Sulfated Polysaccharide-Based Nanocarrier Drives Microenvironment-Mediated Cerebral Neurovascular Remodeling for Ischemic Stroke Treatment.

Stroke is a leading cause of global mortality and severe disability. However, current strategies used for treating ischemic stroke lack specific targeting capabilities, exhibit poor immune escape ability, and have limited drug release control. Herein, we developed an ROS-responsive nanocarrier for targeted delivery of the neuroprotective agent rapamycin (RAPA) to mitigate ischemic brain damage. The nanocarrier consisted of a sulfated chitosan (SCS) polymer core modified with a ROS-responsive boronic ester enveloped by a red blood cell membrane shell incorporating a stroke homing peptide. When encountering high levels of intracellular ROS in ischemic brain tissues, the release of SCS combined with RAPA from nanoparticle disintegration facilitates effective microglia polarization and, in turn, maintains blood-brain barrier integrity, reduces cerebral infarction, and promotes cerebral neurovascular remodeling in a mouse stroke model involving transient middle cerebral artery occlusion (tMCAO). This work offers a promising strategy to treat ischemic stroke therapy.

[Artesunate alleviates hypoxic-ischemic brain damage in neonatal rats by inhibiting NLRP3 inflammasome activation and inflammatory cytokine secretion].

Objective To investigate the protective effect of artesunate on hypoxic-ischemic brain damage (HIBD) and its mechanism in neonatal rats. Methods 7-day-old neonatal SD rats were randomly divided into sham operation group, model group, artesunate 5 mg/kg group, artesunate 10 mg/kg group, artesunate 20 mg/kg group and dexamethasone 6 mg/kg group, with 18 rats in each group. HIBD models were established in groups except for the sham operation group. The sham operation group only needed to separate the left common carotid artery without ligation and nitrogen-oxygen mixed gas ventilation. Each group was injected with drug intraperitoneally right after surgery and the rats in the sham operation group and the model group were injected with an equal volume of normal saline (once a day for a total of 5 times). One hour after the last injection, the rats in each group were scored for neurological defects. After the rats were sacrificed, the brain water content was measured and the pathological changes of the brain tissues of rats were observed. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to detect the neuronal cell apoptosis, and ELISA was applied to detect the levels of IL-1ß, IL-6 and TNF-α in brain tissues and peripheral blood of each group of rats. Western blot analysis was adopted to detect the protein expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 in the rats brain tissues of each group. Results Compared with the model group, the neurological deficit score was decreased; the pathological damage of brain tissues was relieved; the brain water content was significantly reduced; the apoptosis number of hippocampal neurons was decreased significantly; the levels of IL-1ß, IL-6 and TNF-α in brain tissues and peripheral blood were significantly reduced; the protein expression levels of NLRP3, ASC and caspase-1 were significantly lowered in the middle-dose and high-dose artesunate groups and the dexamethasone group. Conclusion Artesunate can improve the neurological function, relieve the brain damage, and alleviate the brain edema in neonatal rats with HIBD. It can protect the HIBD, which may be related to the inhibition of NLRP3 inflammasome activation and reduction of inflammatory cytokine secretion.

Association of duration of skin-to-skin contact after cesarean delivery in China: a superiority, multicentric randomized controlled trial.

