The Transcriptome and DNA Methylome Landscapes of Human Primordial Germ Cells.

Germ cells are vital for transmitting genetic information from one generation to the next and for maintaining the continuation of species. Here, we analyze the transcriptome of human primordial germ cells (PGCs) from the migrating stage to the gonadal stage at single-cell and single-base resolutions. Human PGCs show unique transcription patterns involving the simultaneous expression of both pluripotency genes and germline-specific genes, with a subset of them displaying developmental-stage-specific features. Furthermore, we analyze the DNA methylome of human PGCs and find global demethylation of their genomes. Approximately 10 to 11 weeks after gestation, the PGCs are nearly devoid of any DNA methylation, with only 7.8% and 6.0% of the median methylation levels in male and female PGCs, respectively. Our work paves the way toward deciphering the complex epigenetic reprogramming of the germline with the aim of restoring totipotency in fertilized oocytes.

Deep Learning Model Based on Multisequence MRI Images for Assessing Adverse Pregnancy Outcome in Placenta Accreta.

BACKGROUND: Preoperative assessment of adverse outcomes risk in placenta accreta spectrum (PAS) disorders is of high clinical relevance for perioperative management and prognosis. PURPOSE: To investigate the association of preoperative MRI multisequence images and adverse pregnancy outcomes by establishing a deep learning model in patients with PAS. STUDY TYPE: Retrospective. POPULATION: 323 pregnant women (age from 20 to 46, the median age is 33), suspected of PAS, underwent MRI to assess the PAS, divided into the training (N = 227) and validation datasets (N = 96). FIELD STRENGTH/SEQUENCE: 1.5T scanner/fast imaging employing steady-state acquisition sequence and single shot fast spin echo sequence. ASSESSMENT: Different deep learning models (i.e., with single MRI input sequence/two sequences/multisequence) were compared to assess the risk of adverse pregnancy outcomes, which defined as intraoperative bleeding ≥1500 mL and/or hysterectomy. Net reclassification improvement (NRI) was used for quantitative comparison of assessing adverse pregnancy outcome between different models. STATISTICAL TESTS: The AUC, sensitivity, specificity, and accuracy were used for evaluation. The Shapiro-Wilk test and t-test were used. A P value of <0.05 was considered statistically significant. RESULTS: 215 cases were invasive placenta accreta (67.44% of them with adverse outcomes) and 108 cases were non-invasive placenta accreta (9.25% of them with adverse outcomes). The model with four sequences assessed adverse pregnancy outcomes with AUC of 0.8792 (95% CI, 0.8645-0.8939), with ACC of 85.93% (95%, 84.43%-87.43%), with SEN of 86.24% (95% CI, 82.46%-90.02%), and with SPC of 85.62% (95%, 82.00%-89.23%) on the test cohort. The performance of model with four sequences improved above 0.10 comparing with that of model with two sequences and above 0.20 comparing with that of model with single sequence in terms of NRI. DATA CONCLUSION: The proposed model showed good diagnostic performance for assessing adverse pregnancy outcomes. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Serum lipid reference values recommended during a twin pregnancy and evaluating its association with perinatal outcomes.

BACKGROUND: Maternal lipid metabolism fluctuations have been shown to increase the risk of adverse pregnancy outcomes. However, there is no consensus over what constitutes normal maternal lipid values during twin pregnancy. Therefore, the aim of this study was to establish a serum lipid reference range for a twin pregnancy. METHODS: A retrospective survey was conducted, from 2011 to 2021, at the Peking University Third Hospital. A total of 881 twin pregnancies, with lipid data from early and middle pregnancies, were included. After excluding those with adverse pregnancy outcomes, we performed a descriptive analysis of total cholesterol (TC), triglycerides (TG), high-density lipid cholesterol (HDL-C), and low-density lipid cholesterol (LDL-C) levels, using the mean and standard deviation to determine appropriate percentiles. We later determined the lipid reference range in early and middle pregnancy based on the initial results. We evaluated Inappropriate lipid levels associations with pregnancy outcomes, including gestational diabetes, pregnancy-induced hypertension, small for gestational age. RESULTS: (1) Serum levels of TC, TG, LDL-C, and HDL-C increased significantly from early to late pregnancy, where the greatest increase was observed in TG. (2) Based on the results, we recommend that TC, TG, and LDL-C serum reference values during early and middle pregnancy should be less than the 95th percentile. On the other hand, HDL-C should be greater than the 5th percentile. During early pregnancy, the values recommended are TC < 5.31 mmol/L, TG < 2.25 mmol/L, HDL > 1.02 mmol/L and LDL < 3.27 mmol/L, and those during middle pregnancy are TC < 8.74 mmol/L, TG < 4.89 mmol/L, HDL > 1.25 mmol/L and LDL < 5.49 mmol/L, while the values during late pregnancy are TC < 9.11 mmol/L, TG < 6.70 mmol/L, HDL > 1.10 mmol/L and LDL < 5.81 mmol/L. Higher levels of blood lipids were associated with GDM, PE, SGA. CONCLUSIONS: We suggested a reference ranges for blood lipids during the twin pregnancy in a Chinese population. The reference ranges recommended by this study can be used to identify women with twin pregnancies using unfavorable lipid values. Higher levels of blood lipids were associated with adverse pregnancy outcomes.

