ICP placenta. The pathway analysis revealed these lipids are mainly enriched in glycerophospholipid metabolism and autophagy pathway. Weighted correlation network analysis (WGCNA) identified the correlation network module of lipids highly related to ICP. Using multiple logistic regression analysis, we identified three and four combined metabolites that had an area under receiver operating characteristic curves (AUC) ≥ 0.90. Conclusion: Our results systematically revealed the lipid signature in mild and severe ICP placenta. The results may provide new insight into the treatment and early prediction of ICP.

Associations of clinical subtypes and bile acid levels of intrahepatic cholestasis of pregnancy with pregnancy outcomes

Intrahepatic cholestasis of pregnancy (ICP) can lead to many adverse pregnancy outcomes, and the influencing factors remain unclear at present. This study retrospectively analyzed clinical data from 1815 pregnant women with ICP and evaluated the relationship between ICP subtypes, gestational age at onset, and pregnancy outcomes. The results of this study show that during pregnancy, the levels of biochemical indicators (TBA, DBIL and ALT) in the serum of pregnant women initially diagnosed with subtypes of ICP were noted to constantly change, and the subtype of ICP and its severity also changed. The incidence of adverse pregnancy outcomes [meconium-stained amniotic fluid (MSAF), NICU transfer, Apgar score ≤ 7 at 1 min, and preterm birth] in patients with ICP1 (icteric type) was significantly higher than for patients with ICP2, ICP3 or ICP4. The preterm birth rate of early-onset ICP was higher than that of late-onset ICP in ICP1 and ICP3 subtypes. In conclusion, the outcome of pregnancy in women with ICP is closely related to the serum TBA level and ICP subtype, which should be recognized in the clinic.

Cord blood troponin I levels: biomarker evidence of fetal cardiac injury in intrahepatic cholestasis of pregnancy

BackgroundIntrahepatic cholestasis of pregnancy (ICP) has been linked to sudden stillbirth. The suddenness of the stillbirths in these cases have led clinicians to suspect that the pathogenesis of stillbirth in women with ICP is not related to asphyxia but rather to an undefined etiology. One leading hypothesis relates certain bile acid metabolites to myocardial injury. ObjectiveThe purpose of this study is to determine whether cord blood troponin I levels are increased in fetuses born to mothers with the diagnosis of ICP. Study DesignA prospective case-control study was performed at a single institution between 2017-2019 which enrolled 87 pregnant patients with the diagnosis of ICP (total bile acids (TBA) ≥10μmol/L) as cases and 122 randomly selected pregnant patients (asymptomatic with intrapartum total bile acids <10μmol/L) as controls. Cord blood troponin I collection was performed at delivery in both groups using a commercially available chemiluminescent immunoassay. Values ≤0.04ng/ml were considered as negative. Values >0.04ng/ml were considered positive. The primary outcome was the presence of elevated troponin levels in both cases and controls as a surrogate marker for cardiac status. Our secondary outcomes included. NICU stay, low APGAR scores, neonatal acidosis and hypoxia represented by cord blood pH and base excess levels at time of birth. Chi square and t-tests were performed to compare social and obstetrical variables. A p value of <0.05 was considered significant. A stratification by TBA range of <40μmol/L, 40-100μmol/L, and >100μmol/L was performed to assess the relationship between the different severities of ICP (by risk of fetal demise, with TBA of >100μmol/L considered most at risk) and the likelihood of a positive troponin I result. Finally, a logistic regression analysis was performed in order to determine if levels of ≥10μmol/L were associated with elevated troponin levels. ResultsThe mean gestational age of at delivery was 38.96±1.47 and 37.71±1.59 weeks of gestation in the controls and cases respectively (p value <0.001). The mean TBA value for was 5.2±1.28ng/ml and 43.2±40.62ng/ml in the controls and cases respectively (p value <0.001). Cord blood troponin I was positive in 15 of 122 (12.30%) controls and in 20 of 87 (22.99%) cases. (p<0.001). When further stratified by TBA levels of <40, 40-100, and >100, we found a positive correlation between higher TBA levels and a positive troponin I test (p=0.002). When controlling for gestational age at delivery, maternal age and BMI, higher TBA levels were associated with a positive troponin I level (aOR 1.015 95% CI 1.004,1.026). ConclusionElevated troponin I was more likely to be found in patients with ICP than those without ICP. When stratified by TBA levels, a positive troponin I level was more likely to be found with higher levels of TBA. Additionally, as TBA levels increased, they were more likely to be associated with a positive troponin I level. Though there were no stillbirths in our cohort, our findings suggest a potential relationship between cardiac injury and high levels of TBA demonstrated by the presence of elevated troponin I levels in cord blood at the time of birth.

