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Background: The existing evidence on the association between interpregnancy interval (IPI) and pregnancy outcomes primarily focuses on singleton pregnancies, with limited research on twin pregnancies., Objective: This study aimed to investigate the association between IPI and adverse perinatal outcomes in twin pregnancies., Study Design: This population-based, retrospective cohort study analyzed data from the National Center for Health Statistics in the United States between 2016 and 2020. We included multiparous women aged 18 to 45 years with live-born twins without congenital anomalies, born between 26 and 42 weeks of gestation. Poisson regression models, adjusted for potential confounders, were used to evaluate the associations between IPI and adverse outcomes, including preterm birth (PTB) <36 weeks, small for gestational age (SGA), neonatal intensive care unit (NICU) admission, neonatal composite morbidity, and infant death. Missing data on covariates were managed using multiple imputations. Dose-response analyses were performed using the restricted cubic splines (RCS) approach. Subgroup analyses were stratified by maternal age, parity, and combination of neonatal sex. Sensitivity analyses were conducted using complete data and excluding pregnancies with intervening events during the IPI., Results: A total of 143,014 twin pregnancies were included in the analysis. Compared to the referent group (IPI of 18-23 months), an IPI of less than 6 months was associated with an increased risk of PTB<36 weeks (RR, 1.21; 95% confidence interval [95% CI]: 1.17-1.25), SGA (RR, 1.11; 95% CI: 1.03-1.18), neonatal composite morbidity (RR, 1.19; 95% CI: 1.12-1.27), NICU admission (RR, 1.18; 95% CI: 1.14-1.22), and infant death (RR, 1.29; 95% CI: 1.05-1.60). An IPI of 5 years or more was associated with an increased risk of PTB<36 weeks (RR, 1.18; 95% CI: 1.15-1.21), SGA (RR, 1.24; 95% CI: 1.18-1.30), neonatal composite morbidity (RR, 1.10; 95% CI: 1.05-1.15), and NICU admission (RR, 1.14; 95% CI: 1.11-1.17). The dose-response analyses showed that these outcomes had U-shaped or J-shaped associations with IPI. The associations between IPI and the outcomes slightly differed by advanced maternal age, parity, and combination of neonatal sex. The sensitivity analyses yielded similar results to the main findings., Conclusion: Extreme IPI, less than 6 months or more than 5 years, was associated with adverse outcomes in twin pregnancies. IPI could be used as a predictor for risk stratification in high-risk twin pregnancies., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The growing popularity of e-cigarettes and the associated risks of nicotine addiction present a new challenge to global public health security. Measuring the nicotine levels in e-cigarette aerosols is essential to assess the safety of e-cigarettes. In this study, a rapid in situ method was developed for online quantification of nicotine in e-cigarette aerosols by using a homemade vacuum ultraviolet photoionization aerosol mass spectrometer (VUV-AMS). E-cigarette liquids with different nicotine concentrations were prepared to generate aerosols containing different levels of nicotine, which were employed as the calibration sources for nicotine quantification by VUV-AMS. The results showed that the mass concentration of nicotine in e-cigarette aerosols has a good linear relationship with its signal intensity in the mass spectrum, and the limits of detection and quantitation of nicotine by VUV-AMS were found to be 2.0 and 6.2 μg per puff respectively. Then the online method was utilized to measure five commercial e-cigarettes, and their nicotine yields were determined to be between 31 and 188 μg per puff with the nicotine fluxes from 7.7 to 70 μg s -1 , agreeing with the results of the gas chromatography with a flame ionization detector (GC-FID). This study demonstrated the feasibility and advantages of VUV-AMS for quick quantification of nicotine in e-cigarette aerosols within seconds.

