Cholestasis Of Pregnancy Research Articles

#5268 PREGNANCY OUTCOMES IN DIALYSIS PATIENTS: A TEN-YEAR SERIES FROM A TERTIARY CENTER

Abstract Background and Aims Pregnancy in dialysis patients was almost prohibited a decade ago, as fetal and maternal outcomes were very poor. In the last years, there has been a paradigm shift, as the introduction of intensive hemodialysis (HD) schedules has been associated with an impressive improvement on fetal outcomes, making motherhood a possibility in these women. Nevertheless, pregnancy in women on dialysis remains associated with a high incidence of complications and is extremely demanding for both patients and clinicians. We describe the maternal, obstetric, and perinatal outcomes of pregnancies in women on dialysis followed at the Nephro-Obstetric Clinic at Centro Hospitalar Universitário Lisboa Norte (CHULN). Method Retrospective analysis of pregnancies in women on dialysis and surveilled at the Nephro-Obstetric Clinic at CHULN from 2011 to 2022. Results We considered 17 pregnancies from 16 women. One of the women accounted was submitted to voluntary termination of pregnancy. Mean age was 31.5 ± 6.1 years; 70.6% were Black (n = 11) and 29.4% (n = 5) Caucasian; 58.8% were nulliparous (n = 10). All patients had chronic hypertension (HTN), although only 75.0% were under therapy (12/16). Additionally, 3/16 patients had diabetes and 2/16 hyperthyroidism. The mean of overall renal replacement therapy (RRT) duration was 9.1 ± 8.2 years (dialysis and renal transplantation time), being on dialysis program 43.7 ± 37.5 months before gestation. One patient was on peritoneal dialysis (PD) and two patients started HD during pregnancy. Five patients (31.2%) were exposed to teratogenic drugs during gestation. Pregnancy diagnosis occurred at 13.4 ± 5.6 weeks; 70.6% of the patients were on low dose acetylsalicylic acid (n = 12). HD mean time per week according to each trimester was 13.7 ± 2.8 hours/week, 24.5 ± 7.3 hours/week and 28.0 ± 8.0 hours/week during the 1st/2nd/3rd respectively. Mean pre-dialysis urea was 62.1 ± 28.0 mg/dL during gestation. Regarding maternal outcomes, worsening HTN occurred in 62.5% (n = 10) of patients during the 1st (4/10) and 2nd trimester (7/10) and pre- eclampsia (PE) occurred in 6/16 patients (1 with HELLP syndrome). One patient developed polyhydramnios and another one cholestasis of pregnancy. Premature rupture of membranes (PRM) occurred in 3 patients (at 17, 25 and 36 weeks); One patient asked for medical termination of pregnancy due to severe growth restriction and oligohydramnios at 20 weeks. Stillbirth occurred in 4 gestations (cervical insufficiency in a twin pregnancy, severe congenital fetal cardiopathy in a patient with PE, severe growth restriction and premature rupture of membranes (PRM). In the 2 patients with early PRM, the neonates died in the following week due to severe prematurity complications. Labor was induced in 9 patients, mainly due to PE (7/9). Cesarean was performed in 10/17 patients and mean gestation age at delivery was 29.8 ± 6.6 weeks. Extreme prematurity (<28 weeks) occurred in 3 pregnancies and there were three term babies. Mean birth weight was 1554.0±613.6 grams with 4 newborns having extremely low birth weight (<1000g) and 6 requiring neonatal care. Conclusion Our study reveals that pregnancy in women on dialysis is challenging and still associated with significant maternal, obstetric and perinatal complications. This population was highly heterogenous, with a significant number of patients living under unfavorable social conditions, and with significant comorbidities. The diagnosis of pregnancy took place mainly during the 2nd trimester, preventing early initiation of intensive dialysis schedules which could have significantly improved outcomes. Pregnancy planning, early diagnosis and management by a multidisciplinary experienced team are of paramount importance to improve outcomes and reduce complications.

Ultrasound-assessed lung aeration, oxygenation and respiratory care in neonatal bile acid pneumonia: a nested case-control study.

