Outcomes In Intrahepatic Cholestasis Of Pregnancy Research Articles

Early Detection of Intrahepatic Cholestasis of Pregnancy: Correlation Between Liver Enzymes and Adverse Fetal Outcomes

Background: Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder that occurs in late pregnancy and leads to elevated bile acid levels in the maternal serum, posing risks to fetal health, including preterm labor and fetal distress. Understanding the relationships between liver enzyme levels and fetal outcomes can guide early diagnostic and management strategies. Objective: To evaluate the significance of early detection of ICP through routine liver enzyme tests (AST and ALT) and its correlation with adverse fetal outcomes to inform clinical practices in regions with limited access to advanced diagnostic tools. Methods: This cross-sectional study was conducted at the Ittefaq Hospital Trust, Lahore, involving 90 pregnant women categorized into three groups based on gestational age and ICP symptoms. Group A consisted of 30 women at 30-34 weeks of gestation, Group B included 30 women at 34-37 weeks, and Group C comprised 30 healthy pregnant women as controls. Serum AST and ALT levels were measured at day 0, 30, and 45. Fetal outcomes were monitored through ultrasound and medical records. Statistical analysis was performed using SPSS version 25, employing descriptive statistics and ANOVA to compare enzyme levels and fetal outcomes across groups. Results: Group 2 exhibited significantly higher mean AST levels (96.58 U/L) and ALT levels (183.10 U/L) compared to Group 1 (AST: 49.95 U/L, ALT: 100.90 U/L) and Group 3 (AST: 25.30 U/L, ALT: 35.05 U/L). Adverse fetal outcomes, including intrauterine growth restriction (IUGR), were notably higher in Group 2 (76.7%) compared to Group 1 (13.33%) and Group 3 (0%). The statistical significance was marked with a p-value < 0.05 across all comparisons. Conclusion: Elevated liver enzymes, specifically AST and ALT, are strongly associated with adverse fetal outcomes in ICP. Early detection and monitoring of these enzymes can be crucial in preventing fetal complications, particularly in resource-limited settings where traditional diagnostic measures are inaccessible.

Evaluating the Utility of Liver Transaminases as Predictors of Feto-Maternal Outcome in Lieu of Serum Bile Acids in Intrahepatic Cholestasis of Pregnancy: A Prospective Observational Study.

Intrahepatic Cholestasis of Pregnancy (ICP) is a disorder of the second half of pregnancy causing pruritus and abnormal liver function tests (LFT). Incidence in India is 1.2-1.5%. ICP leads to adverse feto-maternal outcomes with early delivery indicated before serum bile acids (SBA) (gold standard) and hepatic transaminases are critically high. With paucity of evidence these levels are not well defined. To determine the association of liver transaminases with pregnancy outcomes in ICP and evaluate critical levels for prediction of adverse outcomes. A prospective observational study was conducted comprising 88 pregnant women with pruritus not associated with rash. After history and examination, LFT and SBA levels were done, treatment given and followed till pregnancy termination to determine the feto-maternal outcome. The mean age of participants was 26.43 ± 3.35 years. The mean SBA, ALT and AST levels were 18.97 ± 10.320 μmol/L, 206.06 ± 45.71units/litre and 175.37 ± 101.088 units/litre respectively. 39.7% of participants were symptomatic for ICP while 38.6% responded to treatment. 34.1% underwent LSCS majorly (43.3%) formeconiumand 23.3% had foetal distress. 33% had preterm delivery. 5.68% of the neonates needed NICU admission and 6.8% had respiratory distress syndrome. The cut off for ALT on ROC curve analysis was 151.5 units/litre with AUC as 0.905, sensitivity and specificity of 89.7 and 70% respectively. ICP leads to adverse pregnancy outcomes. ALT is a promising predictor of adverse outcome and termination of pregnancy can be planned accordingly.