Background: There is limited evidence regarding optimal gestational weight gain in women with twin pregnancies and gestational diabetes mellitus., Objective: This study aimed to examine the association between gestational weight gain and perinatal outcomes among women with gestational diabetes mellitus and twin pregnancies and to explore the gestational weight gain targets by prepregnancy body mass index category., Study Design: A national population-based cohort study of twin pregnancies with gestational diabetes mellitus was conducted between 2014 and 2020. Women with gestational diabetes mellitus aged between 18 and 45 years with live-born twins without congenital malformations between 24 and 42 weeks of gestation were included in the analysis. Two approaches were used to determine the optimal gestational weight gain targets by body mass index category: an interquartile range method to calculate targets in low-risk gestational diabetes mellitus pregnancies and a logistic model method to identify the odds ratio targets at which a composite adverse outcome decreased., Results: Of 29,308 women with gestational diabetes mellitus and twin pregnancies, 8239 (28.1%) were normal-weight, 7626 (26.0%) were overweight, and 13,443 (45.9%) were obese. The continuous standardized gestational weight gain by 36 weeks was associated with preterm birth <36 weeks, large-for-gestational-age infants, small-for-gestational-age infants, and gestational hypertensive disorders. The interquartile range targets were 13.6 to 20.9 kg, 10.9 to 20.4 kg, and 7.7 to 17.7 kg for normal-weight, overweight, and obese women, respectively. The odds ratio targets were 14.1 to 20.0 kg, 12.1 to 16.0 kg, and 6.1 to 12.0 kg for normal-weight, overweight, and obese women, respectively. Gestational weight gain outside these targets was associated with preterm birth <36 weeks, large-for-gestational-age and small-for-gestational-age infants, and gestational hypertensive disorders, and exhibited significant population attributable fractions for preterm birth <36 weeks, large-for-gestational-age infants, and gestational hypertensive disorders across body mass index categories., Conclusion: Compared with the Institute of Medicine guidelines, more stringent gestational weight gain targets would be beneficial for improved perinatal outcomes in women with gestational diabetes mellitus and twin pregnancies., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Gestational weight gain (GWG) has been understudied among twin pregnancies. This systematic review aimed to review the data on the associations between GWG, based on the 2009 Institute of Medicine (IOM) guidelines and pregnancy outcomes among twin gestations., Methods: A systematic review was performed according to the PRISMA guidelines. A search for eligible studies published from January 2010 to August 2020 was conducted in the EMBASE, PubMed, Web of Science, ScienceDirect, and Cochrane databases. The methodological quality of the included studies was assessed using the Newcastle-Ottawa Scale. Data on study characteristics and main findings were extracted independently by two reviewers using a standard form. Outcomes of interest included (spontaneous) preterm birth (PTB), gestational hypertensive disorder (gestational hypertension and eclampsia), and small for gestational age (SGA)., Results: Eighteen observational studies of twin gestations met the inclusion criteria. GWG below the IOM recommendations was reported to be associated with increased PTB and SGA while GWG above the recommendation was associated with increased gestational hypertensive disorder. However, the results were inconsistent. Methodological limitations, such as a retrospective design, the use of weekly GWG, a small sample size and insufficient adjustment, impeded the clarification of the association between GWG and perinatal outcomes. In addition, the optimal GWG for underweight women was not fully studied., Conclusions: The maintenance of weight gain within the 2009 IOM guidelines would decrease the risks of adverse outcomes among twin pregnancies. However, rigorous studies are warranted to provide robust evidence to refine the optimal GWG among twin gestations.

Background: The optimal threshold of birthweight discordance (BWD) remains controversial. This study aimed to evaluate the associations between BWD at different thresholds and early neonatal outcomes and to assess their predictive accuracy., Methods: This was a retrospective cohort study using a birthweight data with the chorionicity information of 2348 liveborn twin pairs at a gestational age of ≥26 weeks, from 2012 to 2018. The percentage of BWD was calculated by dividing the actual birthweight difference by the weight of the larger twin and multiplying by 100. Outcomes of interest included neonatal intensive care unit (NICU) admission, neonatal respiratory distress syndrome (NRDS), ventilator support and a composite outcome combining major morbidities and neonatal death. Logistic regression models were performed to estimate the association between neonatal outcomes and BWD with different thresholds (≥15.0%, ≥20.0%, ≥25% and ≥ 30%). Generalized estimated equation (GEE) models were used to address intertwin correlation. Restrictive cubic spline (RCS) models were established to draw the dose-response relationship between BWD and the odds ratios of outcomes. Clustered receiver operating characteristic (ROC) curve analyses were performed to assess the predictive accuracy., Results: Of 2348 twin pairs, including 1946 dichorionic twin pairs and 402 monochorionic twin pairs, BWD was significantly associated with NICU admission, regardless of the thresholds used. The incidence of NRDS, ventilator support and the composite outcome were significantly higher when a threshold of ≥20% or greater was chosen. The dose-response relationship showed nonlinear growth in the risk of adverse neonatal outcomes with increasing BWD. ROC analyses showed a low significant AUROC of 0.569 (95% CI: 0.526-0.612) for predicting NICU admission but no significant AUROCs for predicting other outcomes. A BWD of ≥30% provided a moderate increase in the likelihood of NICU admission [positive likelihood ratio (LR + ) = 5.77]., Conclusion: Although BWD is independently associated with adverse neonatal outcomes, it is not a single predictor for neonatal outcomes given the weak discriminative ability to predict neonatal outcomes. A cutoff of 30% is more practical for risk stratification among twin gestations., (© 2022. The Author(s).)

Purpose: Prenatal depressive symptoms are an important mental health problem during pregnancy. We aimed to explore the moderating role of social support on the association between perceived stress and prenatal depressive symptoms., Materials and Methods: A cross-sectional study was conducted at an obstetrics clinic. A total of 1846 women completed a self-administered questionnaire, with a response rate of 91.8%., Results: Of the 1846 participants, 28.2% reported prenatal depressive symptoms (Edinburgh postnatal depression scale score ≥ 9). After adjusting for demographic characteristics, gestational age, exercise, and passive smoking, both perceived stress (adjusted odds ratio (AOR): 1.210, 95% confidence interval (CI): 1.178-1.242) and social support (AOR: 0.950, 95% CI: 0.932-0.968) were associated with prenatal depressive symptoms. Moreover, social support had a moderating effect on the association between perceived stress and prenatal depressive symptoms ( p < 0.001), and pregnant women with low social support were more likely to be affected by stress and experience prenatal depressive symptoms., Conclusion: Our study suggests that higher social support reduces the impact of stress on pregnant women, which in turn, decreases the risk of prenatal depressive symptoms. Therefore, interventions aimed at improving social support should be considered for the prevention and treatment of prenatal depressive symptoms., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Li et al.)