Assessing the relationship between intrahepatic cholestasis of pregnancy and exogenous progesterone intake

Abstract Aim: Progesterone metabolites are known to be elevated in the serum of patients with intrahepatic cholestasis of pregnancy (ICP), and exogenous progesterone supplementation in early pregnancy may cause an increase in progesterone metabolites. The aim of this study is to investigate the relationship between ICP and exogenous progesterone intake. Materials and Methods: This study is a retrospective case-control study conducted between January 2015 and November 2023. The groups liver function tests, total bile acids, maternal age, body mass index, parity, history of cholestasis, history of progesterone use, gestational week in which pruritus symptoms occurred, gestational week, in which ICP was diagnosed, history of ursodeoxycholic acid intake, obstetric pathology, maternal comorbidities, week of delivery, delivery method, birth weight, APGAR scores were obtained from the database of our hospital and compared. Results: A total of 379 pregnant women including 79 with ICP and 300 control patients were included in the study. Nulliparity, history of cholestasis, and history of progesterone intake were significantly higher in the ICP group than in the control group. Conclusion: Intake of exogenous progesterone in early pregnancy may lead to ICP and have adverse effects on the fetus. Further studies are needed to investigate the role of progesterones in the development of ICP.

Altered placental macrophage numbers and subsets in pregnancies complicated with intrahepatic cholestasis of pregnancy (ICP) compared to healthy pregnancies

IntroductionIntrahepatic cholestasis of pregnancy (ICP) can result in adverse outcomes for both mother and fetus. Inflammatory (M1 subset) or anti-inflammatory (M2 subset) macrophage polarisation is associated with various complications of pregnancy. However, the influence of ICP on macrophage numbers and polarisation remains unknown. This study analyses macrophage density and distribution in placentas of patients with ICP compared to controls. Clinical parameters were correlated to macrophage distribution and ursodeoxycholic acid use (UDCA). MethodsThis study included routinely collected placental tissue samples of 42 women diagnosed with ICP and of 50 control pregnancies. Immunohistochemical staining was performed on placental tissue using CD68 antibody as a pan-macrophage marker, CD206 antibody as an M2 and HLA-DR antibody as an M1 macrophage marker. Macrophage density (cells/mm2) and distribution (CD206+/CD68+ or CD206+/CD68+HLA-DR+) in both decidua (maternal tissue) and villous parenchyma (fetal tissue) were compared between groups. Macrophage density and distribution were correlated to clinical parameters for ICP patients. ResultsThe density of CD68+ macrophages differed significantly between groups in villous parenchyma. In both decidua and villous parenchyma, CD206+/CD68+ ratio was significantly lower in ICP patients compared to controls (p = 0.003 and p=<0.001, respectively). No difference was found based on UDCA use or in CD68+HLA-DR+ cell density. Significant correlations were found between macrophage density and peak serum bile acids and liver enzymes. DiscussionIn ICP patients, an immune shift was observed in both decidual and villous tissue, indicated by a lower CD206+/CD68+ ratio. ICP seems to affect placental tissue, however more research is required to understand its consequences.

