Search Results (25)

Background/Objectives: Antepartum computerized cardiotocography (cCTG) represents an essential tool for assessing fetal well-being. This study aimed to comparatively evaluate antepartum cCTG-derived indices across high-risk pregnancies to identify distinctive fetal autonomic and reactivity profiles. Methods: A comparative analysis of antepartum cCTG parameters was conducted. The cohort included pregnancies beyond 28 weeks of pregnancy, 169 cases of hypertensive disorders of pregnancy (HDP), 146 of gestational diabetes mellitus (GDM), 86 of intrahepatic cholestasis (ICP), and 87 low-risk pregnancies as controls. Results: Baseline FHR remained within the physiological range across all groups (110–160 bpm; p > 0.05). Dynamic cCTG parameters exhibited clear pathology-dependent alterations. Short-term variability (STV) showed a stepwise decline from controls to ICP and GDM, reaching its lowest values in HDP (mean 1.08 bpm; p < 0.00001), accompanied by an increased proportion of epochs with STV < 1 bpm. Long-term variability suppression (LTV < 5 bpm) was significantly higher in GDM and HDP (p = 0.0077). Acceleration frequency decreased across all pathological groups, with the most pronounced reduction observed in HDP, whereas fetal movements were paradoxically elevated in both GDM and HDP. Total decelerations were more frequent in ICP and HDP; however, repetitive, late, prolonged, and >5 min decelerations remained rare and did not differ significantly between groups. Conclusions: HDP showed the most unfavorable cCTG profiles, consistent with impaired fetal autonomic regulation and chronic subclinical hypoxemia. GDM and ICP had moderate changes, suggesting milder adaptive responses. These findings emphasize the value of quantitative cCTG in differentiating fetal autonomic patterns in high-risk pregnancies and the importance of tailored surveillance strategies. Full article

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is associated with adverse perinatal outcomes. However, its metabolic consequences on newborns remain inadequately characterized. This study investigated amino acid, carnitine, and acylcarnitine profiles in neonates born to mothers with ICP. Methods: This retrospective study encompassed 299 neonates born to mothers with ICP. For comparative analysis, term infants without additional complications (ICP-term, n = 150) were compared with term controls (n = 150). Capillary blood samples collected at 24–48 h of life as part of newborn screening were analyzed using LC–MS/MS for acylcarnitine and amino acid profiles. Results: The ICP cohort exhibited a high preterm delivery rate (46.2%), with maternal bile acids negatively correlating with gestational age (r = −0.266, p < 0.001). No inborn errors of metabolism were observed. Elevated levels of amino acids (alanine, leucine/isoleucine, valine, tyrosine, arginine, glycine, and ornithine) and specific acylcarnitines (C5, C5-OH, C10:1, and C18:2), along with decreased levels of amino acids (argininosuccinic acid and glutamic acid) and specific acylcarnitines (C3, C5-DC, C6-DC, C14, C14:1, C16, C16:1, and C18:1-OH), were observed in ICP-term neonates (p < 0.05). Receiver operating characteristic curve analysis identified ornithine (area under the curve [AUC] = 0.74) and leucine/isoleucine (AUC = 0.73) as strong discriminators. A multivariable model integrating multiple metabolites achieved high accuracy (AUC = 0.86 ± 0.03). Conclusions: This first comprehensive characterization of neonatal metabolic alterations in ICP reveals amino acid metabolism, fatty acid oxidation, and mitochondrial function disruptions, suggesting fetal adaptation to a cholestatic intrauterine environment. Metabolomic profiling may improve understanding of maternal–fetal interactions and inform strategies for risk stratification and long-term monitoring. Full article

