Ursodeoxycholic acid (UDCA) is the most commonly prescribed treatment for intrahepatic cholestasis of pregnancy (ICP) worldwide. Clinical studies show that UDCA helps alleviate maternal pruritus and lowers serum bile acid levels. However, despite treatment, women with ICP still experience unpredictable fetal deaths and other serious pregnancy complications. In this study, we hypothesize that while UDCA improves maternal symptoms, it may have harmful effects on the fetus due to its placental barrier crossing, potentially leading to negative pregnancy outcomes. We found that UDCA concentrations above 150 mg/L can exert toxic effects on zebrafish embryos, including increased mortality, slower heart rates, and pericardial edema. At these concentrations, UDCA also triggered apoptosis and elevated oxidative stress in embryonic cardiomyocytes. Importantly, the thyroid hormone T4 was able to partially mitigate these toxic effects. These findings suggest that adverse pregnancy outcomes in ICP may be related to fetal heart damage caused by UDCA's effects on circulation, providing a possible explanation for fetal death in clinical settings. This also underscores the need to optimize UDCA dosing in clinical practice and explore the use of thyroid hormones as a potential protective therapy for the fetus in ICP cases.

Objective: Intrahepatic cholestasis of pregnancy (ICP) is associated with an elevated risk of adverse perinatal outcomes, including perinatal morbidity and mortality. The objectives of this study were to evaluate the bile acid (BA) metabolism profiles in the urine of patients with ICP and to investigate the association between specific BAs and maternal and neonatal outcomes in patients with ICP. Methods: A total of 127 Chinese women with ICP and 55 healthy pregnant women were enrolled in our retrospective study. Spot urine samples and clinical data were collected from pregnant women from January 2019 to December 2022 at the First Affiliated Hospital of Chongqing Medical University, Chongqing. Based on total bile acid (TBA) levels, the ICP group was subdivided into mild (10-40 μmol/L) and severe (≥40 μmol/L) ICP groups. Patients in the ICP group were further divided into two categories according to neonatal outcomes: an ICP with adverse pregnancy outcomes group and an ICP with non-adverse pregnancy outcomes group. Metabolites from maternal urine were collected and analyzed using ultra-high-performance liquid chromatography-triple quadrupole time-of-flight mass spectroscopy (UPLC-triple TOF-MS). Results: Significant differences were observed between the mild and severe ICP groups in the onset time of symptoms, gestational weeks at time of ICP diagnosis, the duration of using ursodeoxycholic acid (UDCA) drugs during pregnancy, gestational age at delivery, premature delivery, and cesarean delivery. The expression levels of the composition of different urinary bile acids including THCA, TCA, T-ω-MCA, TCA-3-S, TCDCA-3-S, TDCA-3-S, GCDCA-3-S, DCA-3-G and GDCA-3-G were remarkably higher in the ICP with adverse pregnancy outcomes group than those in the ICP with non-adverse pregnancy outcomes group and the control group. The single-parameter model used to predict adverse pregnancy outcomes in ICP had similar areas under the curve (AUCs) of the receiver operating characteristic (ROC), ranging from 0.755 to 0.869. However, an AUC of 0.886 and 95% CI were obtained by the index of combined urinary bile acids in multiple prediction models (95% CI 0.790 to 0.983, p < 0.05). TCA-3-S in the urinary bile acids had a strong positive correlation with the aspartate aminotransferase (AST) level (r = 0.617, p < 0.05). Furthermore, TCDCA-3-S and GCDCA-3-S in the urinary bile acids had a strong positive correlation with the alanine aminotransferase (ALT) level (r = 0.607, p < 0.05; r = 0.611, p < 0.05) and AST level (r = 0.629, p < 0.05; r = 0.619, p < 0.05). Conclusions: Maternal urinary bile acid profiles were prominent for the prognosis of maternal and neonatal outcomes of ICP. Elevated levels of TCA-3-S, TCDCA-3-S, and GCDCA-3-S in urine might be important predictors for indicating adverse pregnancy outcomes in ICP.

This study aims to develop and validate a model based on the weighted random forest (WRF) algorithm to predict early-onset preeclampsia (PE) and to assess the importance of various clinical and biochemical markers in early risk identification.

