The correlation between serum total bile acid and adverse perinatal outcomes in pregnant women with intrahepatic cholestasis of pregnancy (ICP) and non-ICP hypercholanemia of pregnancy.

BACKGROUND: The association between excessive serum total bile acid (TBA) and adverse perinatal outcomes in individuals with non-intrahepatic cholestasis of pregnancy (non-ICP) hypercholanemia has not been determined, and it is unclear if this link is similar to that observed in patients with ICP. OBJECTIVE: To examine the adverse perinatal outcomes in two specific subcategories: those with ICP and those with non-ICP, including individuals with liver disease and asymptomatic hypercholanemia of pregnancy (AHP), at different levels of TBA. Investigate the correlation between TBA levels and adverse perinatal outcomes of ICP, liver disease, and AHP. METHODS: From 2013 to 2021, pregnant women with excessive TBA levels were taken from the electronic medical record database of our hospital and categorized into three groups: ICP (n = 160), liver disease (n = 164), and AHP (n = 650). This was done as part of a retrospective cohort research project. Multivariable regression and subgroup analyses were performed to examine the association between TBA levels and adverse perinatal outcomes in each group. RESULTS: The study found no significant differences in adverse perinatal outcomes between the ICP and liver disease groups at different TBA levels. However, at moderate TBA levels, both groups had a higher risk of adverse perinatal outcomes than the AHP group (p < 0.017). Among liver disease cases with TBA ≥ 100µmol/L, three cases of perinatal deaths (6.67%) associated with moderate-to-severe acute hepatitis occurred between 27 and 33 weeks of gestation. A 59% higher chance of perinatal death was found for every 10 µmol/L rise in TBA, even after significant variables and confounders were taken into account (adjusted odds ratio (aOR) = 1.59; 95% confidence interval (CI): 1.06-2.40; p = 0.03). CONCLUSIONS: If a pregnant woman has moderate-to-severe liver disease and TBA ≥ 100µmol/L, preterm termination of pregnancy (before 34 weeks) may be considered.

If someone doesn't have ICP but does have moderate-to-severe hepatitis and TBA levels of 100 µmol/L or more, they should be treated more aggressively, and their pregnancies should be terminated earlier (before 34 weeks) than what is usually done for ICP.

Outcomes of pregnancies complicated by cirrhosis: a retrospective cohort study.

BACKGROUND: Although pregnancy complicated by liver cirrhosis is rare, women with cirrhosis experience increased adverse pregnancy outcomes. This study aimed to evaluate pregnancy outcomes in women with liver cirrhosis and develop a predictive model using maternal factors for preterm birth in such pregnancies. METHODS: A retrospective analysis was conducted on pregnancy outcomes of a cirrhosis group (n = 43) and a non-cirrhosis group (n = 172) in a university hospital between 2010 and 2022. Logistic regression evaluated pregnancy outcomes, and a forward stepwise logistic regression model was designed to predict preterm birth in pregnant women with cirrhosis. The model's predictive performance was evaluated using the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). RESULTS: The incidence of cirrhosis during pregnancy was 0.06% (50/81,554). Pregnant women with cirrhosis faced increased risks of cesarean section, preterm birth, intrahepatic cholestasis of pregnancy, thrombocytopenia, and postpartum hemorrhage. In pregnant women with cirrhosis, preterm birth risk significantly increased at an incidence rate of 46.51% (20/43). According to the prediction model, the key predictors of preterm birth in pregnant women with cirrhosis were intrahepatic cholestasis of pregnancy and total bilirubin. The model demonstrated accurate prediction, with an AUC of 0.847, yielding a model accuracy of 81.4%. CONCLUSIONS: Pregnant women with cirrhosis face a heightened risk of adverse obstetric outcomes, particularly an increased incidence of preterm birth. The preliminary evidence shows that the regression model established in our study can use the identified key predictors to predict preterm birth in pregnant women with cirrhosis, with high accuracy.

Does a longer second stage of labor worsen umbilical artery blood gas parameters in newborns?-a retrospective cohort study of 2,140 cases.