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common reversible liver disorder linked to pregnancy, characterised by pruritus and elevated serum bile acids (BAs). Condition severity correlates with increased maternal and neonatal complications, and recent evidence highlights a significantly elevated risk of adverse perinatal outcomes, including stillbirth, when BA > 100 µmol/L. Methods: This retrospective study, conducted at a tertiary perinatology centre between 2019 and 2023, was performed in two phases. In the first phase, baseline group characteristics and pregnancy outcomes were compared between ICP and non-ICP (control) groups. In the second phase, outcomes were analysed across three ICP severity subgroups: mild (BA < 40 µmol/L), moderate (BA 40–99 µmol/L), and severe (BA ≥ 100 µmol/L). Results: A total of 210 patients diagnosed with ICP and 24,177 controls were included in the analysis. After multivariable regression, the results indicated that patients with severe ICP (BA ≥ 100 µmol/L) experienced significantly worse perinatal outcomes compared to those with mild or moderate disease: spontaneous preterm birth occurred in 26.7% of cases (p = 0.002), iatrogenic preterm birth in 36.7% (p < 0.001), meconium-stained amniotic fluid in 43.3% (p = 0.001), and neonatal intensive care unit (NICU) admission in 23.3% (p = 0.006). This subgroup also had the lowest mean birth weight (2830 g, p < 0.001). Notably, no stillbirths were recorded in any of the subgroups. Compared to controls, no major differences in maternal characteristics were noted, except in pregnancies conceived via in vitro fertilisation (IVF, p = 0.012) and those complicated by gestational diabetes (p = 0.040), both showing elevated risk for ICP development. Conclusions: This study confirms an association between ICP and increased perinatal complications, with severity of disease correlating with poorer outcomes. The findings highlight the need for standardised BA testing and improved strategies for perinatal management. Full article

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is the most prevalent hepatobiliary disorder unique to gestation, characterized by maternal pruritus and elevated serum bile acids. While maternal prognosis is favorable, mounting evidence links ICP to a range of neonatal complications. This narrative review aims to synthesize the current knowledge on the pathophysiological mechanisms, clinical impact and management strategies related to neonatal outcomes in ICP. Methods: A narrative review approach was employed, drawing on recent clinical guidelines, observational studies, mechanistic investigations and meta-analyses. Emphasis was placed on evidence exploring the relationship between maternal bile acid concentrations and neonatal morbidity, as well as on established and emerging therapeutic interventions. No systematic search strategy or formal quality appraisal was undertaken. Results: ICP is associated with an increased risk of adverse neonatal outcomes, including spontaneous and iatrogenic preterm birth, meconium-stained amniotic fluid, respiratory distress syndrome and stillbirth, particularly when bile acid concentrations exceed 100 μmol/L. Proposed mechanisms include placental vasoconstriction, arrhythmogenic effects and surfactant inhibition. Ursodeoxycholic acid remains the most widely used pharmacologic agent for maternal symptom relief, although evidence supporting neonatal benefit is inconclusive. Delivery by 36–37 weeks is generally recommended in cases of severe cholestasis to mitigate fetal risk. Conclusions: Severe ICP confers substantial neonatal risk, requiring individualized, bile-acid-guided management. While current therapies offer symptomatic maternal benefit, optimization of fetal outcomes requires timely diagnosis, vigilant surveillance and evidence-based delivery planning. Further research is warranted to refine therapeutic targets and standardize clinical practice. Full article

Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disorder specific to pregnancy, typically presenting in the third trimester. It is characterized by pruritus, elevated serum bile acids, and abnormal liver function tests. While maternal symptoms resolve postpartum, ICP poses significant risks to fetal health, including spontaneous preterm labor, meconium-stained amniotic fluid, and stillbirth. This review aims to synthesize current knowledge on the pathogenesis, diagnosis, and management and highlight emerging research and possible therapy directions in ICP. A comprehensive review of recent literature was conducted, focusing on molecular mechanisms, clinical management guidelines, fetal outcomes, and novel therapeutics under investigation. Ursodeoxycholic acid (UDCA) remains the primary pharmacologic treatment of intrahepatic cholestasis of pregnancy; however, its effect on perinatal outcomes is debated. Investigational therapies—including Volixibat, FXR agonists, 4-phenylbutyrate, and NorUDCA—are under exploration. These emerging therapies hold the potential to improve both maternal symptoms and perinatal outcomes by addressing the underlying pathophysiology of ICP more effectively than current standard treatment. Additionally, emerging biomarkers and machine-learning tools hold promise for improved diagnosis and personalized care. ICP continues to pose diagnostic and therapeutic challenges. While maternal outcomes are generally favorable, optimizing fetal safety requires timely diagnosis, stratified risk assessment, and evidence-based delivery planning. Future research should prioritize identifying predictive biomarkers, refining treatment algorithms, and assessing long-term outcomes for both mothers and offspring. Special attention should also be given to the investigation of novel therapeutic targets. Full article