Objective: To explore the prospective correlation between serum metals before 24 weeks' gestation and gestational diabetes mellitus (GDM) or glucose in the late second trimester among southern Chinese pregnant women., Methods: A total of 8169 pregnant women were included in our retrospective cohort study. Logistic regression was used to investigate the relationships between metals (Manganese [Mn], copper [Cu], lead [Pb], calcium [Ca], zinc [Zn], magnesium [Mg]) and GDM. Quantile regression was performed to detect the shifts and associations with metals and three time-points glucose distribution of oral glucose tolerance test (OGTT) focused on the 10th, 50th, and 90th percentiles. Weighted quantile sum (WQS) regression was used to explore the relationship of metal mixtures and GDM as well as glucose., Results: Maternal serum concentrations of metals were assessed at mean 16.55 ± 2.92 weeks' gestation. Women with under weight might have 25% decreased risk of GDM for every 50% increase in Cu concentration within the safe limits. A 50% increase in Mn and Zn levels was related to a 0.051 μmol/L (95% CI: 0.033-0.070) and 0.059 μmol/L (95% CI: 0.040-0.079) increase in mean fasting plasma glucose of OGTT (OGTT0), respectively. The magnitude of association with Mn was smaller at the upper tail of OGTT0 distribution, while the magnitude of correlation with Zn was greater at the upper tail. However, there was a 0.012 mmol/L (95% CI: -0.017 to -0.008), 0.028 mmol/L (95% CI: -0.049 to -0.007), and 0.036 mmol/L (95% CI: -0.057 to -0.016) decrease in mean OGTT0 levels for every 50% increase in Pb, Ca, and Mg, respectively. The negative association of Pb, Ca, and Mg was greater at the lower tail of OGTT0 distribution. No significant relationship was observed in Cu and mean OGTT0 level (-0.010 mmol/L, 95% CI: -0.021 to 0.001), however, it showed a protective effect at the upper tail (-0.034 mmol/L, 95% CI: -0.049 to -0.017). No obvious correlation was found between metals and postprandial glucose levels (OGTT1 and OGTT2 from OGTT). The WQS index was significantly related to OGTT0 (P < 0.001). The contribution of Mn (80.19%) to metal mixture index was the highest related to OGTT0, followed by Cu (19.81%)., Conclusions: Higher Mn and Zn but lower Pb, Ca, and Mg concentrations within a certain range before 24 weeks' gestation might prospectively impair fasting plasma glucose during pregnancy; a greater focus is required on Mn. It could provide early markers of metal for predicting later glucose and suggest implement intervention for pregnant women., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to evaluate the preterm birth and additional perinatal outcomes between spontaneous and in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) dichorionic-diamnionic (DCDA) twin pregnancies., Material and Methods: This retrospective cohort study was conducted in a tertiary university-affiliated medical center. All women with DCDA twin pregnancies were considered for inclusion. The primary outcome of interest was preterm birth <37 weeks of gestation and secondary outcomes included spontaneous preterm birth, iatrogenic (induced) preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, preterm premature rupture of membranes (PPROM), intrahepatic cholestasis of pregnancy, placenta previa, neonatal intensive care unit (NICU) admission, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity. These outcomes were compared between IVF/ICSI and spontaneous twin pregnancies. Multivariable logistic regressions were used to adjust for confounders. General estimated equation models were used to address intertwin correlation., Results: A total of 1297 twin pregnancies, including 213 spontaneous and 1084 IVF/ICSI DCDA pregnancies, met the inclusion criteria. Women with IVF/ICSI pregnancies were older and had higher body mass index, adherence with prenatal care and proportion of nulliparity. After adjustment for confounders, IVF/ICSI pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation (adjusted odds ratio [aOR] 1.72; 95% CI 1.24-2.39), iatrogenic preterm birth <37 weeks of gestation (aOR 1.41; 95% CI 1.00-1.97) as well as NICU admission (aOR 1.34; 95% CI 1.00-1.80). IVF/ICSI pregnancies were associated with a decrease in PPROM (aOR 0.64; 95% CI 0.42-0.99). There were no differences between IVF/ICSI and spontaneous DCDA pregnancies in terms of spontaneous preterm birth, gestational diabetes mellitus, pregnancy-induced hypertensive disorder, preeclampsia, intrahepatic cholestasis of pregnancy, placenta previa, birthweight discordance, small for gestational age, neonatal respiratory distress syndrome, ventilator support, and perinatal death and/or severe morbidity., Conclusions: IVF/ICSI DCDA twin pregnancies were associated with a slight increase in preterm birth <37 weeks of gestation, iatrogenic preterm birth <37 weeks of gestation, and NICU admission but with a decrease in PPROM. Other outcomes were comparable between IVF/ICSI and spontaneous DCDA twin pregnancies. Multicenter studies with adequate power remain warranted., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology (NFOG). Published by John Wiley & Sons Ltd.)