BACKGROUND: In China, the rates of early initiation and exclusive breastfeeding are low. The high cesarean delivery rates further contribute to low breastfeeding outcomes. Skin-to-skin contact, a key component of early essential newborn care, is known to be associated with improved breastfeeding initiation and exclusivity; however, the necessary duration has not been subjected to a randomized control trial. OBJECTIVE: This study aimed to determine the association of the duration of skin-to-skin contact after cesarean delivery with breastfeeding outcomes and maternal and neonatal health outcomes in China. STUDY DESIGN: This was a multicentric randomized controlled trial that was conducted at 4 hospitals in China. A total of 720 participants at ≥37 gestational weeks with a singleton pregnancy and who received an elective cesarean delivery with epidural anesthesia or spinal anesthesia or combined spinal-epidural anesthesia were randomly divided into 4 groups at a ratio of 1:1:1:1. The control group received routine care. Intervention group 1 (G1), 2 (G2), and 3 (G3) received 30, 60, and 90 minutes of skin-to-skin contact immediately after the cesarean delivery, respectively. RESULTS: Between January 3 and October 14, 2021, 659 participants were recruited, including 173 in the control group, 176 in G1, 146 in G2, and 164 in G3. Among G1, G2, and G3, the rate of early initiation of breastfeeding within 60 minutes of birth was 56%, 71%, and 72%, respectively, compared with 22% in the control group (P<.001). The exclusive breastfeeding rate at discharge was 69%, 62%, and 71%, respectively, compared with 57% in the control group (P=.003). Early essential newborn care practices were associated with a reduction in postpartum blood loss and neonatal intensive care unit or neonatal ward admission (P<.001; P=.022) . CONCLUSION: Our findings highlight that prolonged skin-to-skin contact after a cesarean delivery was associated with higher initiation and exclusive breastfeeding at discharge rates. It also found associations with reduced postpartum blood loss and neonatal intensive care unit or neonatal ward admission.

Association between short inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery.

OBJECTIVE: To explore the association between inter-pregnancy intervals and placenta previa and placenta accreta spectrum among women who had prior cesarean deliveries with respect to maternal age at first cesarean delivery. METHODS: This retrospective study included clinical data from 9981 singleton pregnant women with a history of cesarean delivery at 11 public tertiary hospitals in seven provinces of China between January 2017 and December 2017. The study population was divided into four groups (<2, 2-5, 5-10, ≥10 years of the interval) according to the inter-pregnancy interval. The rate of placenta previa and placenta accreta spectrum among the four groups was compared, and multivariate logistic regression was used to analyze the relationship between inter-pregnancy interval and placenta previa and placenta accreta spectrum with respect to maternal age at first cesarean delivery. RESULTS: Compared to women aged 30-34 years old at first cesarean delivery, the risk of placenta previa (aRR, 1.48; 95% CI, 1.16-1.88) and placenta accreta spectrum (aRR, 1.74; 95% CI, 1.28-2.35) were higher among women aged 18-24. Multivariate regression results showed that women at 18-24 with <2 years intervals exhibited a 5.05-fold increased risk for placenta previa compared with those with 2-5-year intervals (aRR, 5.05; 95% CI, 1.13-22.51). In addition, women aged 18-24 with less than 2 years intervals had an 8.44 times greater risk of developing PAS than women aged 30-34 with 2 to 5 years intervals (aRR, 8.44; 95% CI, 1.82-39.26). CONCLUSIONS: The findings of this study suggested that short inter-pregnancy intervals were associated with increased risks for placenta previa, and placenta accreta spectrum for women under 25 years at first cesarean delivery, which may be partly attributed to obstetrical outcomes.

Association between Skin-to-Skin Contact Duration after Caesarean Section and Breastfeeding Outcomes.

