Face presentation at term: incidence, risk factors and influence on maternal and neonatal outcomes.

OBJECTIVES: The incidence, diagnosis, management and outcome of face presentation at term were analysed. METHODS: A retrospective, gestational age-matched case-control study including 27 singletons with face presentation at term was conducted between April 2006 and February 2021. For each case, four women who had the same gestational age and delivered in the same month with vertex position and singletons were selected as the controls (control group, n = 108). Conditional logistic regression was used to assess the risk factors of face presentation. The maternal and neonatal outcomes of the face presentation group were followed up. RESULTS: The incidence of face presentation at term was 0.14‰. After conditional logistic regression, the two factors associated with face presentation were high parity (adjusted odds ratio [aOR] 2.76, 95% CI 1.19-6.39)] and amniotic fluid index > 18 cm (aOR 2.60, 95% CI 1.08-6.27). Among the 27 cases, the diagnosis was made before the onset of labor, during the latent phase of labor, during the active phase of labor, and during the cesarean section in 3.7% (1/27), 40.7% (11/27), 11.1% (3/27) and 44.4% (12/27) of cases, respectively. In one case of cervical dilation with a diameter of 5 cm, we innovatively used a vaginal speculum for rapid diagnosis of face presentation. The rate of cesarean section and postpartum haemorrhage ≥ 500 ml in the face presentation group was higher than that of the control group (88.9% vs. 13.9%, P < 0.001, and 14.8% vs. 2.8%, P = 0.024), but the Apgar scores were similar in both sets of newborns. Among the 27 cases of face presentation, there were three cases of adverse maternal and neonatal outcomes, including one case of neonatal right brachial plexus injury and two cases of severe laceration of the lower segment of the uterus with postpartum haemorrhage ≥ 1000 ml. CONCLUSIONS: Face presentation was rare. Early diagnosis is difficult, and thus easily neglected. High parity and amniotic fluid index > 18 cm are risk factors for face presentation. An early diagnosis and proper management of face presentation could lead to good maternal and neonatal outcomes.

Targeting Mitochondrial Oxidative Stress to Protect Against Preterm Birth and Fetal Brain Injury via Nrf2 Induction.

Aims: Preterm birth (PTB), recognized as delivery before 37 weeks of gestation, is a multifactorial syndrome characterizing as the main cause of neonatal mortality. Reactive oxygen species (ROS) have been identified as proinflammatory factors to cause placental inflammation, thereby resulting in several pregnancy outcomes. To date, limited knowledge regarding the underlying mechanisms of ROS-induced PTB has been reported. In this study, we aimed to investigate the role of oxidative stress in PTB and the protective effects of mitochondria-targeted antioxidant MitoTEMPO (MT) on preterm labor and offspring mice. Results: In this study, we found that preterm placentas had abnormal mitochondrial function, oxidative stress, and inflammatory response. In the lipopolysaccharide (LPS)-induced PTB mouse model, MT inhibited PTB by ameliorating maternal oxidative stress and inflammation, especially in placentas, thus improving placental function to maintain pregnancy. Antenatal administration of MT prevented LPS-induced fetal brain damage in acute phase and improved long-term neurodevelopmental impairments. Furthermore, our in vitro investigations validated that MT retarded the ROS accumulation and inflammatory response in LPS-stimulated trophoblast cells by promoting Kelch-like ECH-associated protein 1 (Keap1) degradation and subsequently activating nuclear factor erythroid 2-related factor 2 (Nrf2). By inhibiting Nrf2 activation, we discovered that the anti-inflammation and protective characteristics of MT were Nrf2/ARE pathway dependent. Innovation and Conclusion: MT inhibited PTB and fetal brain injury by inhibiting maternal inflammation and improving placental function through Keap1/Nrf2/antioxidant response element signaling pathway. Our findings provide a novel therapeutic strategy for PTB.

