Perinatal Outcomes In Intrahepatic Cholestasis Research Articles

The effect of disease severity and response to treatment on perinatal outcomes in intrahepatic cholestasis of pregnancy

Amaç: Gebeliğin intrahepatik kolestazı (GİHK) ile komplike olan gebeliklerde, serum safra asiti (SA) düzeyleri ve ursodeoksikolik asit (UDKA) tedavisine verilen cevabın perinatal sonuçlar üzerine etkisini araştırmaktır.
 Gereçler ve Yöntem: Bu çalışmada Ocak 2013 ile Ocak 2018 tarihleri arasında üçüncü basamak bir merkezde GİHK nedeniyle takip edilen gebelikler retrospektif olarak analiz edildi. GİHK şiddeti, serum SA seviyelerine göre hafif (10–40 μmol/L), orta (40-80 μ mol/L) ve şiddetli (>80 μ mol/L) olarak gruplandırıldı. GİHK’nın şiddeti ve UDKA tedavisine verilen olumlu veya olumsuz yanıtın perinatal sonuçlar üzerine etkisi araştırıldı.
 Bulgular: GİHK tanısı koyulan toplamda 200 gebe çalışmaya dahil edildi. Hastaların %65 (n=130)’inde hafif GİHK, %20 (n=40)’sinde orta şiddetli GİHK ve %15 (n=30)’inde şiddetli GİHK saptandı. GİHK tanısıyla takip edilen hastaların 4 (%2.0)’ünde ölü doğum gerçekleşti. Şiddetli GİHK hastalarında spontan preterm doğum oranı, orta ve hafif GİHK hastalarına kıyasla anlamlı olarak daha yüksekti (p=0.001). Şiddetli GİHK hastalarında ve UDKA tedavisine yanıt vermeyen hastalarda, ortalama doğum haftası, ortalama doğum ağırlığı, 1. ve 5. dakika Apgar skorları daha düşük, amniyosta mekonyum varlığı, yenidoğan yoğun bakım ünitesi ihtiyacı ve ölü doğum oranları daha yüksekti.
 Sonuç: GİHK ile komplike olan gebelikler fetal ve neonatal olumsuz sonuçlar açısından artmış riske sahiptir. Maternal serum SA düzeyleri hastalığın siddeti ve olumsuz perinatal sonuçlarla ilişkilidir. Bununla birlikte, UDKA tedavisine verilen klinik cevap, fetal ve neonatal sonuçları öngörmede etkili olabilir.

Retracted: Value of Serum Glycocholic Acid and Total Bile Acids in Predicting Maternal and Perinatal Outcomes in Intrahepatic Cholestasis of Pregnancy

[This retracts the article DOI: 10.1155/2021/3911998.].

Efficacy of fetal left ventricular modified myocardial performance index in predicting adverse perinatal outcomes in intrahepatic cholestasis of pregnancy.

SUMMARYOBJECTIVE:This study aimed to evaluate the effectiveness of fetal left ventricular modified myocardial performance index in predicting adverse perinatal outcomes for intrahepatic cholestasis of pregnancy.METHODS:A cross-sectional study was conducted, including 51 women with intrahepatic cholestasis of pregnancy and 80 healthy controls. Using Doppler ultrasonography, E-wave, A-wave, isovolumetric contraction time, isovolumetric relaxation time, and ejection time were recorded and the left ventricular modified myocardial performance index was measured.RESULTS:Findings showed that the mean left ventricular modified myocardial performance index, isovolumetric contraction time, and isovolumetric relaxation time values were statistically significantly higher while the ejection time and E/A ratios were statistically significantly lower in the intrahepatic cholestasis of pregnancy group than the control group. In the intrahepatic cholestasis of pregnancy group, a statistically significant positive correlation was found between left ventricular modified myocardial performance index and adverse perinatal outcomes in the intrahepatic cholestasis of pregnancy group (r=0.478, p<0.001), while a statistically significant negative correlation was found between the E/A ratio and adverse perinatal outcomes (r=-0.701, p<0.001).CONCLUSIONS:For intrahepatic cholestasis of pregnancy cases, high fetal left ventricular modified myocardial performance index values were an indicator of ventricular dysfunction, and this correlated with negative perinatal outcomes.