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder with a multifactorial pathogenesis and a well-established genetic component. While pathogenic variants in genes such as ABCB4 and ABCB11 are implicated in a subset of cases, many remain genetically unexplained. This study aimed to investigate the genetic background of ICP in a multi-generational family with recurrent hepatobiliary disease. Methods: Whole-exome sequencing was performed on the proband and five female relatives. Variant filtering prioritized rare, exonic or splice-site variants predicted to undergo damage by in silico tools and which were present in all affected family members. Identified variants were assessed using population databases and compared with a control group of 433 unrelated women with uncomplicated pregnancies. Variant confirmation was performed using Sanger sequencing and high-resolution melting analysis. Results: No pathogenic variants were identified in known ICP-associated genes. However, a rare heterozygous missense variant in ABCB5 (c.1610G>A; p.Arg537His; rs779950110) was found in all affected individuals and two younger female relatives. This variant is exceedingly rare in population databases, absent in controls, and predicted to be pathogenic by multiple algorithms. ABCB5, although not previously linked to ICP, is an ATP-binding cassette transporter expressed in various tissues, including liver compartments. Conclusions: This study reports a novel ABCB5 variant segregating with ICP and early-onset hepatobiliary disease in a family. These findings suggest ABCB5 as a potential new susceptibility gene in ICP, warranting further functional investigation. Full article

Intrahepatic cholestasis of pregnancy (ICP) is characterized by the onset of pruritus and elevated serum transaminases and bile acids (BA). The key enzyme in BA synthesis is CYP7A1, and its functions are regulated by various nuclear receptors. The goal of this study is to evaluate the association between CYP7A1, NR1H1, RXRA, and PPARA gene variants and risk of ICP. Five single nucleotide variants (SNVs), rs3808607 (CYP7A1), rs56163822 (NR1H4), rs1800206 (PPARA), rs749759, and rs11381416 (NR2B1), were genotyped in a group of 96 ICP and 211 controls. The T allele of the CYP7A1 (rs3808607) variant may be a protective factor against ICP risk (OR = 0.697, 95% CI: 0.495–0.981, p = 0.038). Genetic model analysis showed that rs3808607 was associated with decreased risk of ICP under dominant (OR = 0.55, 95% CI: 0.32–3.16, p = 0.032, AIC = 380.9) and log-additive models (OR = 0.71, 95% CI: 0.51–1.00, p = 0.046, AIC = 381.4). The A insertion in the rs11381416 NR2B1 variant was associated with the degree of elevation in the liver function tests TBA (34.3 vs. 18.8 μmol/L, p = 0.002), ALT (397.0 vs. 213.0 IU/L, p = 0.017), and AST (186.0 vs. 114.4 IU/L, p = 0.032) in ICP women. Results indicate an association between the CYP7A1 rs3808607 and the risk of ICP and the association of the rs11381416 of the NR2B1 receptor with higher values of liver function tests in women with ICP. A better understanding of the cooperation of proteins involved in BA metabolism may have important therapeutic implications in ICP and other hepatobiliary diseases. Full article