Immune dysfunction mediated by the competitive endogenous RNA network in fetal side placental tissue of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS), a common endocrine and metabolic disorder affecting women in their reproductive years. Emerging evidence suggests that the maternal-fetal immune system is crucial for proper pregnancy. However, whether immune function is altered at the end of pregnancy in PCOS women and the underlying molecular mechanisms is currently unexplored. Herein, the basic maternal immune system was investigated (n = 136 in the control group; n = 103 in the PCOS group), and whole-transcriptome sequencing was carried out to quantify the mRNAs, miRNAs, and lncRNAs expression levels in fetal side placental tissue of women with PCOS. GO, KEGG, and GSEA analysis were employed for functional enrichment analysis. The process of identifying hub genes was conducted utilizing the protein-protein interaction network. CIBERSORT and Connectivity Map were deployed to determine immune cell infiltration and predict potential drugs, respectively. A network of mRNA-miRNA-lncRNA was constructed and then validated by qRT-PCR. First, red blood cell count, neutrophil count, lymphocyte count, hypersensitive C-reactive protein, and procalcitonin were significantly elevated, while placental growth factor was hindered in PCOS women. We identified 308 DEmRNAs, 77 DEmiRNAs, and 332 DElncRNAs in PCOS samples. Functional enrichment analysis revealed that there were significant changes observed in terms of the immune system, especially the chemokine pathway. Eight genes, including FOS, JUN, EGR1, CXCL10, CXCR1, CXCR2, CXCL11, and CXCL8, were considered as hub genes. Furthermore, the degree of infiltration of neutrophils was dramatically decreased in PCOS tissues. In total, 57 ceRNA events were finally obtained, and immune-related ceRNA networks were validated. Some potential drug candidates, such as enalapril and RS-100329, could have a function in PCOS therapy. This study represents the inaugural attempt to evaluate the immune system at the end of pregnancy and placental ceRNA networks in PCOS, indicating alterations in the chemokine pathway, which may impact fetal and placental growth, and provides new therapy targets.

Insight into the potential mechanism of bicarbonate assimilation promoted by mixotrophic in CO2 absorption and microalgae conversion system.

CO2 absorption-microalgae conversion (CAMC) system is a promising carbon capture and utilization technology. However, the use of HCO3- as a carbon source often led to a slower growth rate of microalgae, which also limited the application of CAMC system. In this study, the assimilation efficiency of HCO3- in CAMC system was improved through mixotrophic, and the potential mechanism was investigated. The HCO3- assimilation efficiency and biomass under mixotrophic were 34.79% and 31.76% higher than that of control. Mixotrophic increased chlorophyll and phycocyanin content, which were beneficial to capture more light energy. The content of ATP and NADPH reached 566.86 µmol/gprot and 672.86 nmol/mgprot, which increased by 31.83% and 27.67% compared to autotrophic. The activity of carbonic anhydrase and Rubisco increased by 18.52% and 22.08%, respectively. Transcriptome showed that genes related to photosynthetic and respiratory electron transport were up-regulated. The synergy of photophosphorylation and oxidative phosphorylation greatly improved energy metabolism efficiency, thus accelerating the assimilation of HCO3-. These results revealed a potential mechanism of promoting the HCO3- assimilation under mixotrophic, it also provided a guidance for using CAMC system to serve carbon neutrality.

Maternal Height Is an Independent Risk of Adverse Outcomes in Women with Gestational Diabetes Mellitus.

INTRODUCTION: Maternal height has been shown to be associated with adverse outcomes in women with gestational diabetes mellitus (GDM). The aim of this study is to evaluate the association between maternal height and adverse outcomes stratified for gestational weight gain (GWG) and pre-pregnancy body mass index (BMI) in women with GDM. METHODS: We conducted a retrospective study that included 2048 women diagnosed with GDM during 24-28 gestational weeks from July 1, 2017, to June 30, 2018, in Zhejiang Province, China. Demographic data, maternal characteristics and pregnancy complications were extracted from medical records. Maternal height was divided into three categories by tertiles. Chi-square was used to evaluate categorical data while one-way ANOVA was utilized to analyze continuous variables. The relationship between maternal height and adverse outcomes was examined using logistic regression. RESULTS: We found that shorter women had higher rates of low birth weight (LBW) (p = 0.003) and primary cesarean section (primary CS) (p < 0.001) while taller women had higher rates of abnormal neonatal ponderal index (p < 0.001), postpartum hemorrhage (p = 0.044) and macrosomia (p < 0.001). In taller women who had excess GWG, maternal height was positively associated with the risk of macrosomia (aOR 1.97, 95% CI 0.95-4.10). In shorter women who had inadequate GWG, maternal height was significantly associated with LBW (aOR 2.20, 95% CI 1.13-4.29) and primary CS (aOR 2.08, 95% CI 1.38-3.12). Maternal height was a protective factor of postpartum hemorrhage (aOR 0.15, 95% CI 0.03-0.72) in shorter women with excess GWG. In women with normal pre-pregnancy BMI, maternal height was positively associated with LBW (aOR 2.00, 95% CI 1.15-3.49) and primary CS (aOR 1.71, 95% CI 1.28-2.28) in shorter women while it was negatively associated with the risk of abnormal neonatal ponderal index in both shorter and taller women compared to average height women (aOR 0.71, 95% CI 0.55-0.92; aOR 0.66, 95% CI 0.51-0.85). CONCLUSION: The association between maternal height and adverse pregnancy outcomes varies with pre-pregnancy BMI and GWG in GDM women. Taking maternal height, pre-pregnancy BMI and GWG into account and using personalized prenatal management may reduce the risk of adverse pregnancy outcomes in GDM.

