Intrahepatic Cholestasis Of Pregnancy Patients Research Articles

Intrahepatic Cholestasis of Pregnancy: Role of Baby’s Sex on Itch Severity and Bile Acid Levels

BackgroundIntrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder of pregnancy. It occurs when bile flow from the liver is obstructed, causing bile acid to accumulate. ICP usually presents with itching that lasts for the remainder of pregnancy. Untreated ICP has been shown to increase the incidence of adverse outcomes for the baby, including respiratory distress, meconium aspiration, neonatal intensive care unit hospitalization, and stillbirth. The probability of these events increases when bile acid levels are greater than 40 mmol/L. The current standard of care for ICP patients is a combination of ursodeoxycholic acid by mouth and early delivery, as the risk of stillbirth due to ICP increases in the last weeks of pregnancy. ICP has been linked to preeclampsia and gestational diabetes; studies have shown that the occurrence of both diseases is greater when the baby is male. The purpose of this study was to investigate if the occurrence, timing of diagnosis, peak bile acid levels, or severity of itching is dependent on the baby’s sex in mothers who had ICP.MethodsAn online question-set (survey) was offered to women who had had ICP and were members of three different online support groups.ResultsA total of 1,502 women responded for a total of 2,289 documented ICP pregnancies, in which there were 1,059 female babies and 1,230 male babies. Based on chi-square analysis of differences in frequencies, no difference was found between pregnancies with male versus female babies regarding the occurrence, timing of diagnosis, peak bile acid levels, or severity of itching in the evaluated population. However, surprisingly, the findings revealed that first-trimester diagnosis of ICP was made in 5.6% of the pregnancies, and there were 30 (1.8%) cases of ICP diagnosed in the absence of itching.ConclusionsThe findings suggest that the baby’s sex does not impact the occurrence, timing of diagnosis, peak bile acid levels, or itch severity in ICP. The findings that 5.6% of the ICP pregnancies in the present study were diagnosed in the first trimester and 1.8% were diagnosed without the presence of itching reinforce the need to investigate these less common presentations. More studies are needed to determine if these findings are consistent across other populations.

Clinical profile and screening of exon 6 and 14 of ABCB4 gene in obstetric cholestasis patients at a tertiary care hospital in Rawalpindi, Pakistan.

Intrahepatic Cholestasis of Pregnancy (ICP) is a rare pregnancy specific disorder. Genetic variants of ABCB4 gene increase ICP risk. This study was conducted to determine frequency of ICP cases presented at a tertiary care hospital in Rawalpindi, Pakistan and to screen for genetic variants of exon 6 and 14 of ABCB4 gene in ICP cases. This analytical study included ICP patients presenting at Department of Gynaecology and Obstetrics, Holy Family Hospital Rawalpindi, from February 2017 to May 2017. Sanger's sequencing was performed using genomic DNA extracted from blood samples of patients and controls. Twenty pregnant women out of 1150 (1.74%) had ICP and were enrolled during study period. Overall (19/20) 95% patients had pruritus and among them (8/20) 40%, (4/20) 20% and (2/20) 10% had a history of miscarriages, stillbirths and familial ICP respectively. Genetic analysis revealed an already reported variant i.e., c.504C>T in exon 6 in thirteen patients and a novel variant i.e., c.1686A>G in exon 14 in five patients. Both variants were not present in controls. In silico analysis suggested that both variants might affect pre-mRNA splicing of ABCB4 transcript. ICP had a frequency of 1.74% among pregnant women. Identification of a novel heterozygous variant in five patients and an already reported variant in thirteen patients reaffirms genetic heterogeneity and role of ABCB4 in ICP etiology.

