scholarly journals Studies on Novel Diagnostic and Predictive Biomarkers of Intrahepatic Cholestasis of Pregnancy Through Metabolomics and Proteomics

2021 ◽  
Vol 12 ◽  
Author(s):  
Ruirui Dong ◽  
Ningzhen Ye ◽  
Shaojie Zhao ◽  
Gaoying Wang ◽  
Yan Zhang ◽  
...  

BackgroundIntrahepatic cholestasis of pregnancy (ICP) usually occurs in the third trimester and is associated with increased risks in fetal complications. Currently, the exact mechanism of this disease is unknown. The purpose of this study was to develop potential biomarkers for the diagnosis and prediction of ICP.MethodsWe enrolled 40 pregnant women diagnosed with ICP and 40 healthy pregnant controls. The number of placental samples and serum samples between the two groups was 10 and 40 respectively. Ultra-performance liquid chromatography tandem high-resolution mass spectrometry was used to analyze placental metabolomics. Then, we verified the differentially expressed proteins and metabolites, both placental and blood serum, in the first, second, and third trimesters.ResultsMetabolomic analysis of placental tissue revealed that fatty acid metabolism and primary bile acid biosynthesis were enriched. In the integrated proteomic and metabolomic analysis of placental tissue, peroxisomal acyl-CoA oxidase 1 (ACOX1), L-palmitoylcarnitine, and glycocholic acid were found to be three potential biomarkers. In a follow–up analysis, expression levels of both placental and serum ACOX1, L-palmitoylcarnitine, and glycocholic acid in both placenta and serum were found to be significantly higher in third-trimester ICP patients; the areas under the ROC curves were 0.823, 0.896, and 0.985, respectively. Expression levels of serum ACOX1, L-palmitoylcarnitine, and glycocholic acid were also significantly higher in first- and second-trimester ICP patients; the areas under the ROC curves were 0.726, 0.657, and 0.686 in the first trimester and 0.718, 0.727, and 0.670 in the second trimester, respectively. Together, levels of the three aforementioned biomarkers increased the value for diagnosing and predicting ICP (AUC: 0.993 for the third, 0.891 for the second, and 0.932 for the first trimesters).ConclusionsL-palmitoylcarnitine, ACOX1, and glycocholic acid levels taken together may serve as a new biomarker set for the diagnosis and prediction of ICP.

2006 ◽  
Vol 110 (4) ◽  
pp. 459-465 ◽  
Author(s):  
Gustavo Castaño ◽  
Silvia Lucangioli ◽  
Silvia Sookoian ◽  
Marcelo Mesquida ◽  
Abraham Lemberg ◽  
...  

ICP (intrahepatic cholestasis of pregnancy) is characterized by pruritus and biochemical cholestasis, including raised SBAs (serum bile acids) and, usually, elevated aminotransferases levels. However, AHP (asymptomatic hypercholanaemia of pregnancy) is defined as the presence of total SBA levels above the cut-off value (11 μM) in healthy pregnant women, thus elevation of total SBAs do not necessarily reflect an ICP condition. The aim of the present study was to describe clinical, obstetric, perinatal and biochemical findings, as well as the SBA profile, in pregnant women studied in the third trimester of pregnancy in order to define characteristic patterns of individual bile acids that enable women with ICP to be distinguished from AHP and healthy pregnancies. Free and conjugated ursodeoxycholic (UDCA), cholic (CA), lithocholic (LCA), deoxycholic (DCA) and chenodeoxycholic (CDCA) acids were evaluated by CE (capillary electrophoresis) in 41 patients (15 of them simultaneously by HPLC), in 30 healthy pregnant women and in 10 non-pregnant women. A highly significant correlation between CE and HPLC for total SBAs (r=0.990) and for individual SBAs was found. Normal pregnant women had higher total SBA levels than non-pregnant women (due to an increase in taurine-conjugated dihydroxy SBAs). Women with ICP had higher levels of total SBAs, the free/conjugated ratio, LCA, CA, CDCA and DCA than normal pregnant women. Newborns from women with ICP had lower birth weight and gestational age. Women with AHP had higher levels of conjugated dihydroxy SBAs than normocholanaemic patients, without any evidence of a clinical difference. In conclusion, the present study has shown a clear difference in SBA profiles between ICP and normal pregnancies (including AHP), involving a shift towards a characteristic hydrophobic composition in women with ICP.