Development and validation of a nomogram for individualized prediction of spontaneous extremely preterm birth at < 28 weeks in twin pregnancy: a retrospective cohort study.

PURPOSE: To develop a nomogram to predict spontaneous preterm birth at < 28 weeks in pregnant women with twin pregnancies. METHODS: We retrospectively studied the medical records of twin-pregnancy women with asymptomatic cervical dilation or cervical shortening between December 2015 to February 2022 in two hospitals. Data from one center was used to develop the model and data from the other was used to evaluate the model. RESULTS: A total of 270 twin pregnancies were enrolled in the study. We incorporated 4 items (cervical length, cervical dilation, C-reactive protein and the use of cerclage) to build the 28-week nomogram with satisfactory discrimination and calibration when applied to the validation sets. The C index for the 28-week nomogram in the development and external cohort was 0.88 (95% CI, 0.84-0.93) and 0.89 (95% CI, 0.80-0.98), respectively. The nomogram reached a sensitivity of 70.70%, specificity of 97.10%, positive predicted value of 95.61% and negative predicted value of 78.77%. Moreover, the decision curve analysis indicated that the nomogram showed positive clinical benefit. CONCLUSION: We developed and validated a nomogram with good performance in predicting individual risk of spontaneous preterm birth at < 28 in twin pregnancy.

Efficacy of intermittent versus daily vitamin D supplementation on improving circulating 25(OH)D concentration: a Bayesian network meta-analysis of randomized controlled trials.

Background: Vitamin D deficiency is a widespread issue globally, resulting in increased use of vitamin D supplements. However, it is unclear whether intermittent (weekly or monthly) vitamin D supplementation is as effective as daily supplementation in improving circulating 25-hydroxyvitamin D [25(OH)D] levels. Methods: Three databases including Medline, EMBASE, and the Cochrane Library were systematically searched up to 10 November 2020. The risk of bias was evaluated according to Cochrane Collaboration's tool for rating methodological quality assessment. Direct and indirect comparisons between interventions and controls were performed by a Bayesian network meta-analysis (NMA), where the mean difference (MD) and its 95% confidence interval (CI) were used to indicate the efficacy. Results: This NMA analysis included 116 RCTs with a total of 11,376 participants. Generally, we observed that 25(OH)D concentrations were significantly elevated regardless of vitamin D supplementation frequency. Although the findings of SUCRA indicated that daily vitamin D supplementation had a higher rank value than intermittent supplementation when the supplement dosage was similar, no statistically significant pooled mean differences of 25(OH)D concentration were noted between the daily supplementation group and intermittent supplementation group. Additionally, weekly supplementation with a total of 600,000 IU vitamin D supplementation during 3 months had the best efficacy in elevating 25(OH)D concentration (pooled MD = 63 nmol/L, 95%CI: 49-77). To achieve optimal 25(OH)D concentration (>75 nmol/L), we recommend 60,000 IU vitamin D supplementation monthly (~2,000 IU/day). Conclusion: The efficacy of intermittent vitamin D supplementation was similar to daily supplementation. Coupled with its convenience, the frequency and dosage of intermittent vitamin D supplements were recommended to reach the optimal 25(OH)D level.Systematic review registration:https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=257257, PROSPERO CRD42021257257.

The heterogeneous associations between gestational weight gain and adverse pregnancy outcomes in gestational diabetes mellitus according to abnormal glucose metabolism.

