Association of the Verbal Rating Scale-Measured Dysmenorrhea with Nausea and Vomiting in Pregnancy: A Retrospective Cohort Study.

OBJECTIVES: Nausea and vomiting in pregnancy (NVP) is a common condition that reduces the quality of life by negatively affecting work and family life, physical and mental health, and economic well-being. However, its risk factors remain unclear. This study aimed to explore the association between NVP and verbal rating scale (VRS)-measured dysmenorrhea and to explore potential protective factors. METHODS: This retrospective cohort study was conducted from June 2018 to December 2020 at Tongji Hospital in Wuhan. Information on baseline characteristics, pregnancy-related history, periconceptional micronutrient supplementation, and obstetric outcomes were collected. The severity of dysmenorrhea was assessed using VRS. RESULTS: A total of 443 pregnant women were recruited and divided into the NVP group (n = 76) and the control group (n = 367). A significant association was observed between NVP and VRS-measured dysmenorrhea (c2=10.038, P = 0.007). After adjusting for covariates, the association between moderate/severe dysmenorrhea and NVP remained significant (OR 2.384; 95% CI 1.104-5.148, P = 0.004). First-trimester docosahexaenoic acid supplement (OR 0.443; 95% CI 0.205-0.960, P = 0.039) may be beneficial in reducing the risk of NVP. CONCLUSIONS: Women with moderate to severe dysmenorrhea have a higher risk of experiencing NVP during the first trimester. Periconceptional docosahexaenoic acid supplementation may play a protective role.

Diagnostic yield of copy number variation sequencing in fetuses with increased nuchal translucency: a retrospective study.

OBJECTIVE: To assess the efficacy of copy number variation sequencing (CNV-seq) and karyotyping for prenatal detection of chromosomal abnormalities in fetuses with increased nuchal translucency. METHODS: Amniotic fluid samples were extracted from 205 fetuses with increased nuchal translucency (NT ≥ 2.5 mm), diagnosed by ultrasound between gestational ages of 11 and 13 + 6 weeks. Karyotyping and CNV-seq were performed for detecting chromosomal abnormalities. RESULTS: There are 40 fetuses (19.51%) showing increased NT detected with chromosomal abnormalities in karyotyping, and trisomy 21 was found to be the most common abnormalities. There are 50 fetuses (24.39%) identified with chromosomal abnormalities by CNV-seq. The detection of the applied techniques indicated that CNV-seq revealed higher chromosomal aberrations. The risk of chromosomal abnormalities was significantly increased with NT thickening, from 13.64% in the NT group of 2.5-3.4 mm, 38.64% in the NT group of 3.5-4.4 mm, and to 51.72% in the NT group of over 4.5 mm (P < 0.05). The investigated cases with increased NT with presence of soft markers in ultrasound or high risk in non-invasive prenatal testing presented chromosomal abnormalities in higher rates, comparing with those with isolated NT or low risk (P < 0.05). CONCLUSION: The results indicated that the risk of chromosomal abnormalities was associated with the NT thickness, detected by karyotype or CNV-seq. The combination application of two analysis was efficient to reveal the possible genetic defects in prenatal diagnosis. The finding suggested that the detection should be considered with ultrasonographic soft markers, and the NT thickness of 2.5-3.4 mm could be a critical value for detecting chromosomal abnormalities to prevent the occurrence of missed diagnosis.

PINK1-mediated mitophagy induction protects against preeclampsia by decreasing ROS and trophoblast pyroptosis.

