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Placenta accreta spectrum (PAS) refers to a spectrum of conditions characterized by the abnormal adherence of the placenta to the implantation site and has been a challenge due to the risk of postpartum hemorrhage, peripartum hysterectomy and maternal mortality. Despite of sonographic findings, no consensus on the prenatal evaluation of PAS has been established yet. We are aiming to establish a scoring system to increase the accuracy of prediction of PAS severity, especially to differentiate placenta percreta and placenta increta. We conducted a retrospective study and collected 2,219 cases of placenta increta and placenta percreta obtained from 20 tertiary care centers in China. Demographic information, clinical characteristics, and sonographic findings were collected. Logistic regression analysis was used to determine the risk factors and sonographic features that were significantly associated with a clinical diagnosis of placenta percreta. The formula and subsequent scoring system were generated. This scoring system was then verified in 67 cases of placenta increta or placenta percreta in Peking University First Hospital from 2016 to 2017. Diagnosis of placental invasion was confirmed by surgical findings or histopathologic results. The scoring system was evaluated using a receiver operating characteristic (ROC) curve. The scoring system combined maternal risk factors and ultrasound features and was then verified in 67 cases. According to ROC curve, the area under the curve (AUC) of our scoring system for prenatal diagnosis of placenta percreta is 0.96 (95%CI, 0.91–1.00, p < .001), for severe postpartum hemorrhage (≥1500 ml) is 0.76 (95%CI, 0.62–0.91, p = .005), for hysterectomy is 0.98 (95%CI, 0.93–1.000, p = .023). Our scoring system combining maternal risk factors and ultrasound features can improve the predictive accuracy of placenta percreta and obstetric outcomes (severe hemorrhage and hysterectomy).

BackgroundIt remained controversial whether women with multiple gestation are at higher risk of placenta accreta spectrum (PAS) disorders and large-scale studies are needed. This study aimed to assess whether PAS incidence is higher among women with multiple gestation than among singleton, as well as to compare the characteristics and outcomes of PAS in multiple and singleton gestation.MethodsWomen who underwent cesarean section with live births at Peking University First Hospital from January 2015 to December 2020 were included. Demographic and clinical information was collected through chart review. Logistic regression models were used to analyze the associations between multiple gestation and PAS. The clinical characteristics and perioperative outcomes of PAS in multiple and singleton gestation were further compared.ResultsAmong the 14583 women included, 2.4% (352/14583) were diagnosed with PAS. PAS was slightly more prevalent among multiple gestations than among singletons (2.5% vs 2.4%, P=0.857). After adjusting for known risk factors and pregnancy complications, multiple gestation was associated with a higher risk of PAS (aOR=1.63, 95% CI 1.01-2.62). Among PAS patients, women who had multiple births had a significantly lower rate of previous cesarean deliveries (27.6% vs. 56.3%, P=0.003), placenta previa (17.2% vs. 56.3%, PP=0.002) than singletons. There were no significant differences in perioperative outcomes between these two groups.ConclusionMultiple gestation could be independently associated with an elevated risk of PAS. The clinical characteristics of PAS in the multiple and singleton gestation groups differed significantly in cesarean delivery history and placenta previa. The results of this study may inform guidelines on the screening, early detection and timely intervention of PAS patients among women with multiple births.

OBJECTIVE To examine factors that influence uptake of expanded carrier screening (ECS) among women undergoing preconception and prenatal genetic counseling. METHODS We retrospectively reviewed 500 medical records from women with prenatal or preconception genetic counseling at a prenatal genetic counseling service. We tabulated acceptance of ECS by indication for genetic counseling along with demographic and pregnancy-related factors. RESULTS ECS was offered to 483 of 500 women, and 192 (39.8%) accepted. Of the 67 women counseled preconceptionally, 46 (68.7%) accepted ECS. This was significantly more than for 416 women counseled during pregnancy, of whom 146 (35.1%) accepted (P ≤ 0.001). For pregnant patients, the mean gestational age of those accepting ECS (12 weeks 3 days; n = 146) was significantly lower than those declining (13 weeks 4 days; n = 270; P ≤ 0.001). The acceptance rates were 7 of 12 (58.3%, P = 0.195) for Ashkenazi Jewish women, 12 of 41 (29.3%; P = 0.186) for Asian women, and 7 of 25 (28.0%; P = 0.241) for women of mixed ethnicity. CONCLUSIONS These results suggest that receiving genetic counseling prior to or earlier in the first trimester is associated with acceptance of ECS and support the importance of early genetic counseling about carrier screening options.