The spatial expression of mTORC2-AKT-IP3R signal pathway in mitochondrial combination of endoplasmic reticulum of maternal fetal interface trophoblast in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is complicated by adverse fetal outcomes and even fetal death, the mechanism remains unclear. This study aims at evaluating the differential expression of mTORC2-AKT-IP3R signaling pathway, which accurately regulate Ca2+ transfer across mitochondria-associated membranes (MAMs) and determine the stress intensity experienced by endoplasmic reticulum (ER) and mitochondria, in patients diagnosed withICP. We combined western blot analysis and placental immunofluorescence co-localization detection to assess the expression and co-localization of the mTORC2-AKT-IP3R signaling pathway in severe (maternal total bile acid (TBA) levels≥40 μmol/L) and mild (maternal TBA 10-40 μmol/L) ICP. Compared with the control and mild ICP groups, phosphorylated protein kinase B (p-AKT) levels were significantly upregulated in the severe ICP group. Placental Rictor levels were lower in the mild ICP group than in the control group and were further downregulated in the severe ICP group. IP3R3 and p-IP3R3 levels were lower in placentas in the severe ICP group than in those in the mild ICP and control groups. Moreover, the co-localization of IP3R3 and p-AKT in patients in the mild and severe ICP groups was significantly elevated compared with that in patients in the control group. In patients with severe ICP, limited expression of Rictor and elevated p-AKT levels would suppress IP3R3/p-IP3R3 levels in MAMs. This inhibition might influence the transportation of Ca2+ from the ER to the mitochondria, thus weaken the stress adaptation associated with MAMs. Our results reveal the possible pathophysiological mechanism of adverse fetal outcomes in ICP.

Circulatory Metabolomics Reveals the Association of the Metabolites With Clinical Features in the Patients With Intrahepatic Cholestasis of Pregnancy.

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.

Maternal and Fetal Outcome in Intrahepatic Cholestasis of Pregnancy in a Multicultural Society Conducted at a Tertiary Care Hospital in Dubai

Introduction: Intrahepatic cholestasis of pregnancy (ICP) has been sparsely studied especially in the Middle East. The incidence and outcome of ICP varies worldwide. Its incidence in the Middle East and primary maternal and fetal outcome must be evaluated to ascertain the burden so that appropriate preventive and intervention measures can be formulated and implemented. Objective: To assess the incidence, associations, and maternal-fetal outcomes in ICP. Design: Case-control study. Settings: tertiary care hospital settings affiliated with the academic center in the UAE. Patients and methods: a total of 150 patients were included from October 2016 to September 2018 in the study with 75 cases of ICP and 75 controls matched according to age and date of delivery. The maternal risk factors attributable to ICP were recorded. Biochemical profile of mothers was monitored. Maternal and fetal outcomes were compared in 2 groups. Main outcomes measured: incidence and associations of ICP were evaluated. Maternal and fetal outcomes were compared in cases and controls. Sample size: 150. Result: The incidence of ICP in our study in the UAE was 1.0%. ICP has significant association with past obstetric cholestasis history (p value <0.01, odds ratio [OR] 9.3, 95% CI: 2.1–41.8), gestational diabetes (p value <0.05, OR 2.0, 95% CI: 1.0–3.8), pre-eclampsia (p value <0.05, OR 7.2, 95% CI: 1.6–33.1), and undergoing induction of labor (p value <0.01, OR 8.1, 95% CI: 3.7–17.8). The maternal bile acid level above 40 μmol/L is ­associated with higher chances of preterm delivery (p value <0.01, OR 8.2, 95% CI: 3.0–22.5), intrauterine fetal demise (p value <0.01), low birth weight (p value <0.01, OR 13.6, 95% CI: 4.2–43.5), respiratory distress (p value <0.05, OR 15.5, 95% CI: 1.8–132.7), poor Apgar score (p value <0.05, OR 12.720, 95% CI: 1.5–111.4), and NICU admissions (p value <0.01, OR 9.0, 95% CI: 1.8–45.9). Conclusion: ICP mothers have low incidence in the UAE and significant association with gestational diabetes and pre-eclampsia. High maternal bile acids above 40 μmol/L have poor fetal outcomes.

