Yayi Hu

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder characterized by pruritus and elevated maternal serum total bile acids. While clinical management has focused on bile acid-based risk stratification and delivery planning to reduce perinatal risks, emerging evidence suggests possible longer-term effects on offspring neurodevelopment. This review synthesizes current epidemiologic and mechanistic evidence linking ICP with offspring neurodevelopmental outcomes. PubMed, Embase, and Web of Science were searched using controlled vocabulary and free-text terms. Relevant references were evaluated for inclusion in a stepwise approach. Large Nordic register-based studies report associations between in utero ICP exposure and increased risks of childhood neurodevelopmental diagnoses, particularly in earlier-onset disease. Follow-up cohorts suggest altered early-life growth trajectories related to biochemical severity. Mechanistically, elevated maternal bile acids are a plausible proximal exposure. Maternal bile acid overload can disrupt placental bile acid transport and handling, alter the feto-maternal bile acid gradient, and increase fetal bile acid burden. The placenta may further convert bile acid perturbations into inflammatory, oxidative stress, endoplasmic reticulum stress, and vasoactive signals that reshape the intrauterine milieu during sensitive windows of brain development. By contrast, downstream pathways involving microglial priming, neuroinflammation, and blood-brain barrier vulnerability are supported mainly by indirect evidence and require validation in pregnancy-relevant models. Current evidence supports a life-course perspective on ICP beyond established perinatal risks. Maternal bile acids and placental dysfunction provide a coherent mechanistic framework for possible neurodevelopmental effects, but pregnancy-relevant mechanistic studies and longitudinal cohorts with refined exposure assessment are still needed.

Objective: This study investigates risk factors, prenatal ultrasonographic characteristics, and pregnancy outcomes in patients with umbilical artery thrombosis (UAT) and umbilical vein thrombosis (UVT). Methods: A retrospective study was conducted at West China Second Hospital, Sichuan University, between April 2019 and April 2024. The umbilical cord thrombosis (UCT) group included women with pathologically confirmed UAT or UVT, whereas the control group consisted of women without UCT who registered and delivered during the same period in our hospital. Maternal clinical data, prenatal ultrasound findings, and pregnancy outcomes were collected and compared between the groups. Results: A total of 110 patients, including 30 patients with UAT, 20 patients with UVT, and 60 controls, were included in the study. Compared with the control group, the UCT group showed significantly greater proportions of umbilical cord torsion, fetal hemodynamic abnormalities, prenatal ultrasound findings, preterm birth, emergency cesarean delivery, intrauterine fetal death (IUFD), low birth weight, and neonatal intensive care unit admission (all P < 0.05). The main hemodynamic abnormalities detected in the UCT group included a decreased systolic/diastolic ratio (S/D), pulsatility index (PI), and resistance index (RI) of the umbilical artery, as well as a decreased PI of the fetal middle cerebral artery (MCA). Among patients with UCT, the prevalence of antiphospholipid antibody syndrome (APS) was significantly greater among those who experienced IUFD than in those with live births ( P < 0.05). Compared with the UVT group, more patients in the UAT group had detectable sonographic evidence of thrombosis, an earlier gestational age, and a lower neonatal Apgar score (all P < 0.05). Compared with the control group, the UVT group demonstrated a significantly lower pre‐pregnancy body mass index, less gestational weight gain, and a greater proportion of conceptions via assisted reproductive technology (all P < 0.05). In most patients with UCT, the thrombi were predominantly located near the umbilical cord insertion site at the fetal abdominal wall. Conclusion: Our study demonstrated that UCT was extremely unfavorable to the perinatal outcomes. Umbilical cord torsion may be a risk factor for the development of UCT. The risk of IUFD was further increased in cases with UCT that coexisted with APS. UAT was more likely to be detected prenatally via ultrasound than UVT; however, UVT was more frequently observed in pregnant women who exhibited insufficient gestation weight gain or conceived through assisted reproductive technology. During routine ultrasound examination, color Doppler assessment of key anatomical sites, together with close monitoring of umbilical artery and MCA indices, might facilitate the early detection of UCT. Although prenatal diagnosis of UCT was significantly challenging, it remained feasible and can provide valuable assistance for clinical management.

Fondaparinux, a synthetic pentasaccharide, represents the smallest heparin-based molecule and functions as a potent selective indirect inhibitor of activated factor Xa. Its high bioavailability, ease of dosing, and favorable tolerability profile render it an ideal antithrombotic agent for pregnant patients who are intolerant to unfractionated heparin (UFH) and low-molecular-weight heparins (LMWHs). Recent studies have highlighted the advancements in the use of fondaparinux in pregnant patients over the past decades. This research provides a comprehensive summary of the safety profiles of fondaparinux, noting that its application in pregnant women may elevate the risk of bleeding events during pregnancy and postpartum. Caution is advised when administering fondaparinux to patients with renal insufficiency. The advantages of fondaparinux include a lower risk of thrombocytopenia, liver injury, allergic reactions, and osteopenia compared with UFH and LMWHs. Although fondaparinux can cross the placental barrier and be detected in the umbilical-cord blood, real-world data have not established a direct association between fondaparinux and teratogenicity or adverse fetal outcomes. Overall, fondaparinux appears to be a viable option for certain groups of pregnant patients requiring anticoagulation. However, further research is warranted to provide deeper insights into the benefits and risks associated with fondaparinux use in this population. The long-term effects of intrauterine exposure to fondaparinux remain an important area for future investigation.