Use of data-independent acquisition mass spectrometry for comparative proteomics analyses of sera from pregnant women with intrahepatic cholestasis of pregnancy

We used data-independent acquisition (DIA) proteomics technology followed by ELISAs and automated biochemical analyses to identify and validate protein expression levels in Intrahepatic Cholestasis of Pregnancy (ICP) and healthy pregnant controls. We employed bioinformatics to identify metabolic processes associated with differentially expressed proteins.The expression levels of two proteins (S100-A9 and the L-lactate dehydrogenase A chain) were significantly higher in ICP patients than in controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.774 and 0.828, respectively. The expression levels of two other proteins (apolipoprotein A-I and cholinesterase) were significantly lower in patients, with values of 0.900 and 0.842, respectively. Multiple logistic regression showed that a combination of the levels of the four proteins optimized the AUC (0.962), thus more reliably diagnosing ICP. The levels of all four proteins were positively associated with that of total bile acids. Bioinformatics analyses indicated that the four proteins principally affected neutrophil activation involved in the immune response, cell adhesion, lipoprotein metabolism, and the PPAR signaling pathway. SignificanceThis preliminary work improves our understanding of changes in serum levels of protein in pregnant women with ICP. The four proteins may serve as novel noninvasive biomarkers for ICP.

High burden of future liver disease in intrahepatic cholestasis of pregnancy patients

High burden of future liver disease in intrahepatic cholestasis of pregnancy patients

Hepatitis B infection and intrahepatic cholestasis of pregnancy: A systematic review and meta-analysis.

Background:Viral hepatitis type B is caused by hepatitis B virus (HBV) infection. Several studies have linked HBV infection to a higher risk of developing intrahepatic cholestasis of pregnancy (ICP), although some give contradictory results. To investigate the association and estimated risk of ICP in patients with HBV infection, we conducted this meta-analysis to summarize all available evidence.Methods:This study consists of 2 meta-analyses. A literature search was performed using MEDLINE and EMBASE from inception to July 2019. The first study included studies that reported associations between HBV infection and the risk of ICP. The second analysis included studies comparing the risk of HBV infection in ICP patients with those without ICP. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using a random-effect, inverse variance method.Results:Four studies were included in both analyses. The OR of ICP in HBV-infected pregnant women compared with non-HBV pregnant women was 1.68 (95% CI 1.43–1.97; I2 = 0%). The OR of HBV infection among ICP patients compared with non-ICP patients was 1.70 (95% CI 1.44–2.01; I2 = 0%).Conclusions:Our meta-analysis demonstrates not only a higher risk of ICP among HBV-infected pregnant women but also an increased risk of HBV infection among ICP patients. These findings suggest that HBV is a high-risk factor for ICP and screening for hepatitis B in women with ICP symptoms may be beneficial.

Intrahepatic Cholestasis in Pregnancy: Review of the Literature.

Intrahepatic cholestasis of pregnancy (ICP) is the most common hepatic disorder related to pregnancy in women. It usually develops within the third trimester of pregnancy and presents with pruritus as well as elevated levels of bile acid and/or alanine aminotransferase. Clinical signs quickly resolve after delivery; however, there is a high risk of the disorder recurring in subsequent pregnancies. ICP is associated with an increased risk of perinatal complications (premature birth, respiratory disorders, even stillbirth). Elevated levels of gestational hormones and genetic predispositions are important factors for the development of ICP; among the latter, mutations in hepatobiliary transport proteins (multidrug resistance protein 3-MDR3, bile salt export pump- BSEP) play a major role. Clinical and biochemical symptoms of ICP include pruritus and increased levels of total bile acids (TBA). Serum levels of TBA should be monitored in ICP patients throughout the pregnancy as concentrations above 40 μmol/L, which define that severe ICP isassociated with an increased risk of fetal complications. Therapeutic management is aimed at reducing the clinical symptoms, normalizing maternal biochemistry and preventing complications to the fetus. Pharmacological treatment of intrahepatic cholestasis of pregnancy consists of the administration of ursodeoxycholic acid to lower the levels of TBA and possibly reduce pruritus. If the treatment fails, premature delivery should be considered.

The Impact of Assisted Reproductive Technology in Twin Pregnancies Complicated by Intrahepatic Cholestasis of Pregnancy: a Retrospective Cohort Study.