This study was conducted at the Jiangxi Maternal and Child Health Hospital and involved 12,699 pregnant women from January 2019 to June 2022. Extensive clinical and biochemical markers were collected through prenatal care data, which were used to construct a predictive model for early-onset PE. The model was developed using the WRF and Logistic regression methods, and multivariable analysis was employed to identify markers significantly associated with the risk of PE.

The relative importance of various markers was evaluated using the random forest (RF) model in a sample of 1200 patients diagnosed with PE. Blood pressure and pre-pregnancy body mass index (BMI) were identified as the most critical variables affecting the accuracy of the PE prediction model. The WRF model demonstrated higher predictive accuracy (AUC = 0.9614) than the Logistic regression model (AUC = 0.9138), highlighting its superiority in early risk identification for PE.

The WRF-based predictive model developed in this study effectively predicts the risk of early-onset PE, with blood pressure and BMI as vital predictive factors. These findings underscore the importance of employing a comprehensive predictive model for risk assessment in early pregnancy, facilitating early intervention and improving health outcomes for pregnant women and their newborns.

To investigate the fetal heart using pulsed wave Doppler, M-mode, and tissue Doppler imaging (TDI) in cases of intrahepatic cholestasis of pregnancy (ICP).

This prospective study was conducted at a single tertiary center and included 35 patients with ICP and 70 healthy pregnant women at 28-36 weeks of pregnancy. Among the patients with ICP, 26 had serum bile acid (SBA) levels less than 40 μmol/L and nine had SBA levels of 40 μmol/L or greater. Pulsed wave Doppler, M-mode, and TDI evaluations were performed on the patients to assess fetal cardiac function.

The ICP group exhibited significantly higher myocardial performance index (MPI) and isovolumetric relaxation time (IRT), but similar isovolumetric contraction time (ICT). The tricuspid and mitral valve E, A, and E/A ratios were significantly reduced in the ICP group. The TDI parameters showed significantly reduced tricuspid and mitral valve E'/A' ratios in the ICP group compared with the control group (P < 0.001). The E/E' ratio was significantly increased in the ICP group (P < 0.001). According to the M-mode Doppler findings, tricuspid and mitral annular plane systolic excursion values were significantly decreased in the ICP group (P = 0.005 and P = 0.001, respectively). In the subgroup analysis, MPI and IRT were significantly higher in the severe ICP group.

ICP might induce changes in the fetal heart during the early systolic and diastolic phases. The detection of these early changes using M-mode and TDI during the antenatal period can provide valuable insights into the condition of the fetus.

To investigate the rare obstetric emergency with no specific treatments called acute fatty liver of pregnancy. The primary objective was to evaluate association of adverse perinatal outcomes with blood components transfusion. While the secondary objective focused on further establishing the predictive risk factors for adverse perinatal outcomes.

This retrospective cohort study included patients, who diagnosed with acute fatty liver of pregnancy without hepatic/malignant diseases in Qilu Hospital of Shandong University over 12-year period (collected 2007-2019, aged 20-41years). Chi-square test was used to explore the relevance between blood transfusion therapy and adverse perinatal outcomes. Meanwhile, logistic regression analysis was performed to identify predictive risk factors.

Of 146 patients, 26 (26/146, 17.8%) received prenatal blood transfusions. These patients had reduced gestational ages and exhibited more severe clinical symptoms. The association between blood transfusion and adverse maternal outcomes yielded a P value of 0.044, while the association with fetal outcomes was highly significant (P<0.001). Multivariate logistic regression analysis identified seven high-risk factors for maternal outcomes and six for fetal outcomes, all demonstrating strong discriminatory capacity.

Blood component transfusion may serve as a marker of disease severity. Prompt identification of patients with high-risk factors is crucial to improve maternal and fetal outcomes.

Studies have shown that fine particulate matter (PM2.5) has adverse effects on the liver function, but epidemiological evidence is limited, especially regarding pregnant women. This study aims to investigate the association between PM2.5 exposure in early pregnancy and maternal liver function during pregnancy.

This retrospective cohort study included 13,342 pregnant participants. PM2.5 and Ozone (O3) exposure level, mean temperature, and relative humidity for each participant were assessed according to their residential address. The levels of serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin (TBIL) were measured during the second and third trimesters. Data on PM2.5 and O3 exposure level were sourced from Tracking Air Pollution in China (TAP), while the mean temperature and relative humidity were obtained from the ERA5 dataset. The Generalized Additive Model (GAM) was used to analyze the associations between PM2.5 exposure and maternal liver function during pregnancy, adjusting for potential confounding factors.

