[Retrospective and cost-effective analysis of the result of Changsha Municipal Public Welfare Program by Noninvasive Prenatal Testing].

OBJECTIVE: To assess the practical and health economical values of non-invasive prenatal test (NIPT) in Changsha Municipal Public Welfare Program. METHODS: A retrospective analysis was carried out on 149 165 women undergoing NIPT test from April 9, 2018 to December 31, 2019. For pregnant women with high risks, invasive prenatal diagnosis and follow-up of pregnancy outcome were conducted. The cost-benefit of NIPT for Down syndrome was analyzed. RESULTS: NIPT was carried out for 149 165 pregnant women and succeeded in 148 749 cases (99.72%), for which outcome were available in 148 538 (99.86%). 90% of pregnant women from the region accepted the screening with NIPT. 415 (0.27%) were diagnosed as high risk. Among these, 381 (91.81%) accepted amniocentesis, which led to the diagnosis of 212 cases of trisomy 21 (PPV=85.14%), 41 cases with trisomy 18 (PPV=48.81%) and 10 cases with trisomy 13 (PPV=20.83%). The sensitivity and specificity of NIPT for trisomy 21, trisomy 18 and trisomy 13 were (97.70%, 99.98%), (97.62%, 9.97%) and (100%, 99.97%), respectively. In addition, 213 and 30 cases were diagnosed with sex chromosomal aneuploidies (PPV=46.2%) and other autosomal anomalies (PPV=16.57%), respectively. For Down syndrome screening, the cost and benefit of the project was 120.79 million yuan and 1,056.95 million yuan, respectively. The cost-benefit ratio was 1: 8.75, and safety index was 0.0035. CONCLUSION: NIPT is a highly accurate screening test for trisomy 21, which was followed by trisomy 18 and sex chromosomal aneuploidies, while it was less accurate for other autosomal aneuploidies. The application of NIPT screening has a high health economical value.

Correlation between postpartum pelvic floor dysfunction and vaginal microecological imbalance in late pregnancy. / äº§åŽç›†åº•åŠŸèƒ½éšœç¢ä¸Žå¦Šå¨ æ™šæœŸé˜´é“å¾®ç”Ÿæ€å¤±è¡¡çš„ç›¸å ³æ€§ï¼ˆè‹±æ–‡ï¼‰.

OBJECTIVES: Pelvic floor dysfunction (PFD) seriously affects women's physical and mental health. Pregnancy and childbirth are recognized as high-risk factors for PFD, and studies have shown that vaginal microenvironmental disorders can promote the development of pelvic organ prolapse. In this study, we intend to investigate whether the changes in vaginal microecology during pregnancy affect the pelvic floor function and participate in the development of postpartum PFD, and provide a basis for the prevention and treatment of PFD. METHODS: A total of 358 full-term mothers who delivered in Third Xiangya Hospital, Central South University from November 2019 to April 2020 were selected and underwent review 6 to 8 weeks after delivery. The pelvic floor structures were examined using pelvic floor ultrasound, and ultrasound values were measured at rest and at maximum Valsalva maneuver. One hundred and seventy women with PFD were assigned in a PFD group, and 188 women without PFD were assigned in a control group. The clinical data of all mothers were collected, and the clinical data and the results of microecological testing for vaginal secretions after 36 weeks of gestation and before delivery were compared between the 2 groups. The correlation of PFD with leucorrhoea cleanliness, lactobacillus level, bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) was analyzed, and logistic regression analysis was used to screen for independent risk factors for PFD. RESULTS: The incidences of VVC, BV, Lactobacillus vaginalis deficiency, and leucorrhoea cleanliness ≥III° were all higher in the PFD group than those in the control group (P<0.05). Among them, leukocyte cleanliness ≥III°and lack of Lactobacilli in the vagina were independent risk factors for the development of PFD, while VVC and BV were not independent risk factors for the development of PFD. CONCLUSIONS: Postpartum PFD is related to vaginal microecological imbalance in late pregnancy, among which Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° are independent risk factors for the occurrence of PFD. Therefore, pregnant women with Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° in late pregnancy should pay attention to the occurrence of postpartum PFD, and early diagnosis and effective intervention of postpartum PFD should be enhanced.

Role of alternative splicing events in endometrial cancer prognosis. / é€‰æ‹©æ€§å‰ªæŽ¥äº‹ä»¶åœ¨å­å®«å† è†œç™Œé¢„åŽä¸­çš„ä½œç”¨.