OBJECTIVES: The gestational weight gain (GWG) and hyperglycemia are two key factors affecting adverse pregnancy outcomes among women with gestational diabetes mellitus (GDM). We aimed to investigate the combinatorial effect of abnormal glucose metabolism and GWG on adverse outcomes in GDM. METHODS: This retrospective cohort study included 2611 pregnant women with GDM in Women's Hospital School of Medicine Zhejiang University. Bases on the OGTT glucose levels, we categorized the GDM cohort into three subgroups: impaired fasting glucose (IFG) group, impaired glucose tolerance (IGT) group, and combined impaired glucose (IFG&IGT) group. RESULTS: Among pregnant women with IGT, insufficient GWG (IGWG) was an independent protective factor for pregnancy-induced hypertension syndrome (PIH) (aOR 0.55, 95% CI 0.32-0.95), macrosomia (0.38, 0.19-0.74) and large for gestational age (0.45, 0.32-0.62), as well as an independent risk factor for low birth weight infants (2.29, 1.24-4.22) and small for gestational age (1.94, 1.17-3.19); and excessive GWG (EGWG) was related to increased risks of PIH (1.68, 1.12-2.52), preterm delivery (1.82, 1.28-2.58), postpartum hemorrhage (1.85, 1.05-3.28), cesarean delivery (1.84, 1.38-2.46) and low body weight infants (2.36, 1.33-4.20). Moreover, EGWG was positively associated with PIH (3.27, 1.09-9.80) in the IFG group. But there were no significant associations between either IGWG or EGWG and any pregnancy outcomes in women with combined IFG&IGT. CONCLUSIONS: The relationships between GWG and adverse outcomes were modified by abnormal glucose metabolism in women with GDM. Our results suggest that more specific GWG recommendations according to their metabolic state are needed for GDM.

Differences in prenatal diagnosis rate of congenital anomalies associated with singletons and multiple births: An observational study of more than 1.9 million births in Zhejiang Province, eastern China, during 2012-2018.

OBJECTIVE: To characterize differences in the prenatal detection of congenital anomalies (CAs) associated with singleton and multiple births. METHODS: This observational study covered all births registered in the CA surveillance system in Zhejiang Province of China during 2012-2018. Differences in the incidence and characteristics between singletons and multiple births with CAs were tested. Multivariate logistic regression models were performed to explore the associations of prenatal detection rate of CAs with multiple births. RESULTS: Totals of 49 872 singletons and 3324 multiple births with CAs were analyzed. The mean incidences of CA for single and multiple births were 27.12 and 54.42 per 1000 births, respectively. After adjustment for covariates, CAs associated with multiple births were less likely to be diagnosed prenatally (adjusted odds ratio [OR] 0.38, 95% confidence interval [CI] 0.34-0.43), as were congenital heart defects, congenital hydrocephalus, cleft lip with cleft palate, cleft lip without cleft palate, limb reduction defects, congenital diaphragmatic hernia, trisomy 21 syndrome, congenital malformation of the urinary system, and other chromosomal malformation, compared with singletons with CAs. CONCLUSION: Multiple birth is associated with a significantly higher risk of CA, but a significantly lower prenatal diagnosis rate. Therefore, the healthcare of women with multiple pregnancy and their fetuses should be strengthened.

Hypoxia-inducible factor stabilisation-related lncRNAs in retinopathy of prematurity.

Long non-coding RNAs (lncRNAs) play an important role in the response to many diseases. The previous study reported the transcriptomes of mice that were cured of oxygen-induced retinopathy (OIR, retinopathy of prematurity (ROP) model) by hypoxia-inducible factor (HIF) stabilisation via HIF prolyl hydroxylase inhibition using the isoquinolone Roxadustat or the 2-oxoglutarateanalog dimethyloxalylglycine (DMOG). However, there is little understanding of how those genes are regulated. In the present study, 6918 known lncRNAs and 3654 novel lncRNAs were obtained, and a series of differentially expressed lncRNAs (DELncRNAs) were also identified. By cis- and trans-regulation analyses, the target genes of DELncRNAs were predicted. Functional analysis demonstrated that multiple genes were involved in the MAPK signalling pathway, adipocytokine signalling pathway was regulated by the DELncRNAs. By HIF-pathway analysis, two lncRNAs Gm12758 and Gm15283 were found that can regulate the HIF-pathway by targeting the Vegfa, Pgk1, Pfkl, Eno1, Eno1b and Aldoa genes. In conclusion, the present study provided a series of lncRNAs for further understanding and protecting the extremely premature infant from oxygen toxicity.

What is already known on this subject? Roxadustat can prevent oxygen-induced retinopathy (OIR) by two pathways: direct retinal hypoxia-inducible factor (HIF) stabilisation and induction of aerobic glycolysis or indirect hepatic HIF-1 stabilisation and increased serum angiokines. However, underlying the long non-coding RNAs (lncRNAs) that may regulate the HIF stabilisation-related genes have not been investigated thoroughly.What do the results of this study add? Six thousand nine hundred and eighteen known lncRNAs and 3654 novel lncRNAs were identified. GO and KEGG enrichment analysis showed that the MAPK signalling pathway and adipocytokine signalling pathway were regulated by the differentially expressed lncRNAs (DELncRNAs). Two lncRNAs Gm12758 and Gm15283 were found that may regulate the HIF-pathway by targeting the Vegfa, Pgk1, Pfkl, Eno1, Eno1b and Aldoa genes.What are the implications of these findings for clinical practice and/or further research? It provides a further rationale for protecting severe premature infants from oxygen poisoning.