Background: This study investigates the impact of ovarian endometriosis on pregnancy outcomes. Methods: A retrospective analysis was conducted at Etlik Zübeyde Hanım Women’s Diseases Training and Research Hospital between January 2019 and December 2024, including 1127 pregnant women—170 with ovarian endometriosis and 957 healthy controls. Pregnancies achieved via assisted reproductive techniques were excluded. Statistical analyses were performed using appropriate tests, and a p-value < 0.05 was considered significant. Results: Women with ovarian endometriosis had higher rates of miscarriage (21.8% vs. 7.5%), preterm birth (15.0% vs. 8.8%), and placenta previa (4.7% vs. 0.6%), with adjusted odds ratios (OR) of 3.41, 1.84, and 7.82, respectively. No significant differences were observed in terms of gestational diabetes, hypertensive disorders, fetal growth restriction (FGR), intrahepatic cholestasis of pregnancy (ICP), placental abruption, or preterm premature rupture of membranes (PPROM). Cyst size and bilaterality were not associated with complications. Conclusions: Spontaneously conceiving women with ovarian endometriosis are at increased risk for miscarriage, placenta previa, and preterm birth. Prospective randomized studies are warranted to validate these findings. Full article

Background: Pregnancy induces hormonal, immunologic, and vascular changes that profoundly affect dermatologic health. This systematic review aimed to assess the impact of pregnancy on dermatological disorders in terms of disease incidence, severity, maternal-fetal outcomes, and optimal management strategies. Methods: A systematic search was performed in PubMed, MEDLINE, and Web of Science databases, following PRISMA guidelines. Studies evaluating pregnant women with dermatological disorders, pregnancy-related dermatoses, and pre-existing morbidities, were included. The collaboratively extracted data included patient demographics, disease severity, treatment approaches, and pregnancy outcomes. Results: A total of 8490 pregnant cases with dermatologic changes and conditions caused by pregnancy were studied. The dermatological conditions were divided into physiological changes, pregnancy-related exacerbation of pre-existing skin conditions, and pregnancy-specific dermatoses. Intrahepatic cholestasis of pregnancy and pemphigoid gestationis were associated with increased rates of adverse fetal outcomes in patients with specific dermatoses, including increased preterm birth and fetal distress rates. The atopic eruption of pregnancy and polymorphic eruption of pregnancy were highly relevant, but their effect on fetal health was minimal. The efficacy and safety of treatment modalities, including corticosteroids, antihistamines, and ursodeoxycholic acid, were variable. Conclusions: Pregnancy drastically affects dermatological health, but the nature of the impact depends on the condition. Optimal maternal and fetal outcomes rely on early diagnosis and individualized management strategies. More randomized controlled trials are required to develop standardized diagnostic and treatment guidelines to enhance the quality of dermatologic care during pregnancy. Full article

Objective: Intrahepatic cholestasis of pregnancy (ICP) is associated with an elevated risk of adverse perinatal outcomes, including perinatal morbidity and mortality. The objectives of this study were to evaluate the bile acid (BA) metabolism profiles in the urine of patients with ICP and to investigate the association between specific BAs and maternal and neonatal outcomes in patients with ICP. Methods: A total of 127 Chinese women with ICP and 55 healthy pregnant women were enrolled in our retrospective study. Spot urine samples and clinical data were collected from pregnant women from January 2019 to December 2022 at the First Affiliated Hospital of Chongqing Medical University, Chongqing. Based on total bile acid (TBA) levels, the ICP group was subdivided into mild (10–40 μmol/L) and severe (≥40 μmol/L) ICP groups. Patients in the ICP group were further divided into two categories according to neonatal outcomes: an ICP with adverse pregnancy outcomes group and an ICP with non-adverse pregnancy outcomes group. Metabolites from maternal urine were collected and analyzed using ultra-high-performance liquid chromatography–triple quadrupole time-of-flight mass spectroscopy (UPLC-triple TOF-MS). Results: Significant differences were observed between the mild and severe ICP groups in the onset time of symptoms, gestational weeks at time of ICP diagnosis, the duration of using ursodeoxycholic acid (UDCA) drugs during pregnancy, gestational age at delivery, premature delivery, and cesarean delivery. The expression levels of the composition of different urinary bile acids including THCA, TCA, T-ω-MCA, TCA-3-S, TCDCA-3-S, TDCA-3-S, GCDCA-3-S, DCA-3-G and GDCA-3-G were remarkably higher in the ICP with adverse pregnancy outcomes group than those in the ICP with non-adverse pregnancy outcomes group and the control group. The single-parameter model used to predict adverse pregnancy outcomes in ICP had similar areas under the curve (AUCs) of the receiver operating characteristic (ROC), ranging from 0.755 to 0.869. However, an AUC of 0.886 and 95% CI were obtained by the index of combined urinary bile acids in multiple prediction models (95% CI 0.790 to 0.983, p < 0.05). TCA-3-S in the urinary bile acids had a strong positive correlation with the aspartate aminotransferase (AST) level (r = 0.617, p < 0.05). Furthermore, TCDCA-3-S and GCDCA-3-S in the urinary bile acids had a strong positive correlation with the alanine aminotransferase (ALT) level (r = 0.607, p < 0.05; r = 0.611, p < 0.05) and AST level (r = 0.629, p < 0.05; r = 0.619, p < 0.05). Conclusions: Maternal urinary bile acid profiles were prominent for the prognosis of maternal and neonatal outcomes of ICP. Elevated levels of TCA-3-S, TCDCA-3-S, and GCDCA-3-S in urine might be important predictors for indicating adverse pregnancy outcomes in ICP. Full article