According to the results, each 10 μg/m3 increase in PM2.5 was associated with an increase of 3.57% (95% CI: 0.29%, 6.96%) in ALT and 4.25% (95% CI: 2.33%, 6.21%) in TBIL during the second trimester and 4.51% (95% CI: 2.59%, 6.47%) in TBIL during the third trimester, respectively. After adjusting for O3, these associations remained significant, and the effect of PM2.5 on ALT during the second trimester was further strengthened. No significant association observed between PM2.5 and AST.

PM2.5 exposure in early pregnancy is associated with increasement of maternal ALT and TBIL, suggesting that PM2.5 exposure may have an adverse effect on maternal liver function. Although this finding indicates an association between PM2.5 exposure and maternal liver function, more research is needed to confirm our findings and explore the underlying biological mechanisms.

The association between serum triglyceride to high density lipoprotein cholesterol ratio (THR) in late pregnancy and adverse birth outcomes (ABO) remains controversial because of inconsistent results. The present study assessed the association between maternal serum THR and incidence of ABO [preterm birth (PTB), small and large for gestational age (SGA/LGA), low birth weight (LBW) and macrosomia] in a Chinese population.

A total of 11,553 consecutive participants from a real-world database with data on lipid profiles and birth outcomes were included. Logistic regression models were applied to assess the association between THR and incident ABO. Mediation analysis was performed to investigate the contribution of pregnancy complications [gestational diabetes mellitus (GDM), intrahepatic cholestasis of pregnancy (ICP) and pre-eclampsia (PE)] to this association.

Approximately 6.6% (762/11,553), 8.9% (1023/11,553), 15.5% (1792/11,553), 4.3% (494/11,553), and 7.4% (851/11,553) of individuals developed PTB, SGA, LGA, LBW and macrosomia, respectively. Significant trends across the quintiles of THR toward decreasing incidence of SGA and LBW and increasing incidence of LGA and macrosomia were observed. The multivariate-adjusted odds ratios (OR) in the top quintile of serum THR (> 3.16) versus the bottom quintile (< 1.44) were 0.52 for PTB, 0.48 for SGA, 0.64 for LBW, 2.80 for LGA and 3.80 for macrosomia, respectively. A 1-standard deviation (SD) increase in serum THR was associated with decreased risk of PTB [OR = 0.84, 95% confidence interval (CI): 0.76-0.93), SGA (OR = 0.71, 95% CI:0.65-0.78) and LBW (OR = 0.76, 95% CI:0.65-0.90) and increased risk of LGA (OR = 1.40, 95% CI:1.32-1.49) and macrosomia (OR = 1.49, 95% CI:1.38-1.62). In mediation analyses, PE mediated - 19.8%, -10.6% and - 24.6% of THR-associated PTB, SGA and LBW, respectively, GDM accounted for - 3.7%, 6.8% and 4.3% of THR-associated PTB, LGA and macrosomia, respectively, and ICP explained - 1.9% and - 2.1% of THR-associated PTB and LBW, respectively. In addition, incorporating THR to ABO predictive models significantly improved the area under the curve for SGA (0.743 vs. 0.753, P < 0.001), LGA (0.734 vs. 0.745, P < 0.001) and macrosomia (0.786 vs. 0.800, P < 0.001).

Real-world data showed an association between serum THR in late pregnancy and ABO risk, and this association may be partially mediated by prevalent pregnancy complications (PE/GDM/ICP), suggesting a potential role of THR in predicting ABO (SGA/LGA/macrosomia).

Few factors have been identified that increase the risk of visits (hospital emergency room or inpatient stays) due to hyperemesis gravidarum (HG). The purpose of this study is to understand trends in HG management and identify variables increasing visit frequency so that strategies may be developed to reduce hospital utilization.

An online survey was posted on the Hyperemesis Education and Research Foundation website and social media between June 2022 and May 2023. Participants had previous or current severe pregnancy nausea and vomiting. Respondents were asked about themselves and their HG experience, including weight loss, medications, infusion care, and visit frequency. Odds ratios, p-values, and 95% confidence intervals were calculated via MedCalc to analyze the significance of each factor, and Spearman rank correlations were analyzed via SPSS for associations of ondansetron usage with visits and weight loss. Microsoft Excel and SPSS were used to calculate treatment and visit frequencies.