Our study aims to evaluate the perinatal outcomes in twin pregnancies diagnosed with intrahepatic cholestasis of pregnancy (ICP) and to compare these with normal healthy twin pregnancies for perinatal outcomes. The second outcome of the study was to determine whether in vitro fertilization-embryo transfer (IVF-ET) affects the perinatal outcome in ICP patients. In this study, 59 ICP and 641 healthy twin pregnancies were compared for perinatal outcomes retrospectively. According to the mode of conception, the twin pregnancies with ICP were divided into 2 groups. The twin pregnancies with ICP who were conceived with IVF were referred to as the IVF-ET group. The twin pregnancies with ICP who were conceived spontaneously or by ovulation induction and intrauterine insemination (IUI) were referred to as the non-IVF-ET group. Twin pregnancies with ICP give birth significantly earlier than normal twin pregnancies (p ˂ 0.001). The diagnosis of ICP occurred significantly earlier in the IVF-ET pregnancy with ICP than in the non-IVF-ET group. In twin pregnancies with IVF-ET, patients delivered significantly earlier than in the non-IVF-ET group (p=0.002). Twin pregnancies with ICP were found to have significantly higher rates of meconium-stained amniotic fluid, postnatal intubation, and admission to the neonatal intensive care unit (NICU) than healthy twin pregnancies. ICP is a risk factor for preterm delivery in twin pregnancies. In addition, ICP develops earlier and more frequently in twin pregnancies from IVF-ET than in those from non-IVF twin pregnancies, and the disease may be more serious.

Effect of ursodeoxycholic acid therapy due to pregnant intrahepatic cholestasis on chemerin and irisin levels.

The purpose of the work was to assess changes in chemerin and irisin levels in women with diagnosed intrahepatic cholestasis of pregnant women treated with ursodeoxycholic acid. The study group consisted of 50 patients with diagnosed and confirmed intrahepatic cholestasis of pregnant women at 24-25 weeks of pregnancy treatment by ursodeoxycholic acid (UDCA). The study also included a group of 40 pregnant women, without concomitant intrahepatic cholestasis of pregnancy (ICP). In the pregnant ICP group, whole blood was collected 4 times: before the first dose of drug, 4 and 8 weeks after the first dose, and day after delivery. It was observed that statistically significant differences in the concentration of irisine occur between the time before starting treatment and the 8-week therapy and 1 day after delivery. The Pearson correlation analysis (r's) showed two statistically significant relationships (p < .05). The first of these can be found between the concentration of irisine and chemerin in the group of nonpregnant women and the second in the group of patients with intrahepatic pregnant cholestasis before the first dose of UDCA. A significant relationship between irisin and chemerin concentrations was confirmed in the group of pregnant ICP patients during UDCA acid therapy and among healthy pregnant women.

Maternal serum, placental, and umbilical venous blood irisin levels in intrahepatic cholestasis of pregnancy

Objective To explore the changes of serum, umbilical vein, placental irisin level, and the correlation between irisin level and relevant indicators in pregnant women with intrahepatic cholestasis of pregnancy (ICP), so as to provide a new perspective for in-depth studies on the causes and treatment of ICP. Methods This cross-sectional case–control study method, the serum, umbilical venous blood irisin, liver, kidney function, lipid metabolism, and other indicators of 108 normal pregnant women, 64 patients with mild ICP, and 39 patients with severe ICP were compared, and the changes in the levels of oxidative stress and irisin were observed by dihydroethidium staining and immunohistochemistry. Results The level of placental oxidative stress in severe ICP group and mild ICP group was significantly higher than that in normal pregnant women group, and the mild ICP group was significantly higher than that in severe ICP group (p < .05); the concentration of irisin in umbilical vein was significantly lower than that in peripheral blood; the serum irisin of normal pregnant women (918.51 ± 159.90 pg/ml) was significantly lower than that of pregnant women with mild ICP (1030.05 ± 137.98 pg/ml) and pregnant women with severe ICP (1094.34 ± 154.35 pg/ml). The concentration of irisin in umbilical vein blood of pregnant women with severe ICP (858.78 ± 97.42 pg/ml) was significantly higher than that of normal pregnant women (595.33 ± 162.70 pg/ml) and those with mild ICP (648.82 ± 164.81 pg/ml) (p < .05). Irisin was expressed in placental tissues of normal pregnant women group, mild ICP group and severe ICP group, and the differences were statistically significant in expression intensity of the three groups (χ 2 = 19.959, p < .05). The irisin expression intensity in the ICP group was higher than that in the control group, and the irisin expression intensity in the ICP group was higher than that in the ICP group (β = 0.292; t = 3.063; p < .05). At the best cutoff level of 989.168 pg/ml, irisin accurately predicted ICP [AUC = 0.622 (95%CI 0.543–0.701, p < .05)] with sensitivity and specificity rates of 60.9 and 40.1%, respectively. Conclusion Irisin can reduce the level of oxidative stress and improve lipid metabolism in ICP patients during the pathophysiological process of ICP, and it is possible to become a new auxiliary factor of ICP diagnosis and indexing.