Deep Learning Algorithm-Based Magnetic Resonance Imaging Feature-Guided Serum Bile Acid Profile and Perinatal Outcomes in Intrahepatic Cholestasis of Pregnancy.

This study was aimed to explore magnetic resonance imaging (MRI) based on deep learning belief network model in evaluating serum bile acid profile and adverse perinatal outcomes of intrahepatic cholestasis of pregnancy (ICP) patients. Fifty ICP pregnant women diagnosed in hospital were selected as the experimental group, 50 healthy pregnant women as the blank group, and 50 patients with cholelithiasis as the gallstone group. Deep learning belief network (DLBN) was built by stacking multiple restricted Boltzmann machines, which was compared with the recognition rate of convolutional neural network (CNN) and support vector machine (SVM), to determine the error rate of different recognition methods on the test set. It was found that the error rate of deep learning belief network (7.68%) was substantially lower than that of CNN (21.34%) and SVM (22.41%) (P < 0.05). The levels of glycoursodeoxycholic acid (GUDCA), glycochenodeoxycholic acid (GCDCA), and glycocholic acid (GCA) in the experimental group were dramatically superior to those in the blank group (P < 0.05). Both the experimental group and the blank group had notable clustering of serum bile acid profile, and the experimental group and the gallstone group could be better distinguished. In addition, the incidence of amniotic fluid contamination, asphyxia, and premature perinatal infants in the experimental group was dramatically superior to that in the blank group (P < 0.05). The deep learning confidence model had a low error rate, which can effectively extract the features of liver MRI images. In summary, the serum characteristic bile acid profiles of ICP were glycoursodeoxycholic acid, glycochenodeoxycholic acid, and glycocholic acid, which had a positive effect on clinical diagnosis. The toxic effects of high concentrations of serum bile acids were the main cause of adverse perinatal outcomes and sudden death.

Evaluation of perinatal outcomes in intrahepatic cholestasis of pregnancy

Evaluation of perinatal outcomes in intrahepatic cholestasis of pregnancy

Perinatal outcomes of intrahepatic cholestasis of pregnancy from two birth cohorts: A population-based study.

Intrahepatic cholestasis of pregnancy (ICP) is a complex liver disease with varying incidence worldwide. We compared ICP incidence and pregnancy outcomes with outcomes for normal pregnant controls. We conducted a retrospective data analysis of perinatal registry data for the years 2011 and 2017 to compare the following outcome measures: stillbirths, labour induction, gestational diabetes, pre-eclampsia, antepartum haemorrhage, postpartum haemorrhage, preterm births, low Apgar score, acute neonatal respiratory morbidity, meconium aspiration and in-hospital neonatal death. The incidence of ICP was 8 per 1000 births from a total 31,493 singleton births with more cases in 2017 than in 2011. Women with ICP were almost six times more likely to have labour induced including significantly more moderate preterm births (defined as between 32 weeks and 36 weeks and 6 days of gestation)) seen more in 2011 than in 2017. Women with ICP showed higher incidence of moderate preterm birth and induced labour but favourable maternal and neonatal outcomes.

Value of Serum Glycocholic Acid and Total Bile Acids in Predicting Maternal and Perinatal Outcomes in Intrahepatic Cholestasis of Pregnancy.

Objective To see whether serum glycocholic acid (CG) and total bile acids (TBA) can predict maternal and perinatal outcomes in pregnant women with intrahepatic cholestasis (ICP). Method The observation group consisted of 80 women with ICP who were treated in our hospital, whereas the control group consisted of 50 ordinary women who were also treated at our hospital at the same time. The levels of CG and TBA in the two groups were determined independently, and the differences in poor perinatal outcomes were compared. Finally, the predictive diagnostic value of CG and TBA for poor perinatal outcomes in ICP mothers was displayed using the Spearman correlation between CG and TBA and Apgar. The maternal CG and TBA levels in the observation group were substantially higher than in the control group (P0.05). The observation group had more significant maternal-fetal discomfort, neonatal asphyxia, preterm birth, and perinatal death than the control group (P0.05). The risk of poor perinatal outcomes in ICP mothers rose when TBA and CG levels increased (P0.05). Apgar ratings were inversely associated with CG and TBA (r = −0.8251 and r = −0.5969, respectively, P0.05). The CG and TBA diagnostic AUCs for unfavorable perinatal outcomes in ICP mothers were (P0.05). Conclusion CG and TBA have a high diagnostic value for ICP and may better predict and identify poor prenatal outcomes. It is suitable for clinical use.