The association between maternal HbA1c and adverse outcomes in gestational diabetes.

Background: The role of HbA1c in women with gestational diabetes mellitus (GDM) is still unclear, particularly in the Asian population. Aim: To investigate the association between HbA1c levels and adverse outcomes considering maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) in women with GDM. Method: A retrospective study included 2048 women with GDM and singleton live births. Using logistic regression, the associations between HbA1c and adverse pregnancy outcomes were assessed. Result: Compared to women with HbA1c ≤ 5.0%, HbA1c was significantly associated with macrosomia (aOR 2.63,95%CI1.61,4.31), pregnancy-induced hypertension (PIH, aOR 2.56,95%CI1.57,4.19), preterm birth (aOR 1.64,95%CI 1.05,2.55), and primary Cesarean section (primary C-section, aOR1.49,95%CI1.09,2.03) in GDM women with HbA1c ≥5.5% while significantly associated with PIH (aOR 1.91,95%CI1.24,2.94) in women with HbA1c 5.1-5.4%. The associations between HbA1c and adverse outcomes varied with maternal age, pre-pregnancy BMI, and GWG. In women aged ≤29 years, there's significant association between HbA1c and primary C-section when HbA1c was 5.1-5.4% and ≥5.5%. In women aged 29-34 years and HbA1c ≥5.5%, HbA1c was significantly associated with macrosomia. In women aged ≥35 years, there's significant association between HbA1c and preterm birth when HbA1c was 5.1-5.4% and macrosomia and PIH when HbA1c ≥5.5%. In pre-pregnant normal-weight women, HbA1c was significantly associated with macrosomia, preterm birth, primary C-section, and PIH when HbA1c ≥5.5% while HbA1c was significantly associated with PIH when HbA1c was 5.1-5.4% . In pre-pregnant underweight women with HbA1c 5.1-5.4%, HbA1c was significantly associated with primary C-section. HbA1c was significantly associated with macrosomia among women with inadequate GWG or excess GWG and HbA1c≥5.5%. In women with adequate GWG, there's significant association between HbA1c and PIH when HbA1c was 5.1-5.4% and ≥5.5% . Conclusion: Conclusively, HbA1c at the time of diagnosis is significantly associated with macrosomia, preterm birth, PIH, and primary C-section in Chinese women with GDM.

Association between maternal second-trimester stress and adverse pregnancy outcomes according to pre-pregnancy body mass index and gestational weight gain.

Objective: To investigate the impact of maternal second-trimester stress on pregnancy outcomes according to pre-pregnancy body mass index (BMI) and gestational weight gain (GWG). Methods: We did a prospective study in Women's Hospital, School of Medicine, Zhejiang University and included 960 pregnant women in our final analysis. Obstetric characteristics and the incidence of adverse pregnancy outcomes were examined in stressed and non-stressed women. The associations between maternal prenatal stress with adverse pregnancy outcomes were analyzed by logistic regression. Results: The incidence of premature rupture of membranes (PROM) was significantly higher in stressed pregnant women than non-stressed pregnant women (p = 0.035), whereas no significant difference in the incidence rates of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), primary cesarean delivery, preterm birth, macrosomia, low birth weight, fetal stress, admission into neonatal intensive care unit (NICU) or neonatal jaundice was found between two groups. Maternal second-trimester stress was an independent risk factor for the development of PROM (aOR = 1.468, 95% CI 1.037-2.079). Moreover, maternal second-trimester stress was significantly associated with PROM in pregnant women with normal pre-pregnancy BMI (aOR = 1.587, 95% CI 1.068-2.357) while no association was observed in either underweight or overweight and obese pregnant women. Meanwhile, no difference was found in the odds of PROM with maternal second-trimester stress in all GWG subgroups. Conclusion: Maternal second-trimester stress is associated with a higher risk of PROM and it is significant in pregnant women with normal pre-pregnancy BMI. Therefore, interventions to reduce stress during second-trimester of pregnancy might be essential for lowering the prevalence of PROM in pregnant women with normal pre-pregnancy BMI.

An online derivatization strategy targeting carbon-carbon double bonds by laser-ablation carbon fiber ionization mass spectrometry imaging: Unraveling the spatial characteristic in mountain-cultivated ginseng and garden-cultivated ginseng with different ages.