We aimed to explore the association between skin-to-skin contact (SSC) duration after caesarean sections (CSs) and breastfeeding outcomes. A prospective study was conducted in four hospitals in China during January and August 2021. A total of 679 participants with singleton pregnancy who delivered by elective CS after 37 gestational weeks using epidural or spinal anesthesia were included. Logistic regression was applied to assess the association between SSC duration and early initiation of breastfeeding (EIBF), as well as the promoting factors for exclusive breastfeeding (EBF) at hospital discharge. Immediate SSC after CSs was strongly associated with higher rates of EIBF (p < 0.001) and EBF at hospital discharge (p = 0.002). The EIBF rates increased with longer duration of SSC, with the at least 90 min SSC group having the highest EIBF rate (74.5%). Skin-to-skin contact durations of at least 90 min, 60−89 min and 30−59 min were significantly associated with 8.53 times (OR = 8.53, 95%CI: 4.94−14.72, Padj < 0.001), 8.04 times (95%CI: 4.68−13.80, Padj < 0.001) and 6.28 times (95%CI: 3.75−10.51, Padj < 0.001), respectively, higher EIBF rates compared to those without immediate SSC. After multiple-testing correction, the rates of EBF at hospital discharge were found to be independent of the duration of SSC (Padj = 0.12). Early initiation of breastfeeding was not a significant predictor of EBF. Our results suggested that SSC is important for EIBF in Chinese baby-friendly hospitals. Skin-to-skin contact should be practiced after CS to promote breastfeeding and providing SSC with longer duration is encouraged to obtain the full benefit; if it is not feasible, a minimum of 30 min SSC could achieve improved EIBF and EBF at discharge.

Perinatal maternal characteristics predict a high risk of neonatal asphyxia: A multi-center retrospective cohort study in China.

Objective: This study aimed to identify various perinatal maternal characteristics that contributed to neonatal asphyxia (NA) in term and late-preterm newborns based on the data obtained from a Chinese birth registry cohort and to establish an effective model for predicting a high risk of asphyxia. Method: We retrospectively reviewed and analyzed the birth database from July 1, 2016, to June 30, 2017, in the main economically developed regions of China. Asphyxia was defined as an Apgar score <7 at 5 min post-delivery with umbilical cord arterial blood pH < 7.2 in the infant born after 34weeks. We compared the perinatal maternal characteristics of the newborns who developed asphyxia (NA group, n = 1,152) and those who did not (no NA group, n = 86,393). Candidate predictors of NA were analyzed using multivariable logistic regression. Subsequently, a prediction model was developed and validated by an independent test group. Result: Of the maternal characteristics, duration of PROM ≥ 48 h, a gestational week at birth <37, prolonged duration of labor, hypertensive disorder, nuchal cord, and birth weight <2,500 or ≥4,000 g, abnormal fetal heart rate, meconium-stained amniotic fluid, and placenta previa were included in the predicting model, which presented a good performance in external validation (c-statistic of 0.731). Conclusion: Our model relied heavily on clinical predictors that may be determined before or during birth, and pregnant women at high risk of NA might be recognized earlier in pregnancy and childbirth using this methodology, allowing them to avoid being neglected and delayed. Future studies should be conducted to assess its usefulness.

Food Intake and Diet Quality of Pregnant Women in China During the COVID-19 Pandemic: A National Cross-Sectional Study.

Background: Between January and April 2020, China implemented differentiated prevention and control strategies across the country, based on the severity of the COVID-19 epidemic/pandemic in different regions. These strategies included lockdowns, social distancing, and the closure of public places. These measures may have affected dietary intake to varying degrees. This study aimed to assess variations in food intake and diet quality among pregnant women according to regional severity and related control measures during the most severe period of COVID-19 restrictions in 2020. Methods: A total of 3,678 pregnant women from 19 provinces/municipalities in mainland China were analyzed in this nationwide, multi-center study. Food intake data were obtained and assessed using a validated food frequency questionnaire (FFQ). Diet quality was quantified using the Diet Balance Index for Pregnancy (DBI-P), which included high bound score (HBS, excessive dietary intake), low bound score (LBS, insufficient dietary intake), and diet quality distance (DQD, dietary imbalance). Linear trend tests and multivariable regression analyses were performed to examine the association between food intake, DBI-P and the severity of pandemic. Results: The median daily intake of vegetables, fruit, livestock/poultry meat, dairy, and nuts decreased (p < 0.05) according to low, moderate, and high severity of the pandemic, while no significant differences in cereals/potatoes, eggs, and fish/shrimp intake. The median daily intake of cereals/potatoes exceeded the recommended ranges, and the daily intake of eggs and fish/shrimp was below recommended ranges regardless of the pandemic severity (p < 0.05). Regarding diet quality, HBS decreased (lower excessive consumption) (p = 0.047) and LBS increased (greater insufficient consumption) (p = 0.046) with increased severity of the pandemic. On multivariable analyses, moderate and high pandemic severity were related to lower HBS risk (OR = 0.687, OR = 0.537) and higher LBS risk (ß = 1.517, ß = 3.020) when compared to low pandemic severity. Conclusions: Under more severe COVID-19 pandemic conditions, pregnant women consumed less quality food, characterized by reduced consumption of vegetables, fruit, livestock/poultry meat, dairy and nuts, while the quality of the foods that pregnant women consumed in excess tended to improve, but the overconsumption of cereals/potatoes was a problem.