ERp29 inhibition attenuates TCA toxicity via affecting p38/p53- dependent pathway in human trophoblast HTR-8/SVeno cells

Intrahepatic cholestasis of pregnancy (ICP) is a liver disorder occurred in pregnant women, and the mechanism for such disease is still unclear. The bioinformatics analysis of our previous study has revealed the abnormal expression of endoplasmic reticulum protein 29 (ERp29) in placental tissue of ICP patients. In this study, the function of ERp29 was further explored using in vitro model of ICP. The results showed that up-regulation of ERp29 occurred in TCA (taurocholic acid)-treated human trophoblast HTR-8/SVeno cells, and ERp29 inhibition reversed TCA toxicity via attenuating G2/M arrest and cell apoptosis. Mechanical study revealed ERp29 inhibition suppressed phosphorylation and kinase activity of p38, thus subsequently affecting expression and phosphorylation of p53 (ser18) as well as the transcriptional activity of p53. The conduction of this study might confirm the important role of ERp29 in ICP and which would be helpful for the development of target therapeutic method for ICP.

Probiotic Lactobacillus rhamnosus GG prevents progesterone metabolite epiallaopregnanolone sulfate-induced hepatic bile acid accumulation and liver injury

Intrahepatic cholestasis of pregnancy (ICP) is gestation-specific liver disease associated with liver injury and increased serum and hepatic bile acids. Although the mechanism of ICP is still not fully understood, the reproductive hormones seem to play an important role. Recent studies show that a progesterone metabolite, epiallopregnanolone sulfate (PM5S), is supraphysiologically elevated in the serum of ICP patients, indicating it may play an etiology role in ICP. Bile acid homeostasis is controlled by multiple mechanisms including farnesoid X receptor (FXR)-mediated bile acid export and synthesis. It is known that cholic acid (CA), a primary bile acid, can activate FXR, which is inhibited by PM5S, an FXR antagonist. Here we employed a mouse model of concurrent exposure of CA and PM5S-induced liver injury and determined the effects of probiotic Lactobacillus rhamnosus GG (LGG) in the prevention of the bile acid disorders and liver injury. Mice challenged with CA + PM5S had significantly increased levels of serum and hepatic bile acids and bilirubin and liver enzyme. Pretreatment with LGG significantly reduced bile acid and bilirubin levels associated with reduced liver enzyme level and mRNA expression levels of pro-inflammatory cytokines. We also showed that the beneficial effects of LGG is likely mediated by hepatic FXR activation and bile salt export pump (BSEP) upregulation. In conclusion, our results provide a rationale for the application of probiotics in the management of ICP through gut microbiota-mediated FXR activation.

The urinary bile acid profiling analysis of asymptomatic hypercholanemia of pregnancy: A pseudo-targeted metabolomics study

BackgroundAsymptomatic hypercholanemia of pregnancy (AHP) is a controversial hypercholanemia, which is difficult to distinguish from intrahepatic cholestasis of pregnancy (ICP). Our aim is to elucidate the characteristics of urinary bile acid (BA) profiling of women with AHP and to find potential biomarkers for the diagnosis and differential diagnosis of AHP. MethodsWe developed a pseudo-targeted approach to perform metabolomics analysis of bile acids (BAs) using ultra-high performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Urinary BAs profiles were compared among AHP women (n = 20), ICP patients (n = 33) and normal controls (n = 35). ResultsThe profiling of urinary BAs was significantly different among the AHP, ICP and control groups. Compared to the control group, the AHP group had higher levels of four possible sulfated BAs and trihydroxy BAs, including the species of muricholic acid (MCA), cholic acid (CA) and six possible BAs, whereas, 20 possible sulfated BAs, taurochenodeoxycholic acid (TCDCA), tetrahydrocannabinolic acid (THCA), and seven possible BAs were significantly lower in the AHP group than those in the ICP group. Based on the receiver operating characteristic (ROC) analysis, glycocholic acid (GCA) combined with T-ω-MCA were found to be the potential combination biomarker for the diagnosis (area under the curve was 0.960) of AHP, and mono-S, Gtri-S-2 combined with TLCA-S were found to be the potential combination biomarker for the differential diagnosis (area under the curve was 0.990) of AHP and ICP. ConclusionsThe metabolisms of urinary Bas were altered in the AHP group compared with the ICP group and the control group. Urinary BA profiling analysis can serve as an effective tool for the diagnosis of AHP and the differential diagnosis of AHP and ICP.

