The impact of maternal intrahepatic cholestasis during pregnancy on the growth trajectory of offspring: a population-based nested case‒control cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse fetal outcomes, yet its influence on offspring growth remains unclear. Our study dynamically tracks growth rates in children from ICP and healthy mothers and investigates the link between maternal liver function and developmental abnormalities in offspring. METHOD: Our case‒control study involved 97 women with ICP and 152 with uncomplicated pregnancies nested in a cohort of their offspring, including 50 from the ICP group and 87 from the uncomplicated pregnancy group. We collected pediatric growth and development data, with a maximum follow-up duration of 36 months. Stratified analyses of children's height, weight, and head circumference were conducted, and Spearman's rank correlation was applied to examine the relationships between maternal serological markers and pediatric growth metrics. RESULT: Maternal liver and renal functions, along with serum lipid profiles, significantly differed between the ICP and normal groups. In the ICP group, the offspring showed elevated alanine aminotransferase (ALT), direct bilirubin (DBIT), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein B (APOB) levels. Notably, the length-for-age z score (LAZ), weight-for-age z score (WAZ), and head circumference-for-age z score (HCZ) were lower in ICP offspring compared with those from normal pregnancies within the 1- to 12-month age range (P < 0.05). However, no significant differences in LAZ, weight-for-length z score (WLZ), BMI-for-age z score (BAZ), or HCZ were observed between groups in the 13- to 36-month age range. Maternal maximum lactate dehydrogenase (LDH) and total bile acids (TBA) levels during pregnancy were inversely correlated with LAZ and WAZ in the first year. Furthermore, offspring of mothers with ICP exhibited a greater incidence of stunting (24% vs. 6.9%, P = 0.004) and abnormal HCZ (14% vs. 3.7%, P = 0.034). CONCLUSIONS: Growth disparities in offspring of ICP-affected pregnancies were most significant within the 1- to 12-month age range. During this period, maximum maternal LDH and TBA levels were negatively correlated with LAZ and WAZ values of offspring. The observation of similar growth rates between ICP and control group offspring from 13 to 36 months suggested catch-up growth in the ICP group.

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.

Case report: A relatively rare adverse event caused by carbetocin- placenta interception.

Placenta interception is extremely rare, and herein, we report the case of a 33-year-old woman with placenta interception during cesarean section caused by carbetocin, which was intravenously injected immediately after delivery of the infant to prevent postpartum hemorrhage. There was no sign of placental separation in the third stage of labor. A protuberance with gross subserous blood vessels in the left fundus of the uterus was detected and was misdiagnosed as placental accreta. The patient was transferred to the district referral hospital to manage the protuberance after stitching up the incision. On opening the original incision in the tertiary hospital, the protuberance disappeared, and the placenta was found in the lower segment of the uterus cavity. The intercepted placenta showed a spontaneous resolution from the uterine wall and was removed intact. This case report details the typical presentation of placenta interception to make obstetricians aware of the possibility that carbetocin might lead to this adverse event.

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.

Perinatal Infection with Listeria monocytogenes: A 10-Year Hospital-Based Study in Western China.

Objective: Listeriosis is a rare but severe foodborne disease that is contracted by the consumption of food contaminated with Listeria, and perinatal listeriosis can cause major adverse pregnancy outcomes. In the current study, we sought to retrospectively analyze 10 years of perinatal outcomes due to listeriosis in western China. Methods: Based on the isolation of Listeria monocytogenes (L. monocytogenes), we retrospectively reviewed the pregnancy-associated cases of listeriosis from June 2010 to February 2022 at our hospital. We investigated the crude incidence, clinical manifestations, perinatal management, and outcomes of perinatal listeriosis cases. Results: We diagnosed a total of 28 cases of perinatal listeriosis during the study period at our hospital, including four cases of twin pregnancies. Of the 28 cases, 32.14% (9/28) were infected in the second trimester and 67.86% (19/28) in the third trimester. The fetal or neonatal mortality rate for perinatal listeriosis was high, with a crude fetal mortality rate of 46.88% (15/32) in the 32 offspring and a neonatal mortality rate of 47.06% (8/17) in the 17 live births. Conclusion: Perinatal listeriosis exhibits high fetal or neonatal mortality. We recommend that appropriate antibiotics be administered in cases of perinatal listeriosis.