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..

The Incidence of Intrahepatic Cholestasis of Pregnancy and its Maternal, Fetal, and Neonatal Adverse Outcomes: A Systematic Review and Meta-Analysis.

Intrahepatic cholestasis of pregnancy (ICP) is a problem with an increasing incidence and negative maternal, fetal, and neonatal consequences. This problem is becoming increasingly important. This systematic review and meta-analysis aimed to determine the incidence of ICP and its adverse maternal, fetal, and neonatal adverse outcomes based on primary research studies. This systematic review and meta-analysis used Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and was conducted between June and September 2023 using the following keywords: obstetric cholestasis OR intrahepatic cholestasis AND pregnancy OR pregnant OR prenatal OR antenatal OR perinatal OR maternal OR fetal OR neonatal. Quality assessment of the studies was performed using the Critical Appraisal Checklists developed by the JBI Institute. Data were synthesized using meta-analysis methods. The analysis included 10 studies published between 2013 and 2023. The meta-analysis showed that the incidence of ICP was 1.7% (odds ratio [OR], 0.021; 95% CI, 0.012-0.027), whereas maternal, fetal, and neonatal adverse outcomes included cesarean birth (OR, 2.938; 95% CI, 1.467-5.881), preterm birth or preterm prelabor rupture of membranes (OR, 4.241; 95% CI, 1.996-9.009), hypertensive disorders of pregnancy (OR, 3.715; 95% CI, 1.545-8.929), maternal infection (OR, 3.301; 95% CI, 2.917-3.737), neonatal intensive care unit admission (OR, 2.715; 95% CI, 1.458-5.056), birth weight less than or equal to 2500 g (OR, 2.518; 95% CI, 1.296-4.892), and small for gestational age (OR, 1.915; 95% CI, 1.424-2.573). This systematic review and meta-analysis revealed that ICP has a high incidence and several maternal, fetal, and neonatal adverse outcomes. Therefore, midwives and other health professionals must be aware of these outcomes and provide appropriate care to pregnant individuals with ICP.

Enfermedades hepáticas relacionadas con el embarazo

Pregnancy-related liver diseases are an important cause of maternal and infant morbidity and mortality. The diagnosis should always be a diagnosis of exclusion (viral, autoimmune, or drug-related liver diseases or biliopancreatic diseases). Pregnancy-related liver diseases include hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, preeclampsia, eclampsia, HELLP syndrome, and acute fatty liver of pregnancy.

Genetically predicted lipids mediate the association between intrahepatic cholestasis of pregnancy and cardiovascular disease.

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. 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. 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. 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.

The role of Ca2+ signalling and InsP3R in the pathogenesis of intrahepatic cholestasis of pregnancy

Background In order to contribute new insights for future prevention and treatment of intrahepatic cholestasis of pregnancy (ICP), and to promote positive pregnancy outcomes, we evaluated serum Ca2+ levels and inositol 1,4,5-trisphosphate receptor (InsP3R) expression in the liver tissue of a rat ICP model. Methods After establishing the model by injection of oestradiol benzoate and progesterone into pregnant rats, animals were divided into normal control (n = 5) and ICP model groups (n = 5). The expression of InsP3R protein in the liver, and serum levels of Ca2+, glycocholic acid and bile acid were detected. Results InsP3R mRNA and protein were significantly lower in the ICP model group compared to the normal group, as determined by qPCR and immunohistochemistry, respectively. Serum enzyme-linked immunosorbent assay results revealed significantly higher levels of glycocholic acid and bile acid in the ICP model group compared to the normal group, while Ca2+ levels were significantly lower. The levers of Ca2+ were significantly and negatively correlated with the levels of glycocholic acid. The observed decrease in Ca2+ was associated with an increase in total bile acids, but there was no significant correlation. Conclusions Our results revealed that the expression of InsP3R and serum Ca2+ levels was significantly decreased in the liver tissue of ICP model rats. Additionally, Ca2+ levels were found to be negatively correlated with the level of glycocholic acid.