3555 Intrahepatic Cholestasis of Pregnancy (ICP) is associated with higher prevalence of NAFLD: a case-control study.

OBJECTIVES/SPECIFIC AIMS: Intrahepatic Cholestasis of Pregnancy (ICP) is the most common liver disease unique to pregnancy. Progression of non-alcoholic fatty liver disease (NAFLD) has been linked to the dysregulation of bile acid homeostasis. However, an association of NAFLD with ICP has not been previously evaluated. We evaluated the association between ICP and NAFLD and associated metabolic risk factors, including obesity, dyslipidemia, hypertension, and diabetes. METHODS/STUDY POPULATION: A single-center, retrospective case-control study was conducted between January and December 2017 in a primarily Latina population in a New York City health system with a high prevalence of ICP, 2.53% of all pregnancies (compared to 0.32% nationally). Pearson’s chi-square or Fisher’s exact test and Wilcoxon rank-sum tests were performed to evaluate association of ICP with categorical variables and continuous variables, respectively. Unadjusted odds ratios (OR) with 95% confidence intervals (95% CI) were calculated in comparison with the control group for clinically significant outcomes. RESULTS/ANTICIPATED RESULTS: 149 pregnancies complicated by ICP were identified from electronic medical records; 200 controls were matched by delivery year. Hispanic women were more likely to be diagnosed with ICP than non-Hispanic women (OR 1.90, 95% CI 1.87-3.03). ICP and control patients were similar for: median age (OR 1.02, 95% CI.99-1.06), nulliparity (OR.79, 95% CI.48-1.30) and prevalence of hepatitis C (OR 1.35, 95% CI.08-21.67). In regards to metabolic risk factors, ICP patients and control patients were similar in prevalence of obesity (body mass index&gt;30kg/m^2; OR 1.01, 95% CI.62-1.61), hemoglobin A1c&gt;5.5% (OR.80, 95% CI.34-1.9), total cholesterol &gt;200 mg/dL (OR 4.15, 95% CI.83-20.84), and prevalence of hypertension (OR.69, 95% CI.31-1.52). Median bile acid levels were 30.6 µmol/L (IQR 11.6, 32.7) in the ICP group. ICP patients had higher median alanine aminotransferase (ALT) (32 vs. 16 U/L, p&lt;.0001), alkaline phosphatase (181 vs 128 U/L, p&lt;.0001) and total bilirubin levels (0.5 vs 0.35, p&lt;.0001) compared to controls. ICP patients were more likely to have ALT levels &gt; 50 U/L (2 times the upper limit of normal; OR 3.22, 95% CI 1.48-7.03). ICP patients were significantly more likely to have a history of biliary disease (OR 3.29, 95% CI 1.39-7.80). ICP patients were more likely to have evidence of steatosis on liver imaging (OR 4.69, 95% CI 1.68-13.12) than non-ICP patients. When evaluating a diagnosis of NAFLD based on ICD-10 code or evidence of steatosis on liver imaging, ICP patients were significantly more likely to have a diagnosis of NAFLD than controls (OR 5.7, 95% CI 2.08-15.65). DISCUSSION/SIGNIFICANCE OF IMPACT: ICP appears to be associated with NAFLD independently of metabolic risk factors such as obesity, dyslipidemia, hypertension, and diabetes, suggesting a direct link between NAFLD and ICP. If findings are confirmed, ICP patients, especially those with elevated ALT, would benefit from screening for NAFLD and linkage to liver specialty care postpartum.