2021 ◽  
Author(s):  
Fatemeh Sarhaddi ◽  
Iman Azimi ◽  
Anna Axelin ◽  
Hannakaisa Niela-Vilen ◽  
Pasi Liljeberg ◽  
...  

BACKGROUND Heart rate variability (HRV) is a non-invasive method reflecting autonomic nervous system (ANS) regulations. Altered HRV is associated with adverse mental or physical health complications. ANS also has a central role in physiological adaption during pregnancy causing normal changes in HRV. OBJECTIVE Assessing trends in heart rate (HR) and HRV parameters as a non-invasive method for remote maternal health monitoring during pregnancy and three months postpartum. METHODS Fifty-eight pregnant women were monitored using an Internet-of-Things (IoT)-based remote monitoring system during pregnancy and 3-months postpartum. Pregnant women were asked to continuously wear Gear sport smartwatch to monitor their HR and HRV. In addition, a cross-platform mobile application was utilized for collecting pregnancy-related information. The trends of HR and HRV parameters were extracted using reliable data. We also analyzed the trends of normalized HRV parameters based on HR to remove the effect of HR changes on HRV trends. Finally, we exploited hierarchical linear mixed models to analyze the trends of HR, HRV, and normalized HRV parameters. RESULTS HR increased significantly during the second trimester (P<.001) and decreased significantly during the third trimester (P<.01). Time-domain HRV parameters, average normal interbeat intervals (AVNN), standard deviation of normal interbeat intervals (SDNN), root mean square of the successive difference of normal interbeat intervals (RMSSD), normalized SDNN (nSDNN), and normalized RMSSD (nRMSSD) decreased significantly during the second trimester (P<.001) then increased significantly during the third trimester (P<.01). Some of the frequency domain parameters, low-frequency power (LF), high-frequency power (HF), and normalized HF (nHF) decreased significantly during the second trimester (P<.01), and HF increased significantly during the third trimester (P<.01). In the postpartum period, nRMSSD decreased (P<.05), and the LF to HF ratio (LF/HF) increased significantly (P<.01). CONCLUSIONS Our study showed that HR increased and HRV parameters decreased as the pregnancy proceeded, and the values returned to normal after the delivery. Moreover, our results show that HR started to decrease while time-domain HRV parameters and HF started to increase during the third trimester. Our results also demonstrate the possibility of continuous HRV monitoring in everyday life settings.


2020 ◽  
pp. 205064062096461
Author(s):  
Ana-Marija Grišić ◽  
Maria Dorn-Rasmussen ◽  
Bella Ungar ◽  
Jørn Brynskov ◽  
Johan F K F Ilvemark ◽  
...  

Background Infliximab therapy during pregnancy in inflammatory bowel disease is challenged by a dilemma between maintaining adequate maternal disease control while minimizing fetal infliximab exposure. We investigated the effects of pregnancy on infliximab pharmacokinetics. Methods The study population comprised 23 retrospectively identified pregnancies. Patients with inflammatory bowel disease were generally in clinical remission at pregnancy conception (74%) and received steady infliximab maintenance therapy (5 mg/kg q8w n = 17; q6w n = 4; q10w n = 1; 10 mg/kg q8w n = 1). Trough blood samples had been obtained in the same patients prior to pregnancy ( n = 119), the first trimester ( n = 16), second trimester ( n = 18), third trimester ( n = 7), and post-pregnancy ( n = 12). Data were analyzed using nonlinear mixed-effects population pharmacokinetic modelling. Results Dose-normalized infliximab concentrations were significantly higher during the second trimester (median 15 µg/mL/kg, interquartile range 10–21) compared to pre-pregnancy (7, 2–12; p = 0.003), the first trimester (9, 1–12; p = 0.04), or post-pregnancy (6, interquartile range 3–11; p > 0.05) in patients with inflammatory bowel disease. Similar trends were observed in the third trimester (13, 7–36; p > 0.05). A one-compartment model with linear elimination described the pharmacokinetics of infliximab (volume of distribution = 18.2 L; clearance 0.61 L/day). Maternal infliximab exposure was influenced by the second and third trimester of pregnancy and anti-infliximab antibodies, and not by pregnancy-imposed physiological changes in, for example, body weight or albumin. Infliximab clearance decreased significantly during the second and third trimesters by up to 15% as compared to pre- and post-pregnancy and the first trimester. The increased maternal infliximab exposure was weakly associated with lowered clinical disease activity. Pharmacokinetic model simulations of virtual patients indicated the increased maternal infliximab trough concentrations imposed by pregnancy will not completely counteract the decrease in infliximab concentration if therapy is paused in the third trimester. Conclusion Infliximab clearance decreases significantly in the second and third trimesters, leading to increasing maternal infliximab concentrations in any given regimen. Maternal infliximab levels may thus be maintained as constant in a de-intensified regimen by therapeutic drug monitoring guidance in inflammatory bowel disease.