INTRODUCTION: Preeclampsia (PE) is a multisystemic disorder attributed to the excessive presentation of placenta-derived immunoinflammatory factors. PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy participates in the development and persistence of the inflammation. We hypothesized that dysregulated mitophagy might be involved in the pathogenesis of PE by promoting the activation of trophoblast pyroptosis that augment inflammation. METHODS: The morphology of mitochondrial in placenta were observed by transmission electron microscopy. The localization of PINK1 in the placenta was determined by immunohistochemistry. The expression levels of PINK1, PARKIN, LC3B, and SQSTM1 and pyroptosis-related molecules were compared between normal pregnancies and PE. We used hypoxia/reoxygenation (H/R) to stimulate the trophoblast hypoxia environment. HTR-8/SVneo cells were transfected with PINK1 plasmid and si-PINK1, respectively, and then were treated with H/R, to determine whether PINK1 regulated ROS and HTR-8/Svneo pyroptosis. Finally, ROS production was inhibited by MitoTEMPO to observe whether the pro-pyroptosis effect of PINK1 knockdown is alleviated. RESULTS: Swollen mitochondrial were accumulated in the PE placentae. PINK1 is localized on villus trophoblast (VTs) and extravillous trophoblast (EVTs). PINK1-mediated mitophagy was abolished in the PE placenta, while the levels of pyroptosis were induced. H/R stimulation aggravated the downregulation of mitophagy and the up-regulation of pyroptosis. Overexpression of PINK1 mitigated H/R-induced upregulation of ROS and pyroptosis while silencing PINK1 did the opposite. Reducing ROS production can effectively resist the pro-pyroptosis effect of PINK1 knockdown. DISCUSSION: This study demonstrated that PINK1-mediated mitophagy might played a protective role in PE by reducing ROS and trophoblast pyroptosis.

New Interpretation of Neonatal Outcomes by Phenotypically Classified Preterm Syndrome: A Retrospective Cohort Study.

OBJECTIVE: The global aim to lower preterm birth rates has been hampered by the insufficient and incomplete understanding of its etiology, classification, and diagnosis. This study was designed to evaluate the association of phenotypically classified preterm syndromes with neonatal outcomes; to what extent would these outcomes be modified after the obstetric interventions, including use of glucocorticoid, magnesium sulfate, and progesterone. METHODS: This was a retrospective cohort study conducted at Tongji Hospital (composed of Main Branch, Optical Valley Branch and Sino-French New City Branch) in Wuhan. A total of 900 pregnant women and 1064 neonates were retrospectively enrolled. The outcomes were the distribution of different phenotypes among parturition signs and pathway to delivery, the association of phenotypically classified clusters with short-term unfavorable neonatal outcomes, and to what extent these outcomes could be modified by obstetric interventions. RESULTS: Eight clusters were identified using two-step cluster analysis, including premature rupture of fetal membranes (PPROM) phenotype, abnormal amniotic fluid (AF) phenotype, placenta previa phenotype, mixed condition phenotype, fetal distress phenotype, preeclampsia-eclampsia & hemolysis, elevated liver enzymes, and low platelets syndrome (PE-E&HELLP) phenotype, multiple fetus phenotype, and no main condition phenotype. Except for no main condition phenotype, the other phenotypes were associated with one or more complications, which conforms to the clinical practice. Compared with no main condition phenotype, some phenotypes were significantly associated with short-term adverse neonatal outcomes. Abnormal AF phenotype, mixed condition phenotype, PE-E&HELLP phenotype, and multiple fetus phenotype were risk factors for neonatal small-for gestation age (SGA); placenta previa phenotype was not associated with adverse outcomes except low APGAR score being 0-7 at one min; mixed condition phenotype was associated with low APGAR scores, SGA, mechanical ventilation, and grade HI-W intraventricular hemorrhage (IVH); fetal distress phenotype was frequently associated with neonatal SGA and mechanical ventilation; PE-E&HELLP phenotype was correlated with low APGAR score being 0-7 at one min, SGA and neonatal intensive care unit (NICU) admission; multiple fetus phenotype was not a risk factor for the outcomes included except for SGA. Not all neonates benefited from obstetric interventions included in this study. CONCLUSION: Our research disclosed the independent risk of different preterm phenotypes for adverse pregnancy outcomes. This study is devoted to putting forward the paradigm of classifying preterm birth phenotypically, with the ultimate purpose of defining preterm phenotypes based on multi-center studies and diving into the underlying mechanisms.