Long non-coding RNAs (lncRNAs) are reported to have important roles in placental development and function, but the role of lncRNAs in abnormally invasive placenta (AIP) remains elusive. In the present study, the differential expression profiles of lncRNAs were analyzed to identify novel targets for further study of AIP. A total of 10 lncRNAs were chosen for validation by reverse transcription-quantitative PCR. To further determine the functions of dysregulated lncRNAs and their corresponding mRNAs, functional enrichment analysis, coexpression analysis were performed. A total of 329 lncRNAs and 179 mRNAs were identified to be differently expressed between the invasive and control group. Gene ontology analysis revealed that the 10 most significantly enriched functions included upregulated mRNAs and the most significantly enriched term was related to the proteinaceous extracellular matrix (ECM). In the pathway analysis, the two most significantly enriched pathways were the TGF-β signaling pathway for upregulated mRNAs and the pentose phosphate pathway for downregulated mRNAs. Furthermore, for certain dysregulated lncRNAs, their associated mRNAs were also dysregulated. Of note, BMP and activin membrane-bound inhibitor and TGF-β-induced, as the target genes of the TGF-β pathway, were indicated to be closely related to the ECM and invasive placental cells. Their nearby lncRNAs G008916 and vault RNA2-1 were also significantly dysregulated. In conclusion, significant lncRNAs with the potential to serve as biomarkers for AIP were identified., (Copyright: © Zhang et al.)

Background: Velamentous cord insertion (VCI) has been proposed to be associated with some specific complications among monochorionic (MC) twin pregnancies. This meta-analysis and systematic review aims to determine the role of VCI in MC twin pregnancies. Methods: The PubMed, Embase and Web of Science databases and reference lists were searched for relevant studies. Outcomes of interest included twin-to-twin transfusion syndrome (TTTS), birthweight discordance (BWD) and selective intrauterine growth restriction (sIUGR). The methodological quality of the included studies was assessed by using the Newcastle-Ottawa Scale. The pooled results were calculated by means of a random or fixed effect model to obtain odds ratio with 95% confidential interval (CI). Subgroup analyses were utilized to detect the sources of heterogeneity. Results: Twenty studies were eligible for inclusion. The pooled result suggested a significant association between VCI and TTTS (OR, 1.542; 95% CI, 1.116-2.129) with a moderate level of heterogeneity ( Q test: p = .024; I 2 = 50.2%). Subgroup analysis reported single-center study, methodological quality and exclusion of laser-coagulated TTTS as the sources of heterogeneity. Another analysis revealed an increased risk of BWD among twin pregnancies with VCI (OR, 2.945; 95% CI, 2.176-3.984) with a low heterogeneity ( Q test: p = .347; I 2 = 10.5%). None of study level characteristics was found to be an influencing factor. Three studies reporting on sIUGR suggested a significant association between VCI and sIUGR. Conclusions: The meta-analysis and systematic review suggests an association between VCI and BWD and sIUGR. However, the association between VCI and TTTS may be overestimated and high-quality studies with a representative sample are needed in further research.

Background: Pathological skin scars, caused by cesarean section, affected younger mothers esthetically and psychosocially and to some extent frustrated obstetricians and dermatologists. Umbilical cord mesenchymal stem cells (UC-MSCs), as a population of multipotent cells, are abundant in human tissues, providing several possibilities for their effects on skin scar tissues. Herein, we performed a randomized, double-blind, placebo-controlled, three-arm clinical trial, aiming to assess the efficacy and safety of UC-MSCs in the treatment of cesarean section skin scars among primiparous singleton pregnant women., Methods: Ninety primiparous singleton pregnant women undergoing elective cesarean section were randomly allocated to receive placebo, low-dose (3 × 10 6 cells), or high-dose (6 × 10 6 cells) transdermal hydrogel UC-MSCs on the surface of the skin incision. The primary outcome was cesarean section skin scars followed after the sixth month, assessed by the Vancouver Scar Scale (VSS)., Results: All the participants completed their trial of the primary outcome according to the protocol. The mean score of estimated total VSS was 5.52 in all participants at the sixth-month follow-up, with 6.43 in the placebo group, 5.18 in the low-dose group, and 4.71 in the high-dose group, respectively. No significant difference was found between-group in the mean scores for VSS at the sixth month. Additional prespecified secondary outcomes were not found with significant differences among groups either. No obvious side effects or adverse effects were reported in any of the three arms., Conclusion: This randomized clinical trial showed that UC-MSCs did not demonstrate the effects of improvement of cesarean section skin scars., Trial Registration: ClinicalTrials.gov identifier, NCT02772289. Registered on 13 May 2016.