Incidence and Risk Factors of Postpartum Hemorrhage in China: A Multicenter Retrospective Study.

Background: Postpartum hemorrhage (PPH) is a leading cause of maternal morbidity and mortality worldwide but the incidence and its risk factors in China is limited. The objective of this study is to investigate the incidence and the risk factors of PPH in Chinese women. Methods: A multi-center retrospective study of pregnant women at ≥28 weeks of gestation was conducted. Logistic regression was used to identify potential risk factors of PPH and receiver operating characteristic curve was used to evaluate the predictive performance of the identified risk factors. Subgroup analysis focusing on the number of fetus and the mode of delivery was conducted. Results: A total of 99,253 pregnant women were enrolled and 804 (0.81%) experienced PPH. The subgroup analysis revealed that the incidence of PPH was 0.75, 2.65, 1.40, and 0.31% in singletons, twin pregnancies, cesarean sections, and vaginal deliveries, respectively. Placenta previa and placenta accreta were the predominant risk factors of PPH in the overall population and all subgroups. A twin pregnancy was a risk factor for PPH regardless of the mode of delivery. Obesity, and multiparity were risk factors for PPH in both singletons and cesarean section cases, but the latter predicted a reduced probability of PPH in vaginal deliveries. Macrosomia was associated with increased risk of PPH in singletons or vaginal deliveries. In women who delivered vaginally, preeclampsia was associated with a higher risk of PPH. The areas under the curve for the overall cohort, singletons, twin pregnancies, cesarean section cases, and vaginal deliveries were 0.832 (95% confidence interval [CI] 0.813-0.851), 0.824 (95% CI 0.803-0.845), 0.686 (95% CI 0.617-0.755), 0.854 (95% CI 0.834-0.874), and 0.690 (95% CI 0.646-0.735), respectively. Conclusions: The risk factors of PPH varied slightly based on the number of fetuses and the mode of delivery, while placenta previa and placenta accreta were the two major risk factors. A combination of the identified risk factors yielded a satisfactory predictive performance in determining PPH in the overall cohort, singletons pregnancies, and women who delivered by cesarean section, whereas the performance was moderate in twin pregnancies and in women delivering vaginally.

Previous mode of delivery affects subsequent pregnancy outcomes: a Chinese birth register study.

BACKGROUND: With the comprehensive implementation of the second child policy in China, the proportion of multiparous women has increased dramatically in the past few years. As nearly half of them have a history of previous cesarean delivery, there is widespread concern regarding complications of their pregnancy. METHODS: The aim of this study was to evaluate the effect of the previous delivery mode on subsequent pregnancy outcomes in the real world based on data from a Chinese birth registry. Birth registry data from July 1, 2016 to June 30, 2017 among a Chinese population were collected and analyzed retrospectively. This study included 14 representative hospitals from 10 provinces of China. All delivery data were collected by an internet-based system using a birth registration platform. The study enrolled 36,355 multiparas. Information extracted for analysis included basic demographic characteristics, previous delivery mode, current delivery mode, major maternal complications, and neonatal outcomes. Pregnancy outcomes of women with previous cesarean delivery (PCS group, n=14,774) were compared with the outcomes of women with previous vaginal delivery (PVD group, n=21,581). RESULTS: There were statistically significant differences in the major pregnancy outcomes between the PCS group and the PVD group. The PCS group had a higher incidence of cesarean section (CS), placenta previa, postpartum hemorrhage, uterus rupture, hysterectomy, gestational diabetes, gestational hypertension, delivery before 37 weeks of gestation, low birth weight, and Apgar Score at 5 min ≤3. CONCLUSIONS: Women with previous cesarean delivery had poorer pregnancy outcomes than women with previous vaginal delivery. Avoiding unnecessary CS, especially in primiparas is essential to improving maternal and neonatal outcomes in later pregnancies.