May circulating steroids reveal a predisposition to intrahepatic cholestasis of pregnancy in non-pregnant women?

Intrahepatic cholestasis of pregnancy (ICP) is a frequent liver disorder, mostly occurring in the third trimester. ICP is not harmful to the mothers but threatens the fetus. The authors evaluated steroid alterations in maternal and mixed umbilical blood to elucidate their role in the ICP development. Ten women with ICP were included in the study. Steroids in the maternal blood were measured by Gas Chromatography-Mass Spectrometry (GC-MS) (n=58) and RIA (n=5) at the diagnosis of ICP, labor, day 5 postpartum, week 3 postpartum and week 6 postpartum. The results were evaluated by ANOVA consisting of the subject factor, between subject factors ICP, gestational age at the diagnosis of ICP and gestational age at labor, within-subject factor Stage and ICP × Stage interaction. The 17 controls were firstly examined in the week 36 of gestation. ICP patients showed reduced CYP17A1 activity in the C17,20 lyase step thus shifting the balance between the toxic conjugated pregnanediols and harmless sulfated 5alpha/beta-reduced-17-oxo C19 steroids. Hence, more toxic metabolites originating in maternal liver from the placental pregnanes may penetrate backward to the fetal circulation. As these alterations persist in puerperium, the circulating steroids could be potentially used for predicting the predisposition to ICP even before next pregnancy.

Is It Necessary to Perform the Pharmacological Interventions for Intrahepatic Cholestasis of Pregnancy? A Bayesian Network Meta-Analysis.

Although many meta-analyses have evaluated the pharmacotherapy of intrahepatic cholestasis of pregnancy (ICP) and recommended ursodeoxycholic acid (UDCA) as an effective treatment, the defect of the pair-wise analyses and the mixture of the control group made the outcome uncertain and unclear. We aimed to employ Bayesian network meta-analysis (NMA) to compare the maternal and fetal outcomes after UDCA, S-adenosylmethionine (SAMe) mono-therapy orthe combination treatment of these two drugs for ICP patients. Multiple electronic database searches were conducted for articles published up to 1 September 2018. The relevant information was extracted from the published reports with a predefined data extraction sheet, and the risk of bias was assessed with the Cochrane risk-of-bias tool. Poisson Bayesian network meta-analysis was employed to identify the synthesized evidence from the relevant trials, with reporting hazard risks (HRs) and 95% credible intervals (CrIs). The pooled outcomes of the 13 randomized controlledtrials (RCTs) with 625 participants indicated that none of the three regimens can significantly improve maternal and fetal outcomes. This NMA of the RCTs clarified that the current intervention has no favorable effect on pruritus and other symptoms in ICP patients.

Linc02527 promoted autophagy in Intrahepatic cholestasis of pregnancy

LncRNA plays a crucial role in human disease. However, the expression and function of LncRNA in ICP(Intrahepatic cholestasis of pregnancy) is still not fully elucidated. In this study, we found Linc02527 was increased expression in placenta and serum of ICP patients. Ectopically expression of Linc02527 promoted autophagy and proliferate in HTR8 cells. Silencing Linc02527 suppressed the autophagy and proliferate in HTR8 cells. Mechanically study revealed that Linc02527 regulated the expression of ATG5 and ATG7 by sponging miR-3185. Linc02527 directly binding to YBX1 and activated P21. The growth of C57 mouse was retarded when autophagy was activated. In normal condition, inhibited autophagy using chloroquine did not affect the growth of C57 mouse. However, in the condition of autophagy was activated, inhibited autophagy using chloroquine can improve the growth of C57 mouse. Overall, the results of this study identified Linc02527 as a candidate biomarker in ICP and a potential target for ICP therapy. Chloroquine was a potential drug for ICP therapy.