Objective: To explore the size and shape association of OGTT values with adverse pregnancy complications among women with gestational diabetes mellitus (GDM) in Southern Han Chinese population and further analyze their mediating effects with maternal age in outcomes. Methods: 6,861 women with GDM were included in the study. Logistic regression was used to identify the correlations between OGTT values and adverse pregnancy outcomes of GDM. Restricted cubic spline nested logistic regression was conducted to investigate potential non-linear and linear associations. Mediating effect among maternal age, OGTT and adverse outcomes were explored. Results: Women with GDM had a mean age of 31.83, and 24.49% had advanced maternal age (≥35 years). In logistic regression with adjustment, compared with lower OGTT0 (<5.1 mmol/L), GDM patients with higher OGTT0 (≥5.1 mmol/L) exhibited 1.891 (95% CI: 1.441-2.298, P < 0.001), 1.284 (1.078-1.529, P = 0.005), 1.285 (1.065-1.550, P = 0.009), and 1.302 (1.067-1.590, P = 0.010) times increased risk of hypertensive disorders of pregnancy (HDP), preterm, neonatal hyperbilirubinemia, and macrosomia, respectively. GDM patients with higher OGTT1 (≥10 mmol/L) had only found to exhibited 1.473-fold (1.162-1.867, P = 0.001) increasing risk of HDP than those with lower OGTT1 (<10 mmol/L). No adverse outcome was identified to associate with higher OGTT2 (≥8.5 mmol/L). Linear relationships (non-linear P > 0.05) were observed between OGTT0 and HDP, preterm, neonatal hyperbilirubinemia, and macrosomia in both maternal age groups (<35 and ≥35 years). Non-linear associations of OGTT1 with incidence of HDP, preterm, and neonatal hyperbilirubinemia were detected in GDM patients younger than 35 years (non-linear P = 0.037, P = 0.049, P = 0.039, respectively), rising more steeply at higher values. Similar non-linearity was noted for OGTT2 with HDP in older patients. All OGTT values had significant mediating effects on some special complications caused by higher age. Conclusion: Higher fasting plasma glucose was more strongly linked to adverse pregnancy outcomes among GDM patients. Both linearity and Non-linearity of associations between glucose and complications should be taken into account. A careful reconsideration of GDM with hierarchical and individualized management according to OGTT is needed., (Copyright © 2020 Zhou, Chen, Fan, Rao, Li, Wu, Lin, Ma, Ye, Zhang, Shen, Wan, Luo, Suo, Guo and Liu.)

Objective: No recommendations are available for gestational weight gain (GWG) in underweight women with twin pregnancies. We aimed to evaluate whether underweight women with twin pregnancies should gain more weight than normal-weight women in order to optimize perinatal outcomes., Study Design: This retrospective cohort study compared the GWG and perinatal outcomes among normal-weight and underweight women who gave birth to viable twins between 2015 and 2018 at the Maternal and Child Health Hospital in Foshan, China. Gestational weight gain (GWG) was categorized as adequate or inadequate GWG, based on the US Institute of Medicine 2009 guidelines for normal-weight women (≥ 0.46 kg/week). The outcomes of interest included spontaneous preterm birth (sPTB) <37 weeks, <35 and <32 weeks, small for gestational age (SGA), gestational hypertensive disorder (GHD), gestational diabetes mellitus (GDM), birth weight discordance (BDW) ≥20%, neonatal intensive unit (NICU) admission and neonatal respiratory distress syndrome (NRDS). Propensity score matching (PSM, in a 1:1 ratio) was utilized to minimize the effects of confounders on the differences in the two cohorts. Multivariable logistic models were also used to verify the results from PSM analysis., Results: There were 475 normal-weight and 111 underweight women included in the analysis. Our results suggested that the incidence of adequate GWG was comparable between underweight and normal-weight women (37.5% vs. 45.1%, P = 0.141). The prevalence of GDM was significantly lower among underweight women (9.9%) than among normal-weight women (20.4%) (P = 0.010). There was no evidence of differences in other perinatal outcomes between the two groups. 102 underweight women and 102 normal-weight women were included in PSM analyses. There was a lower incidence of GDM in underweight women than in normal-weight women, but the difference was not significant (9.8% vs. 18.6%, P = 0.071). No evidence of any differences in the other outcomes, including sPTB, GHD, BWD≥20%, SGA, NICU admission and NRDS, was found between the underweight and normal-weight women. Multivariable logistic regression models yielded similar results., Conclusions: For Chinese twin pregnant women with twin pregnancies, our data does provide evidence to suggest underweight women need to gain more weight than normal-weight women to optimize perinatal outcomes. Future studies with larger number of underweight women with twin gestations are warranted to establish an optimal range of GWG., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To investigate the expression profile of long non-coding RNAs (lncRNA) and identify potential lncRNA-related competing endogenous RNAs (ceRNA) in placenta accrete spectrum disorders (PAS)., Methods: Five tissue specimens of placental implantation and 5 adjacent normal placental tissues were collected from cesarean section deliveries complicated by PAS in our hospital between December, 2017 and June, 2018. Human microarrays were used to identify the lncRNAs that were differentially expressed in PAS, and 5 of the identified lncRNAs were further validated using qRT-PCR. GO and KEGG pathway analyses were performed to indentify the most significant enrichment functions. A ceRNA network was constructed based on ENST00000511361 (RP5-875H18.4), NR&#95;027457 (LINC00221) and NR&#95;126415 (FOXP4-AS1) to pinpoint the potential lncRNAs-related ceRNA., Results: A total of 329 lncRNAs and 179 mRNAs were identified to have differential expression in PAS. The results of qRT-PCR were consistent with the human microarrays results. Transforming growth factor-β (TGF-β) signaling pathway was the most significantly enriched pathway. The constructed ceRNA network suggested that RP5-875H18.4--miRNA-218--SLIT2 had a potential ceRNA regulatory mechanism in PAS., Conclusions: The differentially expressed lncRNAs are involved in the occurrence and progression of PAS possibly by regulating the TGF-β signaling pathway. The ceRNA network of RP5-875H18.4--miRNA-218--SLIT2 may play a role in the occurrence of PAS.