Perinatal Outcomes and Risk Factors for Preterm Birth in Twin Pregnancies in a Chinese Population: A Multi-center Retrospective Study.

Background: Twin pregnancies are associated with an increased risk of adverse maternal and neonatal outcomes, mainly owing to prematurity. Few studies have evaluated the risk factors for preterm birth (PTB) in Chinese population. The objective of this study is to present the short-term maternal-neonatal outcomes, investigating the potential risk factors associated with preterm birth in Chinese twin pregnancies. Methods: A multi-center retrospective study of women pregnant with twins ≥28 weeks of gestation was conducted. Maternal and neonatal outcomes were analyzed. Logistic regression was used to identify potential risk factors for PTB before 37, 34, and 32 weeks, respectively. Results: A total of 3,288 twin pregnancies and 6,576 neonates were included in 99,585 pregnancies. The rate of twin pregnancy was 3.3%, while the PTB rate before 37, 34, and 32 weeks among this population were 62.1, 18.8, and 10.4%, respectively. Logistic regression revealed that monochorionicity [Odds ratio (OR) 3.028, 95% confident interval (CI) 2.489-3.683, P < 0.001], gestational weight gain (GWG) <10 kg (OR 2.285, 95% CI 1.563-3.339, P < 0.001) and GWG between 10 and 15 kg (OR 1.478, 95% CI 1.188-1.839, P < 0.001), preeclampsia (PE) (OR 3.067, 95% CI 2.142-4.390, P < 0.001), and intrahepatic cholestasis of pregnancy (ICP) (OR 3.122, 95% CI 2.121-4.596, P < 0.001) were the risk factors for PTB before 37 weeks. Monochorionicity (OR 2.865, 95% CI 2.344-3.501, P < 0.001), age < 25 years (OR 1.888, 95% CI 1.307-2.728, P = 0.001), and GWG <10 kg (OR 3.100, 95% CI 2.198-4.372, P < 0.001) were risk factors for PTB before 34 weeks. Monochorionicity (OR 2.566, 95% CI 1.991-3.307, P < 0.001), age younger than 25 years (OR 1.964, 95% CI 1.265-3.048, P = 0.003), and GWG <10 kg (OR 4.319, 95% CI 2.931-6.364, P < 0.001) were the risk factors for PTB before 32 weeks. Conclusions: Monochorionicity and GWG <10 kg were two major risk factors for PTB before 32, 34, and 37 weeks, whereas maternal age, PE, and ICP were also risk factors for PTB in specific gestational age.

Probability of severe postpartum hemorrhage in repeat cesarean deliveries: a multicenter retrospective study in China.