New insights in diagnostic thresholds for total serum bile acid in intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy specific liver disorder known to be associated with fetal adverse events, in particular stillbirth. At present, an effective treatment to reduce the risk of stillbirth, does not exist. Ursodeoxycholic acid (UDCA) is often given in clinical practice to reduce maternal symptom of pruritus but without strong evidence (Walker KF et al. Pharmacological interventions for treating intrahepatic cholestasis of pregnancy. Cochrane Database Syst Rev. 2020 Jul 27;7(7):CD000493), and iatrogenic preterm birth is induced when the risk of stillbirth is thought to be higher (Ovadia C et al. Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses. Lancet. 2019 Mar 2;393(10174):899-909).

492 Ursodeoxycholic acid and perinatal outcomes in intrahepatic cholestasis of pregnancy: an individual patient data meta-analysis

Ursodeoxycholic acid (UDCA) is a commonly used pharmacological treatment for intrahepatic cholestasis of pregnancy (ICP), yet the largest clinical trial of its use detected minimal benefit for a composite perinatal outcome (stillbirth, preterm birth and neonatal unit admission), and evidence for perinatal benefit was not concluded in the 2020 Cochrane review. We aimed to determine whether UDCA affects adverse fetal and maternal outcomes for singleton pregnancies using an individual patient data meta-analysis of participants of randomized controlled trials (RCTs). Following a systematic review of the literature, authors were invited to submit individual patient data. We performed a fixed-effects meta-analysis using multilevel modelling, adjusting for bile acid concentration at randomization and parity. Analyses were performed in STATA version 16.0; this was part of a study registered in PROSPERO: CRD42019131495. Data were provided for 755 women from four RCTs, of whom 388 (51%) took UDCA. UDCA treatment was not associated with a difference in stillbirth (adjusted odds ratio 0.40, 95% confidence interval 0.04 to 4.68, p=0.469). However, UDCA was associated with a reduced composite of stillbirth and preterm birth (aOR 0.51, 95% CI 0.33 to 0.78, p=0.002), with reduced overall preterm birth for women randomized to UDCA (aOR 0.52, 95% CI 0.34 to 0.80, p=0.003). This was predominantly due to reduced spontaneous preterm birth (aOR 0.46, 95% CI 0.25 to 0.86, p=0.015) as iatrogenic preterm birth was not affected by UDCA treatment (aOR 0.63, 95% CI 0.37 to 1.10, p=0.114). The number needed to treat to prevent one composite outcome was 13.5 (95%CI 8.0 to 41.4), and for spontaneous preterm birth was 24.4 (95% CI 13.0 to 193.2). By using individual patient data, we revealed that spontaneous preterm birth was reduced for women with ICP taking UDCA in singleton pregnancies, as was a composite outcome of stillbirth and preterm birth. This abstract is presented on behalf of an International Study Collaborative.

Role of ursodeoxycholic acid on maternal serum bile acids and perinatal outcomes in intrahepatic cholestasis of pregnancy.