Author(s):  
Wojciech Jelski ◽  
Joanna Piechota ◽  
Karolina Orywal ◽  
Barbara Mroczko

Introduction: Intrahepatic cholestasis of pregnancy (ICP) is the liver disorder in the second or early third trimester of pregnancy. It is characterized by pruritus with increased serum bile acids concentration and other liver function tests. ICP  is connected with increased risk of fetal mortality, but is unfortunately detected quite late. Therefore, it is important to recognize the disease in its early stages. We aimed to investigate the serum alcohol dehydrogenase (ADH) activity and compare it with the concentration of total bile acid (TBA) in women with ICP. Methods: Serum samples were taken for routine investigation from 80 pregnancies with ICP in the second or third trimester of pregnancy and from 80 healthy pregnant women in the same time of pregnancy. For measurement of class I activity we used the spectrofluorometric methods. The total ADH activitiy was measured by the photometric method. Results: The analysis of results shows a statistically significant increase in the activity of ADH I and ADH total (about 60% and 41.3%, respectively). Activity of ADH I well correlated with aminotransferases (alanine ALT and aspartate AST) and total bile acids (TBA) concentration. The total ADH activity was also positively correlated with ALT, AST and total bile acids. Conclusion: We can state that the activity of class I alcohol dehydrogenase isoenzyme in the sera of patients with ICP is increased and seems to be a good indicator of liver cell destruction during this disease and is comparable with the value of other markers.


2021 ◽  
Author(s):  
Wenqian Lu ◽  
Mingjuan Luo ◽  
Xiangnan Fang ◽  
Rong Zhang ◽  
Mengyang Tang ◽  
...  

Abstract Background: Gestational diabetes mellitus (GDM), one of the most common pregnancy complications, can lead to morbidity and mortality in both the mother and the infant. Metabolomics has provided new insights into the pathology of GDM and systemic analysis of GDM with metabolites is required for providing more clues for GDM diagnosis and mechanism research. This study aims to reveal metabolic differences between normal pregnant women and GDM patients in the second- and third-trimester stages and to confirm the clinical relevance of these new findings.Methods: Metabolites were quantitated with the serum samples of 200 healthy pregnant women and 200 GDM women in the second trimester, 199 normal controls, and 199 GDM patients in the third trimester. Both function and pathway analyses were applied to explore biological roles involved in the two sets of metabolites. Then the trimester stage-specific GDM metabolite biomarkers were identified by combining machine learning approaches, and the logistic regression models were constructed to evaluate predictive efficiency. Finally, the weighted gene co-expression network analysis method was used to further capture the associations between metabolite modules with biomarkers and clinical indices. Results: This study revealed that 57 differentially expressed metabolites (DEMs) were discovered in the second-trimester group, among which the most significant one was 3-methyl-2-oxovaleric acid. Similarly, 72 DEMs were found in the third-trimester group, and the most significant metabolites were ketoleucine and alpha-ketoisovaleric acid. These DEMs were mainly involved in the metabolism pathway of amino acids, fatty acids and bile acids. The logistic regression models for selected metabolite biomarkers achieved the area under the curve values of 0.807 and 0.81 for the second- and third-trimester groups. Furthermore, significant associations were found between DEMs/biomarkers and GDM-related indices. Conclusions: Metabolic differences between healthy pregnant women and GDM patients were found. Associations between biomarkers and clinical indices were also investigated, which may provide insights into pathology of GDM.