To determine the factors predicting the probability of severe postpartum hemorrhage (SPPH) in women undergoing repeat cesarean delivery (RCD). This multicenter, retrospective cohort study involved women who underwent RCD from January 2017 to December 2017, in 11 public tertiary hospitals within 7 provinces of China. The all-variables model and the multivariable logistic regression model (pre-operative, operative and simple model) were developed to estimate the probability of SPPH in development data and external validated in validation data. Discrimination and calibration were evaluated and clinical impact was determined by decision curve analysis. The study consisted of 11,074 women undergoing RCD. 278 (2.5%) women experienced SPPH. The pre-operative simple model including 9 pre-operative features, the operative simple model including 4 pre-operative and 2 intraoperative features and simple model including only 4 closely related pre-operative features showed AUC 0.888, 0.864 and 0.858 in development data and 0.921, 0.928 and 0.925 in validation data, respectively. Nomograms were developed based on predictive models for SPPH. Predictive tools based on clinical characteristics can be used to estimate the probability of SPPH in patients undergoing RCD and help to allow better preparation and management of these patients by using a multidisciplinary approach of cesarean delivery for obstetrician.

Obstetric outcomes for twins from different conception methods - A multicenter cross-sectional study from China.

INTRODUCTION: The effects of assisted reproductive technology on the outcomes of twin pregnancies are controversial. Therefore, the purpose of this study was to compare the maternal and perinatal outcomes of twin pregnancies conceived spontaneously and those conceived by assisted reproductive technology. MATERIAL AND METHODS: This was a cross-sectional study performed at Peking Union Medical College Hospital (PUMCH). Data on twin pregnancies (conceived spontaneously and by in vitro fertilization [IVF]/intracytoplasmic sperm injection [ICSI]) were obtained from the National Birth Registry of China for the period between 1 October 2016, and 30 September 2017. The primary obstetric outcomes were compared between twin pregnancies conceived by different methods. Logistic regression analysis with 95% confidence intervals (95% CI) was used for the multivariate analysis. RESULTS: A total of 3270 twin pregnancies (2003 and 1209 conceived spontaneously and by IVF/ICSI, respectively) were identified. The proportion of twin pregnancies among all pregnancies was 3.4% (3332/97 278). Multiple regression analysis indicated that the incidences of gestational diabetes mellitus (adjusted odds ratio [AOR] = 1.42, 95% CI 1.10-1.83, p = 0.007), preterm premature rupture of membranes (AOR = 1.65, 95% CI 1.21-2.25, p = 0.002), placenta accreta spectrum (AOR = 2.12, 95% CI 1.42-3.17, p < 0.001) and postpartum hemorrhage (AOR = 1.38, 95% CI 1.02-1.86, p = 0.037) were significantly higher in the IVF/ICSI group than in the natural pregnancy group. Multivariate analysis also revealed that conception mode was not an independent risk factor for neonate outcomes. CONCLUSIONS: In twin pregnancies, IVF/ICSI is independently associated with multiple maternal complications, including gestational diabetes mellitus, preterm premature rupture of membranes and placenta accreta spectrum compared with spontaneous conception, although potential residual confounders due to indications for assisted reproductive technology exist.

Maternal age at first cesarean delivery related to adverse pregnancy outcomes in a second cesarean delivery: a multicenter, historical, cross-sectional cohort study.