The changing Doppler patterns and perinatal outcomes of monochorionic diamniotic twins with selective fetal growth restriction.

OBJECTIVES: To investigate the clinical outcomes and Doppler patterns changes in monochorionic diamniotic (MCDA) twins with selective fetal growth restriction (sFGR). METHODS: We retrospectively analyzed 362 sFGR cases from January 2010 to May 2016 at a single tertiary referral center. The Doppler waveforms of umbilical artery end-diastolic flow were collected, and all neonates were subjected to an early neonatal brain scan. RESULTS: A total of 66/100 (66 %) type I cases were stable, whereas 25/100 (25 %) cases changed to type II and 9/100 (9 %) changed to sFGR complicated twin-twin transfusion syndrome (TTTS). A total of 48.9 % (22/45) sFGR cases were complicated with polyhydramnios and 30.4 % (7/23) sFGR cases were complicated with oligohydramnios, both of which were progressed to sFGR with TTTS. Mild cerebral injury was significantly associated with Doppler flow abnormalities, earlier gestational age at delivery and type of sFGR diagnosis. Severe cerebral injury was significantly associated with gestational age at delivery (31.6 vs. 34.1, p=0.002) and larger birthweight discordance (43.9 vs. 29.3 %, p=0.011). CONCLUSIONS: Doppler patterns in sFGR can gradually change, with important consequences with regard to management and outcomes. Along with abnormal Doppler findings, earlier occurrence of sFGR and delivery are associated with subsequent neonatal cerebral injury.

Metabolic dynamics and prediction of sFGR and adverse fetal outcomes: a prospective longitudinal cohort study.

BACKGROUND: Selective fetal growth restriction (sFGR) is an extreme complication that significantly increases the risk of perinatal mortality and long-term adverse neurological outcomes in offspring, affecting approximately 15% of monochorionic diamniotic (MCDA) twin pregnancies. The lack of longitudinal cohort studies hinders the early prediction and intervention of sFGR. METHODS: We constructed a prospective longitudinal cohort study of sFGR, and quantified 25 key metabolites in 337 samples from maternal plasma in the first, second, and third trimester and from cord plasma. In particular, our study examined fetal growth and brain injury data from ultrasonography and used the Ages and Stages Questionnaire-third edition subscale (ASQ-3) to evaluate the long-term neurocognitive behavioral development of infants aged 2-3 years. Furthermore, we correlated metabolite levels with ultrasound data, including physical development and brain injury indicators, and ASQ-3 data using Spearman's-based correlation tests. In addition, special combinations of differential metabolites were used to construct predictive models for the occurrence of sFGR and fetal brain injury. RESULTS: Our findings revealed various dynamic patterns for these metabolites during pregnancy and a maximum of differential metabolites between sFGR and MCDA in the second trimester (n = 8). The combination of L-phenylalanine, L-leucine, and L-isoleucine in the second trimester, which were closely related to fetal growth indicators, was highly predictive of sFGR occurrence (area under the curve [AUC]: 0.878). The combination of L-serine, L-histidine, and L-arginine in the first trimester and creatinine in the second trimester was correlated with long-term neurocognitive behavioral development and showed the capacity to identify fetal brain injury with high accuracy (AUC: 0.94). CONCLUSIONS: The performance of maternal plasma metabolites from the first and second trimester is superior to those from the third trimester and cord plasma in discerning sFGR and fetal brain injury. These metabolites may serve as useful biomarkers for early prediction and promising targets for early intervention in clinical settings.

Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta.

Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0 ) synthesis, reduced estradiol (E2 ), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE-like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP-treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2 , but not T0 , actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1-PKA-CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17ß-HSD3 and 3ß-HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.

Outcomes of fetal reduction versus expectant management in dichorionic triamniotic triplets.

OBJECTIVE: To compare the outcomes of dichorionic triamniotic (DCTA) triplets who underwent fetal reduction (FR) to singletons or twins with those managed expectantly. METHODS: We conducted a retrospective study of DCTA triplets with three living fetuses at 11-14 weeks over a 7-year period. Pregnancy outcomes were compared following different management strategies. RESULTS: Of 108 included patients, 22 underwent expectant management (EM), 28 were reduced to dichorionic diamniotic twins, and 58 to singletons. The median gestational age at birth for EM, FR to twins, and singletons was 33.1 weeks, 37.0 weeks, and 38.6 weeks, respectively (P < 0.001). Prematurity before 37 and 34 weeks was less common following FR to singletons and twins than in ongoing triplets (18.9%, 46.2% and 90.5%, P < 0.001; 13.2%, 26.9% and 57.1%, P < 0.001). Neonatal birth weight was higher in triplets reduced to singletons and twins compared with EM cases (3140g, 2315g, and 1860g, P < 0.001). However, rates of miscarriage, pregnancies with ≥1 survivor, maternal complications, and adverse neonatal outcomes were comparable among the three groups. CONCLUSIONS: In our experience, FR in DCTA triplets could reduce prematurity risk compared to EM, but it confers no survival advantage. Fetal reduction to singletons may result in more favorable outcomes than those reduced to dichorionic twins.

Initial establishment and validation of a predictive model for preeclampsia in twin pregnancies based on maternal characteristics and echocardiographic parameters.

INTRODUCTION: The primary objective of this study was to evaluate the association between maternal echocardiographic changes and the occurrence of preeclampsia (PE) in twin pregnancies. Additionally, we established and validated a prediction model for PE in twin pregnancies. MATERIAL AND METHODS: The first part of this study was retrospective and included data from 854 twin pregnancies that received antenatal care at Peking University Third Hospital from April 2017 to April 2021 (training cohort). Overall, 159 women who underwent transthoracic echocardiography were included in the analysis. To build a predictive model, cardiac findings were compared between normotensive women and those with PE. The model was then validated in a prospective longitudinal cohort (test cohort) that included 109 women with twin pregnancies who underwent two consecutive transthoracic echocardiography examinations during the second and third trimesters. RESULTS: Fifty-four normotensive women and 105 women with PE were analyzed in the retrospective cohort that was used to build the model in which later preeclampsia was associated with higher left ventricular mass index (>61 g/m2 ), interventricular septal thickness (>7.87 mm), left atrial anteroposterior diameter (>33.5 mm), mitral inflow late diastolic velocity (A) (>0.685 m/s), ratio of early diastolic velocity (E) and peak early diastolic myocardial velocity of the lateral mitral annulus (>6.5), and lower peak early diastolic myocardial velocity (<13.1 cm/s). The optimized PE prediction model based on the interventricular septal thickness, left atrial anteroposterior diameter, A, peak early diastolic myocardial velocity and pre-pregnancy bodyweight index was then established (area under the curve [AUC] = 0.840, 95% CI 0.778-0.903, P < 0.001). The model was tested in the prospective cohort including 87 normotensive women and 22 women with PE; the validation test showed that the prediction model in the second (AUC = 0.801) and third (AUC = 0.811) trimesters had high discriminative ability and calibration. CONCLUSIONS: Maternal echocardiographic changes in twin pregnancies are associated with the development of preeclampsia. The model constructed, based on the echocardiographic parameters and body mass index, provides novel ideas for the prediction of PE.

A study on the correlation of placental anastomosis and superficial vascular branches of selective fetal growth restriction in monochorionic diamniotic twins.