Human milk extracellular vesicles enhance muscle growth and physical performance of immature mice associating with Akt/mTOR/p70s6k signaling pathway.

Extracellular vesicles (EVs) play an important role in human and bovine milk composition. According to excellent published studies, it also exerts various functions in the gut, bone, or immune system. However, the effects of milk-derived EVs on skeletal muscle growth and performance have yet to be fully explored. Firstly, the current study examined the amino acids profile in human milk EVs (HME) and bovine milk EVs (BME) using targeted metabolomics. Secondly, HME and BME were injected in the quadriceps of mice for four weeks (1 time/3 days). Then, related muscle performance, muscle growth markers/pathways, and amino acids profile were detected or measured by grip strength analysis, rotarod performance testing, Jenner-Giemsa/H&E staining, Western blotting, and targeted metabolomics, respectively. Finally, HME and BME were co-cultured with C2C12 cells to detect the above-related indexes and further testify relative phenomena. Our findings mainly demonstrated that HME and BME significantly increase the diameter of C2C12 myotubes. HME treatment demonstrates higher exercise performance and muscle fiber densities than BME treatment. Besides, after KEGG and correlation analyses with biological function after HME and BME treatment, results showed L-Ornithine acts as a "notable marker" after HME treatment to affect mouse skeletal muscle growth or functions. Otherwise, L-Ornithine also significantly positively correlates with the activation of the AKT/mTOR pathway and myogenic regulatory factors (MRFs) and can also be observed in muscle and C2C12 cells after HME treatment. Overall, our study not only provides a novel result for the amino acid composition of HME and BME, but the current study also indicates the advantage of human milk on skeletal muscle growth and performance.

Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation.

This study introduced whole-exome sequencing (WES) in prenatal diagnosis of fetal bowel dilatation to improve the detection outcome when karyotype analysis and copy number variation sequencing (CNV-seq) were uninformative in detecting pathogenic variants. The work reviewed 28 cases diagnosed with fetal bowel dilatation and analyzed the results of karyotype analysis, CNV-seq, and WES. Among the 28 cases, the detection rate in cases with low risk of aneuploidy was 11.54% (3/26), which is lower than 100% (2/2) in cases with high risk of aneuploidy. Ten low-risk aneuploidy cases with isolated fetal bowel dilatation had normal genetic testing results, while the remaining 16 cases with other ultrasound abnormalities were detected for genetic variants at a rate of 18.75% (3/16). The detection rate of gene variation was 3.85% (1/26) by CNV-seq and 7.69% (2/26) by WES. This study suggested that WES could reveal more genetic risk in prenatal diagnosis of fetal bowel dilatation and has value in prenatal diagnosis to reduce birth defects.

Interactions between ultrasonographic cervical length and placenta accreta spectrum on severe postpartum hemorrhage in women with placenta previa.

OBJECTIVE: To explore the interactions between cervical length (CL) and placenta accreta spectrum (PAS) on severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: A retrospective case-control study was conducted at four medical centers in China, and 588 patients with placenta previa were included. The logistic regression analysis and restricted cubic splines (RCS) were used to evaluate the association between CL and SPPH. Furthermore, the joint effect of CL and PAS on SPPH was assessed, and the additive and multiplicative interactions were calculated. RESULTS: After adjusting for potential confounders, the negative linear dose-response relationship was confirmed by RCS, and the change of odds ratio (OR) was more significant when CL was 2.5 cm or less. The risk of SPPH was significantly higher when CL of 2.5 cm or less co-existed with placenta increta/percreta than when CL of 2.5 cm less, or placenta increta/percreta existed alone (adjusted OR [aOR]CL ≤2.5cm&placenta accreta/non-PAS 3.40, 95% confidence interval [CI] 1.37-8.45; aORplacenta increta/percreta&CL >2.5cm 4.75, 95% CI 3.03-7.47; aORCL ≤2.5cm&placenta increta/percreta 14.51, 95% CI 6.08-34.64), and there might be additive interaction between CL and placenta increta/percreta on SPPH (attributable proportion due to interaction 50.7%, 95% CI 6.1%-95.3%). CONCLUSION: If CL was routinely performed during PAS evaluation, the increased OR of short CL and PAS could allow better patient preparation through counseling.

