Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by pruritus and cholestasis in late pregnancy and results in adverse pregnancy outcomes, including preterm delivery and birth weight, which are affected by the genetic and environmental background. However, until now, the genetic architecture of ICP has remained largely unclear. Methods: Twenty-six clinical data points were recorded for 151 Chinese ICP patients. The data generated from whole-exome sequencing (WES) using the BGISEQ-500 platform were further analyzed by Burrows-Wheeler Aligner (BWA) software, Genome Analysis Toolkit (GATK), ANNOVAR tool, etc. R packages were used to conduct t-test, Fisher’s test and receiver operating characteristic (ROC) curve analyses. Results: We identified eighteen possible pathogenic loci associated with ICP disease in known genes, covering ABCB4, ABCB11, ATP8B1 and TJP2. The loci Lys386Gln, Gly527Gln and Trp708Ter in ABCB4, Leu589Met, Gln605Pro and Gln1194Ter in ABCB11, and Arg189Ser in TJP2 were novel discoveries. In addition, WES analysis indicated that the gene ANO8 involved in the transport of bile salts is newly identified as associated with ICP. The functional network of the ANO8 gene confirmed this finding. ANO8 contained 8 rare missense mutations that were found in eight patients among the 151 cases and were absent from 1029 controls. Out of the eight SNPs, 3 were known, and the remaining five are newly identified. These variants have a low frequency, ranging from 0.000008 to 0.00001 in the ExAC, gnomAD – Genomes and TOPMED databases. Bioinformatics analysis showed that the sites and their corresponding amino acids were both highly conserved among vertebrates. Moreover, the influences of all the mutations on protein function were predicted to be damaging by the SIFT tool. Combining clinical data, it was found that the mutation group (93.36 µmol/L) had significantly (P = 0.038) higher total bile acid (TBA) levels than the wild-type group (40.81 µmol/L). Conclusions: To the best of our knowledge, this is the first study to employ WES technology to detect genetic loci for ICP. Our results provide new insights into the genetic basis of ICP and will benefit the final identification of the underlying mutations.

Background. Placenta accreta spectrum (PAS) disorders seriously threaten the safety of the mother and infant in the perinatal period. Moreover, PAS is associated with poor maternal and perinatal outcomes once complicated with cervical implantation. Dismally, there are few reports about PAS complicated with cervical involvement currently, and the early warning models are also rarely reported. To screen the risk factors of PAS complicated with cervical implantation and construct an early risk warning model, we performed the analysis of clinical indicators and images of PAS patients by artificial intelligence (AI) data processing methods. Methods. The clinical data of 166 patients with PAS in our hospital from January 2016 to September 2020 were retrospectively analyzed. The patients were divided into cervical implantation group and lower uterine implantation group according to the position of placenta implantation. Then, we compared the pregnancy outcomes of the two groups, screened the possible related factors of PAS complicated with cervical implantation by univariate analysis, and established the early warning model by logistic regression analysis. Results. The maternal outcome of PAS complicated with cervical implantation was worse than that of the lower uterine implantation group. Through univariate analysis and logistic regression analysis, we found that the cervical width, abundant cervical blood flow, and bladder line interruption were all risk factors of PAS complicated with cervical implantation, and their contribution to the establishment of the regression model was statistically significant. Conclusion. PAS complicated with cervical implantation was extremely severe. Early identification of risk factors and establishment of a risk warning model have certain guiding significance for clinical formulation of a reasonable treatment plan.

Background: Intrahepatic cholestasis of pregnancy (ICP) can cause adverse pregnancy outcomes, such as spontaneous preterm delivery and stillbirth. It is a complex disease influenced by multiple factors, including genetics and the environment. Previous studies have reported that functioning nuclear receptor subfamily 1 group H member 4 (NR1H4) plays an essential role in bile acid (BA) homeostasis. However, some novel variants and their pathogenesis have not been fully elucidated. Therefore, this research aimed to investigate the genetic characteristics of theNR1H4gene in ICP.Methods: In this study, we sequenced the entire coding region ofNR1H4in 197 pregnant women with ICP disease. SIFT and PolyPhen2 were used to predict protein changes. Protein structure modelling and comparisons between NR1H4 reference and modified protein structures were performed by SWISS-MODEL and Chimera 1.14rc, respectively. T-tests were used to analyse the potential significant differences betweenNR1H4mutations and wild types for 29 clinical features. Fisher’s test was conducted to test the significance of differences in mutation frequencies between ICP and the three databases.Results: We identified four mutations: two novel missense mutations, p.S145F and p.M185L; rs180957965 (A230S); and rs147030757 (N275N). The two novel missense mutations were absent in 1029 controls and three databases, including the 1000 Genomes Project (1000G_ALL), Exome Aggregation Consortium (ExAC) and ChinaMAP. Two web-available tools, SIFT and PolyPhen2, predicted that these mutations are harmful to the function of the protein. Moreover, compared to the wild-type protein structure, theNR1H4p.S145F and p.M185L protein structure showed a slight change in the chemical bond in two zinc finger structures. Combined clinical data indicate that the mutation group had higher levels of total bile acid (TBA) than the wild-type group. Therefore, we hypothesized that these two mutations altered the protein structure ofNR1H4, which impaired the function ofNR1H4itself and its target gene and caused an increase in TBA.Conclusions: To our knowledge, this is the first study to identify the novel p.S145F and p.M185L mutations in 197 ICP patients. Our present study provides new insights into the genetic architecture of ICP involving the two novelNR1H4mutations.