OBJECTIVES: Alternative splicing (AS), as a potent and pervasive mechanism of transcriptional regulation, can expand the genome's coding capacity. Growing evidence suggests that the AS events may be associated with various types of cancer. This study aims to explore the prognostic value of AS in endometrial cancer (EC). METHODS: Differently expressed AS (DEAS) events were screened by pairing the percent spliced in (PSI) value of tumor and paracancerous tissues in The Cancer Genome Atlas (TCGA) database, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were performed on their parental gene analysis of organisms. Subsequently, univariate Cox analysis was used to identify the prognostic AS events and a stepwise multi-factor Cox regression analysis was performed to further construct prognostic models. Furthermore, the diagnostic value of the prognostic model was evaluated by receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. Finally, the regulatory network of AS events and splicing factory in the model was also constructed. RESULTS: A total of 28 281 AS events were detected in EC. Of them, 42 DEAS were identified, and their parental genes were involved in tumor-related processes such as meiotic nuclear division, alpha-amino acid biosynthetic process, nuclear division, and so on. Univariate Cox analysis identified 2 289 prognostic-related AS events and constructed Cox prognostic models based on 7 different types and all types of AS events, in which the area under the curve of ROC of all types was as high as 0.882 and was better than that of 7 different splicing types. Finally, 12 splicing factors and AS events showed an obvious regulatory relationship. CONCLUSIONS: We use the whole genome analysis of AS events to establish a scientific prognostic prediction model for EC patients, which provides a reliable theoretical basis for the evaluation of EC clinical prognosis.

BHLHE40 plays a pathological role in pre-eclampsia through upregulating SNX16 by transcriptional inhibition of miR-196a-5p.

Pre-eclampsia (PE), which results from abnormal placentation, is a primary cause of maternal and neonatal morbidity and mortality. However, the causes of abnormal development of the placenta remain poorly understood. BHLHE40 is a transcriptional repressor in response to hypoxia. Bioinformatics analysis demonstrated that BHLHE40 negatively regulates miR-196a-5p expression, which may decrease miR-196a-5p to target SNX16. Since SNX16 exerts an inhibitory effect on cell migration, it may disrupt trophoblast cell migration in placentation. Therefore, the objective of this study was to explore a possible role of the BHLHE40/miR-196a-5p/SNX16 axis in PE pathogenesis. BHLHE40, miR-196a-5p and SNX16 mRNA and/or protein levels were detected in PE and normal placenta tissues. PE models in vitro and in vivo were constructed by culturing trophoblasts under hypoxia and reducing the uterine perfusion pressure in pregnant C57/BL6N mice, respectively. BHLHE40 and SNX16 were upregulated in PE placenta, while miR-196a-5p was downregulated. Knockdown of BHLHE40 reversed miR-196a-5p expression in trophoblasts under hypoxia, and upregulation of miR-196a-5p inhibited SNX16 expression. As indicated by ChIP assay, BHLHE40 bound to the promoter of the miR-196a-5p gene; luciferase reporter analysis showed that miR-196a-5p could bind to the 3'-untranslated region of SNX16 mRNA. Knockdown of either BHLHE40 or SNX16, or an increase in miR-196a-5p, restored cell viability, migration, invasion and matrix metalloprotein (MMP)-2 and MMP-9 expression under hypoxia. BHLHE40 knockdown also alleviated PE symptoms in pregnant C57/BL6N mice. This study supports involvement of the BHLHE40/miR-196a-5p/SNX16 axis in PE pathogenesis; Proper adjustment of the BHLHE40/miR-196a-5p/SNX16 axis is able to attenuate PE symptoms.

Association between risk of preeclampsia and maternal plasma trimethylamine-N-oxide in second trimester and at the time of delivery.

BACKGROUND: The data on the association between the microbiota-dependent metabolite trimethylamine-N-oxide (TMAO) during pregnancy and risk of preeclampsia (PE) is limited. METHODS: We, therefore, conducted a prospective nested case control study during Sep 2017 to Dec 2018 to examine the association between plasma TMAO measured during pregnancy and the risk of PE. Total of 17 patients diagnosed with early onset PE (EOPE), 49 with late onset PE (LOPE) and 198 healthy controls were enrolled. Blood samples were collected at 15-23 weeks gestation and time at delivery. The Logistic regression model was used to assess the odds ratio (OR) and 95% confidence interval (CI) for TMAO and risk of PE, EOPE, LOPE, mild PE, and severe PE. RESULTS: We found that the mean TMAO levels of overall subjects in the second trimester (T2) and at the time of delivery (TD) were 90.39 µg/m3 (standard deviation (SD) =45.91) and 175.01 µg/m3 (SD = 160.97), respectively. No significant spearman correlation was found between the TMAO in those two periods (p > 0.05). T2 TMAO was not significantly associated with risk of PE or risk of any PE subtypes (p > 0.05). However, TD TMAO was significant associated with risk of PE, EOPE and severe PE (adjusted OR and 95%CI were 1.24(1.09, 1.40), 1.62(1.29, 2.03), and 1.41(1.17, 1.70)) per 50 µg/m3 increment, respectively). CONCLUSION: Our study found that plasma TMAO level would alter over the course of pregnancy. The major role of TMAO in PE development might be in the accelerating process not in the initiation.