Waveform analysis of the fetal ECG in labor in patients with intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is reported to be associated with an increased risk of sudden fetal death. The possible mechanism is thought to be cardiac arrhythmia. Prolonged QT interval of the electrocardiogram (ECG) is associated with arrhytmogenic events. The aim of the study was to compare the fetal ECG QT interval during labor in pregnancies complicated with ICP to healthy controls. The fetal ECG and QT interval was reviewed retrospectively. The intrapartum QT interval was measured in 61 fetuses born to mothers with ICP and in a control group of similar size. The corrected QT interval (QTc) was calculated using Bazett's formula: QT/√RR. The occurrence of ST segment depression was also included in the analysis. The groups were similar regarding to maternal age, parity, BMI, gestational age and smoking habits. The rate of labor induction was significantly higher in ICP patients (P < 0.001). The QTc at the beginning and the end of recording was analyzed and there were no significant differences in these values between the ICP patients and healthy controls (P = 0.467). Most ICP patients used ursodeoxycholic acid (UDCA) for mediation. We analyzed separately patients who had elevated liver enzymes before labor. No significant differences in the QTc were noted in these patients either. Nor were there any significant ST depressions in ICP patients. The etiology of adverse perinatal outcome and even sudden fetal death in ICP is still controversial. No differences in QTc intervals and ST waveforms during labor were found in our study material.

Effect of inducible nitric oxide synthase and neuropeptide Y in plasma and placentas from intrahepatic cholestasis of pregnancy.

To analyze inducible nitric oxide synthase (iNOS) and neuropeptide Y (NPY) expression in maternal plasma and placentas of human with intrahepatic cholestasis of pregnancy (ICP). The plasma and placentas were collected from 35 women with normal pregnancies and 33 women with ICP. Enzyme-linked immunosorbent assays were used to investigate maternal plasma iNOS and NPY levels. The mRNA levels and cell-specific localization of iNOS and NPY were determined by quantitative PCR, Western Blotting and immunohistochemical analysis in placentas. In human placentas, it revealed iNOS and NPY were mainly localized in syncytiotrophoblast, cytotrophoblastin and vascular endothelium cells using immunohistochemistry analysis. iNOS protein and mRNA expression in ICP maternal plasma and placental tissue were significantly lower than in control groups (P <0.01). In maternal plasma and placentas tissue from ICP patients, a marked up-regulation of NPY protein and mRNA expression were observed (P <0.01). iNOS and NPY may play a role in the effect of maternal cholestasis on the placenta. The down-regulation of iNOS and up-regulation of NPY in ICP may influence the blood flow of the utero-placental-fetal unit, which may play a significant role in poor fetoplacental vascular perfusion, acute hypoxia and adverse pregnancy outcomes.

The Serum microRNA Profile of Intrahepatic Cholestasis of Pregnancy: Identification of Novel Noninvasive Biomarkers

Background/Aims: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific disease that significantly increases the risk of fetal complications. Here, we measured serum miRNA levels in ICP patients to identify candidate biomarkers for ICP. Methods: We used the Agilent miRNA array followed by reverse transcription-polymerase chain reaction assays to identify and validate the serum miRNA profiles of 40 pregnant women with ICP and 40 healthy pregnant controls. We used bioinformatics to identify metabolic processes related to differentially expressed miRNAs. Results: The expression levels of three miRNAs (miR-371a- 5p, miR-6865-5p, and miR-1182) were significantly increased in ICP patients compared to controls; the areas under the receiver operating characteristic (ROC) curves (AUCs) were 0.771, 0.811, and 0.798, respectively. Multiple logistic regression analysis showed that a combination of the levels of the three miRNAs afforded a greater AUC (0.845), thus more reliably diagnosing ICP. The levels of all three miRNAs were positively associated with that of total bile acids. Furthermore, bioinformatics analysis indicated that the three miRNAs principally affected lipid phosphorylation, apoptosis, and the MAPK signaling pathway. Conclusion: This preliminary work improves our understanding of serum miRNA changes in pregnant women with ICP. The three miRNAs may serve as novel noninvasive biomarkers of ICP.

Outcome After Implementation of a Modern Management Strategy for Intrahepatic Cholestasis of Pregnancy

(Abstracted from J Matern Fetal Neonatal Med 2017;30(11):1342–1346) Intrahepatic cholestasis of pregnancy (ICP) is associated with increased risk of adverse outcomes, including stillbirth, spontaneous preterm birth, and passage of meconium. Management of ICP patients consists of both controlling symptoms and minimizing fetal/neonatal risk for complications.