Serving as a world-renowned tonic, ginseng contains various types of bioactive metabolites. The comprehensive profiling of these metabolites may help explore the nutritional value of ginseng. Due to high variety in chemical structures, simultaneous monitoring of these metabolites remains a challenge. Herein, a high-throughput and high-selectivity online derivatization mass spectrometry imaging strategy targeting CC was developed. As a widely existed chemical group, CC acts like a bridge connecting different kinds of metabolites. [d0]/[d10]-Bis(pyridine) iodine tetrafluoroboride reagent was chosen for the derivatization of CC, the detection sensitivity of which increased about 3 magnitudes after derivatization. Assisted by laser ablation carbon fiber ionization mass spectrometry, the spatial distribution of bioactive metabolites in mountain-cultivated and garden-cultivated ginseng were visualized. The correlation heatmap results revealed that metabolites in mountain-cultivated ginseng hold higher correlation than those in garden-cultivated ginseng. The proposed method showed potential in providing comprehensive information on the nutrient content of foods.

Independent and Joint Associations of Age, Pre-pregnancy BMI, and Gestational Weight Gain with Adverse Pregnancy Outcomes in Gestational Diabetes Mellitus.

INTRODUCTION: To explore the independent and combined effects of maternal age, pre-pregnancy body mass index (BMI), and gestational weight gain (GWG) on pregnancy outcomes in gestational diabetes mellitus (GDM). METHODS: A total of 2171 pregnant women with GDM attending the Women's Hospital of Zhejiang University were retrospectively included. We compared pregnancy outcomes in different age, BMI, and GWG groups after adjusting for confounding variables. RESULTS: Results showed that (1) advanced maternal age increased the risk of primary Cesarean section and hypertensive disorders of pregnancy (HDP) in normal weight; (2) independent of age and GWG, high BMI significantly increased the risk of HDP, primary Cesarean section, and macrosomia; (3) Women with excessive GWG had a higher risk of primary Cesarean section and HDP, even they were ≤ 29 years old or normal weight, respectively; (4) Pregnant women with inadequate GWG had a higher risk of preterm birth and a lower risk of macrosomia in both the 30-34 age group and the normal weight group; (5) BMI was a better predictor of HDP than GWG among women younger than 30. CONCLUSIONS: Among the GDM population, women over the age of 35, overweight and obese, or with an excessive GWG were more prone to adverse pregnancy outcomes, especially primary Cesarean delivery and HDP.

Trends in the prevalence, prenatal diagnosis, and outcomes of births with chromosomal abnormalities: a hospital-based study in Zhejiang Province, China during 2014-2020.

BACKGROUND: To investigate the prevalence and prenatal diagnosis rate of chromosomal abnormalities (CA) in Zhejiang Province, China. METHODS: We estimated the annual changes in the detected prevalence of CA and prenatal diagnosis rate among 681,590 births in Zhejiang Province, China, between 2014 and 2020. Data were derived from the provincial birth defects surveillance system, which represents 30% of annual births in Zhejiang Province. The effect of maternal age was also evaluated. RESULTS: The detected prevalence of sex chromosomal abnormalities (1.70-7.30 per 10,000 births, Ptrend < 0.001) and microdeletion and microduplication (0.30-6.81 per 10,000 births, Ptrend < 0.001) gradually increased, contributing to an upward trend in overall CA (12.09-39.22 per 10,000 births). The diagnosis rate before 22 gestational weeks constantly increased from 20.8 to 70.1% for trisomy 21 (Ptrend = 0.003). The prevalence rate ratio for maternal age of ≥ 35 years was higher than that for maternal age of 25-29 years for trisomy 21 (5.40, 95% confidence interval [CI] 4.59-6.35) and sex chromosomal abnormalities (3.28, 95% CI 2.48-4.33). CONCLUSIONS: The rising prevalence of CA in China may be attributable to the elevated maternal age and the innovation of prenatal diagnosis tools, Thus, studies should pay attention to the rare CA that were previously ignored, and select rational screening tools.

Epidemiology of birth defects in teenage pregnancies: Based on provincial surveillance system in eastern China.