Gestational weight gain in Chinese women -- results from a retrospective cohort in Changsha, China.

BACKGROUND: The generalizability of the gestational weight gain (GWG) ranges recommended by the Institute of Medicine (IOM) to Chinese women is disputed. METHODS: In 2016, 16,780 pregnant women who gave birth to live singletons in Changsha, China, were enrolled. First, subjects with optimal pregnancy outcomes were identified for the GWG percentile distribution description and for comparison to the IOM recommendations. Second, all subjects with optimal GWG according to the IOM body mass index (BMI) cutoffs and those with optimal GWG according to the Asian BMI cutoffs were selected. Pregnancy outcomes were compared between those two groups. RESULTS: A total of 13,717 births with optimal pregnancy outcomes were selected to describe the GWG distribution. The height and central position of the GWG distributions determined by the Asian BMI cutoffs differed from those determined by the IOM BMI cutoffs among the overweight and obese groups. The recommended IOM GWG ranges were narrower than and shifted to the left of the observed distributions. In both BMI classification schemes, however, the IOM-recommended ranges were within the middle 70% (Pc 15th-85th) and 50% (Pc 25th-75th) of the observed distribution. A total of 6438 (38.37%) and 6110 (36.41%) women gained optimal GWG, according to the IOM and Asian BMI classifications, respectively. Compared with those with optimal GWG according to IOM BMI cutoffs, women with optimal GWG according to the Asian BMI cutoffs had lower risks of both macrosomia (adjusted OR = 0.79, 95%CI: 0.67-0.94) and large-for-gestational age (adjusted OR = 0.86, 95%CI: 0.76, 0.98). However, no significantly different risks of preterm, low birthweight, small-for-gestational age, pregnancy-induced hypertension, or gestational diabetes were found between them. CONCLUSIONS: The IOM-recommended GWG ranges are within the middle 70% of the distributions in Chinese women, and pre-pregnancy weight status should be determined by the Asian BMI cut-off points for monitoring and making GWG recommendations to Chinese women.

A first look at the effects of long inter-pregnancy interval and advanced maternal age on perinatal outcomes: A retrospective cohort study.

BACKGROUND: After China's One-child Policy was replaced with the Two-child Policy in 2013, the rate of second pregnancies with a longer inter-pregnancy interval (IPI) has suddenly increased in that country; however, the effect of long IPIs (≥49 months) on perinatal outcomes remains unreported. METHODS: This was a retrospective cohort study in China from July 2015 through June 2016. We used univariate and multivariate logistic regression models to test the associations among IPI, maternal age, and perinatal outcome (preterm delivery, term low birthweight, and small-for-gestational age). We included baseline factors and variables with biological plausibility as confounders. RESULTS: Our analytic sample included 3309 second pregnancies. The mean IPI was 75.36 months. Compared with second pregnancies with a short IPI of 7-24 months, those with long IPIs had higher adjusted odds ratios (ORs) of preterm delivery (1.70-2.00 [95% CI 1.20-3.33]) and term low birthweight (2.16-2.68 [1.10-6.17]), but not small-for-gestational age. The mean maternal age at current delivery was 32.0 years. Compared with the reference group (25-29 years), second pregnancies for the oldest maternal age group (≥35 years) showed no statistically significant increased ORs for adverse perinatal outcomes. CONCLUSION: Long IPI is a significant contributor to preterm delivery and term low birthweight. Health care providers need to pay close attention to preterm delivery prevention and fetal growth during prenatal care for second pregnancies where the mothers have long IPIs.

[Risk factors for the formation of aberrant artery collaterals in the uterus with scar in pregnancy womenunderwent cesarean].