INTRODUCTION: The main purpose of the present study was to investigate the correlation between placental anastomosis and superficial vascular branches in selective fetal growth restriction (sFGR) in monochorionic diamniotic twins. MATERIALS AND METHODS: This was a retrospective analysis of the pregnancy data and placental perfusion of 395 patients with monochorionic diamniotic (MCDA) twin pregnancies delivered at our hospital from April 2013 to April 2020. We divided the patients into two groups and compared the number of placental superficial vascular branches in sFGR twins and normal MCDA twins. The correlation between the placental anastomosis and the number of superficial vascular branches in sFGR and normal MCDA twins was also investigated. RESULTS: The number of umbilical arterial branches and umbilical venous branches was less than larger twins in sFGR, larger twins in normal MCDA and smaller twins in normal MCDA. (11.83 [4-44], 21.82 [7-50], 19.72 [3-38], 14.85 [0-31], p < 0.001, 6.08 [1-18], 9.60 [3-22], 9.96 [2-22], 8.38 [1-20], p < 0.00) For smaller twins in the sFGR group, the number of umbilical venous branches was positively associated with AA anastomosis overall diameter, AV anastomosis overall diameter and all anastomosis overall diameter. (r = 0.194, 0.182 and 0.211, p < 0.05) CONCLUSIONS: The risk of sFGR may arise when the placenta from MCDA twins shows a poor branching condition of placental superficial vessels. For the smaller twin of sFGR, regular ultrasound examination of the number of the umbilical venous branches may help to predict artery-to-artery (AA) overall diameter, artery-to-vein (AV) overall diameter and all anastomosis overall diameter.

Unfavourable intrauterine environment contributes to abnormal gut microbiome and metabolome in twins.

OBJECTIVE: Fetal growth restriction (FGR) is a devastating pregnancy complication that increases the risk of perinatal mortality and morbidity. This study aims to determine the combined and relative effects of genetic and intrauterine environments on neonatal microbial communities and to explore selective FGR-induced gut microbiota disruption, metabolic profile disturbances and possible outcomes. DESIGN: We profiled and compared the gut microbial colonisation of 150 pairs of twin neonates who were classified into four groups based on their chorionicity and discordance of fetal birth weight. Gut microbiota dysbiosis and faecal metabolic alterations were determined by 16S ribosomal RNA and metagenomic sequencing and metabolomics, and the long-term effects were explored by surveys of physical and neurocognitive development conducted after 2~3 years of follow-up. RESULTS: Adverse intrauterine environmental factors related to selective FGR dominate genetics in their effects of elevating bacterial diversity and altering the composition of early-life gut microbiota, and this effect is positively related to the severity of selective FGR in twins. The influence of genetic factors on gut microbes diminishes in the context of selective FGR. Gut microbiota dysbiosis in twin neonates with selective FGR and faecal metabolic alterations features decreased abundances of Enterococcus and Acinetobacter and downregulated methionine and cysteine levels. Correlation analysis indicates that the faecal cysteine level in early life is positively correlated with the physical and neurocognitive development of infants. CONCLUSION: Dysbiotic microbiota profiles and pronounced metabolic alterations are associated with selective FGR affected by adverse intrauterine environments, emphasising the possible effects of dysbiosis on long-term neurobehavioural development.

Hypoxic stress disrupts HGF/Met signaling in human trophoblasts: implications for the pathogenesis of preeclampsia.