Survey data from 1220 respondents who reported a current or prior pregnancy with HG were included in this study. Respondents were primarily White, from the US, and had at least one visit due to HG. Participants with a visit were significantly more likely to be a person of color (POC), unable to work, have no children, and lose over 15 pounds (6.8 kg). Those who took medications as prescribed had fewer visits. No medication combination or dose was found to be significantly more effective in preventing weight loss or repeat hospital visits.

Risk factors predicting visits included POC, not having children, being too sick to work, and having extreme weight loss. Utilization of medication and nutritional therapies is inconsistent and inadequate in this population, which may increase visit frequency.

The aim of this study was to examine the utility of the albumin-bilirubin score in cases of intrahepatic cholestasis of pregnancy.

A total of 413 patients (182 intrahepatic cholestasis of pregnancy, 50 suspected intrahepatic cholestasis of pregnancy, 181 healthy controls) enrolled in this study. Patients with typical pruritus and bile acid levels >10 μmol/L are defined as the intrahepatic cholestasis of pregnancy group. Patients with pruritus have the same pattern as intrahepatic cholestasis of pregnancy, but who are ultimately diagnosed with other dermatoses of pregnancy are defined as suspected intrahepatic cholestasis of pregnancy. Demographic data, laboratory parameters, and albumin-bilirubin scores were compared between three groups. Correlation analysis was performed on the albumin-bilirubin score and bile acid levels. Also, receiver operating curve analyses were performed to evaluate the predictive performance of the albumin-bilirubin score for intrahepatic cholestasis of pregnancy diagnosis.

The albumin-bilirubin score of the intrahepatic cholestasis of pregnancy group was significantly higher than the other groups. A positive, weak correlation was found between the albumin-bilirubin score and bile acid levels in the intrahepatic cholestasis of pregnancy group. The receiver operating curve curve analyses showed albumin-bilirubin score has significant performance for the prediction of intrahepatic cholestasis of pregnancy in all subjects (area under the curve: 0.726, 95%CI 0.679-0.774, p<0.001) (sensitivity: 69%, specificity: 64%). The detection rate for albumin-bilirubin score was calculated as 67.3%. The positive predictive value was 3.95% (CI 2.9-5.3%), and the negative predictive value was 98.9% (CI 98.6-99.2%).

This study indicated higher albumin-bilirubin score levels in the intrahepatic cholestasis of pregnancy group and a positive relationship between serum bile acid levels and albumin-bilirubin score. Therefore, albumin-bilirubin score could be a cost-effective liver function test for pregnant women with intrahepatic cholestasis of pregnancy.

The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update is to review the available published evidence and expert advice regarding the clinical management of patients with pregnancy-related gastrointestinal and liver disease.