Effects of KCa channels on biological behavior of trophoblasts.

The Ca2+-activated potassium (KCa) channels are involved in many cellular functions, but their roles in trophoblasts are unclear. This study aimed to clarify the effects of KCa channels on the biological behavior of trophoblasts. The localization and expression of the three types of KCa channels, including large-conductance KCa channels (BKCa), intermediate-conductance KCa channels (IKCa), and small-conductance KCa channels (SKCa), were detected in human chorionic villi taken from pregnant women between 5 and 8 weeks of gestation (n = 15) and HTR-8/SVneo cells. The effects of KCa channels on proliferation, apoptosis, and migration of HTR-8/SVneo cells were examined by using the activators or inhibitors of KCa channels. Results showed that KCa channels were mainly localized on the membrane and in the cytoplasm of trophoblasts in human chorionic villi and HTR-8/SVneo cells. The proliferation and migration of HTR-8/SVneo cells were inhibited by activating KCa channels. Apoptosis of trophoblasts was promoted through activating BKCa channels but was not affected by neither activating nor inhibiting IKCa and SKCa channels. This study substantiated the abovementioned biological roles of KCa channels in trophoblast cells, which is fundamental to further research on whether dysfunction of KCa channels is involved in the pathogenesis of pregnancy-related complications.

The Evaluation of Genetic Diagnosis on High-Risk Fetal CAKUT.

Background: It is challenging to make an accurate prenatal diagnosis for congenital anomalies of the kidney and urinary tract (CAKUT) because of its pathologic diversity. This study aims to evaluate the performance of whole-exome sequencing (WES) combined with karyotype analysis and copy number variations (CNVs) in diagnosing high-risk fetal CAKUT. Methods: We conducted a retrospective study on prenatal diagnoses of CAKUT in our hospital from January 2020 to April 2021. The research studied 24 high-risk fetuses with CAKUT who were scanned by ultrasonography at the prenatal diagnosis center of Tongji Hospital affiliated to Tongji Medical College of Huazhong University of Science and Technology. The likely pathogenic gene variants were screened for the patients and their parents by multiple approaches, including karyotype analysis, CNVs and WES, and further verified with Sanger sequencing. Results: ①We detected abnormal CNVs in 20.8% (5/24) of the fetuses but only 8.3% (2/24) fetuses had abnormal karyotypes. ②Of the 15 CAKUT fetuses, positive findings (40%) were detected by WES. Of the 9 high-risk fetuses with CAKUT (negative findings in ultrasound scan but with family history), we found abnormal variants (77.8%) through WES. Conclusion: The application of CNVs and WES showed advance in prenatal diagnosis of CAKUT and the pathogenic gene variants were detectable especially for high-risk fetuses with negative ultrasound findings on CAKUT in the preliminary study. The applied strategy could be used to improve the accuracy of prenatal diagnosis for CAKUT in the future.

Immunopathogenesis of patients with COVID-19: from the perspective of immune system 'evolution' and 'revolution'.