BACKGROUND: Preeclampsia (PE), a placenta-associated pregnancy complication, is the leading cause of maternal and perinatal morbidity and mortality. Met/Erk signaling is inhibited in the placentas of patients with early-onset preeclampsia (E-PE), but the underlying mechanisms remain elusive. In this study, the expression modes of Met and endocytic vesicles in normal and preeclamptic placentas were compared. Biotinylation internalization/recycling assays were used to measure the endocytosis of Met under hypoxia and normoxia in HTR8/SVneo cells. In addition, the expression level of Cbl, a specific E3 ligase of Met, was measured under hypoxia and normoxia, and the endocytosis of Met was studied by using confocal microscopy. RESULTS: We found considerable intracellular accumulation of Met, which was colocalized with caveolin-1 (CAV-1), in trophoblasts from E-PE placentas. Prolonged hypoxic stimulation led to the remarkable augmentation of CAV-1-mediated Met endocytosis in HTR8/SVneo cells. In addition, the expression of Cbl was substantially repressed by sustained hypoxia, disrupting ubiquitin degradation and the subsequent intracellular accumulation of Met in HTR8/SVneo cells. The abnormal degradation of Met hampered the ability of hepatocyte growth factor (HGF) to promote trophoblast cell invasion. In E-PE placentas, aberrant upregulation of CAV-1 and downregulation of Cbl were observed in parallel to the intracellular accumulation of Met. CONCLUSIONS: These findings reveal that prolonged hypoxic stress induces the augmentation of endocytosis and repression of ubiquitin-mediated Met degradation, which leads to the impaired regulation of trophoblast invasion by HGF/Met signaling. These data provide novel evidence for elucidating the pathogenesis of preeclampsia, especially of the early-onset subtype.

Is there a relationship between plasma, cytokine concentrations, and the subsequent risk of postpartum hemorrhage?

BACKGROUND: Postpartum hemorrhage remains the leading cause of maternal mortality. However, there is an insufficient understanding of atonic postpartum hemorrhage. Uterine atony is the most common cause of postpartum hemorrhage. Although an association between myometrium inflammatory cytokines and atonic postpartum hemorrhage has been demonstrated preliminarily, it is not clinically useful in predicting postpartum hemorrhage. Plasma is more readily available, and the assessment of its inflammatory status is more relevant to biological markers of postpartum hemorrhage and might explain the pathophysiology of atonic postpartum hemorrhage. OBJECTIVE: Our objective was to examine changes in maternal plasma cytokines in women with atonic postpartum hemorrhage. STUDY DESIGN: This was a retrospective longitudinal case-control study of pregnant women with singleton gestations at term undergoing vaginal delivery. Cases were women with atonic postpartum hemorrhage, and 1:1 propensity-score matching was used to match the control group. Maternal plasma was collected in the first trimester, early third trimester, and late third trimester, and multiplex Luminex assay was used to determine the cytokine concentrations. Multivariate logistic regressions were used to determine the association between maternal cytokines at different stages of pregnancy and atonic postpartum hemorrhage. RESULTS: A total of 36 pregnant women met the clinical diagnostic criteria for atonic postpartum hemorrhage, and 36 patients without postpartum hemorrhage were matched as the control group. Concentrations were lower for most cytokines in the atonic postpartum hemorrhage group in the first and early third trimester. However, in the late third trimester, higher plasma concentrations of basic fibroblast growth factor, interleukin-1 alpha, interleukin-1 beta, interleukin-1 receptor antagonist, interleukin-2 receptor alpha, interleukin-16, interleukin-18, macrophage colony stimulating factor, macrophage inflammatory protein-1 alpha, beta-nerve growth factor, tumor necrosis factor-related apoptosis-induced ligand, and stem cell factor were significantly associated with increased risk of atonic postpartum hemorrhage. Multiple testing correction showed that basic fibroblast growth factor (P<.001; fold change [FC]=1.16), macrophage inflammatory protein-1 alpha (P<.001; FC=1.15), and stem cell factor (P=.001; FC=1.25) had the most significant difference (P<.001). The prediction model of atonic postpartum hemorrhage constructed by these significantly changed cytokines had a high predictive efficiency (area under the curve, 0.84; sensitivity, 0.78; specificity, 0.83; +likelihood ratio, 4.66; -likelihood ratio, 0.27). CONCLUSION: Higher concentrations of maternal plasma cytokines in the late third trimester are associated with high risk of subsequent atonic postpartum hemorrhage. These indicators may be potential biomarkers for predicting atonic postpartum hemorrhage.

A randomized controlled trial of low-dose aspirin for the prevention of preeclampsia in women at high risk in China.