This expert review was commissioned and approved by the AGA Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership and underwent internal peer review by the Clinical Practice Updates Committee and external peer review through the standard procedures of Gastroenterology. This article provides practical advice for the management of pregnant patients with gastrointestinal and liver disease based on the best available published evidence. The Best Practice Advice statements were drawn from a review of the published literature and from expert opinion. Because formal systematic reviews were not performed, these Best Practice Advice statements do not carry formal ratings regarding the quality of evidence or strength of the presented considerations. Best Practice Advice Statements BEST PRACTICE ADVICE 1: To optimize gastrointestinal and liver disease before pregnancy, preconception and contraceptive care counseling by a multidisciplinary team should be encouraged for reproductive-aged persons who desire to become pregnant. BEST PRACTICE ADVICE 2: Procedures, medications, and other interventions to optimize maternal health should not be withheld solely because a patient is pregnant and should be individualized after an assessment of the risks and benefits. BEST PRACTICE ADVICE 3: Coordination of birth for a pregnant patient with complex inflammatory bowel disease, advanced cirrhosis, or a liver transplant should be managed by a multidisciplinary team, preferably in a tertiary care center. BEST PRACTICE ADVICE 4: Early treatment of nausea and vomiting of pregnancy may reduce progression to hyperemesis gravidarum. In addition to standard diet and lifestyle measures, stepwise treatment consists of symptom control with vitamin B6 and doxylamine, hydration, and adequate nutrition; ondansetron, metoclopramide, promethazine, and intravenous glucocorticoids may be required in moderate to severe cases. BEST PRACTICE ADVICE 5: Constipation in pregnant persons may result from hormonal, medication-related, and physiological changes. Treatment options include dietary fiber, lactulose, and polyethylene glycol-based laxatives. BEST PRACTICE ADVICE 6: Elective endoscopic procedures should be deferred until the postpartum period, whereas nonemergent but necessary procedures should ideally be performed in the second trimester. Pregnant patients with cirrhosis should undergo evaluation for, and treatment of, esophageal varices; upper endoscopy is suggested in the second trimester (if not performed within 1 year before conception) to guide consideration of nonselective β-blocker therapy or endoscopic variceal ligation. BEST PRACTICE ADVICE 7: In patients with inflammatory bowel disease, clinical remission before conception, during pregnancy, and in the postpartum period is essential for improving outcomes of pregnancy. Biologic agents should be continued throughout pregnancy and the postpartum period; use of methotrexate, thalidomide, and ozanimod must be stopped at least 6 months before conception. BEST PRACTICE ADVICE 8: Endoscopic retrograde cholangiopancreatography during pregnancy may be performed for urgent indications, such as choledocholithiasis, cholangitis, and some cases of gallstone pancreatitis. Ideally, endoscopic retrograde cholangiopancreatography should be performed during the second trimester, but if deferring the procedure may be detrimental to the health of the patient and fetus, a multidisciplinary team should be convened to decide on the advisability of endoscopic retrograde cholangiopancreatography. BEST PRACTICE ADVICE 9: Cholecystectomy is safe during pregnancy; a laparoscopic approach is the standard of care regardless of trimester, but ideally in the second trimester. BEST PRACTICE ADVICE 10: The diagnosis of intrahepatic cholestasis of pregnancy is based on a serum bile acid level >10 μmol/L in the setting of pruritus, typically during the second or third trimester. Treatment should be offered with oral ursodeoxycholic acid in a total daily dose of 10-15 mg/kg. BEST PRACTICE ADVICE 11: Management of liver diseases unique to pregnancy, such as pre-eclampsia; hemolysis, elevated liver enzymes, and low platelets syndrome; and acute fatty liver of pregnancy requires planning for delivery and timely evaluation for possible liver transplantation. Daily aspirin prophylaxis for patients at risk for pre-eclampsia or hemolysis, elevated liver enzymes, and low platelets syndrome is advised beginning at week 12 of gestation. BEST PRACTICE ADVICE 12: In patients with chronic hepatitis B virus infection, serum hepatitis B virus DNA and liver biochemical test levels should be ordered. Patients not on treatment but with a serum hepatitis B virus DNA level >200,000 IU/mL during the third trimester of pregnancy should be considered for treatment with tenofovir disoproxil fumarate. BEST PRACTICE ADVICE 13: In patients on immunosuppressive therapy for chronic liver diseases or after liver transplantation, therapy should be continued at the lowest effective dose during pregnancy. Mycophenolate mofetil should not be administered during pregnancy.

To summarize the current evidence and to make recommendations for the diagnosis and management of intrahepatic cholestasis of pregnancy.

Pregnant people with intrahepatic cholestasis of pregnancy.

Diagnosing the condition using fasting or non-fasting bile acids, classifying disease severity, determining what treatment to offer, establishing how to monitor for antenatal fetal wellbeing, identifying when to perform elective birth.

Individuals with intrahepatic cholestasis of pregnancy are at increased risk of adverse perinatal outcomes including preterm birth, neonatal respiratory distress and admission to a neonatal intensive care unit, with an increased risk of stillbirth when bile acid levels are ≥100 μmol/L. There is inequity in bile acid testing availability and timely access to results, along with uncertainly of how to treat, monitor. and ultimately deliver these pregnancies. Optimization of diagnostic and management protocols can improve maternal and fetal postnatal outcomes.

Medline, PubMed, Embase, and the Cochrane Library were searched from inception to March 2023, using medical subject headings (MeSH) and keywords related to pregnancy, intrahepatic cholestasis of pregnancy, bile acids, pruritis, ursodeoxycholic acid, and stillbirth. This document presents an abstraction of the evidence rather than a methodological review.

The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations).

Obstetric care providers, including obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, and radiologists.

Intrahepatic cholestasis of pregnancy requires adequate diagnosis with non-fasting bile acid levels which guide optimal management and delivery timing.