The pandemic caused by severe acute respiratory syndrome coronavirus 2 is sweeping the world, threatening millions of lives and drastically altering our ways of living. According to current studies, failure to either activate or eliminate inflammatory responses timely and properly at certain stages could result in the progression of the disease. In other words, robust immune responses to coronavirus disease 2019 (COVID-19) are critical. However, they do not theoretically present in some special groups of people, including the young, the aged, patients with autoimmunity or cancer. Differences also do occur between men and women. Our immune system evolves to ensure delicate coordination at different stages of life. The innate immune cells mainly consisted of myeloid lineage cells, including neutrophils, basophils, eosinophils, dendritic cells and mast cells; they possess phagocytic capacity to different degrees at different stages of life. They are firstly recruited upon infection and may activate the adaptive immunity when needed. The adaptive immune cells, on the other way, are comprised mainly of lymphoid lineages. As one grows up, the adaptive immunity matures and expands its memory repertoire, accompanied by an adjustment in quantity and quality. In this review, we would summarise and analyse the immunological characteristics of these groups from the perspective of the immune system 'evolution' as well as 'revolution' that has been studied and speculated so far, which would aid the comprehensive understanding of COVID-19 and personalised-treatment strategy.

Systematic external evaluation of four preoperative risk prediction models for severe postpartum hemorrhage in patients with placenta previa: A multicenter retrospective study.

AIM: To compare and evaluate the validity of the existing risk prediction models for severe postpartum hemorrhage (SPPH) in patients with placenta previa. METHODS: We conducted a systematic literature review to collect the existing risk prediction models for SPPH in patients with placenta previa, and recruited patients with placenta previa who underwent cesarean section in Tongji Hospital (Wuhan, China) and 4 cooperative hospitals from January 2018 to June 2021. We defined SPPH as total blood loss ≥1500 mL or transfusion packed red blood cell ≥4 U. The risk of SPPH of each patient was predicted by the collected models, respectively. Then we calculated the sensitivity, specificity, coincidence rate (CCR), positive predictive value (PPV), negative predictive value (NPV) and drawn the receiver operating characteristic (ROC) curve and decision curve analysis (DCA) curve of each model. RESULTS: This external cohort contained 1172 patients of whom 284 patients (24.23%) experienced SPPH, and 4 risk prediction models were collected in this study. After evaluated by this external cohort, the area under the ROC curve (AUC), sensitivity, specificity, CCR, PPV and NPV of the four models ranged from 0.644 to 0.755, 38.38% to 86.31%, 42.75% to 86.49%, 56.23% to 74.83%, 38.68% to 47.60%, 81.15% to 87.45%, respectively. The model established by Kim JW et al. had the highest sensitivity, NPV, AUC and net benefit, the model established by Lee JY et al. had the highest specificity, CCR and PPV. CONCLUSIONS: The four prediction models showed moderate predictive performance, the discrimination indicators and benefit indicators of each model were not simultaneously ideal in this population. The prediction models should be further optimized to improve the discrimination ability and benefit, and prospective external validation studies should also be carried out before they are applied to clinical practice.

TREM-1 amplifies trophoblastic inflammation via activating NF-κB pathway during preeclampsia.

INTRODUCTION: Excessive activation of maternal systemic inflammation is one of the underlying causes of pathology during the disease course of preeclampsia (PE). The triggering receptor expressed on myeloid cells-1 (TREM-1) participates in the development and persistence of inflammation. We hypothesized that dysregulated TREM-1 may be involved in the pathogenesis of PE by promoting the secretion of trophoblastic pro-inflammatory cytokines that augment inflammation. METHODS: The localization of TREM-1 in placenta and the extravillous trophoblast cell line (TEV-1) was determined by immunohistochemical staining. The expression level of TREM-1 and pro-inflammatory cytokines in placentas were compared between normal pregnancies and PE. We used lipopolysaccharide (LPS) to simulate trophoblastic inflammation. TEV-1 cells were transfected with TREM-1 plasmid and si-TREM-1 respectively, and then were incubated with LPS. The expression levels of pro-inflammatory cytokines and key molecules featured in nuclear transcription factor-kappaB (NF-κB) pathway were detected. Transwell assays were used to detect the effects of TREM-1 on cell migration and invasion. RESULTS: TREM-1 was localized on both villous trophoblasts (VTs) and extravillous trophoblasts (EVTs). TREM-1 and pro-inflammatory cytokines were up-regulated in preeclamptic placenta. Overexpression of TREM-1 promoted the activation of NF-κB pathway and the release of pro-inflammatory factors induced by LPS, and enhanced migration and invasion of TEV-1 cells. Inhibition of TREM-1 significantly attenuated LPS-induced effects and suppressed migration and invasion. DISCUSSION: This study suggested that TREM-1 was up-regulated in PE, and may promote the production of downstream inflammatory factors by activating NF-κB pathway in trophoblastic cells, thus exerting pro-inflammatory effects in the pathogenesis of PE.