Placenta previa is widely acknowledged as a risk factor for placenta accreta spectrum (PAS) disorders, which are severe maternal complications; however, data are limited regarding whether placenta previa is associated with a higher risk of worse maternal outcomes among patients with PAS disorders.To examine the association between placenta previa and the risk of severe maternal morbidities (SMMs) and higher resource use among patients with PAS disorders.This retrospective cohort study extracted records of 3793 patients with PAS diagnosis and delivery indicators between October 1, 2015, and December 31, 2019, from the US National Inpatient Sample database.Placenta previa.Data on 21 Centers for Disease Control and Prevention-defined SMMs and 25 study-defined surgical morbidities associated with PAS were extracted. Six surgical procedures (cystoscopy, intra-arterial balloon occlusion, cesarean delivery, hysterectomy, cystectomy, and oophorectomy), hospital length of stay, and inpatient costs were compared. Multivariable Poisson regression models built in the generalized estimating equation framework were used.Among 3793 patients with PAS (median [IQR] age at admission, 33 [29-37] years), 621 women (16.4%) were Black, 765 (20.2%) were Hispanic, 1779 (46.9%) were White, 441 (11.6%) were of other races and/or ethnicities (47 [1.2%] were American Indian, 220 [5.8%] were Asian or Pacific Islander, and 174 [4.6%] were of multiple or other races and/or ethnicities), and 187 (4.9%) were of unknown race and ethnicity. A total of 1323 patients (34.9%) had placenta previa and 2470 patients (65.1%) did not; of those with placenta previa, 405 patients (30.6%) had invasive PAS. Patients with vs without placenta previa had a significantly higher rate and risk of any SMM (935 women [70.7%] vs 1087 women [44.0%]; P.001; adjusted risk ratio [aRR], 1.19; 95% CI, 1.12-1.27) and any surgical morbidity (1170 women [88.4%] vs 1667 women [67.5%]; P.001; aRR, 1.18; 95% CI, 1.13-1.23). With regard to specific outcomes, those with vs without placenta previa had a significantly higher rate of peripartum hemorrhage (878 patients [66.4%] vs 1217 patients [49.3%]; P.001), blood product transfusion (413 patients [31.2%] vs 610 patients [24.7%]; P.001), shock (83 patients [6.3%] vs 108 patients [4.4%]; P = .01), disseminated intravascular coagulation or other coagulopathy (77 patients [5.8%] vs 105 patients [4.3%]; P = .04), and urinary tract injury (44 patients [3.3%] vs 41 patients [1.7%]; P = .002). Patients with vs without placenta previa were more likely to undergo cesarean delivery (1292 patients [97.7%] vs 1787 patients [72.3%]; P.001), hysterectomy (786 patients [59.4%] vs 689 patients [27.9%]; P.001), cystoscopy (301 patients [22.8%] vs 203 patients [8.2%]; P.001), cystectomy (157 patients [11.9%] vs 98 patients [4.0%]; P.001), and intra-arterial balloon occlusion (121 patients [9.1%] vs 77 patients [3.1%]; P.001) and to have significantly longer hospital length of stay (median [IQR], 5 [4-11] days vs 3 [3-5] days; P.001) and total inpatient costs (median [IQR], $17 496 [$10 863-$30 619] vs $9728 [$6130-$16 790]; P.001). Hypertensive disorder of pregnancy was associated with a decreased risk of placenta previa (aRR, 0.67; 95% CI, 0.46-0.96) among patients with PAS.In this study, placenta previa was associated with an increased risk of maternal and surgical morbidities and higher resource use among women with PAS. These findings suggest that interventions to alleviate maternal and surgical morbidities are especially needed for patients with placenta previa-complicated PAS disorders.