Role of ursodeoxycholic acid on maternal serum bile acids and perinatal outcomes in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is associated with safe maternal outcomes but perinatal outcomes have been variable. We assessed clinical factors and impact of bile acid levels on maternal and neonatal outcomes in ICP. Patients with ICP (defined as pruritus with serum bile acids ≥ 10 mmol/l) were included prospectively with an assessment of risk factors, modes of delivery as well as maternal and neonatal outcomes. Mild and severe ICP were diagnosed when serum bile acid was always <40 mmol/l and ≥40 mmol/l, respectively. Patients with gestational pruritus served as controls. Out of 643 patients, 375 patients (mean age 29 ± 7.6 years, 45.8% primigravida) met inclusion criteria. Pregnancy-induced hypertension [PIH: 10.5%; odds ratio (OR): 4.8; 95% confidence interval (CI): 2.4-8.5; P = 0.0014], gestational diabetes (GDM: 12.5%; OR: 2.6; 95% CI: 2.3-4.1; P = 0.045) and spontaneous preterm labor (15.1%; OR: 2.5; 95% CI: 1.2-3.5; P = 0.040) were higher in patients with ICP. Ursodeoxycholic acid (UDCA) (median dose 900 mg; 600-1800 mg) ameliorated symptoms of cholestasis, bile acid levels and liver aminotransferases in 79% cases. When compared with patients with mild ICP, patients with severe ICP presented at a lower gestational period (26 vs. 32 weeks, P = 0.036), required frequent induction (12.5%; OR: 3.2; 95% CI: 2.1-5.6; P = 0.045) and had increased fetal distress (15%; OR: 1.9; 95% CI: 1.3-4.9; P = 0.048).Overall eight stillbirths were recorded. Severe ICP is associated with a higher incidence of GDM and PIH, risk of pre-term labor, elective induction and stillbirths. UDCA remains a first-line agent in treating ICP.

Assessment of fetal left ventricular modified myocardial performance index and its prognostic significance for adverse perinatal outcome in intrahepatic cholestasis of pregnancy

Objective: To investigate the association between fetal left ventricular modified myocardial performance index (LMPI) and intrahepatic cholestasis of pregnancy (ICP) and to evaluate the value of LMPI in predicting adverse perinatal outcomes in ICP.Study design: In a cross-sectional case–control study, 40 women with ICP were compared with 40 gestational age-matched healthy controls. The isovolumetric contraction time (ICT), isovolumetric relaxation time (IRT), and ejection time (ET) were measured using the Doppler signals of the opening and closing of the mitral and aortic valves. LMPI was calculated as (ICT + IRT)/ET. An adverse perinatal outcome was defined with at least one of the following: non-reassuring fetal heart rate tracing, umbilical cord pH <7.20, the presence of meconium in amnion, and neonatal intensive care unit (NICU) admission.Results: Mean gestational age at delivery and mean birth weight were significantly lower and the incidences of cesarean section rate, non-reassuring fetal heart rate tracing, the presence of meconium in amnion, and NICU admission were significantly higher in the ICP group (p < .01). Mean LMPI, ICT, and IRT values were significantly higher in the ICP group (p < .01). The area under the receiver operating characteristic (ROC) curve for LMPI in prediction of adverse perinatal outcome was 0.740 (95% CI: 0.607–0.873, p = .001) and a cut-off LMPI of 0.41 conferred a sensitivity of 85% and a specificity of 61%.Conclusions: There is an impaired global ventricular function in ICP fetuses demonstrated by increased LMPI. High LMPI is associated with adverse perinatal outcome in ICP.

Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy with dichorionic diamniotic twin pregnancies

Objective: The aim of our study was to investigate the predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with dichorionic diamniotic (DCDA) twin pregnancies. Methods: This study was a retrospective study of women diagnosed with ICP and DCDA twin pregnancies in Chengdu’s women and children’s central hospital. These patients were subdivided into mild and severe ICP groups according to total bile acid (TBA) level. The clinical characteristics and perinatal outcomes were collected and compared between the two groups. Logistic regression analysis was developed to evaluate predictors of adverse perinatal outcomes. Results: About 134 cases were included in the study. Eighty-four cases were in the mild ICP group, and the other 50 cases were in the severe ICP group. Level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and direct bilirubin (DBIL) in the severe ICP group were significant higher than those in the mild ICP group. The rate of delivery before 34 gestational weeks, meconium-stained amniotic fluid, and composite adverse neonatal outcome were higher in the severe ICP group than those in the mild ICP group. After adjusting for confounders, ICP onset gestational age (GA) <30 weeks and AST >200U/l were associated with GA at delivery <34 weeks. ALP >400U/l was an independent risk factor of meconium-stained amniotic fluid. ICP onset GA <30 weeks was an independent risk factor of composite adverse neonatal outcome. Conclusion: ICP onset GA <30 weeks, TBA >40 µmol/l, AST >200U/l, and ALP >400U/l were associated with composite adverse perinatal outcomes in ICP with DCDA twin pregnancies. For those patients with these characteristics, fetal surveillance and treatment should be enhanced.