BACKGROUND: To determine the effects of maternal age at first cesarean on maternal complications and adverse outcomes of pregnancy with the second cesarean. METHODS: This was a multicenter, historical, cross-sectional cohort study involving singleton pregnancies ≥28 gestational weeks, with a history of 1 cesarean delivery, and who underwent a second cesarean between January and December 2017 at 11 public tertiary hospitals in 7 provinces of China. We analyzed the effects of maternal age at first cesarean on adverse outcomes of pregnancy in the second cesarean using multivariate logistic regression analysis. RESULTS: The study consisted of 10,206 singleton pregnancies. Women were at first cesarean between 18 and 24, 25-29, 30-34, and ≥ 35 years of age; and numbered 2711, 5524, 1751, and 220 cases, respectively. Maternal age between 18 and 24 years at first cesarean increased the risk of placenta accreta spectrum (aOR, 1.499; 95% CI, 1.12-2.01), placenta previa (aOR, 1.349; 95% CI, 1.07-1.70), intrahepatic cholestasis of pregnancy (aOR, 1.947; 95% CI, 1.24-3.07), postpartum hemorrhage (aOR, 1.505; 95% CI, 1.05-2.16), and blood transfusion (aOR, 1.517; 95% CI, 1.21-1.91) in the second cesarean compared with the reference group (aged 25-29 years). In addition, maternal age ≥ 35 years at first cesarean was a risk factor for premature rupture of membranes (aOR, 1.556; 95% CI, 1.08-2.24), placental abruption (aOR, 6.464, 95% CI, 1.33-31.51), uterine rupture (aOR, 7.952; 95% CI, 1.43-44.10), puerperal infection (aOR, 6.864; 95% CI, 1.95-24.22), neonatal mild asphyxia (aOR, 4.339; 95% CI, 1.53-12.32), severe asphyxia (aOR, 18.439; 95% CI, 1.54-220.95), and admission to a neonatal intensive care unit (aOR, 2.825; 95% CI, 1.54-5.17) compared with the reference group (aged 25-29 years). CONCLUSIONS: Maternal age between 18 and 24 years or advanced maternal age at first cesarean was an independent risk factor for adverse maternal outcomes with the second cesarean. Advanced maternal age at the first cesarean specifically increased adverse neonatal outcomes with the second. Therefore, decisions as to whether to perform a first cesarean at a young or advanced maternal age must be critically evaluated.

Association of histological and clinical chorioamnionitis with perinatal and neonatal outcome.

Objectives: We investigated the incidence and outcome of clinical and histological chorioamnionitis (CA) and the associated risk factors in an emerging provincial perinatal center in 2014-2015.Study design: Based on the suspected and proven clinical infection in the third trimester of pregnancy, placenta and accessories from singleton deliveries were routinely examined histologically. The incidence of CA and associated fetal and neonatal outcome were compared by the total deliveries.Results: Of the 14,166 deliveries in 12 months, infection and inflammation were found in 373 out of 2372 (15.7%) placentas subjected to histological examination and diagnosed as CA (2.6%). These cases were divided into four groups as histological CA only (HCA, n = 335), clinical and histological CA (HCC, n = 20), clinical CA only (CCA, n = 18) and non-CA control (CON, n = 1999). Thus, an incidence of histological CA was 2.5% (355/14 166) in this birth population. Compared to CON, HCA group was more likely to have premature rupture of membrane, antenatal antibiotic use, gestational age <34 weeks, fetal distress, positive bacterial culture from vaginal secretions, and early-onset sepsis in newborns (all p ≤ .01), which were associated with perinatal risk factors of CA. In the very preterm subgroups, more stillbirths and death at delivery and neonatal intensive care unit admissions (p < .001) were found in the CA group.Conclusions: The results suggested that histological CA was associated with early-onset sepsis and combined perinatal comorbidities which are of more diagnostic importance than clinical only CA. The placental histological examination should be routinely performed in very preterm births to better assess perinatal and neonatal outcome.

Development and Validation of Predictive Models for Vaginal Birth After Cesarean Delivery in China.

BACKGROUND The rate of delivery by cesarean section is rising in China, where vaginal birth after cesarean (VBAC) is in its early stages. There are no validated screening tools to predict VBAC success in China. The objective of this study was to identify the variables predicting the likelihood of successful VBAC to create a predictive model. MATERIAL AND METHODS This multicenter, retrospective study included 1013 women at ≥28 gestational weeks with a vertex singleton gestation and 1 prior low-transverse cesarean from January 2017 to December 2017 in 11 public tertiary hospitals within 7 provinces of China. Two multivariable logistic regression models were developed: (1) at a first-trimester visit and (2) at the pre-labor admission to hospital. The models were evaluated with the area under the receiver operating characteristic curve (AUC) and internally validated using k-fold cross-validation. The pre-labor model was calibrated and a graphic nomogram and clinical impact curve were created. RESULTS A total of 87.3% (884/1013) of women had successful VBAC, and 12.7% (129/1013) underwent unplanned cesarean delivery after a failed trial of labor. The AUC of the first-trimester model was 0.661 (95% confidence interval [CI]: 0.61-0.712), which increased to 0.758 (95% CI: 0.715-0.801) in the pre-labor model. The pre-labor model showed good internal validity, with AUC 0.743 (95% CI: 0.694-0.785), and was well calibrated. CONCLUSIONS VBAC provides women the chance to experience a vaginal delivery. Using a pre-labor model to predict successful VBAC is feasible and may help choose mode of birth and contribute to a reduction in cesarean delivery rate.