OBJECTIVE: To evaluate the prevalence and risk factors for the formation of aberrant artery collaterals in the uterus during uterine artery embolization (UAE).
 METHODS: The data of 144 women with scar in the uterus due to cesarean were retrospectively analyzed. They underwent UAE in the period of 2009-2014 and were divided into two groups according to a standard with or without the aberrant artery collaterals in the uterus. The risk factors were analyzed.
 RESULTS: Aberrant artery collaterals were found in thirty-four patients. According to multiple logistic regression analysis, the presence of placenta previa (RR=78.556, 95% CI: 2.869-2 150.651, P=0.010), pelvic inflammatory disease (RR=6.633, 95% CI: 1.595-27.592, P=0.009), pregnancy complications (RR=7.264, 95% CI: 1.622-32.531, P=0.010), abortions (RR=18.381, 95% CI: 1.683-200.752, P=0.017) and uterine fibroids or adenomyosis (RR=12.580, 95% CI: 1.004-157.550, P=0.050) were the factors for the presence of aberrant artery collaterals.
 CONCLUSION: Aberrant artery collaterals were more frequent in patients with pelvic inflammatory disease, pregnancy complications, abortions and uterine fibroids or adenomyosis.

Relationships Among Pre-Pregnancy BMI, Gestational, and Postpartum Oral Glucose Tolerance Results in Women With Gestational Diabetes Mellitus.

Background and Aims: To investigate the relationship among maternal demographic and clinical characteristics, gestational and postpartum oral glucose tolerance test (ppOGTT) results in patients with gestational diabetes mellitus (GDM). Methods: Patients with gestational diabetes mellitus from January 1, 2016, to August 31, 2019, were enrolled. General characteristics, dietary energy intake, pre-gestational body mass index (BMI), gestational oral glucose tolerance test (gOGTT), and 42 days ppOGTT results of all participants were collected. The relationships among maternal clinical characteristics, fasting glucose of gOGTT (gOGTT-FPG), 1 h postprandial glucose of gOGTT (gOGTT-1h PG), 2 h postprandial glucose of gOGTT (gOGTT-2h PG), and maternal postpartum glucose outcomes were evaluated. Results: A total of 156 patients with GDM were included in this study. Among them, 73.7% had inadequate daily total energy intake, an insufficient ratio of carbohydrates and protein, and an excessive fat ratio. Most of the patients (81.4%) were normal in their ppOGTT examination. Less than 20% of the patients (16.7%) were in the pre-diabetic situation, and 3 patients (1.9%) had diabetes. Pre-pregnancy BMI of patients with GDM was a risk factor for increased gOGTT-FPG levels. Those who were overweight before pregnancy had a greater risk for a higher gOGTT-FPG compared to those who had normal pre-pregnancy BMI (P = 0.021, odds ratio [OR] = 4.583). Abnormal gOGTT-2hPG was a risk factor for abnormal ppOGTT (P = 0.04). Those who had an elevated gOGTT-2hPG (≧8.5 mmol/L) had a 2.426 times higher risk for abnormal ppOGTT than those who had normal gOGTT-2hPG (<8.5 mmol/L) results. Conclusion: For women who are overweight before pregnancy, it is better to control their BMI to normal before getting pregnant. Women who had abnormal gOGTT-2h PG should pay more attention to the ppOGTT results.

[Expression of aspartyl-(asparaginyl) beta-hydroxylase in villi in patients with missed abortion].

OBJECTIVE: To determine the difference in aspartyl-(asparaginyl) beta-hydroxylase (AAH) expression level in villi between patients with missed abortion and normal women with early pregnancy, and to confirm the expression loci of AAH in villi. METHODS: A total of 50 patients of missed abortion were collected and categorized into a test group, which was subdivided into Group 1 and Group 2. Patients in Group 1 (n=20) were of confirmed etiological disorders while those in Group 2 (n=30) showed no obviously etiological clues. In addition, 20 women of early pregnancy with artificial abortion were categorized into a control group, whose embryos were sonographically confirmed alive before surgery. The 50 patients of missed abortion were also subdivided into a group within 4 weeks and a group over 4 weeks according to the time that the embryo stayed in utrine after death. Immunohistochemical technique and computer image analysis were used to detect the expression loci and the level of AAH in villi. RESULTS: AAH was expressed in the endochylema and nucleus of trephocyte both in missed abortion and normal early pregnancy. The expression level of AAH in villi of missed abortion was much lower than that of in villi of normal early pregnancy (P<0.05). The expression level had no difference between different groups of patients with missed abortion(P>0.05). CONCLUSION: Low expression of AAH in the endochylema and nucleus of trephocyte may play a role in patients with missed abortion.

A potential regulatory network among WDR86-AS1, miR-10b-3p, and LITAF is possibly involved in preeclampsia pathogenesis.