BACKGROUND: Low-dose aspirin has been the most widely studied preventive drug for preeclampsia. However, guidelines differ considerably from country to country regarding the prophylactic use of aspirin for preeclampsia. There is limited evidence from large trials to determine the effect of 100 mg of aspirin for preeclampsia screening in women with high-risk pregnancies, based on maternal risk factors, and to guide the use of low-dose aspirin in preeclampsia prevention in China. OBJECTIVE: The Low-Dose Aspirin in the Prevention of Preeclampsia in China study was designed to evaluate the effect of 100 mg of aspirin in preventing preeclampsia among high-risk pregnant women screened with maternal risk factors in China, where preeclampsia is highly prevalent, and the status of low-dose aspirin supply is commonly suboptimal. STUDY DESIGN: We conducted a multicenter randomized controlled trial at 13 tertiary hospitals from 11 provinces in China between 2016 and 2019. We assumed that the relative reduction in the incidence of preeclampsia was at least 20%, from 20% in the control group to 16% in the aspirin group. Therefore, the targeted recruitment number was 1000 participants. Women were randomly assigned to the aspirin or control group in a 1:1 allocation ratio. Statistical analyses were performed according to an intention-to-treat basis. The primary outcome was the incidence of preeclampsia, diagnosed along with a systolic blood pressure of ≥140 mm Hg or a diastolic blood pressure of ≥90 mm Hg after 20 weeks of gestation, with a previously normal blood pressure (systolic blood pressure of <140 mm Hg and diastolic blood pressure of <90 mm Hg), and complicated by proteinuria. The secondary outcomes included maternal and neonatal outcomes. Logistic regression analysis was used to determine the significance of difference of preeclampsia incidence between the groups for both the primary and secondary outcomes. Interaction analysis was also performed. RESULTS: A total of 1000 eligible women were recruited between December 2016 and March 2019, of which the final 898 patients were analyzed (464 participants in the aspirin group, 434 participants in the control group) on an intention-to-treat basis. No significant difference was found in preeclampsia incidence between the aspirin group (16.8% [78/464]) and the control group (17.1% [74/434]; relative risk, 0.986; 95% confidence interval, 0.738-1.317; P=.924). Likewise, adverse maternal and neonatal outcomes did not differ significantly between the 2 groups. Meanwhile, the incidence of postpartum hemorrhage between the 2 groups was similar (6.5% [30/464] in the aspirin group and 5.3% [23/434] in the control group; relative risk, 1.220; 95% confidence interval, 0.720-2.066; P=.459). We did not find any significant differences in preeclampsia incidence between the 2 groups in the subgroup analysis of the different risk factors. CONCLUSION: A dosage of 100 mg of aspirin per day, initiated from 12 to 20 gestational weeks until 34 weeks of gestation, did not reduce the incidence of preeclampsia in pregnant women with high-risk factors in China.

Outcome of monochorionic triamniotic triplet pregnancies: Expectant management versus fetal reduction.

OBJECTIVE: To compare the outcomes of monochorionic triamniotic (MCTA) triplets managed expectantly with those reduced to twins. METHOD: This was a retrospective cohort study comparing expectant management (EM) with fetal reduction (FR) to twins in 43 consecutive MCTA triplets with 3 live fetuses at 11-14 weeks between 2012 and 2021. RESULTS: Nineteen patients managed expectantly and 24 triplets reduced to twins were included. The rate of pregnancy with at least one survivor was 84.2% in the EM group and 66.7% in the FR group (P = 0.190). Compared to the EM cases, triplets reduced to twins had a higher median gestational age at delivery (36.0 vs. 33.3 weeks; P < 0.001), a higher mean birth weight (2244.3 ± 488.6 g vs. 1751.1 ± 383.2 g; P < 0.001) and a lower risk of preterm birth before 34 weeks (11.8% vs. 64.7%; P = 0.001). There were no significant differences in the risk of miscarriage, pregnancy complications and composite adverse neonatal outcomes. CONCLUSION: In MCTA triplets, FR to twins could reduce the risk of preterm birth, whereas EM seems to be a reasonable choice when the priority is at least one survivor. However, due to the small sample size of this study, these findings must be interpreted with great caution.

Analysis of risk factors for massive intraoperative bleeding in patients with placenta accreta spectrum.