RECOMMENDATIONS.

Data on the liver transplant (LT) outcomes of women with acute liver failure (ALF) due to liver diseases unique to pregnancy (P-ALF) are limited. Using United Network of Organ Sharing (UNOS) data (1987-2021), we analyzed waitlist and post-LT outcomes of ALF in women of childbearing age comparing P-ALF versus ALF due to liver diseases not unique to pregnancy. Baseline characteristics were compared between groups at the time of listing for LT. Of 3542 females aged 16-43 years and listed for LT for ALF, 84 (2%) listed for P-ALF were less likely to be Black (11 vs. 21%, p =0.033), have lower international normalized ratio (2.74 vs. 4.53 p <0.002), but more likely to have respiratory failure (56% vs. 41%, p <0.005), be on pressors (58% vs. 43%, p <0.005), and require dialysis (23% vs. 10%, p <0.001). The cumulative 90-day waitlist mortality (WLM) was lower in P-ALF vs. ALF due to liver diseases not unique to pregnancy (7.4 vs. 16.6%, p <0.001). Posttransplant survival rates at 5 years were similar (82% vs. 79%, p =0.89). In a Fine and Gray regression model controlled for listing year and Model for End-Stage Liver Disease score, 90-day WLM was lower in P-ALF with a sub-HR of 0.42 (95% CI: 0.19-0.94, p =0.035). Of 84 women with P-ALF and listed for LT, 45 listed for hemolysis-elevated liver enzymes-low platelets (HELLP) versus 39 for acute fatty liver of pregnancy had higher 90-day WLM (19.3% vs. 5.7% p <0.005). The 90-day WLM was about 10-fold higher in HELLP versus acute fatty liver of pregnancy with a sub-HR of 9.97 (95% CI: 1.64-60.55, p =0.013). In this UNOS database analysis of ALF among women of childbearing age, the waitlist outcome is better in women with P-ALF compared to women with ALF due to liver diseases not unique to pregnancy. Among women with P-ALF, the 90-day WLM is worse for HELLP versus acute fatty liver of pregnancy. Further studies are needed to improve the management of HELLP and prevent the development of ALF in this subgroup population.

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.

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.

Preeclampsia is a progressive multi-systemic disorder characterized by proteinuria, critical organ damage, and new-onset hypertension. It can be further complicated by HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), resulting in critical liver or renal damage, disseminated coagulation, and grand mal seizures. This study aimed to examine the involvement of ADAMTS13, von Willebrand, and the complement system in the pathogenesis of preeclampsia/HELLP syndrome. We studied 30 Caucasian preeclamptic pregnant women and a control group of 15 healthy pregnancies. Genetic sequencing of ADAMTS13 and complement regulatory genes (MiniSeq System, Illumina) was performed. The modified Ham test was used to check for complement activation, ADAMTS13 activity, von Willebrand antigen (vWFAg) levels, and soluble C5b-9 levels were measured. Patients with preeclampsia had a decreased ADAMTS13 activity and increased C5b-9 levels. The vWFAg was significantly correlated with ADAMTS13 activity (r = 0.497, p = 0.003). Risk-factor variants were found in the genes of ADAMTS13, C3, thrombomodulin, CFB, CFH, MBL2, and, finally, MASP2. A portion of pregnant women with preeclampsia showed a decline in ADAMTS13 activity, correlated with vWFAg levels. These patients also exhibited an elevated complement activation and high-risk genetic variants in regulatory genes. Further research is needed to determine if these factors can serve as reliable biomarkers.

Preeclampsia and decompensated chronic liver disease are known triggers of acute hepatic dysfunction in pregnancy, rarely including hepatic encephalopathy. Differentiating the driver of acute hepatic dysfunction in patients with concomitant preeclampsia and preexisting liver disease presents a diagnostic challenge with important management implications. A 42-year-old woman, gravida 3 para 0201, at 24 1/7 weeks of gestation presented with hepatic encephalopathy, transaminitis, and hyperbilirubinemia in the setting of cirrhosis and severe new-onset preeclampsia. The preeclampsia was thought to be the leading etiology of hepatic encephalopathy, prompting emergent Cesarean delivery at 24 2/7 weeks. Hepatic encephalopathy, blood pressure, and laboratory derangements improved promptly post-delivery. Preeclampsia can trigger acute hepatic dysfunction, including hepatic encephalopathy, in the setting of previously compensated preexisting liver disease. Recognizing this association has important implications for management and treatment.