Gestational diabetes mellitus (GDM) is a glucose metabolism disorder with an unclear etiology that occurs specifically during pregnancy. While elevated serum ferritin levels have been reported to increase the risk of GDM, these findings lack validation in large-scale studies and have yet to inform clinical practice effectively. This study enrolled 12,434 controls and 3599 GDM patients and employed binary multifactorial logistic regression, restricted cubic spline, propensity score matching, and a random forest algorithm to explore the relationship between serum ferritin and GDM, as well as the effect size of ferritin on GDM. The results indicated that GDM patients have higher serum ferritin levels compared to controls in the second and third trimesters. A weak correlation was found between serum ferritin levels and OGTT 1-hour and 2-hour blood glucose levels in the second trimester. Logistic regression (LR) and restricted cubic spline (RCS) analyses showed a significant positive correlation between serum ferritin levels and GDM in the second and third trimesters. Propensity score matching analysis indicated that the association between second-trimester serum ferritin levels and GDM remained nearly constant before and after matching. The random forest algorithm suggested that among all confounders, serum ferritin had a minimal effect on GDM risk. In conclusion, our study provides further compelling evidence for the association between serum ferritin levels and gestational diabetes mellitus. However, additional research is still needed to clarify the specific mechanisms underlying this association.

Objective: To evaluate the effectiveness of the YEARS algorithm for excluding pulmonary embolism (PE) in hospitalized women after cesarean section. Methods: This retrospective study included postpartum women who gave birth by cesarean section and received computed tomography pulmonary angiography (CTPA) because of suspected PE in the obstetric department between 2015 and 2021. We used the YEARS algorithm in these women retrospectively and assessed its performance to evaluate whether the algorithm could be reliably applied in such cases. Results: In all, 225 women were included in the study, of whom 29 (12.9%) women were positive for PE according to the results of CTPA. Upon retrospective application of the YEARS algorithm, 188 (83.6%) women had no YEARS items, while 37 (16.4%) women had YEARS items. Combining the results with D‐dimer levels revealed that only 12 (5.3%) women did not need to undergo CTPA, and none showed PE. Conclusion: The YEARS algorithm could be applied to exclude PE in hospitalized women in the early post‐cesarean period. However, the specificity of the YEARS algorithm was very low, and the D‐dimer cut‐off for ruling out PE in women after early cesarean section should be further studied and optimized.

Purpose The “en caul” cesarean section (CS) is a method to keep the amnion intact during CS. This amnion protection effect may have benefits in preterm twin pregnancy. This study aimed to explore the benefits and risks of this method in preterm twin pregnancy. Methods This study is a retrospective analysis of preterm twin pregnancies underwent CS in West China Second University Hospital of Sichuan University from January 2011 to December 2022. Data on maternal and fetal outcomes were collected. Univariable analyses and multivariate logistic regression analyses were applied. The level of significance was set at p < 0.05. Results A total of 182 patients were included (90 in the “en caul” group, 92 in the conventional group). “en caul” CS was associated with lower incidence for respiratory distress (aOR 0.47, 95% CI 0.25–0.88, for the first fetus; aOR 0.42, 95% CI 0.21–0.82, for the second fetus). This method was proved to have beneficial effects in improving the Apgar scores at 1st minute and reducing the mechanical ventilation rate in the second neonates (aOR 0.41, 95% CI 0.19–0.88). Conclusion “En caul” CS is an easy and safe technique to perform during CS for preterm twin pregnancy. The efficacy and safety of this method could be tested by future studies with larger sample size.

Low-molecular-weight heparins (LMWH) are the most commonly used anticoagulants during pregnancy. It is considered to be the drug of choice due to its safety in not crossing placenta. Considering the beneficial effect in the impro vement of microcirculation, prophylactic application of LMWH in patients with preeclampsia became a trend. However, the bleeding risk related with LMWH in preeclampsia patients has seldomly been evaluated. This current study aimed to identify the potential risks regarding LMWH application in patients with pree clampsia. Herein we present a case series of three pregnant women diagnosed with preeclampsia on LMWH therapy during pregnancy. All the cases experienced catastrophic hemorrhagic events. After reviewing the twenty-one meta-analyses, the bleeding risk related with LMWH seems ignorable. Only one study analyzed the bleeding risk of LMWH and found a significantly higher risk of developing PPH in women receiving LMWH. Other studies reported minor bleeding risks, none of these were serious enough to stop LMWH treatment. Possibilities of bleeding either from uterus or from intrabdominal organs in preeclampsia patients on LMWH therapy should not be ignored. Intensive management of blood pressure even after delivery and homeostasis suture in surgery are crucial. Consideration should be given to the balance between benefits and risks of LMWH in patients with preeclampsia.

Trace elements are important components in the body and have fundamental roles in maintaining a healthy and balanced pregnancy process. Either deficiency or excess of trace elements, including selenium, iron, zinc, copper, and magnesium can lead to pregnancy complications. As a rare disorder during pregnancy of unknown aetiology, intrahepatic cholestasis of pregnancy (ICP) poses a significant risk to the fetus of perinatal mortality. ICP is a multifactorial complication of which the pathogenesis is still an enigma. Epidemiological studies have demonstrated the association of ICP with some trace elements. Evidence from retrospective studies in humans further revealed the possible contributing roles of trace elements in the pathogenesis of ICP. The published literature on the association of trace elements with ICP was reviewed. Recent advances in molecular biological techniques from animal studies have helped to elucidate the possible mechanisms by how these trace elements function in regulating oxidative reactions, inflammatory reactions and immune balance in the maternal-fetal interface, as well as the influence on hepato-intestinal circulation of bile acid. The scenario regarding the role of trace elements in the pathogenesis of ICP is still developing. The administration or depletion of these trace elements may have promising effects in alleviating the symptoms and improving the pregnancy outcomes of ICP.