Background. Forceps delivery is one of the most important measures to facilitate vaginal delivery. It can reduce the rate of first cesarean delivery. Frustratingly, adverse maternal and neonatal outcomes associated with forceps delivery have been frequently reported in recent years. There are two major reasons: one is that the abilities of doctors and midwives in forceps delivery vary from hospital to hospital and the other one is lack of regulations in the management of forceps delivery. In order to improve the success rate of forceps delivery and reduce the incidence of maternal and neonatal complications, we applied form-based management to forceps delivery under an intelligent medical model. The aim of this work is to explore the clinical effects of form-based management of forceps delivery. Methods. Patients with forceps delivery in Maternal and Child Health Hospital Affiliated to Nanchang University were divided into two groups: form-based patients from January 1, 2019, to December 31, 2020, were selected as the study group, while traditional protocol patients from January 1, 2017, to December 31, 2018, were chosen as the control group. Then, we compared the maternal and neonatal outcomes of these two groups. Results. There were significant differences in the maternal and neonatal adverse outcomes such as rate of postpartum hemorrhage, degree of perineal laceration, and incidence of neonatal facial skin abrasions between the two groups, whereas differences in the incidence of asphyxia and intracranial hemorrhage were not significant. Conclusions. Form-based management could help us assess the security of forceps delivery comprehensively, as it could not only improve the success rate of the one-time forceps traction scheme but also reduce the incidence of maternal and neonatal adverse outcomes effectively.

Intrahepatic cholestasis of pregnancy (ICP) poses significant risks to maternal and neonatal health. Our study at Jiangxi Provincial Maternal and Child Health Hospital analyzed clinical and biochemical markers in singleton pregnancies diagnosed with ICP from October 2016 to December 2022. This research, supported by a systematic review and meta-analysis of existing studies, highlights the increasing incidence of ICP and its association with elevated levels of total bile acids, transaminases, and bilirubin. Our findings indicate a marked increase in the risk of preterm birth, cesarean delivery, and neonatal asphyxia as the severity of ICP escalates. This underscores the need for vigilant monitoring and management of affected pregnancies. By confirming the relationship between biochemical marker abnormalities and adverse pregnancy outcomes, our study advocates for enhanced clinical strategies and paves the way for future research aimed at improving prevention, diagnosis, and treatment methods for ICP.

Background. In a global environment of increasing cesarean delivery rate, promoting vaginal delivery, reducing the rate of first cesarean section, and the incidence of vaginal delivery complications are the objectives of obstetric medical quality and safety in China. As a common obstetric complication, preeclampsia affects the safety of many pregnant women. It is the obstetricians great responsibility to promote vaginal delivery and improve delivery outcomes in preeclampsia. To this end, we explored the roles of active labor management under the smart medical model in improving the outcomes of vaginal delivery for pregnant women with preeclampsia. Methods. The clinical data of 219 cases of preeclampsia pregnant women who delivered vaginally in our hospital from January 2017 to December 2020 were retrospectively analyzed. According to different labor process management, they were divided into study group (active labor process management group) and control group (normal labor process management group). Active labor process management methods included intrapartum ultrasound, central fetal heart rate monitoring, Doula delivery, labor analgesia, and quality of life care. The differences in delivery process, delivery outcome, bleeding causes, and hemostatic measures were compared between the two groups. Results. (1) The incidence of preeclampsia in our hospital showed an increasing trend in recent four years; (2) in smart hospitals, the active management of labor process reduced the probability of transferring to the cesarean section in preeclampsia pregnant women with vaginal trial failure; and (3) active labor process management reduced the rate of lateral episiotomy, decreased the postpartum hemorrhage volume within two hours, and improved the vaginal delivery outcome of preeclampsia pregnant women. Conclusions. In the era of the rapid development of the Internet, vigorously promoting the construction of smart hospitals and actively managing the delivery process can reduce the failure rate of vaginal trial delivery and improve the outcomes of vaginal delivery in preeclampsia women.