Intrahepatic cholestasis of pregnancy (ICP) is associated with safe maternal outcomes but perinatal outcomes have been variable. We assessed clinical factors and impact of bile acid levels on maternal and neonatal outcomes in ICP. Patients with ICP (defined as pruritus with serum bile acids ≥ 10 mmol/l) were included prospectively with an assessment of risk factors, modes of delivery as well as maternal and neonatal outcomes. Mild and severe ICP were diagnosed when serum bile acid was always <40 mmol/l and ≥40 mmol/l, respectively. Patients with gestational pruritus served as controls. Out of 643 patients, 375 patients (mean age 29 ± 7.6 years, 45.8% primigravida) met inclusion criteria. Pregnancy-induced hypertension [PIH: 10.5%; odds ratio (OR): 4.8; 95% confidence interval (CI): 2.4-8.5; P = 0.0014], gestational diabetes (GDM: 12.5%; OR: 2.6; 95% CI: 2.3-4.1; P = 0.045) and spontaneous preterm labor (15.1%; OR: 2.5; 95% CI: 1.2-3.5; P = 0.040) were higher in patients with ICP. Ursodeoxycholic acid (UDCA) (median dose 900 mg; 600-1800 mg) ameliorated symptoms of cholestasis, bile acid levels and liver aminotransferases in 79% cases. When compared with patients with mild ICP, patients with severe ICP presented at a lower gestational period (26 vs. 32 weeks, P = 0.036), required frequent induction (12.5%; OR: 3.2; 95% CI: 2.1-5.6; P = 0.045) and had increased fetal distress (15%; OR: 1.9; 95% CI: 1.3-4.9; P = 0.048).Overall eight stillbirths were recorded. Severe ICP is associated with a higher incidence of GDM and PIH, risk of pre-term labor, elective induction and stillbirths. UDCA remains a first-line agent in treating ICP.

Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-Analyses

(Lancet. 2019;393:899–909) Intrahepatic cholestasis of pregnancy has been associated with adverse perinatal outcomes, including preterm labor, fetal asphyxia, meconium-stained amniotic fluid, and stillbirth. Although studies have found an increased risk of these complications when the serum bile acid concentration is &gt;40 µmol/L, there currently are no studies to indicate a specific concentration threshold that is predictive of fetal death. The purpose of this systematic review and meta-analysis was to quantify adverse perinatal complications in relation to serum bile acid concentrations and to determine whether specific concentration levels were associated with the risk of stillbirth and preterm birth.

Perinatal outcomes of intrahepatic cholestasis during pregnancy: An 8-year case-control study.

IntroductionPrevious studies of fetal effects have suggested that intrahepatic cholestasis of pregnancy is associated with a higher rate of adverse neonatal outcomes including preterm birth, neonatal respiratory distress syndrome, meconium-stained amniotic fluid, neonatal intensive care unit admission, and stillbirth. The objective was to compare the neonatal and maternal consequences in pregnancies affected by intrahepatic cholestasis and normal pregnancies.Material and methodsThis case-control study compares pregnancies affected by intrahepatic cholestasis (pruritus and bile acid ≥ 10 μmol/L) with low-risk pregnancies managed between December 2006 and December 2014 at a French university hospital center.ResultsThere were 83 (59.3%) cases of mild cholestasis (10≤ BA ≤39 μmol/L), 46 (32.8%) of moderate cholestasis (40≤ BA ≤99 μmol/L), and 11 (7.9%) of severe cholestasis (BA ≥100 μmol/L). No in utero fetal deaths occurred in the 140 women with cholestasis or the 560 controls analyzed. The rate of respiratory distress syndrome was higher in neonates of women with intrahepatic cholestasis (17.1% vs. 4.6%, P<0.001; crude OR 4.46 (CI95% 2.49–8.03)). This risk was also significant after adjustment for gestational age at birth and mode of delivery, adjusted OR 2.56 (CI95%1.26–5.18). The postpartum hemorrhage rate was twice as high among the case mothers (25% versus 14.1% for controls, P = 0.002).ConclusionAfter adjustment on the confounding factors we found a higher rate of respiratory distress syndrome and neonatal morbidity among neonates of the cholestasis group.

Perinatal outcomes of intrahepatic cholestasis of pregnancy in twin versus singleton pregnancies: is plurality associated with adverse outcomes?