Neonatal bile acid pneumonia (NBAP) occurs in neonates following obstetric cholestasis. We aimed to study the lung aeration and respiratory support of NBAP. Nested, case/control study enrolling age-matched neonates with NBAP, respiratory distress syndrome (RDS) or transient tachypnoea (TTN). Lung aeration and oxygenation were assessed with lung ultrasound score, oxygenation index and SpO2 /FiO2 . Nineteen, 22 and 25 neonates with NBAP, RDS and TTN, respectively were studied (mean gestational age 33 (2.2) weeks, 30 (45.5%) males). Upon admission, RDS patients had worst lung ultrasound score (p=0.022) and oxygenation index (p=0.001), while NBAP and TTN neonates had similar values. At the worst time-point, NBAP and RDS patients showed similar oxygenation index (NBAP: 4.6 (2), RDS: 5.7 (3)) and SpO2 /FiO2 (NBAP: 3.1 (1.1), RDS: 2.7 (1)) which were worse than those of TTN patients (oxygenation index: p=0.015, SpO2 /FiO2 : p=0.001). RDS neonates needed the longest continuous positive airway pressure and highest mean airway pressure, but NBAP neonates needed invasive ventilation (26.3%, p=0.01) and surfactant (31.6%, p=0.003) more often than TTN patients who never needed these. NBAP was a mild disorder in the first hours of life but subsequently worsened and became similar to RDS.

Platelet counts affect the association between hyperhomocysteinemia and pregnancy complications

BackgroundThe joint effect of platelet and other modifiers on the risk of pregnancy complications is unknown. This study investigated whether platelet count (PC) and total homocysteine (tHcy) level have a synergistic effect on the incidence of pregnancy complications in a Chinese population.MethodsTotal 11,553 consecutive pregnant women who received whole blood cell and biochemical tests at the time of admission for labor in Changzhou Maternal and Child Health Care Hospital were analyzed. The primary outcome was the prevalence of pregnancy complications: gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP), pre-eclampsia (PE), and pregnancy induced hypertension (PIH).ResultsThe prevalence of GDM, ICP, PE, and PIH was 8.4%, 6.2%, 3.4%, and 2.1%, respectively. The highest rate of ICP (28.6%) was observed in women with high tHcy (> 15 μmol/L) and low PC (quartile 1); and the lowest rate of GDM (0.6%) was found in women with high tHcy and high PC (quartiles 2 to 4). In low PC group, the prevalence of ICP in women with high tHcy was significantly higher than that in women with low tHcy (≤ 15 μmol/L) (28.6% vs. 8.4%), representing an absolute risk increment of 20.2% and a relative risk increment of 3.3-fold (OR: 3.34; 95% CI: 1.55, 7.17; P = 0.002), whereas no joint effect was observed among high PC group.ConclusionsAmong Chinese pregnant women, one subgroup (high tHcy and low PC) has the highest risk of ICP and another (high tHcy and high PC) has the lowest risk of GDM; tHcy and platelet could be used as indicators to identify the women with high risk of ICP or low risk of GDM.

THU-311 - Intrahepatic cholestasis of pregnancy: genetic testing and genotype-phenotype relations in a cohort from a Danish tertiary liver center

THU-311 - Intrahepatic cholestasis of pregnancy: genetic testing and genotype-phenotype relations in a cohort from a Danish tertiary liver center

Clinical Profile, Laboratory Parameters & Complications in Pregnancy with Jaundice: A Study in DMCH, Dhaka, Bangladesh