Background: Healthcare for adolescents and birth defects (BD) prevention are highlighted public health issues. The epidemiology of birth defects in teenage pregnancies has not been studied extensively. Objectives: To investigate the prevalence trend and spectrum of BDs among teenage mothers. Methods: This observational study covered all births registered in the BD surveillance system in Zhejiang Province, China, during 2012-2018. The annual change in the prevalence of BDs among adolescent mothers was estimated. Crude relative ratios using the BD categories in teenage pregnancies were calculated and compared with those in women aged 25-29 years. Results: Overall, 54,571 BD cases among 1,910,977 births were included in this study, resulting in an overall prevalence of 234.64 to 409.07 per 10,000 births from 2012 to 2018 (P trend < 0.001) in total population. The prevalence of birth defects in teenage pregnancies increased from 247.19 to 387.73 per 10,000 births in 2012-2018 (P trend = 0.024). The risks of neural tube defects (relative risk [RR] = 3.15, 95% confidence interval [CI] 2.56, 3.87), gastroschisis (RR = 7.02, 95% CI 5.09, 9.69), and multiple birth defects (RR=1.27, 95% CI 1.07, 1.52) were higher in teenage pregnancies than those in women aged 25-29 years. Conclusions: We found a distinctive spectrum of BDs, with higher proportions of fatal or multiple anomalies in infants born to teenage mothers than in those born to adults aged 25-29 years. These results emphasize the importance of providing adolescents with better access to reproductive and prenatal care.

Chemerin-Induced Down-Regulation of Placenta-Derived Exosomal miR-140-3p and miR-574-3p Promotes Umbilical Vein Endothelial Cells Proliferation, Migration, and Tube Formation in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) leads to poor pregnancy outcomes and fetoplacental endothelial dysfunction; however, the underlying mechanisms remain unknown. This study aimed to investigate the effect of placenta-derived exosomal miRNAs on fetoplacental endothelial dysfunction in GDM, as well as to further explore the role of chemerin to this end. Placenta-derived exosomal miR-140-3p and miR-574-3p expression (next-generation sequencing, quantitative real-time PCR), its interactions with cell function (Cell Counting Kit-8, Transwell, tube formation assay), chemerin interactions (Western blotting), and placental inflammation (immunofluorescence staining, enzyme-linked immunosorbent assay) were investigated. Placenta-derived exosomal miR-140-3p and miR-574-3p were downregulated in GDM. Additionally, miR-140-3p and miR-574-3p inhibited the proliferation, migration, and tube formation ability of umbilical vein endothelial cells by targeting vascular endothelial growth factor. Interestingly, miR-140-3p and miR-574-3p expression levels were negatively correlated with chemerin, which induced placental inflammation through the recruitment of macrophage cells and release of IL-18 and IL-1ß. These findings indicate that chemerin reduces placenta-derived exosomal miR-140-3p and miR-574-3p levels by inducing placental inflammation, thereby promoting the proliferation, migration, and tube formation of umbilical vein endothelial cells in GDM, providing a novel perspective on the underlying pathogenesis and therapeutic targets for GDM and its offspring complications.

[Clinical Comparative Analysis of Early-Onset Preeclampsia Combined with HELLP Syndrome].

Objective: To explore the clinical characteristics of early-onset preeclampsia (PE) combined with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome, and to improve the capacity for early diagnosis and treatment. Methods: Pregnant women who received treatment at Women's Hospital, School of Medicine, Zhejiang University between March 2014 and October 2021 were retrospectively enrolled. There were two patient groups, the HELLP group consisting of 70 cases of early-onset PE combined with HELLP syndrome and the control group consisting of 140 cases of early-onset PE without HELLP syndrome. Patients in the two groups were matched by age. The general clinical data, characteristics of pathogenesis, and laboratory findings of the patients were collected and the perinatal outcomes of the two groups were compared and analyzed. Results: 1) There was no significant difference in gravidity, pre-delivery body mass index, years from the last delivery, and family history of diabetes mellitus and hypertension between the two groups. 2) The highest systolic blood pressure, highest diastolic blood pressure during the pregnancy, and the postpartum hospital length-of-stay ( P<0.001) in the HELLP group were higher than those in the control group. The gestational age at the time of the diagnosis of PE ( P=0.001) and the gestational age at delivery ( P<0.001) in the HELLP group were significantly earlier than those in the control group. The difference between the gestational age at the time of blood pressure elevation and that at the time of delivery ( P<0.001), and the gestational age difference between the diagnosis of early-onset PE and delivery ( P=0.027) were lower than those in the control group. The incidences of eclampsia in the HELLP group, pleural effusion, and ascites were higher than those of the control group. 3) Neonates in the HELLP group had a higher probability of being admitted to NICU and developing cyanotic/pale asphyxia ( P<0.001). 4) Before the termination of pregnancy, the HELLP group had higher levels of alanine aminotransferase, aspartate aminotransferase, total bilirubin, creatinine, urea, random glucose, lactate dehydrogenase, activated partial thromboplastin time, and the last 24-hour urine protein quantification than those of the control group (all P<0.05), while the platelet (PLT) counts were significantly lower than those of the control group ( P<0.001). 5) There was a significant correlation between PLT counts in the second trimester and the onset of HELLP syndrome ( P=0.006), with the area under the ROC curve reaching 0.746 (95% CI: 0.596-0.897). Conclusion: In comparison with early-onset PE patients without HELLP syndrome, patients with early-onset PE combined with HELLP syndrome are diagnosed for PE at an earlier gestational age, have higher blood pressure, are more prone to serious pregnancy complications, and have longer postpartum hospital length-of-stay and worse neonatal outcomes. Close monitoring of PLT counts of early-onset PE patients in the second trimester may help predict subsequent HELLP syndrome.