To determine the rate of obstetric and neonatal complications associated with intrahepatic cholestasis of pregnancy in twin versus singleton gestations. A retrospective cohort study including patients diagnosed with intrahepatic cholestasis of pregnancy at a single tertiary center between 2011 and 2016. Women were allocated into two groups: twin pregnancies (n = 56) and singleton pregnancies (n = 186). Obstetric and neonatal outcomes were compared between the two groups. Intrahepatic cholestasis of pregnancy was diagnosed earlier in gestation in twin compared to singleton pregnancies (33.1 ± 2.8 vs. 35.1 ± 3.0weeks, respectively; adjusted P < 0.001). Maternal serum levels of fasting total bile acids were significantly higher in twin pregnancies compared to singletons [27 (IQR 16-44) vs. 16 (IQR 10-26) µmol/L, respectively; P = 0.01]. None of the pregnancies in our cohort was complicated by fetal death. Apgar score at 5min and umbilical artery and vein PH at delivery were comparable between the two groups. Intrahepatic cholestasis of pregnancy in twin pregnancies appears to be more severe compared to singletons, as reflected by an earlier presentation and higher levels of maternal serum total bile acids. Large prospective studies are required to customize a management strategy specific for women with twin pregnancies and intrahepatic cholestasis of pregnancy.

Association of Adverse Perinatal Outcomes of Intrahepatic Cholestasis of Pregnancy With Biochemical Markers: Results of Aggregate and Individual Patient Data Meta-analyses

(Abstracted from Lancet 2019;393(10174):899–909) Intrahepatic cholestasis of pregnancy (ICP) affects less than 0.1% to 0.2% of pregnant women. It is diagnosed in women with gestational pruritus and increased serum bile acids and can be complicated by preterm labor, fetal asphyxia, meconium-stained amniotic fluid, and stillbirth.

Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy.

Our objective was to evaluate in our clinic the perinatal outcomes of patients diagnosed with ICP based on pre-treatment maternal serum bile acid levels, attempt to identify the risk group and review the literature in light of this information. In total, 370 patients diagnosed with ICP were included in the study, divided into two groups based on the fasting total serum bile acid level before UDCA (Group 1: 10 ≥ 40 μmol/L, and Group 2: ≥ 40 μmol/L). The groups were examined for clinical characteristics and pregnancy outcomes. It was found that preterm delivery and neonatal intensive care need increased at a serum bile acid cut-off value of 34 μmol/L. Regardless of serum bile acid, significantly higher rates of meconium-stained amniotic fluid and foetal distress were observed in patients whose diagnoses were made before 34 weeks of gestation. Foetal complications over 40 μmol/L of serum bile acid were significantly increased. However, slightly lower levels cut-off values (34 μmol/L) were obtained in terms of preterm birth and neonatal intensive care need. The incidence of meconium-stained amniotic fluid and foetal distress was higher in patients whose diagnosis were made before 34 weeks of gestation.

Association of adverse perinatal outcomes of intrahepatic cholestasis of pregnancy with biochemical markers: results of aggregate and individual patient data meta-analyses