Background: Pregnancy with jaundice is considered a high-risk pregnancy. It is the most usual health complaint in pregnant women found more often in developing countries than in developed ones. Jaundice can be concurrent with 1st trimester due to pathological infection for instance viral hepatitis or gall stones or due to the drug administered during pregnancy. These patients may feel better if initial diagnosis and suitable management are provided. This present study intended to evaluate the clinical profile & complications of jaundice during pregnancy. Material & Methods: This descriptive cross-sectional study was conducted in the Department of Obstetrics and Gynecology, Dhaka Medical College Hospital, Dhaka, Bangladesh from January 2012 to June 2012. A total (N=50) of pregnant women with symptoms of jaundice were enrolled in the study. Completed data forms were reviewed, edited, and processed for computer data entry. The data analysis was performed using Statistical Package for the Social Sciences (SPSS) Version 16.0. Descriptive inferential statistics were performed to determine the results of this study. Results: Among the study population (N=50), the majority of patients (34, 68.0%) age were between 20 to 24 years. The mean gestational age of patients was 35.3±3.2 weeks and twelve patients (12, 24.0%) underwent caesarean delivery. Based on clinical features, twenty-seven respondents (27, 54.0%) had mild jaundice, fourteen respondents (14, 28.0%) had moderate jaundice & about one-fifth of the patients (9, 18.0%) had severe jaundice. Fifteen pregnant (15, 30.0%) women had a fever, around two-fifth of the patients (19, 38.0%) had vomiting, pruritus in one patient (1, 2.0%), vaginal bleeding in twelve patients (12, 24.05), & more than half of the patients (27, 54.0%) had ruptured membrane. The causes of jaundice during pregnancy were viral hepatitis in forty-three patients (43, 86.0%). The majority of the patients (27,54.0%) had serum bilirubin less than 10mg, fourteen patients (14,28.0%) had 10 to 15mg of serum bilirubin & only one patient (1,2.0%) had serum bilirubin more than 20mg. SGOT & SGPT was found 100-500 IU/ml in twenty-three patients (23,46.0%) & 500-1000 IU/ml in ten patients (10,20.0%). Alkaline was raised in eighteen cases (18, 36.0%) Based on maternal complications, the majority of patients (31, 62.0%) had a postpartum haemorrhage, and ten patients (10, 20.0%) experienced encephalopathy. Thirty-eight babies (38, 76.0%) were born alive, intrauterine death was in seven cases (7, 14.0%), and stillborn in five cases (5, 10.0%). Conclusion: Hepatitis E was the most common cause of viral hepatitis in our study. Major complications were postpartum haemorrhage and encephalopathy. This study also prevailed, jaundice in pregnancy is related to an increase in maternal mortality and morbidity, obstetric complications, and perinatal complications.

Vaginal Progesterone Is Associated with Intrahepatic Cholestasis of Pregnancy.

The frequency of intrahepatic cholestasis of pregnancy (ICP) peaks during the third trimester of pregnancy when plasma progesterone levels are the highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17α-hydroxyprogesterone caproate for the prevention of preterm birth. We identified 1,776,092 live-born singleton pregnancies between 2010 and 2014. We confirmed second and third trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events or progesterone treatment prescribed only during the first trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17α-hydroxyprogesterone caproate compared with those not treated with any type of progestogen (the reference group). The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the second and third trimester, the frequency of cholestasis was significantly higher than the reference group (0.75 vs. 0.23%, adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.23-4.49). In contrast, there was no significant association between 17α-hydroxyprogesterone caproate and cholestasis (0.27%, aOR: 1.12, 95% CI: 0.58-2.16) CONCLUSION: Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17α-hydroxyprogesterone caproate was associated with an increased risk for ICP. · Previous studies have been underpowered to detect potential association between progesterone and ICP.. · Vaginal progesterone was significantly associated with ICP.. · Intramuscular 17α-hydroxyprogesterone was not associated with ICP..

Stress regulation of WFS1 and PERK-p-eIF2α-ATF4 signaling pathway in placental tissue cells of intrahepatic cholestasis of pregnancy

IntroductionThe placental tissue stress of intrahepatic cholestasis of pregnancy (ICP) is activated by ERS under hypoxia condition. PERK signaling pathway is the key pathway for UPR regulation, and is first to activated during ERS. WFS1, as an important regulatory gene of UPR pathway, participates in ERS regulation. The purpose of our study is to explore the expression level and mutual regulation mechanisms of WFS1 and PERK-mediated UPR pathway in ICP placental tissue cell under stress. MethodsBlood and placenta samples were obtained from the ICP patients and ethinylestradiol (EE)-induced intrahepatic cholestasis pregnant rats. IHC and WB were used to detect the expression of WFS1, key factors of PERK pathway (GRP78, PERK, eIF2a, P-eIF2α, ATF4) and placental stress peptides (CRH, UCN). Furthermore, qPCR was carried out to detect mRNA expression of above indicators. ResultsThe expression levels of WFS1 and key factors of PERK pathway were significantly increased in severe ICP placental tissues. Moreover, qPCR and WB showed that relative mRNA and protein expression levels of WFS1 and key factors of PERK pathways in placenta tissues of severe ICP and EE-induced intrahepatic cholestasis pregnant rats were higher than those in control group to varying degrees, while CRH and UCN were descended. Meanwhile, after WFS1-siRNA targeted silencing of the WFS1 gene, the protein expression levels of PERK, P-eIF2α, ATF4 were significantly increased, while CRH and UCN protein were significantly decreased. DiscussionOur study revealed that the activation of WFS1 and PERK-p-eIF2α-ATF4 signaling pathway may contribute to stress regulation in placental tissue cells of intrahepatic cholestasis of pregnancy, thereby avoiding adverse pregnancy outcomes.