Comparison of composite adverse perinatal outcomes in early- and late-onset intrahepatic cholestasis of pregnancy

Comparison of composite adverse perinatal outcomes in early- and late-onset intrahepatic cholestasis of pregnancy

Expression and clinical significance of short-chain fatty acids in patients with intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver condition that typically arises in the middle and late stages of pregnancy. Short-chain fatty acids (SCFAs), prominent metabolites of the gut microbiota, have significant connections with various pregnancy complications, and some SCFAs hold potential for treating such complications. However, the metabolic profile of SCFAs in patients with ICP remains unclear. To investigate the metabolic profiles and differences in SCFAs present in the maternal and cord blood of patients with ICP and determine the clinical significance of these findings. Maternal serum and cord blood samples were collected from both patients with ICP (ICP group) and normal pregnant women (NP group). Targeted metabolomics was used to assess the SCFA levels in these samples. Significant differences in maternal SCFAs were observed between the ICP and NP groups. Most SCFAs exhibited a consistent declining trend in cord blood samples from the ICP group, mirroring the pattern seen in maternal serum. Correlation analysis revealed a positive correlation between maternal serum SCFAs and cord blood SCFAs [r (Pearson) = 0.88, P = 7.93e-95]. In both maternal serum and cord blood, acetic and caproic acids were identified as key metabolites contributing to the differences in SCFAs between the two groups (variable importance for the projection > 1). Receiver operating characteristic analysis demonstrated that multiple SCFAs in maternal blood have excellent diagnostic capabilities for ICP, with caproic acid exhibiting the highest diagnostic efficacy (area under the curve = 0.97). Compared with the NP group, significant alterations were observed in the SCFAs of maternal serum and cord blood in the ICP group, although they displayed distinct patterns of change. Furthermore, the SCFA levels in maternal serum and cord blood were significantly positively correlated. Notably, certain maternal serum SCFAs, specifically caproic and acetic acids, demonstrated excellent diagnostic efficiency for ICP.

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.

Navigating Perinatal Challenges: A Comprehensive Review of Cholestasis of Pregnancy and Its Impact on Maternal and Fetal Health.

Cholestasis of pregnancy (CP), or intrahepatic CP (ICP), represents a condition peculiar to pregnancy, marked by impaired bile acid flow and consequent accumulation in the maternal bloodstream. Primarily emerging in the third trimester, CP is linked with considerable risks to both the mother and fetus, including heightened incidences of preterm birth, fetal distress, and stillbirth, alongside maternal complications such as intense pruritus and liver dysfunction. Despite its clinical significance, the etiology of CP, which involves genetic, hormonal, and environmental factors, remains partially understood. This comprehensive review delves into the physiology and pathophysiology of CP, outlines its clinical manifestations and diagnostic criteria, and discusses the associated maternal and fetal complications. Furthermore, it evaluates current management strategies, prognostic implications, and potential long-term effects on maternal and child health. It also explores future research directions, emphasizing the need for advancements in understanding the pathophysiology of CP, developing novel therapeutic interventions, and improving risk stratification models. By offering a thorough overview of CP, this review aims to enhance clinical awareness, guide management practices, and identify areas requiring further investigation, ultimately contributing to better health outcomes for affected women and their babies.

Intrahepatic cholestasis of pregnancy and its association with preeclampsia and gestational diabetes: a retrospective analysis.