lncRNA FAM99A is downregulated in preeclampsia and exerts a regulatory effect on trophoblast cell invasion, migration and apoptosis.

Preeclampsia (PE) is a complication of pregnancy, and a leading cause of maternal mortality and morbidity worldwide. Recently, the dysregulation of long non­coding RNAs (lncRNAs) has been reported to contribute to the pathogenesis and progression of PE. This study aimed to examine the alterations in the lncRNA family with sequence similarity 99 member A (FAM99A) in PE and its effects on trophoblasts. The results of reverse transcription­quantitative PCR indicated that the expression levels of FAM99A were downregulated in placental tissues from women with severe PE compared with in those from controls. A Transwell invasion assay and wound healing assay revealed that overexpression of FAM99A promoted invasion and migration of HTR­8/SVneo cells; conversely, knockdown of FAM99A suppressed the invasive and migratory abilities of HTR­8/SVneo cells. Flow cytometry demonstrated that FAM99A overexpression induced a decrease in the apoptotic rate of cells, whereas knockdown of FAM99A increased the apoptotic rate of HTR­8/SVneo cells. Western blot analysis revealed that overexpression of FAM99A decreased the protein expression levels of cleaved caspase­3, cleaved caspase­9 and Bax, and increased Bcl­2 protein expression, whereas knockdown of FAM99A had the opposite effects on these protein levels. Overexpression of FAM99A also decreased caspase­3 activity in HTR­8/SVneo cells; however, knockdown of FAM99A increased caspase­3 activity. In addition, overexpression of FAM99A enhanced Wnt/ß­catenin signaling activity, whereas FAM99A knockdown exerted an inhibitory effect on the Wnt/ß­catenin signaling activity in HTR­8/SVneo cells. In conclusion, these results indicated that FAM99A may serve a role in modulating the functions of trophoblasts, partially via targeting Wnt/ß­catenin signaling.

[Association of CLOCK gene T3111C polymorphism with attention deficit hyperactivity disorder and related sleep disturbances in children].

OBJECTIVE: To examine the association between CLOCK gene T3111C polymorphism with attention deficit hyperactivity disorder (ADHD) and ADHD related sleep disturbances in children. METHODS: One hundred and sixty-six unrelated children with ADHD diagnosed according to DSM-IV criteria and a control group of 150 normal children were enrolled in this study. Parents filled out the Sleep Disturbance Scale for Children (SDSC). Genotype and allele frequencies of T3111C of the CLOCK gene were examined by PCR-restriction fragment length polymorphisms (PCR-RFLP). RESULTS: There were significant differences in the genotype and allele frequencies of T3111C of the CLOCK gene between the ADHD and control groups (P<0.05). C allele frequency in the ADHD group was significantly higher than in the control group (χ2=7.254, P=0.007, OR=1.740, 95%CI=1.160-2.612). The ADHD children with sleep disturbances were found to have higher C allele frequency than those without sleep disturbances (χ2=13.052, P<0.001, OR=2.766, 95%CI=1.573-4.865). CONCLUSIONS: There is an association between CLOCK gene T3111C polymorphism and both ADHD and related sleep disturbances in children. The individuals with C allele are susceptible to ADHD as well as ADHD related sleep disturbances.