Association between intrahepatic cholestasis of pregnancy and gestational diabetes mellitus

Gestational diabetes mellitus is one of the most prevalent prenatal illnesses (ranging from 5% to 18%), while intrahepatic cholestasis of pregnancy takes the first place among liver diseases during pregnancy (ranging from 0.2% to 27%). In our summary, we examined the relationship between the two gestation-related medical conditions and their combined presence affects on the outcome of pregnancy. Based on research available, it can be stated that intrahepatic cholestasis of pregnancy may be a predisposing factor to late-onset gestational diabetes mellitus. This connection stems from the modulating role of serum bile acids, as due to the regulation of farnesoid X receptor and Takeda G protein-coupled receptor 5 the bile acids affect glucose and lipid homeostasis. Common fetal complications of gestational diabetes and intrahepatic cholestasis of pregnancy are stillbirth, acute respiratory distress syndrome and preterm delivery. Gestational diabetes mellitus may be more common in patients with intrahepatic cholestasis of pregnancy, and the co-occurrence of the two diseases can increase the risk of fetal and maternal complications, therefore special attention must be paid to the prevention and treatment of these by the prenatal caregiver. Orv Hetil. 2023; 164(21): 831-835.

Ursodeoxycholic acid: unique properties and clinical applications

Ursodeoxycholic acid (UDCA) is a natural hydrophilic bile acid, which is present in humans as a small fraction of the total amount of bile acids (5%). Its unique properties underlie its use in a number of liver diseases as a first-line therapy. The ability of UDCA to reduce the secretion of cholesterol into bile, form mixed micelles (liquid crystals) with cholesterol molecules and interact with multifunctional nuclear receptors, are actively used in the treatment and prevention of cholelithiasis. UDCA has the ability to stimulate hepatobiliary secretion, promotes the secretion of bicarbonate by cholangiocytes, which is relevant for patients with primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC). UDCA activates transporter proteins such as bile acid export pump (BSEP), multiresistance protein 2 (MRP2) – conjugates transporter, type 2 anion exchanger (AE2), and promotes their movement to the canalicular membrane of cells. UDCA acts as a pleiotropic agent that plays a unique role in modulating the classical mitochondrial pathway of apoptosis in various cell types. Double molecular bonds of UDCA serve as a trap for free radicals, which suppresses the processes of lipid peroxidation. The ability of UDCA to penetrate into mitochondrial membranes leads to suppression of the activity of mitochondrial oxidase enzymes responsible for the production of superoxide anion. UDCA activates autophagy and promotes the elimination of toxic fatty acids from hepatocytes, reducing liver steatosis, UDCA has anti-inflammatory, antifibrotic, immunomodulatory and anticarcinogenic effects. UDCA is included in international and Russian clinical guidelines for the treatment of patients with various liver diseases (PBC, PSC, intrahepatic cholestasis of pregnancy, drug-induced cholestasis, alcoholic liver disease with cholestatic component), cholelithiasis, cystic fibrosis. In the pharmacotherapy of non-alcoholic fatty liver disease, UDCA is the only drug that has a bi-directional effect on the liver and cardiovascular system.

Effects of HBsAg carriers on pregnancy complications in pregnant women: a retrospective cohort study.