The characteristics of microbial community changes in pregnant women are still unclear. To investigate the changes in gut microbiota during pregnancy and after delivery in healthy women, we enrolled 47 healthy pregnant women who received obstetric care in our hospital from October 2016 to April 2017 and obtained their fecal samples at different time periods: T1 (11–13 W), T2 (23–28 W), and T3 (33–38 W) during pregnancy, and PP6W (6 weeks postpartum) and PP6M (6 months postpartum). Based on 16S rRNA gene sequencing results, there was no significant difference (p > .05) in the index of alpha-diversity between the pregnancy and postpartum periods. Principal coordinate analysis indicated that gut microbiota clustering during the postpartum period was significantly different from that during pregnancy. Phylum-level comparison of species identified using T1, T2, T3, PP6W, and PP6M samples showed higher abundance of Actinobacteria, Firmicutes, and Proteobacteria, while the abundance of Bacteroidetes decreased. At the genus level, 31 types of bacteria were found to be significantly different among these five groups. Akkermansia, Bacteroides, Subdoligranulum, Oscillospira, Ruminococcacea UCG-004), and Alistipes showed higher abundance during pregnancy, while Bifidobacterium, [Eubacterium] rectale group and Hungatella showed higher abundance after delivery. Therefore, the diversity and function of the gut microbiota in healthy pregnant women remained unchanged during pregnancy; however, the composition of the intestinal microbiota in the postpartum period changed significantly. Our results provide the basis for in-depth studies of the composition of perinatal gut microbial communities in women.

Shifts in the maternal gut microbiota have been implicated in the development of gestational diabetes mellitus (GDM). Understanding the interaction between gut microbiota and host glucose metabolism will provide a new target of prediction and treatment. In this nested case-control study, we aimed to investigate the causal effects of gut microbiota from GDM patients on the glucose metabolism of germ-free (GF) mice. Stool and peripheral blood samples, as well as clinical information, were collected from 45 GDM patients and 45 healthy controls (matched by age and prepregnancy body mass index (BMI)) in the first and second trimester. Gut microbiota profiles were explored by next-generation sequencing of the 16S rRNA gene, and inflammatory factors in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Fecal samples from GDM and non-GDM donors were transferred to GF mice. The gut microbiota of women with GDM showed reduced richness, specifically decreased Bacteroides andAkkermansia, as well as increasedFaecalibacterium. The relative abundance ofAkkermansiawas negatively associated with blood glucose levels, and the relative abundance ofFaecalibacteriumwas positively related to inflammatory factor concentrations. The transfer of fecal microbiota from GDM and non-GDM donors to GF mice resulted in different gut microbiota colonization patterns, and hyperglycemia was induced in mice that received GDM donor microbiota. These results suggested that the shifting pattern of gut microbiota in GDM patients contributed to disease pathogenesis.

To compare conservative management and cesarean hysterectomy in patients with placenta increta or percreta.In this multicenter retrospective study, we recorded data on 2219 patients with placenta increta or percreta from 20 tertiary care centers in China from 1 January 2011 to 31 December 2015. Propensity score analysis was used to control for baseline characteristics. We divided patients into conservative management (C) and hysterectomy (H) groups. The primary outcome was operative/postoperative maternal morbidity; secondary outcomes were maternal-neonatal outcomes.In total, 17.9% (398/2219) of patients had placenta increta and percreta; 82.1% (1821/2219) of the patients were in group C. After propensity score matching, 140 pairs of patients from the two groups underwent one-to-one matching. Group C showed less average blood loss within 24 h of surgery (1518 ± 1275 vs. 4309 ± 2550 ml in group H,Either conservative management or hysterectomy should be considered after thorough evaluation and detailed discussion of risks and benefits. A balance between bleeding control and fertility can be achieved.