Preeclampsia (PE), a pregnancy-specific disorder, is a leading cause of perinatal maternal and fetal mortality and morbidity. Impaired migration and invasion of trophoblastic cells and an imbalanced systemic maternal inflammatory response have been proposed as possible causes of pathogenesis of PE. Comparative analysis of PE-affected placentas and healthy placentas has uncovered differentially expressed long noncoding RNAs, microRNAs, and mRNAs. This study was conducted to investigate the effect of a regulatory network among these RNAs on PE pathogenesis. Long noncoding RNA WDR86-AS1, microRNA miR-10b-3p, and mRNA of protein LITAF were identified by screening of genes in existing databases with aberrant expression in PE-affected placentas and potential mutual interactions as revealed by TargetScan, miRanda, and PicTar analyses. This study identified their expression in PE-affected and healthy placentas by RT-PCR. An in vitro experiment was performed on human trophoblast HTR-8/SVneo cells cultured under normoxic or hypoxic conditions. MiR-10b-3p targets were identified in luciferase reporter assays and RNA pull-down assays. The mouse model of PE was set up using a soluble form of FLT-1 for in vivo testing. Lower levels of miR-10b-3p but higher expression of WDR86-AS1 and LITAF were observed in PE-affected placentas and trophoblast cells under hypoxia. WDR86-AS1 and LITAF mRNA were confirmed as targets of miR-10b-3p. WDR86-AS1 downregulated miR-10b-3p but promoted LITAF expression. Microarray analyses revealed that LITAF controlled the inflammatory responses and migration and proliferation of HTR-8/SVneo cells under hypoxia. Indeed, knockdown of WDR86-AS1 and LITAF or overexpression of miR-10b-3p attenuated the hypoxia-induced inhibition of cellular viability, migration, and invasion. Moreover, miR-10b-3p overexpression attenuated the pathological symptoms caused by soluble FLT-1 in vivo. In summary, the WDR86-AS1/miR-10b-3p/LITAF network is probably involved in PE pathogenesis.

Does previous cesarean section influence neonatal birth weight? A path analysis in China.

BACKGROUND: Since the One-child Policy was revised to a Two-child policy in 2013, the number of pregnancies with previous cesarean section suddenly increased in China. The aim of this study was to test if a previous cesarean section influenced the neonatal birth weight under Chinese background. METHODS: A retrospective study was conducted. Path analysis was used to test the hypothesized model for the association among previous cesarean section, placenta previa, gestational age and neonatal birth weight. Comparative fit index, the root-mean-square error of approximation and weighted root-mean-square residual were used to evaluate the model fit. RESULTS: 3466 electronic records for second pregnancies met the criteria; a modified model was established (the root-mean-square error of approximation=0.049, comparative fit index=0.992, weighted root-mean-square residual=0.960). The effects of previous cesarean section on neonatal birth weight were mediated via four paths. The direct effects (coefficient: 0.056) showed opposite signs compared to indirect effects (coefficient: -0.127) in this path analysis. It meant that the negative effects of the previous cesarean section were suppressed by other factors which bring positive effects. CONCLUSION: This study showed that previous cesarean section had negative effects on neonatal birth weight with increasing incidence of placenta previa and preterm birth. But these effects were suppressed by other positive factors, such as maternal body mass index, just after the child policy updated in China.

Cognition, emotion, and behaviour in women undergoing pregnancy termination for foetal anomaly: A grounded theory analysis.

OBJECTIVE: To understand the cognition, emotions, and behaviour of women who had recently undergone termination due to a foetal anomaly. In this study, we developed and tested a theoretical model to describe how women went through the process after termination. STUDY DESIGN: A grounded theory study. SETTING: Three general hospitals and one special hospital in Changsha, Hunan, China. PARTICIPANTS: 41 women who had recently undergone a pregnancy termination. METHODS: In-depth interviews were conducted from May to September 2017. A combination of convenience sampling and theoretical sampling was used, and conceptual depth criteria were used to measure the progress of the theoretical sampling. FINDINGS: This study developed a cognitive-behavioural experience framework of women undergoing pregnancy termination due to a foetal anomaly. The model included 4 phases: 1. Denial Phase, 2. Confirmation Phase, 3. Decision-making Phase and 4. Recovery Phase. Different cognitive appraisal, emotional, and behavioural reactions were included in each phase, and the different reactions influenced one another. KEY CONCLUSIONS & IMPLICATIONS FOR PRACTICE: We built and tested a theoretical framework by interviewing women who had gone through a pregnancy termination. The framework describes their experiences more clearly from three dimensions, including cognitive appraisal, emotional reaction, and behavioural response in the different phases. This framework provides a basic understanding of the women's emotional process and, therefore, provides baseline data for developing an effective intervention to help women cope with termination stresses.