Risk-stratified management strategies for intrahepatic cholestasis of pregnancy: A tertiary center population review over nearly 5 years.

OBJECTIVE: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes, resulting in a higher risk of perinatal morbidity and mortality. METHODS: The authors conducted a retrospective study of 2385 singletons with ICP who underwent risk-stratified management strategies. To explore the risks of perinatal outcomes of ICP, subgroup analyses were performed using different total bile acid (TBA) levels. RESULTS: In this study, there was only one stillbirth and one neonatal death. Among the study cohort, 2299 patients had ICP with a TBA level ≥10 µmol/L and 86 had ICP with a TBA level <10 µmol/L. The 2299 patients with ICP (TBA level ≥ 10 µmol/L) were divided into three groups: mild ICP (n = 1803), severe ICP (n = 400), and extremely severe ICP (n = 96). Increased TBA concentration was associated with an increased incidence of preterm birth, newborn asphyxia, neonatal intensive care unit hospitalization, meconium-stained amniotic fluid, and low birth weight in the three groups (P < 0.05). Furthermore, severe and extremely severe ICP with hypotonic absonant uterine contraction had a significant effect on neonatal asphyxia (odds ratio, 5.06 [95% confidence interval, 1.09-23.37]; P < 0.05) and meconium-stained amniotic fluid (odds ratio, 2.37 [95% confidence interval, 1.43-3.93]; P < 0.05). CONCLUSIONS: Hypotonic absonant uterine contractions could be high-risk stressors for severe and extremely severe ICP; hence, proper prenatal care is recommended. Risk-stratified management strategies for ICP are critical to obtaining better maternal-fetal outcomes.

Intrahepatic cholestasis of pregnancy and fetal cardiac dysfunction: a systematic review and meta-analysis.

OBJECTIVE: Intrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes. Fetal cardiac dysfunction may be 1 part of the pathophysiology of pregnancies complicated by intrahepatic cholestasis of pregnancy. This systematic review and meta-analysis aimed to evaluate the association between intrahepatic cholestasis of pregnancy and fetal cardiac dysfunction. DATA SOURCES: Systematic searches were performed on the databases of Medline, Embase, and Cochrane Library (up to March 2, 2023) for studies evaluating fetal cardiac function in pregnancies complicated by intrahepatic cholestasis of pregnancy in addition to the reference lists of included studies. STUDY ELIGIBILITY CRITERIA: Studies were eligible for inclusion if they assessed the fetal cardiac function by fetal echocardiography in women with intrahepatic cholestasis of pregnancy (mild or severe) and compared with fetuses of healthy pregnant women. The studies published in English were included. METHODS: The quality of the retrieved studies was assessed using the Newcastle-Ottawa Scale. Data on fetal myocardial performance index, E wave/A wave peak velocities ratio, and PR interval were pooled for the meta-analysis using random-effects models. The results were presented as weighted mean differences and 95% confidence intervals. This meta-analysis was registered with the International Prospective Register of Systematic Reviews (registration number: CRD42022334801). RESULTS: A total of 14 studies were included in this qualitative analysis. Of note, 10 studies that reported data on fetal myocardial performance index, E wave/A wave peak velocities ratio, and PR interval were included in the quantitative analysis and showed a significant association between intrahepatic cholestasis of pregnancy and fetal cardiac dysfunction. Significantly higher fetal left ventricular myocardial performance index values (weighted mean difference, 0.10; 95% confidence interval, 0.04-0.16) and longer fetal PR intervals (weighted mean difference, 10.10 ms; 95% confidence interval, 7.34-12.86) were revealed in pregnancies complicated by intrahepatic cholestasis of pregnancy. Compared with the situation in pregnancies complicated by mild intrahepatic cholestasis of pregnancy, PR intervals were even longer in pregnancies complicated by severe intrahepatic cholestasis of pregnancy (weighted mean difference, 5.98 ms; 95% confidence interval, 0.20-11.77). There was no significant difference in fetal E wave/A wave peak velocities ratio between the group with intrahepatic cholestasis of pregnancy and the healthy pregnant group (weighted mean difference, 0.01; 95% confidence interval, -0.03 to 0.05). CONCLUSION: Our findings supported the idea that intrahepatic cholestasis of pregnancy is associated with overall impaired fetal myocardial performance and impaired fetal cardiac conduction system. However, current evidence about the association between fetal cardiac dysfunction and intrahepatic cholestasis of pregnancy-induced stillbirth is lacking. Further studies are needed to reveal the relationship between fetal cardiac dysfunction and adverse perinatal outcomes in pregnancies complicated by intrahepatic cholestasis of pregnancy.

Unique microRNA expression profiles in plasmic exosomes from intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is strongly associated with an increased risk of adverse perinatal outcomes. Total bile acid (TBA) levels in the late second or third trimester are a major factor in the diagnosis. Here, we sought to establish the miRNA expression profile of plasm exosomes of ICP and identify possible biomarkers for the diagnosis of ICP. METHODS: This case-control study involved 14 ICP patients as the experimental group and 14 healthy pregnant women as the control group. Electron microscopy was used to observe the presence of exosomes in plasma. Nanosight and Western blotting of CD63 was used to assess exosome quality. Among them, three ICP patients and three controls were used for isolation plasmic exosome and preliminary miRNA array analysis. The Agilent miRNA array was utilized to dynamically monitor the miRNA expression in plasmic exosomes of included patients in the first trimester(T1), second trimester (T2), third trimester (T3), and delivery (T4). Then, Quantitative real-time Polymerase chain reaction was used to identify and validate differentially expressed miRNAs in plasma-derived exosomes. RESULTS: The expression levels of hsa-miR-940, hsa-miR-636, and hsa-miR-767-3p in plasma-derived exosomes of ICP patients were significantly higher than those of healthy pregnant women. Besides, these three miRNAs were also significantly up-regulated at the plasma, placental, and cellular levels (P < 0.05). The diagnostic accuracy of hsa-miR-940, hsa-miR-636, and hsa-miR-767-3p was further evaluated by the ROC curve, the area under the curve (AUC) values for each were 0.7591, 0.7727, and 0.8955, respectively. CONCLUSIONS: We identified three differentially expressed miRNAs in the plasma exosomes of ICP patients. Hence, hsa-miR-940, hsa-miR-636, and hsa-miR-767-3p may be potential biomarkers for enhancing the diagnosis and prognosis of ICP.