Hepatitis B virus (HBV) infection is a major health threat worldwide, especially in developing countries. We aimed to investigate the impact of hepatitis B carrier on pregnancy complications in pregnant women, in China. This retrospective cohort study was conducted by using data from the EHR system of Longhua District People's Hospital in Shenzhen, China, from January 2018 to June 2022. Binary logistic regression was used to evaluate the relationship between HBsAg carrier status and pregnancy complications and pregnancy outcomes. The study included 2095 HBsAg carriers (exposed group) and 23,019 normal pregnant women (unexposed group). Pregnant women in the exposed group were older than the pregnant women in the unexposed group (29 (27,32) vs. 29 (26,32), p < 0.001). In addition, the incidence of some adverse pregnancy complications in the exposure group was lower than that in the unexposed group, including hypothyroidism of pregnancy (adjusted odds ratio [aOR], 0.779; 95% confidence interval [CI], 0.617-0.984; p = 0.036), hyperthyroidism of pregnancy (aOR, 0.388; 95% CI, 0.159-0.984; p = 0.038), pregnancy induced hypertension (aOR, 0.699; 95% CI, 0.551-0.887; p = 0.003), antepartum hemorrhage (aOR, 0.294; 95% CI, 0.093-0.929; p = 0.037). However, compared with the unexposed group, the exposed group had a higher risk of lower birth weight (aOR, 1.12; 95% CI, 1.02-1.23; p = 0.018) and intrahepatic cholestasis of pregnancy (aOR, 2.888, 95% CI, 2.207-3.780; p < 0.001). The prevalence rate of HBsAg carriers in pregnant women in Longhua District of Shenzhen was 8.34%. Compared with normal pregnant women, HBsAg carriers have a higher risk of ICP, a lower risk of gestational hypothyroidism and PIH, and a lower birth weight of their infants.

Beyond Stillbirth: Association of Intrahepatic Cholestasis of Pregnancy Severity and Adverse Outcomes

(Am J Obstet Gynecol. 2022;227:517.e1–517.e7) While the incidence of intrahepatic cholestasis of pregnancy (IHCP) is infrequent (0.3% to 0.5%) in most regions, rates are elevated (15%) in certain populations and confer significant risk to the fetus. Maternal pruritus and elevated bile acids often begin in the second or third trimester, with the total bile acid (TBA) level being correlated to severity of disease and predictive of stillbirth. In addition to fetal demise, recent research has highlighted the association of IHCP with increased iatrogenic preterm birth, spontaneous preterm birth, respiratory distress syndrome and meconium-stained amniotic fluid. While severity-based analysis based on TBA levels is established for stillbirth, this study aimed to delineate an analysis of TBA correlation to other adverse outcomes beyond stillbirth.

MDR3 rs2109505 and rs1202283 polymorphisms are associated with susceptibility to intrahepatic cholestasis of pregnancy: A meta-analysis.

Many studies have assessed the relationship between gene polymorphisms in multidrug resistance protein 3 (MDR3) and the risk of intrahepatic cholestasis of pregnancy (ICP); however, there are many conflicting narratives. This meta-analysis was conducted to assess the association between MDR3 gene polymorphisms and ICP. A multi-database search was conducted using Web of Science, Embase, PubMed, and Chinese Biomedical Literature (CBM) databases. Eleven eligible studies focusing on 4 single nucleotide polymorphisms (SNPs) in the MDR3 gene were selected for analysis. A fixedor random-effects model was utilized for allelic, dominant, recessive, and superdominant genes. The pooled results indicated a statistically significant association between MDR3 polymorphism rs2109505 and an increased risk of ICP in both the general population and the Caucasian population. No statistically significant associations were found between MDR3 polymorphism rs2109505 and ICP in Italian or Asian populations for the 4 genetic models. The MDR3 polymorphism rs1202283 was associated with susceptibility to ICP in both the general and Italian populations. The MDR3 rs2109505 and rs1202283 polymorphisms are associated with ICP susceptibility: however, they displayed no correlation with an increased risk of ICP.