2021 ◽  
Author(s):  
Zuoxi He ◽  
Chuan Xie ◽  
Xiaorong Qi ◽  
Zhengjun Hu ◽  
Yuedong He

Abstract ObjectiveCervical cancer diagnosed during pregnancy is a rare event, and data regarding efficacy of cancer treatment during pregnancy is limited. This study aimed to assess the safety of continuation of the pregnancy for mother and fetus when concomitantly diagnosed with cervical cancer.MethodsThis study retrospectively analyzed all cervical cancer patients diagnosed while pregnant or immediately postpartum, inclusive from Jan 2010 to June 2019 at our institute. Patient clinical details and follow-up were obtained from hospital records. ResultsThe study comprised 40 patients with clinical cancer stages of ⅠA1 (1/40, 2.5%); ⅠB1 (15/40, 37.5%); IB2 (10/40, 25%); ⅡA (12/40, 30%); and ⅡB (2/40, 5%). There were 38 patients diagnosed during pregnancy, and 2 diagnosed in the postpartum period. Of the 38 patients, 17 were diagnosed in the first trimester, 13 in the second trimester, and 8 in the third trimester. Ten of 38 patients (26.3%) continued their pregnancy after learning of their diagnosis; 7 (70%) in the third trimester and 3 (30%) in the second trimester. The mean time from diagnosis to surgery in the patients who continued their pregnancy was 52.7 days, which was statistically significantly greater than the termination of pregnancy group (52.7 vs 16.3 days, P < 0.01). Notably, there was no survival difference between the 2 groups (100% vs 90.91%, P =0.54), and none of the pregnant women who ultimately died had delayed treatment due to pregnancy. Similarly, the surgical estimated blood loss and operative duration comparing the 2 groups were not significantly different. ConclusionsIn the present study, the gestational age of pregnancy at the time of initial diagnosis of cervical cancer was an important determinant in the disease management. Continuation of the pregnancy when diagnosed with cervical cancer did not affect the oncologic outcome of the mother nor increase either surgical or obstetric complications. Additionally, the use of neoadjuvant chemotherapy did not threaten the health of the fetus. These results may be useful in counseling patients facing the diagnosis of cervical cancer during pregnancy.


2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Olawumi Adaramodu ◽  
Anthony Kodzo-Grey Venyo

Obstetric cholestasis (OC) is a liver disorder that occurs in the late second and early third trimester of pregnancy characterized by pruritus with increased serum bile acids and other liver function tests. The pathophysiology of OC is still not completely understood. The symptoms and biochemical abnormality rapidly resolve after delivery. OC is associated with an increased risk of adverse obstetrical outcomes. The aetiology of obstetric cholestasis of pregnancy is poorly understood and is thought to be complicated and multifactorial.  OC typically occurs in the late second trimester when the oestrogen levels are the highest in pregnancy. The most common complaint is generalized intense pruritus, which usually starts after the 30th week of pregnancy. Pruritus can be more common in the palms and soles and is typically worse at night. Other symptoms of cholestasis, such as nausea, anorexia, fatigue, right upper quadrant pain, dark urine, and pale stool, can be present. Clinical jaundice is rare but may present in 14% to 25% of patients after 1 to 4 weeks of the onset of pruritus. Some patients also complain of insomnia as a result of pruritus. Generally, physical examination is unremarkable except for scratch marks on the skin from pruritus. Pruritus is a cardinal symptom of intra-hepatic cholestasis of pregnancy (ICP) and may precede biochemical abnormalities. The diagnosis of intrahepatic cholestasis of pregnancy is via the presence of clinical symptoms pruritus in the third trimester with elevated maternal total serum bile acids and excluding other diagnoses, which can cause similar symptoms and lab abnormalities. Fasting blood samples should be used to check for the total bile salt acid level as it can become elevated in the postprandial state. Once the diagnosis of OC of pregnancy is confirmed, immediate treatment is necessary, and the primary goal of therapy is to decrease the risk of perinatal morbidity and mortality and to alleviate maternal symptoms. Maternal pruritus can be alleviated with use of moisturisers and oral antihistamines. Ursodeoxycholic acid (UDCA) is the drug of choice for the treatment of ICP. Many authors have advocated elective early delivery of women with intrahepatic cholestasis of pregnancy to reduce the risk of sudden foetal death. The Royal College of Obstetricians and Gynaecologists recommends induction of labour after 37+0 weeks of gestation. Obstetric cholestasis of pregnancy is not an indication for Caesarean delivery. Postpartum pruritus typically disappears in the first 2 to 3 days following delivery, and serum bile acid concentrations will normalize eventually. ICP is not a contraindication to breastfeeding, and mothers with a history of ICP in pregnancy can breastfeed their infants. Postpartum monitoring and follow up of bile acids and liver function tests should be done in 4-6 weeks to ensure resolution. Women with the persistent abnormality of liver function test after 6 to 8 weeks require investigation for other aetiologies.