Introduction: Complete placenta previa (CPP) is one of the most problematic types of abnormal placenta, which is further complicated by placenta accreta or percreta that can unexpectedly lead to catastrophic blood loss, infection, multiple complications, emergency hysterectomy, and even death. The present study aimed to assess the efficacy of random placenta margin incision in controlling intraoperative and total blood loss during cesarean section for CPP women. Methods: A prospective cohort study, including a total of 100 consecutive pregnant women with CPP, was performed at a tertiary university-affiliated medical center between March 2016 and July 2017. All of them underwent random placenta margin incision, and intraoperative and total blood loss were analyzed. Through antenatal diagnosis using color Doppler, women were further divided into abnormally invasive placenta (AIP) and non-AIP groups, and anterior and posterior placenta groups. The protocol was registered with the Clinical Trial Registry under registration number NCT02695069. Results: Mean maternal age and gestational age at delivery were 32.26 ± 5.03 years old and 36.21 ± 2.07 weeks, respectively. Total duration of the surgical procedure time was 52.50 (42.43-64.00) min. Median estimated intraoperation blood loss was 746.43 (544.44-1092.86) ml. Total blood loss was 875.00 (604.50-1196.67) ml, and 38 (38.0%) had post-partum hemorrhage. The change from baseline in the median hemoglobin level was -0.33 (6.00-13.20). No women underwent hysterectomy due to massive hemorrhage during the study period. No women had an intraoperative urinary bladder injury, postoperative wound infection, and required relaparotomy, owing to intra-abdominal bleeding. The median hospitalization time was 5.41 (4.18-7.58) d. Conclusion: The random placenta margin incision may be a potentially valuable surgical procedure to control the volumes of intraoperative and postoperative blood loss and reduce the incidence of postpartum hemorrhage among women with complete placenta previa.

This retrospective cohort study aimed to investigate the effect of placental location on birthweight discordance among diamniotic-dichorionic twin pregnancies. Medical records and sonographic reports of 978 diamniotic-dichorionic twin pregnancies delivered at Foshan Maternal and Fetal Health Hospital were reviewed. Pregnancies with congenital malformation, intrauterine death or placenta previa were excluded. The placental location for each twin was determined by last sonographic examination before delivery, and the pregnancies were grouped by different versus same placental location in each pregnancy. Maternal and fetal characteristics were summarized. The primary outcome of interest was birthweight discordance (BWD) ≥20%, and secondary outcomes included small for gestational age (SGA) as a binary outcome and mean value and absolute difference in birthweight as continuous outcomes. Student's t test and the chi-square test were used for univariate analyses, while multivariate regressions were used to adjust for confounders. General estimated equation (GEE) models were used to address the correlation between fetuses when assessing SGA. A total of 866 eligible subjects were included in the analysis. In total, 460 pregnancies had placentas with different locations, and 406 had placentas with same locations. The gestational age at delivery was slightly younger in the same placental location group than in the different placental location group (35.8 ± 0.1 vs. 36.1 ± 0.1 weeks, P = 0.067). Other maternal and fetal characteristics were comparable between the two study groups. There was no significant difference in BWD ≥20% (aOR = 1.06; 95% CI: 0.71-1.59) or SGA (aOR = 1.32; 95% CI: 0.76-2.28) between the same and different placental location groups. Neither the mean value nor the absolute difference in birth weight was associated with placental location combination (P = 0.478 and P = 0.162, respectively). In conclusion, discordant birthweight is not affected by same location of diamniotic-dichorionic placentas.