Rare variant contribution to cholestatic liver disease in a South Asian population in the United Kingdom

This study assessed the contribution of five genes previously known to be involved in cholestatic liver disease in British Bangladeshi and Pakistani people. Five genes (ABCB4, ABCB11, ATP8B1, NR1H4, TJP2) were interrogated by exome sequencing data of 5236 volunteers. Included were non-synonymous or loss of function (LoF) variants with a minor allele frequency < 5%. Variants were filtered, and annotated to perform rare variant burden analysis, protein structure, and modelling analysis in-silico. Out of 314 non-synonymous variants, 180 fulfilled the inclusion criteria and were mostly heterozygous unless specified. 90 were novel and of those variants, 22 were considered likely pathogenic and 9 pathogenic. We identified variants in volunteers with gallstone disease (n = 31), intrahepatic cholestasis of pregnancy (ICP, n = 16), cholangiocarcinoma and cirrhosis (n = 2). Fourteen novel LoF variants were identified: 7 frameshift, 5 introduction of premature stop codon and 2 splice acceptor variants. The rare variant burden was significantly increased in ABCB11. Protein modelling demonstrated variants that appeared to likely cause significant structural alterations. This study highlights the significant genetic burden contributing to cholestatic liver disease. Novel likely pathogenic and pathogenic variants were identified addressing the underrepresentation of diverse ancestry groups in genomic research.

Interactive effects of gestational diabetes mellitus and maximum level of total bile acid in maternal serum on adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy

ObjectiveTo study the combined effect of gestational diabetes mellitus (GDM) and maximum level of maternal serum total bile acid (TBA) on the incidence of adverse pregnancy outcomes in women with intrahepatic cholestasis of pregnancy (ICP).MethodsThis was an observational study with 724 women with ICP. Perinatal outcomes were compared by the presence of GDM. Logistic regression was used to assess the independent and multiplicative interactions of GDM and maximum maternal serum TBA on adverse pregnancy outcomes. Additive interactions were calculated using an Excel sheet developed by Andersson to calculate relative excess risks.ResultsThe incidence of GDM in patients with ICP was 21.55%. Maternal age, pre-pregnancy weight, parity, and gravidity were positively correlated with GDM. Hypertensive disorders of pregnancy (HDP) and fetal distress rates were higher in the GDM vs. non-GDM group. There were no significant differences in biochemical outcomes (i.e., Triglyceride (TG), low density lipoprotein (LDL), alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bile acid (TBA)) between the two groups. In terms of adverse pregnancy outcomes, GDM was only associated with maximum TBA concentration for cesarean section. No additive or pairwise interactions were detected between GDM and maximum TBA concentration and HDP, PPH, preterm delivery, LGA, SGA, and cesarean section.ConclusionGDM independently contributes to adverse pregnancy outcomes among women with ICP. However, the combined effects of GDM and maximum TBA concentration on adverse pregnancy outcomes do not appear to be multiplicative or additive.

Prior History of Cholestasis Is Not Associated With Worsening Outcomes in Subsequent Pregnancy With Cholestasis [ID: 1363296

INTRODUCTION: Intrahepatic cholestasis of pregnancy (IHCP) is associated with adverse pregnancy outcomes including intrauterine fetal demise, spontaneous preterm labor, and meconium-stained amniotic fluid. Studies have yet to determine whether a prior pregnancy complicated by cholestasis is associated with more severe adverse outcomes in a subsequent pregnancy complicated by cholestasis. METHODS: This was a retrospective cohort study of multiparous, singleton, nonanomalous live gestations complicated by IHCP at Elmhurst Hospital Center from 2005 to 2019. We compared rates of adverse outcomes in multiparous pregnancies complicated by IHCP with or without history of prior IHCP. Our primary outcome of interest was rates of spontaneous preterm labor. Our secondary outcomes included rates of iatrogenic preterm birth, meconium-stained amniotic fluid, cesarean delivery (CD) for nonreassuring fetal heart tracing, umbilical artery pH less than 7.20, and neonatal intensive care unit (NICU) admission. Chi-square and multivariate regression tests were used to determine the strength of association. In all analyses, a P value less than 0.05 and 95% CI not crossing 1.00 indicated statistical significance. Mount Sinai Icahn School of Medicine IRB approval was obtained for this project. RESULTS: Of the 795 multiparous pregnancies complicated by IHCP, 618 (77.7%) had no prior history of IHCP and 177 (23.3%) had prior history of IHCP. Multiparous pregnancies with prior history of IHCP had higher rates of prior preterm birth, had earlier gestational age at diagnosis and delivery, and were more likely to receive ursodeoxycholic acid therapy. In subsequent pregnancies with IHCP, history of IHCP was associated with iatrogenic preterm birth and NICU admission. After adjusting for confounders, the association with iatrogenic preterm birth and NICU admission were no longer statistically significant. There was no significant association between history of prior IHCP and other adverse obstetric outcomes. CONCLUSION: Findings suggest that history of prior IHCP is not associated with worsening outcomes in subsequent pregnancies complicated by cholestasis.