2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Mengyang Tang ◽  
Mingjuan Luo ◽  
Wenqian Lu ◽  
Rong Zhang ◽  
Wei Liang ◽  
...  

Abstract Objective Inflammation-related factors have been shown to play a significant role throughout pregnancy. In this study, we aimed to explore the relationships between selected inflammatory cytokines and gestational diabetes (GDM) in Chinese pregnant women. Design and methods This was a 1:1 matched case–control study that included 200 pairs of subjects in the second trimester and 130 pairs of subjects in the third trimester. Serum levels of nerve growth factor (NGF), Interleukin-6 (IL-6), leptin, Interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-alpha (TNF-α) and Interleukin-1beta (IL-1β) were measured by enzyme immunoassay. The associations of these inflammatory factors with metabolic parameters were analysed. Results In the second trimester, GDM patients had higher NGF levels and lower IL-8 levels than did normal controls (P < 0.001 and P = 0.015, respectively). However, in the third trimester, only lower leptin levels were observed in the GDM group (P = 0.031). Additionally, in the second trimester, NGF levels were not only positively associated with fasting, 1-h and 2-h glucose levels and the area under curve of glucose, but also positively related to insulin sensitivity and secretion, as suggested by fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment index of β-cell secretion (HOMA-β) (all P < 0.05). Moreover, IL-6 and leptin levels were positively correlated with HOMA-IR and HOMA-β, and TNF-α levels were positively related to HOMA-IR (all P < 0.05). Except for the relationships between NGF and HOMA-β and TNF-α and HOMA-IR, the other correlations still existed even after adjusting for confounding factors (all P < 0.05). Conclusion In addition to the positive associations of IL-6 and leptin with insulin resistance and secretion, NGF was higher in the GDM patients and strongly linked to glucose metabolism, insulin resistance and pancreatic β cell function in Chinese pregnant women in the second trimester.


2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Alec Szlachta-McGinn ◽  
Alexandra Aserlind ◽  
Lunthita Duthely ◽  
Sean Oldak ◽  
Ruchi Babriwala ◽  
...  

Background. The CDC and ACOG have issued guidelines for HIV screening in pregnancy for patients living in areas with high prevalence of HIV in order to minimize perinatal vertical transmission. There is a lack of data examining providers’ compliance with these guidelines in at-risk patient populations in the United States. Objective. To evaluate if HIV screening in pregnant women was performed according to guidelines at a large, urban, tertiary care medical center in South Florida. Study Design. A retrospective review was performed on 1270 prenatal and intrapartum records from women who delivered a live infant in 2015 at a single institution. Demographic and outcome data were chart abstracted and analyzed using arithmetic means and standard deviations. Results. Of the 1270 patients who met inclusion criteria, 1090 patients initiated prenatal care in the first or second trimester and delivered in the third trimester. 1000 (91.7%) patients were screened in the first or second trimester; however, only 822 (82.2%) of these were retested in the third trimester during prenatal care. Among the 178 patients lacking a third trimester test, 159 (89.3%) received rapid HIV testing upon admission for delivery. Of the 1090 patients who initiated prenatal care in the first or second trimester and delivered in the third trimester, 982 (90.1%) were screened in accordance with recommended guidelines. Of the 1270 patients initiating care in any trimester, 24 (1.9%) had no documented prenatal HIV test during prenatal care, however 22 (91.7%) had a rapid HIV test on admission for delivery. Two (0.16%) patients were not tested prenatally or prior to delivery. Conclusion. Despite 99.8% of women having at least one HIV screening test during pregnancy, there is room for improvement in routine prenatal screening in both early pregnancy and third trimester prior to onset of labor in this high-risk population.


Sign in / Sign up

Export Citation Format

Share Document