Background: Gestational weight gain (GWG) has implications for perinatal outcomes, the guidelines for maternal weight gain, however, remain understudied among twin pregnancies. This study aimed to assess the associations between perinatal outcomes and GWG among twin pregnancies, based on the US institute of Medicine (IOM) 2009 guidelines., Methods: A retrospective cohort study of pregnant women with viable twins ≥26 weeks of gestation, was conducted in Foshan, China, during July 2015 and June 2018. Maternal BMI was categorized based on Chinese standard and GWG was categorized as below, within and above the IOM 2009 recommendations. Underweight women were excluded for analysis. Perinatal outcomes were compared among these groups. To assess the independent impact of GWG on the perinatal outcomes, conventional multivariable regression and general estimated equation (GEE) were utilized for maternal outcomes and neonatal outcomes, respectively., Results: A total of 645 mothers with twin pregnancies were included, of whom 15.0, 41.4 and 43.6% gained weight below, within and above guidelines, respectively. Compared to weight gain within guidelines, inadequate weight gain was associated with increased risks in spontaneous preterm birth < 37 weeks (aOR:3.55; 95% CI: 1.73-7.28) and < 35 weeks (aOR:2.63; 95% CI: 1.16-5.97). Women who gained weight above guidelines were more likely to have gestational hypertension disorder (aOR: 2.36; 95% CI: 1.32-4.21), pre-eclampsia (aOR: 2.59; 95% CI: 1.29-5.21) and have fetuses weighted >90th percentile and less likely to have fetuses weighted < 2500 g and < 1500 g., Conclusions: Maintenance of gestational weight gain within the normal range could decrease the risk of adverse perinatal outcomes. However, the causality between pre-eclampsia and gestational weight gain requires further investigations.

The aim of this study was to compare the accuracy of cystoscopy and ultrasonography for the prenatal diagnosis of abnormally invasive placenta (AIP), including its subgroups: placenta accreta (PA), placenta increta (PI), and placenta percreta (PP).A retrospective observational study including a total of 85 pregnant women at high risk for AIP underwent prenatal cystoscopy and ultrasonography evaluations. The sensitivity (Se), specificity (Sp), positive predictive value, negative predictive value, and exact diagnosed were calculated and compared for both cystoscopy and ultrasonography. Se and Sp values of cystoscopy and ultrasonography were compared by means of the McNemar test.Of the 85 patients, there were 24 (28.2%) PA, 35 (41.2%) PI, 4 (4.7%) PP, and 22 (25.9%) nonadherent placenta. The mean maternal age and gestational age of delivery were 31.88 ± 4.42 years and 36.14 ± 1.84 weeks, respectively. No one was found to develop any complications with cystoscopy like urinary tract infection, or ureteral injury or perforations. Se in the diagnosis of AIP was 50.8% with ultrasonography and 61.9% for cystoscopy. Sp was 86.4% with cystoscopy and 72.7% for ultrasonography. In subgroups, Se with cystoscopy was 25.0%, 62.9%, and 100.0% in PA, PI, and PP, respectively, and 37.5%, 74.3%, and 100.0%, respectively, for ultrasonography; Sp remained unchanged with 86.4% for cystoscopy and 72.7% for ultrasonography. After McNemar test, no difference was found in either Se or Sp between cystoscopy and ultrasonography in AIP and its subgroups.According to the depth of invasion, the diagnostic value of cystoscopy and ultrasonography is all conspicuous increased and they have similar test validity for prenatal diagnosis of AIP and its subgroups.

Background: Cesarean delivery has already become a very common method of delivery around the world, especially in low-income countries. Hypertrophic scars and wound infections have affected younger mothers and frustrated obstetricians for a long time. Mesenchymal stem cells (MSCs) have strong potential for self-renewal and differentiation to multilineage cells. Previous studies have demonstrated that MSCs are involved in enhancing diabetic wound healing. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment of Cesarean section skin scars., Methods: This trial is a prospective, randomized, double-blind, placebo-controlled, single-center trial with three parallel groups. Ninety eligible participants will be randomly allocated to placebo, low-dose (transdermal hydrogel MSCs; 3 × 10 6 cells) or high-dose (transdermal hydrogel MSCs; 6 × 10 6 cells) groups at a 1:1:1 allocation ratio according to a randomization list, once a day for six consecutive days. Study duration will last for 6 months, comprising a 1 week run-in period and 24 weeks of follow-up. The primary aim of this trial is to compare the difference in Vancouver Scar Scale rating among the three groups at the 6th month. Adverse events, including severe and slight signs or symptoms, will be documented in case report forms. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan., Discussion: This trial is the first investigation of the potential for therapeutic use of MSCs for the management of women's skin scar after Cesarean delivery. The results will give us an effective therapeutic strategy to combat Cesarean section skin scars, even with uterine scarring., Trial Registration: ClinicalTrials.gov, NCT02772289 . Registered on 10 May 2016.

The percentages of low birth weight (LBW) increased from 7.7% in 2005 to 11.3% in 2011 and declined to 8.1% in 2017. For very low birth weight (VLBW) individuals, the proportion declined -1.0% annually, from 2.5% in 2005 to 1.4% in 2017. Among moderately low birth weight (MLBW) individuals, the proportion first increased 12.8% annually, from 5.0% in 2005 to 9.3% in 2011, and then declined -3.8% annually, from 9.4% in 2011 to 7.0% in 2017. The percentages of macrosomia monotone decreased from 4.0% in 2005 to 2.5% in 2017, an annual decline of -4.0%. Multiple regression analyses showed that boys, maternal age, hypertensive disorders complicating pregnancy (HDCP), and diabetes were significant risk factors for LBW. Boys, maternal age, gestational age, HDCP, diabetes, and maternal BMI were significant risk factors for macrosomia. Although the relevant figures declined slightly in our study, it is likely that LBW and macrosomia will remain a major public health issue over the next few years in China. More research aimed at control and prevention of these risk factors for LBW and macrosomia and their detrimental outcome in the mother and perinatal child should be performed in China.