BACKGROUND: To analyze relevant factors for massive postpartum hemorrhage in women with placenta accreta spectrum in order to improve the ability to identify those at risk for intraoperative bleeding and improve outcome. METHODS: This study is a retrospective study and based on data from Hospital electronic medical record. Placenta accreta patients who delivered by cesarean section at Peking University Third Hospital from September 2017 to December 2019 were selected and included. According to the amount of intraoperative bleeding, they were categoried into the massive bleeding group (bleeding volume ≥ 2000 mL, 68 cases) and non-massive bleeding group (bleeding volume < 2000 mL, 99 cases). Univariate analysis and multivariate logistic regression were used to analyze the correlations between related risk factors or ultrasound imaging characteristics and the severity of bleeding during operation. RESULTS: (1) There were statistically significant differences in gravidity, parity, number of prior cesarean deliveries and placenta accreta ultrasound scores (P < 0.05) between the two groups of patients. (2) Among the ultrasonographic indicators, the disappearance of the post-placental clear space, the emergence of cross-border blood vessels in the region of subplacental vascularity, interruption or disappearance of the bladder line, and the presence of the cervical blood sinus had the most significant correlation with hemorrhage during PAS (P < 0.05). CONCLUSION: The presence of cervical blood sinus, interruption or disappearance of bladder line, the disappearance of the post-placental clear space and abnormal subplacental vascularity are independent risk factors for massive hemorrhage during PAS. We should pay more attention to these indicators in prenatal ultrasound examination in order to reduce the intraoperative bleeding and improve maternal outcomes.

Comparison of pregnancy outcomes and placental characteristics between selective fetal growth restriction with and without thick arterio-arterial anastomosis in monochorionic diamniotic twins.

BACKGROUND: Unequal placental territory in monochorionic diamniotic twins is a primary cause of selective fetal growth restriction (sFGR), and vascular anastomoses play important role in determining sFGR prognosis. This study investigated differences in placental characteristics and pregnancy outcomes in cases of sFGR with and without thick arterio-arterial anastomosis (AAA). METHODS: A total of 253 patients diagnosed with sFGR between April 2013 and April 2020 were retrospectively analyzed. An AAA greater than 2 mm in diameter was defined as a thick AAA. We compared placental characteristics and pregnancy outcomes between cases of sFGR with and without thick AAA. RESULTS: Prevalence of AAA, thick arterio-venous anastomosis (AVA), veno-venous anastomosis (VVA), and thick VVA were significantly higher in the thick AAA group relative to the non-thick AAA group (100.0 vs. 78.5%, P < 0.001; 44.3 vs. 15.4%, P < 0.001; 27.1 vs. 10.8%, P = 0.017, and 24.3 vs. 6.2%, P = 0.004, respectively). The total numbers of AVA and total anastomoses were significantly higher in thick AAA group relative to the non-thick AAA group (5 [1, 14] vs. 3 [1, 15, P = 0.016; and 6 [1, 15] vs. 5 [1, 16], P = 0.022, respectively). The total diameter of AAA, AVA, VVA, and all anastomoses in the thick AAA group was larger than in the non-thick AAA group (3.4 [2.0,7.1] vs. 1.4 [0.0, 3.3], P < 0.001; 6.3 [0.3, 12.0] vs. 2.5 [0.3, 17.8], P < 0.001; 4.2±1.8 vs. 1.9±1.2, P =0.004; and 10.7 [3.2,22.4] vs. 4.4 [0.5, 19.3], P < 0.001, respectively). Growth-restricted fetuses in the thick AAA group exhibited significantly increased birthweight relative to those in thenon-thick AAA group (1570 (530, 2460)g vs. 1230 (610, 2480)g, p = 0.002). CONCLUSIONS: In the placentas associated with sFGR, thick AAA can co-occur with thick AVA and VVA, and placental angiogenesis may differ significantly based upon whether or not thick AAA is present. The birth weights of growth-restricted fetuses in cases of sFGR with thick AAA are larger than in cases without thick AAA.

Placental characteristics of selective intrauterine growth restriction with changing patterns in umbilical artery Doppler flow in monochorionic diamniotic twins.