Liver diseases in pregnancy can be specific to gestation or only coincidental. In the latter case, the diagnosis can be difficult. Rapid diagnosis of maternal-fetal emergencies and situations requiring specialized interventions are crucial to preserve the maternal liver and guarantee materno-fetal survival. While detailed questioning of the patient and a clinical examination are highly important, imaging is often essential to reach a diagnosis of these liver diseases and lesions. Three groups of liver diseases may be observed during pregnancy: (1) diseases related to pregnancy: intrahepatic cholestasis of pregnancy, pre-eclampsia, eclampsia, hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, and acute fatty liver of pregnancy; (2) liver diseases that are more frequent during or exacerbated by pregnancy: acute herpes simplex hepatitis, Budd-Chiari syndrome, hemorrhagic hereditary telangiectasia, hepatocellular adenoma, portal vein thrombosis, and cholelithiasis; (3) coincidental conditions, including acute hepatitis, incidental focal liver lesions, metabolic dysfunction-associated steatotic liver disease, cirrhosis, hepatocellular carcinoma, liver abscesses and parasitosis, and liver transplantation. Specific knowledge of the main imaging findings is required to reach an early diagnosis, for adequate follow-up, and to avoid adverse consequences in both the mother and the fetus.Critical relevance statement Pregnancy-related liver diseases are the most important cause of liver dysfunction in pregnant patients and, in pregnancy, even common liver conditions can have an unexpected turn. Fear of radiations should never delay necessary imaging studies in pregnancy.Key points• Pregnancy-related liver diseases are the most frequent cause of liver dysfunction during gestation.• Fear of radiation should never delay necessary imaging studies.• Liver imaging is important to assess liver emergencies and for the diagnosis and follow-up of any other liver diseases.• Common liver conditions and lesions may take an unexpected turn during pregnancy.• Pregnancy-specific diseases such as pre-eclampsia and HELLP syndrome must be rapidly identified. However, imaging should never delay delivery when it is considered to be urgent for maternal-fetal survival.

Hyperemesis gravidarum can result in life-threatening physical and psychological maternal morbidity, including severe dehydration, weight loss, electrolyte imbalance, depression, and suicidal ideation. The reported prevalence of hyperemesis gravidarum ranges from 0.3% to 3.6%. The purpose of this qualitative study was to investigate what blogs can tell us about women's experiences of hyperemesis gravidarum. Thirty-three blogs written by hyperemesis gravidarum survivors posted on Hyperemesis Australia's website were analyzed using Krippendorff's qualitative content analysis method. Clustering was used and yielded 6 themes: (1) debilitating physical and mental health problems: digging deep to persevere, (2) heartbreaking choices, (3) lack of understanding and dismissed, (4) so much guilt surrounding their unborn infant, (5) it takes a village to support women with hyperemesis gravidarum, and (6) warriors and survivors: giving back. Infusion nurses are in a perfect position to provide support and compassionate care for women who are repeatedly coming to the hospital for rehydration treatment. Infusion nurses can validate women's physical and emotional struggles with hyperemesis gravidarum and help to no longer make women feel stigmatized.

Liver disease is not uncommon during pregnancy and is associated with increased maternal and fetal/neonatal morbidity and mortality. Physiological changes during pregnancy, including a hyperestrogenic state, increase in circulating plasma volume and/or reduction in splanchnic vascular resistance, and hemostatic imbalance, may mimic or worsen liver disease. For the clinician, it is important to distinguish among the first presentation or exacerbation of chronic liver disease, acute liver disease non-specific to pregnancy, and pregnancy-specific liver disease. This last group classically includes conditions such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, liver disorders associated with the pre-eclampsia spectrum, and an acute fatty liver of pregnancy. All of these disorders often share pathophysiological mechanisms, symptoms, and laboratory findings (such as elevated liver enzymes), but a prompt and correct diagnosis is fundamental to guide obstetric conduct, reduce morbidity and mortality, and inform upon the risk of recurrence or development of other chronic diseases later on in life. Finally, the cause of elevated liver enzymes during pregnancy is unclear in up to 30-40% of the cases, and yet, little is known on the causes and mechanisms underlying these alterations, or whether these findings are associated with worse maternal/fetal outcomes. In this narrative review, we aimed to summarize pragmatically the diagnostic work-up and the management of subjects with elevated liver enzymes during pregnancy.