Intrahepatic Cholestasis of Pregnancy Complicated by COVID-19 Infection [ID: 1381429

INTRODUCTION: Recent studies show that COVID has been associated with liver injury. Our study presents a case series of pregnant patients with intrahepatic cholestasis of pregnancy (ICP) complicated by prior COVID infection. METHODS: A retrospective review of singleton pregnancies delivered in an academic center between January 2020 and April 2022 identified patients with ICP (bile acids [BA]&gt;10 mmol/L) with prior COVID infection in pregnancy. Maternal demographics, clinical/laboratory findings, medication use, and perinatal outcomes were collected. Secondary outcomes included BA greater than 40 mmol/L, BA trends in pregnancy, use of ursodiol, and rate of adverse perinatal outcomes (maternal/neonatal death). Institutional review board approval was exempted for this study. RESULTS: Of 138 cases of ICP and 743 cases of COVID during our study period, 14 patients were evaluated, 9 of whom met inclusion criteria. All cases of COVID resolved prior to delivery except one. Most cases (77.8%, 7/9) used ursodiol for treatment of ICP with mean duration of 6.9 weeks (±4.7). Six cases (66.7%) had BA greater than 40 mmol/L. One reported BA as high as 153 mmol/L at 23.5 weeks after COVID was diagnosed at 23.2 weeks. In this case, BA levels resolved by 26 weeks to less than 10 mmol/L and remained normal until delivery at 37 weeks. No adverse perinatal outcomes were reported. CONCLUSION: ICP cases in the setting of prior COVID in pregnancy are rare, but liver injury related to COVID may increase BA levels in pregnancy. Further studies are needed to evaluate possible associations between elevated BA due to COVID-19 and adverse perinatal outcomes.

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.

Diagnosis and management of intrahepatic cholestasis in pregnancy

Intrahepatic cholestasis of pregnancy is caused by a dysfunction of the hepatocytes, typical of pregnancy. High concentrations of sex hormones and genetic predisposition appear to be important factors for their development. The incidence depends on the ethnic composition of the population and the diagnostic criteria used. It is characterized by increasing and persistent pruritus, increased concentrations of bile acids, usually in the late second or third trimester of pregnancy. It leads to the occurrence of uteroplacental hypoxia that increases the risk of meconium amniotic fluid, preterm delivery, preeclampsia, postpartum hemorrhage, neonatal respiratory distress syndrome, and perinatal death. Therapeutic management is aimed at reducing clinical symptoms, normalizing maternal biochemical changes, and preventing fetal complications. The main pharmacological treatment consists of the administration of ursodeoxycholic acid. The objective of this research is to evaluate the diagnosis and management of intrahepatic cholestasis of pregnancy

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.

Intrahepatic cholestasis of pregnancy worsening perinatal depressive tendency: A follow-up study from the second trimester to the sixth week postpartum

The total bile acid (TBA) is usually used to diagnose intrahepatic cholestasis of pregnancy (ICP) as a common clinical index. Recently many research reports on the microbiota-gut-brain axis (MGB axis) suggest that bile acids have an influence on human mental illnesses such as anxiety and depression, linked closely to intestinal microbial population. However, there is still a lack of clinical data to support intrinsic relationships about human cases. In this study, we conducted a follow-up study of 25 ICP and 98 healthy pregnant women to investigate the influence of ICP disease on perinatal depression. To further explore the effect of TBA concentration, we reviewed data of another 41 ICP women then added their cross-sectional data. The results showed that ICP disease increased mental scale scores but a conventional efficient treatment by using ursodeoxycholic acid (UDCA) could not decrease scores, suggesting intrahepatic cholestasis might make some key bile acids not to be processed by gut microbiota. UDCA could not replace the function of gut microbiota for easing depression and the change of bile acid composition in intestines worsened perinatal depressive tendency through the MGB axis.