Background/Objectives: Intrahepatic cholestasis of pregnancy (ICP) is characterised by unexplained intense pruritus during pregnancy. While serum bile acid (BA) is the standard diagnostic marker for ICP, we explored the potential of serum calprotectin as an alternative diagnostic marker for ICP. Methods: Leftover serum specimens with known serum BA levels, collected from non-pregnant women and pregnant women with an ICP, were used to measure serum calprotectin levels using the Human calprotectin L1/S100-A8/A9 ELISA kit. Results: Serum calprotectin levels were measured in 79 pregnant women with ICP (median [interquartile range] 28 year; serum BA 20 [13.7–35.7] μMol/L; calprotectin159 pg/mL [122.2–212.3]); 43 pregnant women without ICP (age 28 years; serum BA 3.6 [2.1–5.8] μMol/L; calprotectin 146.5 pg/mL [75.8–194.8]), and 59 non-pregnant women (age 28 years; serum BA 3.5 [1.6–5.1 μMol/L; calprotectin 82.4 pg/mL [48.8–137.2]). Compared to non-pregnant women, calprotectin levels were significantly elevated among pregnant women with (p < 0.001) or without ICP (p = 0.01). Calprotectin levels were comparable between pregnant women with and without ICP (p = 0.15). The areas under the ROC curve, to differentiate the presence and absence of ICP, were 0.940 (0.903–0.977; p < 0.001) and 0.681 (0.604–0.759; p < 0.001) for BA and calprotectin, respectively. Conclusions: Serum calprotectin is raised in pregnant women regardless of the presence or absence of ICP and had an inferior diagnostic performance for ICP compared to BA. This information is crucial for understanding the challenges in ICP diagnosis and the limitations of serum calprotectin as an alternative marker. Full article

Background and Objectives: Intrahepatic cholestasis of pregnancy (ICP) stands as one of the most prevalent concerns in maternal–fetal medicine, presenting a significant risk to fetal health and often associated with liver dysfunction. Concurrently, the coronavirus-19 (COVID-19) infection can lead to hepatic cell injury through both direct and indirect pathways. Hypothetically, these two conditions may coincide, influencing each other. This study aimed to comparatively assess the incidence and severity of ICP before and during the COVID-19 pandemic. Methods: A retrospective cohort study was conducted, comparing the incidence and severity of ICP between January 2018 and February 2020 (pre-COVID-19 period) and March 2020 to March 2022 (COVID-19 period) across two hospitals, encompassing 7799 deliveries. The diagnosis of ICP was established using the ICD-10 code and defined as total bile acids (BA) levels ≥ 10 μmol/L. Statistical analysis included descriptive statistics, Chi-square and Mann–Whitney U tests, as well as multiple or logistic regression analysis. Results: A total of 226 cases of ICP were identified. The incidence of mild cholestasis (BA < 40 μmol/L) was lower during the pandemic compared to before (3% before versus 2%, p < 0.05), while the incidence of moderate and severe ICP remained unchanged (0.6% before vs. 0.4%, p = 0.2). Overall, the total incidence of ICP was lower during the pandemic (3.6% before versus 2.4%, p = 0.01). No significant differences were observed in severity (as defined by BA and liver function test levels), rates of caesarean section, or neonatal birth weights. Conclusions: During the COVID-19 pandemic, the total incidence of ICP appeared to be lower. However, this reduction was primarily observed in cases of mild ICP, potentially indicating challenges in detection or reduced access to medical services during this period. The incidence of moderate and severe ICP remained unchanged, suggesting that these forms of the condition were unaffected by the pandemic’s circumstances. Full article