Non-syndromic orofacial clefts (NSOFC), which include cleft lip and palate (CLP), cleft lip only (CLO), and cleft palate only (CPO), contains a range of disorders affecting the lips and oral cavity. No systematic review and meta-analysis has been carried out to synthesize the prevalence of NSOFC in Chinese perinatal infants. We aimed to quantify and understand the variation of prevalence national and regional levels. Four English databases and four Chinese databases were searched using a comprehensive search strategy from inception to April 2017. The random effect model was used for this meta-analysis. To determine the sources of heterogeneity, subgroup analyses and meta-regression were conducted based on different categories. The protocol has been pre-registered in the PROSPERO, number CRD42017062293. 110 studies, including 15,094,978 Chinese perinatal infants, were eligible for inclusion. The pooled prevalence rate for NSOFC was 1.67‰ (95% CI 1.53-1.82), varying with provinces. The pooled prevalence estimate was 0.56‰ (0.50-0.63) for CLO, 0.82‰ (0.73-0.90) for CLP, and 0.27‰ (0.24-0.30) for CPO. Significant associations were found between overall prevalence estimates and survey year and study region. The prevalence of NSOFC was severe in Chinese perinatal infants, varying with provinces. The results will serve as a baseline for future assessment of the overall effectiveness of NSOFC control, and will also support and inform health policy for planning and helping health debates., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

Background: Uterine niche is defined as a triangular anechoic structure at the site of the scar or a gap in the myometrium at the site of a previous caesarean section. The main clinical manifestations are postmenstrual spotting and intrauterine infection, which may seriously affect the daily life of nonpregnant women. Trials have shown an excellent safety and efficacy for the potential of mesenchymal stem cells (MSCs) as a therapeutic option for scar reconstruction. Therefore, this study is designed to investigate the safety and efficacy of using MSCs in the treatment for the uterine niche., Methods/design: This phase II clinical trial is a single-center, prospective, randomized, double-blind, placebo-controlled with 2 arms. One hundred twenty primiparous participants will be randomly (1:1 ratio) assigned to receive direct intramuscular injection of MSCs (a dose of 1*10 cells in 1 mL of 0.9% saline) (MSCs group) or an identical-appearing 1 mL of 0.9% saline (placebo-controlled group) near the uterine incision. The primary outcome of this trial is to evaluate the proportion of participants at 6 months who is found uterine niche in the uterus by transvaginal utrasonography. Adverse events will be documented in a case report form. The study will be conducted at the Department of Obstetric of Southern Medical University Affiliated Maternal & Child Health Hospital of Foshan., Discussion: This trial is the first investigation of the potential for therapeutic use of MSCs for the management of uterine niche after cesarean delivery., Conclusion: This protocol will help to determine the efficacy and safety of MSCs treatment in uterine niche and bridge the gap with regards to the current preclinical and clinical evidence., Trial Registration Number: NCT02968459 (Clinical Trials.gov: http://clinicaltrials.gov/).

Background: Abnormally invasive placenta (AIP) or placenta accreta (PA) is considered numerous adverse maternal and fetal-neonatal complications. There has been no detailed study to characterize the prevalence of AIP among deliveries in mainland China., Objectives: We aimed to fill this gap and obtained overall and regional estimates of AIP prevalence via a systematic review and meta-analysis., Methods: This systematic review and meta-analysis was totally performed following the Meta-analysis of Observational Studies in Epidemiology guidelines for systematic reviews of observational studies, and the Preferred Reporting Items for Systematic reviews and Meta-Analysis statement for reporting systematic reviews and meta-analysis., Results: A total of 23 articles (including 350,939) were included. Most studies (22) focused on the placenta increta (PI), only 2 articles in PA, and none in placenta percreta (PP). In this meta-analysis, the overall prevalence of AIP was 0.22% (95% confidence interval 0.18%-0.27%) in a heterogeneous set of studies (I = 93.5%). In a subgroup, the prevalence of PA and PI was 0.48% and 0.23%, respectively. Stratified analyses of PI found that the prevalence was similar in North (0.23% [0.14%-0.32%]) and South (0.23% [0.15%-0.32%]), and lower in Central (0.20% [0.09-0.31%]); the inlanders (0.17% (0.12%-0.23%]) had a lower prevalence of PI than those living in coastal areas (0.24% [0.35%-0.63%]). As time goes on, the prevalence, from 0.03% (0.02%-0.04%) in 1970 to 1979 to 0.48% (0.30%-0.66%) in 2010 to present, was higher and higher. The different prevalence was also found in different in maternal age groups., Conclusions: This first systematic review and meta-analysis found that the prevalence differed among different geographic areas and maternal age groups. The results would be useful for the design of abnormally invasive placenta planning and implementation adequate health care systems and treatment programs in mainland China.