SummaryBackgroundIntrahepatic cholestasis of pregnancy is associated with adverse perinatal outcomes, but the association with the concentration of specific biochemical markers is unclear. We aimed to quantify the adverse perinatal effects of intrahepatic cholestasis of pregnancy in women with increased serum bile acid concentrations and determine whether elevated bile acid concentrations were associated with the risk of stillbirth and preterm birth.MethodsWe did a systematic review by searching PubMed, Web of Science, and Embase databases for studies published from database inception to June 1, 2018, reporting perinatal outcomes for women with intrahepatic cholestasis of pregnancy when serum bile acid concentrations were available. Inclusion criteria were studies defining intrahepatic cholestasis of pregnancy based upon pruritus and elevated serum bile acid concentrations, with or without raised liver aminotransferase concentrations. Eligible studies were case-control, cohort, and population-based studies, and randomised controlled trials, with at least 30 participants, and that reported bile acid concentrations and perinatal outcomes. Studies at potential higher risk of reporter bias were excluded, including case reports, studies not comprising cohorts, or successive cases seen in a unit; we also excluded studies with high risk of bias from groups selected (eg, a subgroup of babies with poor outcomes were explicitly excluded), conference abstracts, and Letters to the Editor without clear peer review. We also included unpublished data from two UK hospitals. We did a random effects meta-analysis to determine risk of adverse perinatal outcomes. Aggregate data for maternal and perinatal outcomes were extracted from case-control studies, and individual patient data (IPD) were requested from study authors for all types of study (as no control group was required for the IPD analysis) to assess associations between biochemical markers and adverse outcomes using logistic and stepwise logistic regression. This study is registered with PROSPERO, number CRD42017069134.FindingsWe assessed 109 full-text articles, of which 23 studies were eligible for the aggregate data meta-analysis (5557 intrahepatic cholestasis of pregnancy cases and 165 136 controls), and 27 provided IPD (5269 intrahepatic cholestasis of pregnancy cases). Stillbirth occurred in 45 (0·83%) of 4936 intrahepatic cholestasis of pregnancy cases and 519 (0·32%) of 163 947 control pregnancies (odds ratio [OR] 1·46 [95% CI 0·73–2·89]; I2=59·8%). In singleton pregnancies, stillbirth was associated with maximum total bile acid concentration (area under the receiver operating characteristic curve [ROC AUC]) 0·83 [95% CI 0·74–0·92]), but not alanine aminotransferase (ROC AUC 0·46 [0·35–0·57]). For singleton pregnancies, the prevalence of stillbirth was three (0·13%; 95% CI 0·02–0·38) of 2310 intrahepatic cholestasis of pregnancy cases in women with serum total bile acids of less than 40 μmol/L versus four (0·28%; 0·08–0·72) of 1412 cases with total bile acids of 40–99 μmol/L (hazard ratio [HR] 2·35 [95% CI 0·52–10·50]; p=0·26), and versus 18 (3·44%; 2·05–5·37) of 524 cases for bile acids of 100 μmol/L or more (HR 30·50 [8·83–105·30]; p<0·0001).InterpretationThe risk of stillbirth is increased in women with intrahepatic cholestasis of pregnancy and singleton pregnancies when serum bile acids concentrations are of 100 μmol/L or more. Because most women with intrahepatic cholestasis of pregnancy have bile acids below this concentration, they can probably be reassured that the risk of stillbirth is similar to that of pregnant women in the general population, provided repeat bile acid testing is done until delivery.FundingTommy's, ICP Support, UK National Institute of Health Research, Wellcome Trust, and Genesis Research Trust.

817: Correlation of bile acids and aspartate-aminotransferase with adverse perinatal outcomes in intrahepatic cholestasis of pregnancy

To identify laboratory data that correlate with a non-reassuring prognosis and poor obstetrical and neonatal outcomes. A retrospective review of women with intrahepatic cholestasis of pregnancy (ICP), admitted for delivery between January 1, 2013 and December 31, 2017, was performed. Chi-square and Student’s T-test statistical analysis was performed, and receiver-operator characteristic curves were plotted for the prediction of each category of perinatal outcome and the areas under the curves were determined. All p-values were two-sided, and P <0.05 was considered statistically significant. Examination of the pregnancy outcomes and clinical features of the 61 patients diagnosed with ICP showed no occurrence of IUFD, stillbirth, abruption, or neonatal demise. In our cohort, no single factor was identified that correlated with a reassuring outcome and would permit expectant management of pregnancy beyond 37 weeks gestation. ROC curve analysis revealed a statistically significant correlation between bile acid and AST levels and perinatal outcomes. A bile acid level equal to or greater than 37 μmol/L strongly predicted spontaneous preterm labor in women affected by ICP with a sensitivity of 100% and specificity of 60.70% (P value 0.002). A bile acid level equal to or greater than 42 μmol/L strongly predicted meconium-stained amniotic fluid with a sensitivity of 85.70% and specificity of 66.70% (P value 0.006). AST levels equal to or greater than 62 IU/L strongly predicted NICU admission with a sensitivity of 81.30% and specificity of 62.20% (P value 0.002). AST levels equal to or greater than 75 IU/L strongly predicted hyperbilirubinemia in the neonates with a sensitivity of 87.50% and specificity of 69.80% (P value 0.001). There is a statistically significant correlation between elevated bile acid and AST levels and adverse perinatal outcomes. Given this statistically significant correlation, patients with ICP should undergo serial liver function tests, specifically AST levels, along with serial bile acid levels.