Optimal Delivery Timing for Intrahepatic Cholestasis of Pregnancy (ICP) [36D

INTRODUCTION: While consensus exists regarding delivery timing for pregnancies affected by ICP, the differential impact of varying gestational age (GA) remains incompletely understood. This study evaluated the impact of GA at delivery in affecting maternal and neonatal outcomes in ICP. METHODS: We performed a retrospective cohort study of patients with ICP who were delivered at a tertiary teaching hospital from Jan 2008 to Dec 2015. The study cohort was divided into 3 groups: less than 37, at 37, greater than 37 weeks. We compared the maternal and neonatal outcomes using one way ANOVA and chi-squared / Fisher exact test for continuous and categorical data, respectively. Multivariable logistic regression analyses were performed to predict the likelihood of adverse perinatal outcomes while adjusting for sociodemographic, clinical and laboratory characteristics. RESULTS: Out of a total of 110 patients with ICP - 53 (48.19%) delivered at 37 weeks, with 28 (25.46%) and 29 (26.37%) patients delivered at less than 37 and greater than 37 weeks, respectively. Preterm delivery was significantly associated with higher bile acid levels, Hepatitis C, earlier diagnosis, lower Apgar scores, higher rates of hyperbilirubinemia, NICU admission, and length of NICU stay. Induction prior to 37 weeks resulted in higher cesarean rates, with vaginal delivery being higher for inductions ≥ 37 weeks. CONCLUSION: In our study, advanced ICP disease, often resulted in spontaneous preterm labor before a scheduled induction. Further prospective studies are warranted to characterize the influence of gestational age at delivery in modulating perinatal outcomes in ICP.

Can fetal left ventricular modified myocardial performance index predict adverse perinatal outcomes in intrahepatic cholestasis of pregnancy?

Objective: To investigate fetal left ventricular function using the left ventricular modified myocardial performance index (mod-MPI) and E wave/A wave peak velocity (E/A) ratio, and to explore the success of mod-MPI in the prediction of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP).Methods: Forty-one ICP cases were compared with 41 gestational age-matched healthy controls. Opening and closing clicks of the mitral and aortic valves were used to define the three time periods [ejection time (ET), isovolumetric contraction time (ICT) and isovolumetric relaxation time (IRT)], which were employed in the calculation of mod-MPI [mod-MPI = (ICT + IRT)/ET]. The E/A ratio was calculated as well.Results: Fetal left ventricular mod-MPI values were significantly higher in the ICP group compared to controls (0.56 ± 0.09 versus 0.37 ± 0.04, p < 0.001), whereas the E/A ratio was lower (0.62 ± 0.11 versus 0.69 ± 0.10, p = 0.011). The optimal cutoff level for mod-MPI in prediction of adverse perinatal outcomes was >0.48 [sensitivity: 81.8%, specificity: 67.6%, area under the curve (AUC): 0.750, 95% CI: 0.613–0.887, p = 0.008].Conclusions: Fetuses of ICP cases have significant left ventricular dysfunction. Mod-MPI can be used in the prediction of adverse perinatal outcomes in ICP.

Serum bile acids in intrahepatic cholestasis of pregnancy: Not just a diagnostic test

Serum bile acids in intrahepatic cholestasis of pregnancy: Not just a diagnostic test

Intrahepatic cholestasis of pregnancy: Biochemical predictors of adverse perinatal outcomes

This study aimed to identify biochemical predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP). A total of 106 ICP cases were analyzed retrospectively by the combination of receiver operating characteristic curve and binary logistic regression analysis. "Adverse perinatal outcomes" included spontaneous preterm labor, meconium-staining of amniotic fluid, stillbirth and Apgar score ≤7 at 1 or 5 min. Total bile acid (TBA) [AUC=0.658, 95%CI (0.536, 0.781), P=0.031] was a valuable predictor for adverse perinatal outcomes. The critical value of TBA above which adverse perinatal outcomes were observed was 40.15 μmol/L (Youden's index=0.3). Binary multivariate logistic regression analysis revealed that the risk of adverse perinatal outcomes increased when TBA ≥40.15 μmol/L [OR=3.792, 95%CI (1.226, 11.727), P=0.021]. It is concluded that the risk of adverse perinatal outcomes in ICP increases when maternal TBA ≥40.15 μmol/L.