Exploring the Immunopathogenesis of Pregnancy With COVID-19 at the Vaccination Era.

Since December 2019, Wuhan, China, has experienced an outbreak of coronavirus disease (COVID-19), which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Pregnant women are deductively considered to be in immunosuppressive condition for the safety of semi-allograft fetuses, which increases the risk of being infected by the virus. In this review, we analyzed the unique immunological characteristics of pregnant women and reviewed their known outcomes at different trimesters from the perspective of underlying mechanisms that have been studied and speculated so far.

Molecular evidence suggesting the persistence of residual SARS-CoV-2 and immune responses in the placentas of pregnant patients recovered from COVID-19.

OBJECTIVES: Recent studies have shown the presence of SARS-CoV-2 in the tissues of clinically recovered patients and persistent immune symptoms in discharged patients for up to several months. Pregnant patients were shown to be a high-risk group for COVID-19. Based on these findings, we assessed SARS-CoV-2 nucleic acid and protein retention in the placentas of pregnant women who had fully recovered from COVID-19 and cytokine fluctuations in maternal and foetal tissues. MATERIALS AND METHODS: Remnant SARS-CoV-2 in the term placenta was detected using nucleic acid amplification and immunohistochemical staining of the SARS-CoV-2 protein. The infiltration of CD14+ macrophages into the placental villi was detected by immunostaining. The cytokines in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens at delivery were profiled using the Luminex assay. RESULTS: Residual SARS-CoV-2 nucleic acid and protein were detected in the term placentas of recovered pregnant women. The infiltration of CD14+ macrophages into the placental villi of the recovered pregnant women was higher than that in the controls. Furthermore, the cytokine levels in the placenta, maternal plasma, neonatal umbilical cord, cord blood and amniotic fluid specimens fluctuated significantly. CONCLUSIONS: Our study showed that SARS-CoV-2 nucleic acid (in one patient) and protein (in five patients) were present in the placentas of clinically recovered pregnant patients for more than 3 months after diagnosis. The immune responses induced by the virus may lead to prolonged and persistent symptoms in the maternal plasma, placenta, umbilical cord, cord blood and amniotic fluid.

COVID-19 and Pregnancy: A Case Study.

The 2019 novel coronavirus disease is spreading all over the world. Pregnant women and infants require particular concern, owing to the special immune conditions. A case of a pregnant woman who was exposed to SARS-CoV-2 at 34+1 weeks gestation and chose to continue pregnancy is reported. Without obvious symptoms or signs, the woman did not receive any treatment before delivery, and gave birth at 37+5 weeks to a neonate with positive immunoglobulin G for SARS-CoV-2 and negative nucleic acid tests. The mother was given anti-infection, oxytocin, and fluid rehydration treatment after delivery. Both mother and infant recovered well after a three-month follow-up. Continued expectation to deliver at term instead of preterm can decrease the potential risk of severe perinatal and infant complications and is beneficial to the development of the neonate. More studies are required to confirm the presence of vertical transmission.

A Participant-assigned Interventional Research of Precesarean Internal Iliac Artery Balloon Catheterization for Managing Intraoperative Hemorrhage of Placenta Previa and Placenta Accreta Spectrum Disorders After Cesarean Section.