273. Adverse perinatal outcomes of intrahepatic cholestasis of pregnancy and association with biochemical markers: Results of aggregate and independent patient data meta-analyses

Background Whilst intrahepatic cholestasis of pregnancy (ICP) is associated with adverse perinatal outcomes, the relationship between specific biochemical markers and individual pregnancy complications has not been established. Methods We performed a systematic review of the literature (PubMed, Web of Science, Embase databases from inception to August 2017, selecting studies reporting perinatal outcomes for women with ICP with serum bile acid concentrations reported. Random effects meta-analysis was performed to determine risk of adverse perinatal outcomes. Individual patient data (IPD) were collected to assess associations between biochemical markers and adverse outcomes using logistic and stepwise linear regression (PROSPERO: CRD42017069134). Findings 22 studies were included in the meta-analysis (5515 ICP cases, 165 081 controls), with IPD from 18 studies (4163 ICP cases). Stillbirth complicated 0.83% ICP and 0.32% control pregnancies (OR 1.46 (0.73–2.89)). Stillbirth was associated with maximum total bile acid concentration (ROC AUC 0.80 (0.69–0.90)) but not alanine transaminase (ROC AUC 0.46, 95% CI 0.35–0.58). Prevalence of stillbirths was 0.20% (0.05–0.50%) with serum total bile acids Interpretation The risk of stillbirth is increased in women with ICP, but not significantly greater than population rates until serum bile acids ⩾100 μmol/L. The clear bile acid threshold of 100 μmol/L beneath which stillbirth rates were not elevated is a novel and important finding in our study. As most women with ICP have bile acids below this level, they can be reassured, provided repeat bile acid testing is performed.

Perinatal outcomes in intrahepatic cholestasis of pregnancy with monochorionic diamniotic twin pregnancy

BackgroundThe primary aim of the study is to investigate the perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with monochorionic diamniotic (MCDA) twin pregnancy.MethodsThis study is a retrospective observational study for women with ICP and MCDA twin pregnancy. Included cases were divided into mild ICP group (10–39 mmol/L) and severe ICP group (> = 40 mmol/L), whose perinatal outcomes were compared between this two groups and whose predictors of adverse perinatal outcomes were evaluated.Results37 cases and 21 cases are in mild and severe ICP group respectively, of which, the incidence of gestational diabetes mellitus (GDM) and iatrogenic preterm delivery in severe ICP group are higher than those in mild ICP group. Gestational age (GA) at diagnosis of ICP < 32 weeks is an independent risk factor for GA at delivery < 35 weeks and for composite adverse neonatal outcome. Total bile acids (TBA) > 40 mmol/l is an independent risk factor for meconium-stained amniotic fluid.ConclusionFor women with ICP and MCDA twin pregnancy, GA at diagnosis of ICP < 32 weeks and TBA > 40umol/L are associated with adverse perinatal outcomes.

Predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy with dichorionic diamniotic twin pregnancies

Objective: The aim of our study was to investigate the predictors of adverse perinatal outcomes in intrahepatic cholestasis of pregnancy (ICP) with dichorionic diamniotic (DCDA) twin pregnancies. Methods: This study was a retrospective study of women diagnosed with ICP and DCDA twin pregnancies in Chengdu’s women and children’s central hospital. These patients were subdivided into mild and severe ICP groups according to total bile acid (TBA) level. The clinical characteristics and perinatal outcomes were collected and compared between the two groups. Logistic regression analysis was developed to evaluate predictors of adverse perinatal outcomes. Results: About 134 cases were included in the study. Eighty-four cases were in the mild ICP group, and the other 50 cases were in the severe ICP group. Level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), total bilirubin (TBIL), and direct bilirubin (DBIL) in the severe ICP group were significant higher than those in the mild ICP group. The rate of delivery before 34 gestational weeks, meconium-stained amniotic fluid, and composite adverse neonatal outcome were higher in the severe ICP group than those in the mild ICP group. After adjusting for confounders, ICP onset gestational age (GA) <30 weeks and AST >200U/l were associated with GA at delivery <34 weeks. ALP >400U/l was an independent risk factor of meconium-stained amniotic fluid. ICP onset GA <30 weeks was an independent risk factor of composite adverse neonatal outcome. Conclusion: ICP onset GA <30 weeks, TBA >40 µmol/l, AST >200U/l, and ALP >400U/l were associated with composite adverse perinatal outcomes in ICP with DCDA twin pregnancies. For those patients with these characteristics, fetal surveillance and treatment should be enhanced.