Perinatal outcomes associated with ICP in twin pregnancies were worse than singletons: an almost 5-year retrospective cohort study.

BACKGROUND: Intrahepatic cholestasis of pregnancy (ICP) is associated with an increased risk of adverse perinatal outcomes leading to high perinatal morbidity and mortality. However, few studies have examined twin pregnancies complicated by ICP. To assess the perinatal outcomes of twin pregnancies with ICP, a retrospective cohort study was conducted. METHODS: A total of 633 twin pregnancies and 1267 singleton pregnancies with ICP were included. In addition, a correlation study was performed on the matched total bile acid (TBA) levels from maternal serum, fetal umbilical venous blood, and amniotic fluid of 33 twin pregnancies from twin groups. RESULTS: When compared to singletons, twin pregnancies with ICP had a higher risk of cesarean section (CS) (96.4% vs. 76.1%), preterm birth (PTB) (82.6% vs. 19.7%), fetal distress (2.0% vs. 1.3%), and neonatal intensive care unit (NICU) admission (23.6% vs. 5.1%), which was significantly related to increasing TBA levels (P < 0.05). In twin pregnancies with TBA ≥100 µmol/L, the incidences of CS, PTB, fetal distress, neonatal asphyxia, and meconium-stained amniotic fluid were 94.4, 100, 11.1, 5.6, and 36.1%, respectively. Furthermore, the maximum maternal TBA levels were positively correlated with TBA levels in the amniotic fluid (r = 0.61, P < 0.05) and umbilical cord blood (r = 0.44, P < 0.05), and a similar correlation was found for maternal TBA levels at delivery. TBA levels in umbilical cord blood and amniotic fluid also had a significant and positive correlation (r = 0.52, P < 0.05). CONCLUSIONS: Twin pregnancies with ICP had a higher risk for adverse perinatal outcomes than singletons, which was associated with higher TBA levels. TBA can be transported through the placenta and is involved in uterus-placenta-fetal circulation.

Intrahepatic cholestasis of pregnancy and maternal dyslipidemia: a systematic review and meta-analysis.

INTRODUCTION: The association between intrahepatic cholestasis of pregnancy (ICP) and maternal lipid metabolism remains unknown. This systematic review and meta-analysis aimed to evaluate the association between ICP and maternal lipid metabolism. MATERIAL AND METHODS: We systematically searched Medline, Embase and the Cochrane Library (up to December 11, 2021) to identify relevant studies that investigated ICP and maternal plasma lipid concentrations. The weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated using random-effects models. A subgroup analysis was conducted to identify the potential sources of heterogeneity. Potential publication bias was tested using funnel plots and the Egger's and Begg's tests. This meta-analysis was registered with PROSPERO (CRD42021293783). RESULTS: Eleven studies were included in this qualitative analysis. A random-effects meta-analysis of data from the final included nine studies (n = 786 participants) showed a significant association between ICP and maternal dyslipidemia, with elevated levels of triglycerides (WMD, 0.67 mmol/L; 95% CI 0.39-0.95; P < 0.001), total cholesterol (WMD, 1.08 mmol/L; 95% CI 0.58-1.58; P < 0.001), low-density lipoprotein cholesterol (WMD, 1.08 mmol/L; 95% CI 0.53-1.64; P < 0.001), and reduced high-density lipoprotein cholesterol level (WMD, -0.38 mmol/L; 95% CI -0.53 to -0.23; P < 0.001) vs normal pregnancies. CONCLUSIONS: The present study's findings support an association between ICP and maternal dyslipidemia. ICP pregnancies have dysregulated lipid metabolism vs normal pregnancies.