Objectives To analyze the association between pre-operational coagulation indicators and the severity of placenta accreta spectrum (PAS), as well as blood loss volume during operation. Methods Hospitalized patients of the obstetric department in a major hospital from 2018 to 2020 who were clinically and/or pathologically diagnosed with invasive PAS were included. Univariate and multivariate logistic regression and Poisson regression models were used to quantify the association between each of the 6 coagulation indicators and PAS severity (measured by FIGO grade) as well as maternal outcomes. Results Ninety-five patients (46 FIGO grade 2 and 49 FIGO grade 3) were included. Higher PT [adjusted OR (aOR): 5.54; 95% CI, 1.80 to 17.07] and FDP (aOR: 1.19; 95% CI, 1.01–1.42) levels were associated with an increased risk of FIGO grade 3 after adjusting for covariates. D-dimer [incidence rate ratio (IRR): 1.19; 95% CI, 1.05 to 1.35)] and FDP (IRR: 1.03; 95% CI, 1.01–1.04) levels were significantly associated with higher blood loss volume after adjusting for covariates. Conclusion Preoperative coagulation indicators, especially PT, D-dimer and FDP, are associated with disease severity and blood loss volume during operation of invasive PAS. The underlying mechanism for the coagulation profile of PAS patients warrants further analysis. Synopsis Preoperative coagulation indicators, especially PT, D-dimer and FDP, are associated with disease severity and blood loss volume during operation among invasive placenta accreta spectrum patients.

Background: To investigate the benefits and cost effectiveness of NIPT as primary or contingent strategies within high risk population, in accordance with increasing advanced maternal age (AMA) and NIPT rapid application. Methods: A theoretical model involving 1,000,000 single pregnancies was established. NIPT together with or without traditional triple serum screening constitutes five screening scenarios. All related parameters were referred to publication or on-site verification. Strategy 1, NIPT is primarily offered to all pregnant women. Strategy 2, NIPT is offered to all pregnancies with risks higher than 1:300 (Strategy 2-1) or 1:1000 (Strategy 2-2) after triple serum screening. Strategy 3 is stratified based on maternal age in which 1) for age 40 and more, prenatal diagnosis is directly offered, 2) for population of maternal age for 35~39, primary NIPT is introduced, 3) if younger than 35y, contingent strategy with risk higher than 1:300 (Strategy 3-1) or 1:1000 (Strategy 3-2) as the indication for NIPT. The primary outcome is incremental cost analysis on baseline and alterative assumptions. The second outcomes are total cost, cost-effect and cost-benefit analysis. The strategy is defined as "cost-effective" if the incremental cost is less than 0.16million US$, needed for raising one T21 livebirth or the benefit-to-cost ratio is above 1. Findings: With the advantage of lower false positive rate of NIPT, anticipated prenatal diagnosis are greatly reduced. In cost-effectiveness analysis, strategy 2-1 costs least with 112.9million US$ in total, 33.4 thousand US$ in cost-effect analysis and ratioed as 3.53 in cost-benefit analysis. Setting 2-1 as baseline, incremental costs of strategy 1, 3-2, 2-2 and 3-1 are 0.67million US$, 0.25million US$, 0.22million US$ and 0.17million US$, which are all more than costs for raising one visible T21. In sensitivity analysis of age proportion, when AMA account for more than 15.5% in population, incremental costs of strategy 3-1 are lower than 0.16million US$. All strategies are considered as "appropriate" if NIPT costs less than 106 US$. When it's less than 309 US$, the incremental cost of strategy 3-1 is least and lower than 0.16million US$. Strategy 1 needs least money when it's lower than 47 US$. Interpretation: Strategy 2-1 is optimal in cost-effectiveness analysis. AMA proportion and NIPT costs are two important factors. Strategy 3-1 is more prominent as AMA increases. Strategy 1 is the most effective and cost-effectiveness method under an affordable price. Funding: National Key Technologies R&D program of China (2016YFC1000303). Declaration of Interest: The authors have no conflict of interests. Ethical Approval: This study was exempted from ethics committee approval for the pure theoretical model involving 1,000,000 single pregnant women in China.