This study aimed to investigate the impacts of home quarantine on pregnancy outcomes of women with intrahepatic cholestasis of pregnancy (ICP) during the COVID-19 outbreak and whether the rational use of drugs will change these impacts.

This multi-center study was conducted to compare the pregnancy outcomes in women with ICP between the home quarantine group and the non-home quarantine group in southwest China. Propensity score matching was performed to confirm the pregnancy outcomes of the medication group and the non-medication group in women with ICP during the epidemic period.

A total of 3,161 women with ICP were enrolled in this study, including 816 in the home quarantine group and 2,345 in the non-home quarantine group. Women with ICP in the home quarantine group had worse pregnancy outcomes, such as a growing risk of gestational diabetes mellitus A1, fetal growth restriction, pre-eclampsia, preterm delivery, and even stillbirth. Drug therapy could alleviate some adverse pregnancy outcomes caused by home quarantine, including pre-eclampsia, preterm delivery, and meconium-stained amniotic fluid.

COVID-19 quarantine would increase the incidence of ICP and lead to adverse pregnancy outcomes in women with ICP. The rational use of drugs reduced some obstetrical complications and improved partial pregnancy outcomes. Our findings suggested that the government and hospitals should enhance their management and life guidance for women with ICP and speed up developing home quarantine guidelines.

The liver plays pivotal roles in immunologic responses, and correct hepatic adaptations in maternal immunology are required during pregnancy. In this review, we focus on anatomical and immunological maternal hepatic adaptations during pregnancy, including our recent reports in this area. Moreover, we summarize maternal pregnancy-associated liver diseases, including hyperemesis gravidarum; intrahepatic cholestasis of pregnancy; preeclampsia, specifically hemolysis, elevated liver enzymes, and low platelet count syndrome; and acute fatty liver of pregnancy. In addition, the latest information about the factors that regulate hepatic immunology during pregnancy are reviewed for the first time, including human chorionic gonadotropin, estrogen, progesterone, growth hormone, insulin like growth factor 1, oxytocin, adrenocorticotropic hormone, adrenal hormone, prolactin, melatonin and prostaglandins. In summary, the latest progress on maternal hepatic anatomy and immunological adaptations, maternal pregnancy-associated diseases and the factors that regulate hepatic immunology during pregnancy are discussed, which may be used to prevent embryo loss and abortion, as well as pregnancy-associated liver diseases.

Pregnant women are affected by gastrointestinal and liver disorders. These may or may not be related to pregnancy. Unrelated conditions are pre-existent or coincidental during pregnancy. Pregnancy may promote symptoms/alter course of new or pre-existing disease resulting in complications only during pregnancy. This in turn can have adverse effect on clinical course affecting mother and fetus. The management remains same but its effect on mother and fetus needs to be kept in mind with pro-active treatment. Severe liver diseases though rare during pregnancy can occasionally be life threatening. Pregnancy after bariatric surgery/liver transplant is possible but with thorough counseling and needs multidisciplinary approach. Endoscopy for GI problems, if required can be carried out by gastroenterologist with special attention. Hence, this article, for quick reference to tackle GI and liver disorders in pregnancy.

Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11β-Hydroxysteroid dehydrogenase-2 (11β-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11β-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down-regulation of 11β-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis-induced placental dysfunction and subsequent FGR.

Liver injury is an increasingly recognized extra-pulmonary manifestation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Coronavirus disease 2019 (COVID-19) associated liver injury (COVALI) is a clinical syndrome encompassing all patients with biochemical liver injury identified in the setting of SARS-CoV-2 infection. Despite profound clinical implications, its pathophysiology is poorly understood. Unfortunately, most information on COVALI is derived from the general population and may not be applicable to individuals under-represented in research, including pregnant individuals. This manuscript reviews: Clinical features of COVALI, leading theories of COVALI, and existing literature on COVALI during pregnancy, a topic not widely explored in the literature. Ultimately, we synthesized data from the general and perinatal populations that demonstrates COVALI to be a hepatocellular transaminitis that is likely induced by systemic inflammation and that is strongly associated with disease severity and poorer clinical outcome, and offered perspective on approaching transaminitis in the potentially COVID-19 positive patient in the obstetric setting.