Placenta accreta spectrum disorder (PASD) and placenta previa (PP) are two of the most hideous obstetric complications which are usually associated with a history of cesarean section (CS). Moreover, women with PASD, PP and/or a cesarean scarred uterus are more likely to have adverse pregnancy outcomes, including blood transfusion, hysterectomy, pelvic organs damage, postpartum hemorrhage, disseminated intravascular coagulation, multi-organ dysfunction syndrome and even maternal or fetal death. This study aimed to investigate the efficacy of precesarean internal iliac artery balloon catheterization (BC) for managing severe hemorrhage caused by PASD and PP with a history of CS. This participant-assigned interventional study was conducted in Tongji Hospital. We recruited 128 women with suspected PASD, PP and a history of CS. Women in the BC group accepted precesarean BC of bilateral internal iliac arteries before the scheduled cesarean delivery. Women in the control group underwent a conventional cesarean delivery. Intraoperative hemorrhage, transfusion volume, radiation dose, exposure time, complications and neonatal outcomes were discussed. There were significant differences in calculated blood loss (CBL) between BC group and control group (1015.0±144.9 vs. 1467.0±171.0 mL, P=0.04). Precesarean BC could reduce intraoperative red blood cell (RBC) transfusion as compared with control group (799.5±136.1 vs. 1286.0±161.6 mL, P=0.02) and lessen the rate of using blood products (57.1% vs. 76.4%, P=0.02). The incidence of hysterectomy was also lower in BC group than in control group. Postpartum outcomes showed no significant differences between the two groups, except that postoperation hospitalization was longer in BC group than in control group (6.7±0.4 vs. 5.8±0.2 days, P=0.03). Precesarean BC of internal iliac artery is an effective method for managing severe hemorrhage caused by PASD and PP with a cesarean scarred uterus, as it could reduce intraoperative blood loss, lessen intraoperative RBC transfusions and potentially decrease hysterectomies.

Integrated analysis of multiple microarray studies to identify potential pathogenic gene modules in preeclampsia.

BACKGROUND: Preeclampsia is a life-threatening hypertensive disorder during pregnancy, while underlying pathogenesis and its diagnosis are incomplete. METHODS: In this study, we utilized the Robust Rank Aggregation method to integrate 6 eligible preeclampsia microarray datasets from Gene Expression Omnibus database. We used linear regression to assess the associations between significant differentially expressed genes (DEGs) and blood pressure. Functional annotation, protein-protein interaction, Gene Set Enrichment Analysis (GSEA) and single sample GSEA were employed for investigating underlying pathogenesis in preeclampsia. RESULTS: We filtered 52 DEGs and further screened for 5 hub genes (leptin, pappalysin 2, endoglin, fms related receptor tyrosine kinase 1, tripartite motif containing 24) that were positively correlated with both systolic blood pressure and diastolic blood pressure. Receiver operating characteristic indicated that hub genes were potential biomarkers for diagnosis and prognosis in preeclampsia. GSEA for single hub gene revealed that they were all closely related to angiogenesis and estrogen response in preeclampsia. Moreover, single sample GSEA showed that the expression levels of 5 hub genes were correlated with those of immune cells in immunologic microenvironment at maternal-fetal interface. CONCLUSIONS: These findings provide new insights into underlying pathogenesis in preeclampsia; 5 hub genes were identified as biomarkers for diagnosis and prognosis in preeclampsia.

Epidural analgesia during labor and its optimal initiation time-points: A real-world study on 400 Chinese nulliparas.