Background: Intrahepatic cholestasis of pregnancy (ICP) is the most common pregnancy-related liver disease, usually presented in the third trimester with pruritus, elevated transaminase, and serum total bile acids. Evidence shows that it can be developed in the first trimester, more commonly after in vitro fertilization (IVF) procedures, with the presence of ovarian hyperstimulation syndrome (OHSS). Methods: A literature search was conducted in the PubMed/MEDLINE database of case reports/studies reporting early-onset ICP in spontaneous and IVF pregnancies published until July 2023. Results: Thirty articles on early-onset ICP were included in the review analysis, with 19 patients who developed ICP in spontaneous pregnancy and 15 patients who developed ICP in IVF pregnancies with or without OHSS. Cases of 1st and 2nd trimester ICP in terms of “early-onset” ICP were pooled to gather additional findings. Conclusions: Proper monitoring should be applied even before expected pregnancy and during IVF procedures in patients with known risk factors for OHSS and ICP development (patient and family history), with proper progesterone supplementation dosage and genetic testing in case of ICP recurrence. Full article

Intrahepatic cholestasis of pregnancy (ICP) complicates among 0.2–2% of pregnancies and has been associated with adverse perinatal outcomes, including sudden stillbirth, meconium strained fluid, preterm birth, perinatal asphyxia, and transient tachypnea of the newborn. The diagnosis of “bile acids pneumonia” was previously proposed and a causative role of bile acids (BA) was supposed with a possible mechanism of action including surfactant dysfunction, inflammation, and chemical pneumonia. In the last few years, the role of lung ultrasound (LUS) in the diagnosis and management of neonatal respiratory distress syndrome has grown, and LUS scores have been introduced in the literature, as an effective predictor of the need for surfactant treatment among neonates with respiratory distress syndrome. We present four cases of infants born from pregnancies complicated by ICP, who developed respiratory distress syndrome early after birth. Lung ultrasound showed the same pattern for all infants, corresponding to a homogeneous alveolar–interstitial syndrome characterized by a diffuse coalescing B-line pattern (white lung). All infants evaluated require non-invasive respiratory support and in three cases surfactant administration, despite the near-term gestational age, with rapid improvement of respiratory disease and a good clinical outcome. Full article

The aims of our study were to evaluate the maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP). In this observational, retrospective case–control study, we included all pregnant women who gave birth with a diagnosis of ICP between January 2010 and December 2020 at the Unit of Obstetrics and Gynecology, University Hospital of Messina. The data were compared with those from a control group of pregnant women who did not have ICP. One hundred twenty-nine and eighty-five patients were included, respectively, in the study and in the control group. There was a significant difference between the two groups in the incidence of hypothyroidism, thrombophilia, gestational diabetes, gestational hypertension, postpartum hemorrhage, and preterm delivery, which were more frequent in the ICP patients. No neonatal adverse events were recorded, although a significant difference in the meconium-stained amniotic fluid condition was noted. After a 24-month follow-up, 48/129 patients with ICP accepted to be reassessed by liver ultrasound, elastographic examination, and liver function blood tests. No patient showed signs of chronic liver disease. This study confirmed a higher probability of adverse short-term maternal outcomes in ICP pregnant patients, but a lower probability of adverse short-term fetal outcomes and the absence of a long-term maternal risk of chronic liver disease. Full article