IntroductionThe gut microbiota participates in multiple human biological processes, including metabolism and immune responses. During pregnancy, the dynamics of gut microbiota is involved in physiological adaptation. The disturbed profile of microbiome is associated with maternal complications, such as gestational diabetes mellitus (GDM), which further transfers to the offspring and influence their metabolic and immunological functions in the long term. Prebiotics targeting the gut microbiota and modulating metabolic and immune functions have been shown to be effective in non-pregnant populations with metabolic syndrome. Hence, we propose the use of a prebiotic supplement, oligosaccharide-sialic acid (OS) from the first trimester until delivery in pregnant women, can benefit maternal/new-born gut microbiome, glucose metabolism and innate immunity.Methods and analysisIn this prospective double-blinded randomised clinical trial, recruited singleton pregnancies will be stratified by body mass index (BMI) and randomly assigned to consume the OS preparation or placebo daily from the first trimester. At seven later time points (before and after recruitment in the first trimester, in the middle and third trimesters, before delivery, at birth and 42 days postpartum), compliance will be evaluated and/or biological samples will be collected. Along with maternal clinical information, questionnaires on lifestyle and infant development will be recorded. The primary outcomes are the effect of OS on the maternal-offspring gut microbiome and GDM incidence. The secondary outcomes are maternal glycolipid biochemical parameters, cytokine profiles, weight gain during pregnancy and infant morbidities, growth and development. The study aims to validate the effects of OS on reducing maternal morbidity within different BMI groups. The multiple dimensional dataset generated from the study includes clinical and lifestyle-related information, various biological markers and associated protective or risk factors for morbidity and prognosis. An extended follow-up through 42 days after birth could further explore the intrauterine influence on the long-term health of offspring.Ethics and disseminationThis protocol has been approved by Peking University First Hospital, National Unit of Clinical Trial Ethics Committee (reference number: 164). The results are expected to be published in scientific manuscripts by 2021.Trial registration numberChiCTR1800017192.

To determine the proportion of women with advanced maternal age (AMA) undergoing amniocentesis and assess the recommended indication of 35 years or older in China.Data were retrospectively evaluated from 9641 patients who underwent diagnostic prenatal amniocentesis in Beijing, China, between January 2001 and December 2012. Maternal age, indication for testing, and karyotype data were collected. Patients referred for AMA were stratified in 2 ways: 35-37 years, 38-40 years, and 41 years or older; and indication of AMA alone or combined with other screening. Outcomes and safety performance were compared among the groups.From 2001 to 2012, the annual rate of amniocentesis and the proportion of AMA-related indications increased (P0.01). Overall, 82 abnormalities were detected. In the AMA group, the spontaneous abortion rate was 0.5% (22/4748). The positive predictive value (PPV) of AMA alone was 0.5% for women aged 35-37 years. Only among women aged 41 years or older was the PPV of AMA alone better than that of AMA plus other indications (2.3% vs 1.5%, respectively).The PPV of 35 years or older did not offset the risk of spontaneous abortion. AMA alone should not be used as an indication for amniocentesis especially among women aged 35-40 years.

Insulin resistance (IR) is a critical factor of the pathophysiology of Gestational diabetes mellitus (GDM). Studies on key organs involved in IR, such as livers and adipose tissues, showed that Toll-like receptor 4 (TLR4) can regulate insulin sensitivity. As a maternal-fetal interface with multi-functions, placentae could contribute to the development of IR for GDM. Thus, we investigated the expressions of TLR4/Myeloid Differentiation factor 88 (MyD88)/Nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-kB) in term placentae from 33 GDM women and 36 healthy pregnant women with normal glucose tolerance, evaluated local and systemic IR and furthermore identified the association between placental TLR4 and IR. TLR4 protein was expressed in various cells of term placenta, particularly in syncytiotrophoblast of villi. Compared with normal pregnancy, the expression of TLR4/MyD88/NF-kB pathway increased in the placenta of GDM (p

To evaluate the application of non-invasive prenatal testing (NIPT) in high-risk pregnancies before invasive prenatal diagnosis.This prospective study involved all pregnancies participating in the clinical trial of NIPT validation. The indication, age and gestational week were recorded. And the results of karyotype and NIPT risk were compared.A total of 2 439 high-risk pregnancies were enrolled from 18 prenatal diagnosis clinics in China. After excluding 48 cases (36 missing clinical information, 9 karyotype failures and 3 NIPT failures), 2 391 cases were analyzed. Their gestational ages were 10 to 31 weeks. And 56.3% (1 345/2 691) were at a high risk for mid-trimester screening, following by advanced maternal age (26.0%, 621/2 391). Forty-six aneuploidies (trisomy 21, n = 38; trisomy 18, n = 7; trisomy 13, n = 1) were diagnosed by karyotyping. And it was consistent with the NIPT results of high-risk distribution.NIPT may be used to reduce unnecessary invasive prenatal diagnosis by improving the efficacy of current mid-trimester screening strategy, particularly for trisomy 21.