To evaluate maternal and neonatal outcomes in patients with intrahepatic cholestasis of pregnancy (ICP). Patients who gave birth in our hospital between January 2018 and March 2022 were retrospectively reviewed from the hospital database and patient file records. The study comprised 1686 patients, 54 in the ICP group and 1632 controls. Patients who had ICP after 20weeks of gestation and were monitored and delivered at our facility were enrolled. Maternal demographic and obstetric characteristics data were examined. Perinatal outcomes were also assessed. Logistic regression analysis was used to determine adverse maternal outcomes. The mean age was 29years. ART, GDM, and preeclampsia were significantly higher in the ICP group. The mean serum bile acid level was 19.3 ± 3μmol/L in the ICP group. There was a higher risk of GDM and pre-eclampsia in women with ICP compared with those without and a significant association between ICP and adverse perinatal outcomes. There was a statistically significant relation between the presence of ICP and spontaneous preterm delivery, iatrogenic preterm delivery, 5th-minute Apgar scores < 7, and NICU requirement. No significant relationship was found between the presence of ICP and SGA and meconium. There was a significant relationship between the presence of ICP, mode of delivery, and PPH (p < 0.05). Those with ICP had a lower gestational week and birth weight, and higher rates of cesarean delivery and PPH. ICP should prompt close monitoring and management to mitigate the potential exacerbation of adverse outcomes, including preeclampsia, GDM, and preterm birth.

The effect of intrahepatic cholestasis in pregnancy combined with different stages of hepatitis B virus infection on pregnancy outcomes: a retrospective study.

To investigate the impact of intrahepatic cholestasis of pregnancy (ICP) with hepatitis B virus (HBV) infection on pregnancy outcomes. We selected 512 pregnant women, collected the data including maternal demographics, main adverse pregnancy outcomes and maternal HBV infected markers HBeAg and HBV-DNA loads status, then have a comparative analysis. There were 319 solitary ICP patients without HBV infection (Group I) and 193 ICP patients with HBV infection. Of the latter, there were 118 cases with abnormal liver function(Group II) and 80 cases with normal liver function(Group III). All HBV-infected pregnant women with ICP were divided into hepatitis Be antigen (HBeAg)-positive group (102 cases) and HBeAg-negative group (91 cases), according to the level of the serum HBeAg status; and into high viral load group (92 cases), moderate viral load group (46 cases) and low viral load group (55 cases) according to the maternal HBV-DNA level. Group II had a higher level of serum total bile acids, transaminase, bilirubin as well as a higher percentage of premature delivery, neonatal intensive care unit (NICU) admission and meconium-stained amniotic fluid (MSAF) compared with the other two groups(P < 0.05), but there were no significant differences in the above indicators between the Group I and Group III. Among the HBV-infected patients with ICP, HBeAg-positive group had a higher level of serum transaminase, bilirubin and bile acid as well as earlier gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission than HBeAg-negative group (P < 0.05). Those with a high viral load (HBV-DNA > 106IU/ml) had a higher level of transaminase, bilirubin, and bile acid as well as shorter gestational weeks of delivery, lower birth weight of new-borns and a higher rate of NICU admission compared with those with a low or moderate viral load (P < 0.05). HBV-infected pregnant women with ICP combined with abnormal liver function have more severe liver damage, a higher percentage of preterm birth and NICU admission. HBeAg-positive status and a high HBV-DNA load will increase the severity of conditions in HBV-infected pregnant women with ICP. HBV-infected patients with ICP who have abnormal liver function, HBeAg-positive or a high viral load should be treated more actively.

Intrahepatic cholestasis of pregnancy - Are you listening?

Through their personal experience of having intrahepatic cholestasis of pregnancy (ICP), this paper covers the development of current understanding of ICP. It summarises how research and clinical practice was developed through clinicians and followed by the inception of an ICP research group in the 1990s. This group's work has led to a better understanding of the mechanisms behind ICP, the risk threshold for stillbirth, and a genomic understanding of the condition. It focuses on how collaborative work between the author and researchers led to the formation of a charity for ICP. Despite this, some obstetric healthcare professionals continue to provide misinformation about ICP to women and birthing people. Furthermore, the views of those affected by ICP, together with the research they present to clinicians, are being ignored. It highlights a need for those managing ICP to listen to their patients and to pay closer attention to the research being published.