Background: With the application of the new labor management model in China, the normal length of the second stage of labor is significantly longer than that of the old model. It is unclear whether a longer stage of labor worsens umbilical artery blood gas analysis (UABGA) in newborns. The aim of this study was to investigate the correlation between the second stage of labor length, UABGA results, and neonatal intensive care unit (NICU) transfer rates under the new labor management model. Methods: This is a retrospective cohort study including full-term, cephalic, vaginal deliveries. Exclusion criteria were preterm deliveries or deliveries by cesarean section during labor. The pH, base excess (BE), and lactate results of UABGA in newborns clearly reflect neonatal metabolic acidosis and intrauterine oxygenation of the fetus. The correlation between the length of the second stage of labor and the results of UABGA and NICU transfer rate was analyzed using linear or logistic regression and curve fitting. Results: Of the total 2,140 cases, after adjusting for maternal age, gestational week, high-risk pregnancy factors, body mass index (BMI) before pregnancy, induced delivery, oxytocin during labor stage, labor analgesia, abnormal fetal position in labor stage, vaginal device delivery, length of first labor stage, and weight of the newborn, every 1 hour increase in the length of the second stage of labor decreased the UABGA pH by 0.01 [95% confidence interval (CI): -0.02 to -0.01, P<0.001], decreased the UABGA BE by 0.66 mmol/L (95% CI: -0.84 to -0.48, P<0.001), increased the UABGA lactate level by 0.39 mmol/L (95% CI: 0.29 to 0.50, P<0.001), and increased the NICU transfer rate by 26% (95% CI: 1.07 to 1.48, P=0.005). In the stratified analysis, when the length of the second stage of labor increased from 3 to 4 or more hours, there was no significant change in UABGA pH, BE, lactate, or NICU transfer rates. Conclusions: Under the new criteria for the management of labor stage, the length of the second stage increasing from 3 to 4 or more hours did not negatively impact newborns. Therefore, clinician should not be too worried about the longer second stage of labor worsening adverse outcomes in newborns.

The Role of Amnioreduction in Emergency Cervical Cerclage with Bulging Membranes: A Retrospective Comparative Study.

The purpose of this study was to investigate the role of amnioreduction in patients who underwent emergency cervical cerclage (ECC) with bulging membranes during the second trimester. This retrospective comparative study included 46 singleton pregnant women who had cervical dilation at least 1 cm with bulging membranes beyond the external cervical os and underwent ECC at the Third Affiliated Hospital of Sun Yat-sen University between December 2016 and December 2021. Cases were categorized as amnioreduction group (n = 16) and non-amnioreduction group (n = 30) according to whether amnioreduction was performed prior to ECC. The gestational age and cervical dilation at cerclage, operative time, prolongation of pregnancy, and outcomes of pregnancy were compared between the two groups. All 46 patients underwent successful ECC excepted one case with intraoperative rupture of membrane in non-amnioreduction group. In the amnioreduction group, the cervical dilation at cerclage was larger than that in the non-amnioreduction group (4.5 ± 2.2 vs. 2.2 ± 1.2 cm, P < 0.001), and had more patients with cervical dilation ≥4 cm (50.0% vs. 10.0%, P = 0.004). However, the gestational age at cerclage, operative time, prolongation of pregnancy, gestational age at delivery were not significantly different between the two groups (22.9 ± 2.8 vs. 22.9 ± 3.2 weeks, 31.1 ± 9.2 vs. 27.9 ± 11.4 min, 21.3 ± 21.5 vs. 38.7 ± 40.2 days, 25.9 ± 4.5 vs. 28.4 ± 6.1 weeks; P > 0.05). The rates of delivery ≥28 weeks, ≥32 weeks, and live birth were 20.0% vs. 80.0%, 12.5% vs. 26.7%, 56.3% vs. 66.7% (P > 0.05) in amnioreduction group and non-amnioreduction group, respectively. In conclusion, even in cases with larger cervical dilation, the application of amnioreduction with ECC is possible to get the acceptable pregnancy outcomes. These findings suggested that amnioreduction may be a safe and feasible option to be applied before ECC, especially for those with advanced cervical dilation and bulging membranes.

Expression Profile and Prognostic Values of Mini-Chromosome Maintenance Families (MCMs) in Breast Cancer.

BACKGROUND Mini-chromosome maintenance families (MCMs) were considered the key factors for DNA replication initiation. Emerging evidences indicate that MCM2-7 (MCMs) are highly expressed in tissues from various malignant tumors. However, little is known about the clinical values of MCMs in breast cancer. MATERIAL AND METHODS In our study, a comprehensive bioinformatics analysis was performed to investigate expression patterns, potential functions, and prognostic values of MCMs in breast cancer, through ONCOMINE, bc-GenExMiner v4.1, Kaplan-Meier Plotter, cBioPortal and GeneMANIA databases. RESULTS We found that mRNA levels of MCMs were significantly elevated in breast cancer, especially in fast-growing and spreading tumor subtypes. These over-expressed MCMs predicted worse prognosis for breast cancer patients with shorter relapse-free survival (RFS) and overall survival. Among these six factors, high expression of MCM2/4/5/7 significantly reduced the RFS for patients with Luminal-A or B breast cancer and elevated MCM6/7 indicated shorter RFS for patients with basal-like or HER2-positive breast cancer. We also found that genomic alteration of MCMs was frequently found in breast cancer and the most common alteration was mRNA upregulation and amplification. Furthermore, MCMs were highly correlated with CDC45, CDC7, TIMELESS, ORC6, MCM10, ORC5, ORC4 and ORC3, mainly functioning to control the DNA replication initiation and genome stability. CONCLUSIONS These results suggest that MCMs are attractive prognostic biomarkers for breast cancer. Our study also provides useful clinical information about the potential of MCMs as therapeutic targets.