ABSTRACT: Recent research has suggested that 6 cm of cervical dilation should be the threshold for the active labor phase, and it has confirmed that epidural analgesia (EA) is a safe method of pain relief during labor. However, the evidence provided for these findings comes mainly from randomized controlled clinical trials (RCTs), which suffer from the limitation of real-world generalizability.To test the generalizability of the conclusions from these previous RCTs, we conducted a prospective cohort, real-world study (RWS) on 400 Chinese term nulliparas. A total of 200 of the participants (the EA group) received EA upon request. The participants in the EA group were further subdivided as follows according to their cervical dilation when the EA administration was initiated (CDE): [EA1 group (CDE < 3 cm), EA2 group (3 cm ≤ CDE < 6 cm), and EA3 group (CDE ≥ 6 cm)]. We compared the labor duration of the EA group versus the non-EA (NEA) group, and the NEA group versus the 3 EA subgroups. We also compared delivery outcomes between the EA and NEA groups.The median total labor duration for the EA group [676 (511-923) minutes] was significantly longer than that of the NEA group [514 (373-721) minutes] (P < 0.001). The median durations of both the first- and second-stages of labor for the EA group [600 (405-855) minutes, 68 (49-97) minutes] were longer than those of the NEA group [420 (300-630) minutes, 50 (32-85) minutes] (P < .001, P < .001)]. In addition, the median total labor durations in both the EA1 [720 (548-958) minutes] and EA2 groups [688 (534-926) minutes] were longer than in the NEA group (P < .001 and P < .001, respectively), and the first- and second-stage labor durations of these subgroups were similar to their total labor durations. A Cox regression analysis showed that EA was associated with longer first-stage labor [hazard ratio (HR) 0.55, 95% confidence interval (CI) 0.42-0.71, P < .001] and longer second-stage labor (HR 0.66, 95% CI 0.51-0.85, P = .001). The delivery modes and neonatal outcomes between the EA and NEA groups were not statistically different, however.Our findings suggest that EA administered before a cervical dilation of 6 cm may be associated with longer total, first-, and second-stage labor durations compared with no EA, while later EA administration is not. In addition, though EA prolongs labor duration, it does not impact delivery outcomes. These results confirm the significance of a 6 cm cervical dilation threshold in real-world labor settings.

Developing and Validating Nomogram to Predict Severe Postpartum Hemorrhage in Women With Placenta Previa Undergoing Cesarean Delivery: A Multicenter Retrospective Case-Control Study.

OBJECTIVE: Developing and validating nomogram to predict severe postpartum hemorrhage (SPPH) in women with placenta previa (PP) undergoing cesarean delivery. METHODS: We conducted a multicenter retrospective case-control study in five hospitals. In this study, 865 patients from January, 2018 to June, 2020 were enrolled in the development cohort, and 307 patients from July, 2020 to June, 2021 were enrolled in the validation cohort. Independent risk factors for SPPH were obtained by using the multivariate logistic regression, and preoperative nomogram and intraoperative nomogram were developed, respectively. We compared the discrimination, calibration, and net benefit of the two nomograms in the development cohort and validation cohort. Then, we tested whether the intraoperative nomogram could be used before operation. RESULTS: There were 204 patients (23.58%) in development cohort and 80 patients (26.06%) in validation cohort experienced SPPH. In development cohort, the areas under the receiver operating characteristic (ROC) curve (AUC) of the preoperative nomogram and intraoperative nomogram were 0.831 (95% CI, 0.804, 0.855) and 0.880 (95% CI, 0.854, 0.905), respectively. In validation cohort, the AUC of the preoperative nomogram and intraoperative nomogram were 0.825 (95% CI, 0.772, 0.877) and 0.853 (95% CI, 0.808, 0.898), respectively. In the validation cohort, the AUC was 0.839 (95% CI, 0.789, 0.888) when the intraoperative nomogram was used before operation. CONCLUSION: We developed the preoperative nomogram and intraoperative nomogram to predict the risk of SPPH in women with PP undergoing cesarean delivery. By comparing the discrimination, calibration, and net benefit of the two nomograms in the development cohort and validation cohort, we think that the intraoperative nomogram performed better. Moreover, application of the intraoperative nomogram before operation can still achieve good prediction effect, which can be improved if the severity of placenta accreta spectrum (PAS) can be accurately distinguished preoperatively. We expect to conduct further prospective external validation studies on the intraoperative nomogram to evaluate its application value.