A nomogram to predict extremely preterm birth in women with singleton pregnancies undergoing cervical cerclage.

Objective: To develop a nomogram to predict preterm birth before 28 weeks in pregnant women undergoing cervical cerclage. Study design: We retrospectively studied the medical records on pregnant women who underwent cervical cerclage in January 2016 to September 2020. We developed the model from a development cohort in Women's Hospital, Zhejiang university, School of medicine, which randomly divided by 7:3 into training cohort for nomogram development, and internal validation cohort to confirm the model's performance. We then tested the nomogram in an external validation cohort over a similar period. The Harrell's C-index, calibration curve, decision curve analyses (DCA) were performed to assess the model. Results: 528 patients formed the development cohort, and 97 patients formed the external validation cohort. The model initially incorporated 10 baseline variables, while 5 variables were estimated in the nomogram at last: history of prior second-trimester loss, use of in-vitro fertilization (IVF), cervical dilation at cerclage, C-reactive protein (CRP) and platelet-lymphocyte ratio (PLR). The nomogram achieved good concordance indexes of 0.82(95%CI 0.77-0.88), 0.80(95%CI 0.72-0.88) and 0.79 (95%CI 0.68-0.90) in the training, internal and external validation cohort, respectively. And the nomogram had well-fitted calibration curves. Decision curve analysis demonstrated that the nomogram was clinically useful. Conclusions: The well-performed nomogram graphically represents the risk factors and a pre-operative predicted model in predicting the risk of preterm birth at <28 weeks in singleton pregnant women undergoing cervical cerclage. The model can provide a useful guide for clinicians and patients in making appropriate clinical decisions.

Investigation of the pharmacological effect and mechanism of mountain-cultivated ginseng and garden ginseng in cardiovascular diseases based on network pharmacology and zebrafish experiments.

Ginseng (Panax ginseng C.A. Mey) is a kind of perennial herb of the Panax genus in the Araliaceae family. The secondary metabolites of mountain-cultivated ginseng (MCG) and garden ginseng (GG) vary greatly due to their different growth environments. To date, the differences in their pharmacological effects on cardiovascular diseases (CVDs) and their clinical applications remain unclear. To distinguish between the components of MCG and GG, ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) was performed. Next, the relationship between the expression of metabolites and the categories of the sample were analyzed using supervised partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis. A network-based pharmacology approach was developed and applied to determine the underlying mechanism of different metabolites in CVD. In the present study, the role of MCG and GG in angiogenesis and their protective effects on damaged blood vessels in a vascular injury model of zebrafish were investigated. Using UPLC-Q-TOF/MS, 11 different metabolites between MCG and GG were identified. In addition, 149 common target genes associated with the metabolites and CVD were obtained; these targets were related to tumor protein P53, proto-oncogene tyrosine-protein kinase Src, human ubiquitin-52 amino acid fusion protein, ubiquitin-40S ribosomal protein S27a, polyubiquitin B, signal transducer and activator of transcription 3, isocitrate dehydrogenase 1, vascular endothelial growth factor A, glycose synthase kinase-3B, and coagulation factor II and were associated with the regulation of the phosphoinositide 3-kinase-Akt signaling pathway, the tumor necrosis factor signaling pathway, and the hypoxia-inducible factor-1 (HIF-1) signaling pathway, which play important roles in the curative effect in CVD treatment. Both types of ginseng can promote the growth of the subintestinal vessel plexus and protect injured intersegmental vessels through the HIF-1α/vascular endothelial growth factor signaling pathway in a dose-dependent manner. In addition, MCG has a stronger impact than GG. This is the first time metabolomics and network pharmacology methods were combined to study the difference between MCG and GG on CVDs, which provides a significant theoretical basis for the clinical treatment of CVD with two kinds of ginseng.