Telbivudine treatment of hepatitis B virus-infected pregnant women at different gestational stages for the prevention of mother-to-child transmission: Outcomes of telbivudine treatment during pregnancy.

This prospective study evaluated the viability of telbivudine for blocking mother-to-child transmission (MTCT) of hepatitis B virus (HBV) infection.Pregnant women positive for the hepatitis B surface antigen began telbivudine treatment before 14 weeks of gestation (i.e., early), between 14 and 28 weeks of gestation (late), or not at all (control). In the late-treatment group, 55 women terminated telbivudine therapy within puerperium. All neonates underwent routine hepatitis B immunoglobulin plus vaccination. Mothers and infants were followed for 7 months after birth.Pregnancy outcomes were similar among the 3 groups. HBV MTCT rates in the early and late treatment and control groups were 0, 0, and 4.69%, respectively. The rates of infant vaccination success among the 3 groups were similar, as were neonatal outcomes including birth weights, asphyxia, hyperbilirubinemia, Apgar score, birth defects, and weight and height at 7 months. Puerperal discontinuation of telbivudine did not increase the alanine transaminase value at 7 months after birth, but increased serum HBV DNA levels, and rates of positive hepatitis Be-antigen.Telbivudine treatment in HBV-infected pregnant women was associated with lower serum HBV DNA levels and reduced rates of HBV MTCT; there were no associated changes in pregnancy or neonatal outcomes at birth or 7 months after birth, or in the rate of infant vaccination success. Puerperal drug withdrawal after short-term antiviral therapy will not influence hepatic function, but may increase virus replication.

The Association of Pre-S/S Gene Mutations and Hepatitis B Virus Vertical Transmission.

BACKGROUND: HBV Pre-S/S gene mutations can occur before or after implementation of combined vaccination program. HBV Prs-S/S gene mutation is a risk factor of vaccination failure and frequently causes HBV vertical transfection. OBJECTIVES: To assess the association of hepatitis B virus (HBV) S gene mutations with vertical transmission. PATIENTS AND METHODS: In this prospective nested case-control study, a total of 60 pregnant women with positive serum HBsAg and HBV DNA ≥ 10(7) IU/mL were divided into a case group (15 cases with vaccination failure) and a control group (45 cases with vaccination success) according to whether their infants tested positive for HBV infection. Mothers and their children in the case group were further sub-divided into groups including mothers, newborns and infant (the same newborns at age of seven months). The pre-S/S gene mutations were detected by PCR and sequenced and its association with vertical transmission of HBV was analyzed. RESULTS: HBV genotype B was the dominant genotype in the both groups' mothers. Each mother-child pair in case group had the same HBV genotype. There were no significant differences in mutation frequencies of HBV Pre-S/S gene between case and control groups' mothers (Fragment 1 (M): 2 vs. 4, P > 0.05; Fragment 2 (M): 10 vs. 10, P > 0.05), or among the mothers, newborns and infants in the case group (Fragment 1 (M): 2, 2, and 3, respectively, P > 0.05; Fragment 2 (M): 10, 10 and 10 respectively, P > 0.05). Mutation site analysis of the both groups' mothers demonstrated 108 different mutation sites in the HBV pre-S/S gene, with 105 silent mutations and 5 missense mutations including ntA826G, ntC531T, ntT667C, ntC512T and ntC546A. Among 15 mother-newborn-infant pairs with successful PCR and sequence in case group, 7 (41.17%) mother-newborn pairs, 9 (60.00%) mother-infant pairs and 3 (20.00%) infant-newborn pairs had different mutation sites. CONCLUSIONS: HBV in children due to vaccination failure was resulted from vertical transmission. HBV Pre-S/S gene mutations were prevalent and could occur before or after vaccination. Therefore, simply analyzing mutation frequency of HBV gene was not of value. To advance blocking HBV vertical transmission, future studies should focus on specific mutation sites, potentially associated with vaccination failure.