OBJECTIVES: To compare the placental features between selective intrauterine growth restriction (sIUGR) patients, with dynamic classification (DC) and stable classifications (SC). METHODS: A cohort study was conducted from 1st April 2013 to 1st April 2020, we recruited sIUGR patients who had delivered at our center and examined placental characteristics with dye injection. The primary outcome was placental characteristics. RESULTS: The prevalence of large artery-artery anastomosis (AAA) was significantly higher in sIUGR with DC than sIUGR with SC (88.2 vs. 46.6%, p=0.001). The total diameter of AAA was significantly larger in sIUGR with DC than sIUGR with SC [2.9 (1.4, 7.0) vs. 2.4 (0.3, 7.1) mm, p=0.032]. The total number of artery-vein anastomosis was significantly smaller in sIUGR with DC than sIUGR with SC [3 (1, 12) vs. 5 (1, 15), p=0.023]. The incidence of neonatal asphyxias of growth-restricted fetuses were higher in sIUGR with DC than sIUGR with SC (23.5 vs. 5.9%, p=0.033). CONCLUSIONS: Large AAA is probably associated to sIUGR with dynamic classification.

The relationship between placental characteristics and birthweight discordance in different types of selective intrauterine growth restriction in monochorionic diamniotic twins: A single-center 7 year cohort study.

OBJECTIVE: To clarify the relationships between placental characteristics and birthweight discordance in three types of selective intrauterine growth restriction (sIUGR) in monochorionic diamniotic twins. METHODS: A retrospective cohort study was conducted between april 2013 and april 2020. Associations between placental characteristics and birthweight discordance were evaluated through multiple linear regression analyses with two models for each sIUGR type. Model A was adjusted for gestational age, Model B additionally adjusted for the impact of placental characteristics interacted. RESULTS: In cases of type I sIUGR, birthweight discordance ratio was positively associated with placental territory discordance ratio [(ß = 0.181,95%CI(0.072,0.290), p < 0.05), (ß = 0.239,95%CI(0.125, 0.353), p < 0.05)] under both Model A and Model B. In-type II sIUGR [(ß = -0.012,95%CI(-0.020, -0.004), p < 0.05) (ß = -0.010,95%CI (-0.018, -0.002), p < 0.05)] and type III sIUGR [(ß = -0.011,95%CI (-0.021, -0.001), p < 0.05), (ß = -0.012,95%CI(-0.022, -0.003), p < 0.05)], birthweight discordance ratio was negatively associated with the total diameter of all the anastomoses as calculated with both Model A and Model B. CONCLUSION: Birthweight discordance is primarily related to placental territory discordance in type I sIUGR, whereas vascular anastomoses play important roles for growth-restricted fetal compensation in type II and III sIUGR.

Longer distance between umbilical cord insertions is associated with spontaneous twin anemia polycythemia sequence.

INTRODUCTION: The aim of the study was to investigate the placental characteristics in spontaneous twin anemia polycythemia sequence. MATERIAL AND METHODS: A retrospective case-control study of spontaneous twin anemia polycythemia sequence, twin-to-twin transfusion syndrome and normal monochorionic diamniotic twin pregnancies was performed. The primary outcome was placental characteristics. RESULTS: The prevalence of artery-artery anastomoses in spontaneous twin anemia polycythemia sequence and twin-to-twin transfusion syndrome groups was significantly lower than in the normal monochorionic diamniotic twin group (40.0% vs 33.3% vs 88.8%, respectively, P < .001). The total number of vascular anastomoses in the spontaneous twin anemia polycythemia sequence group (with range given in parentheses) was significantly lower than in the two control groups (3 [1-6] vs 5 [1-14] vs 6 [1-20], P = .001/<.001/.794). The number of artery-vein anastomoses in the spontaneous twin anemia polycythemia sequence was significantly lower than in the two control groups (2 [1-5] vs 4 [1-13] vs 5 [1-19], P = .011/.001/1.000). The total diameter of all vascular anastomoses was significantly smaller in the spontaneous twin anemia polycythemia sequence than in the two control groups (0.9 mm [0.3-4.7] vs 5.2 mm [0.8-24.6] vs 7.3 mm [1.0-25.1], P < .001/<.001/.104), as was the total diameter of artery-to-artery anastomoses (0.5 mm [0.3-1.3] vs 2.0 mm [0.5-11.8] vs 2.3 mm [0.7-9.7], P = .003/<.001/1.000) and the total diameter of artery-to-vein anastomoses (0.8 mm [0.3-2.1] vs 4.6 mm [0.8-15.3] vs 4.0 mm [0.2-21.8], P < .001/<.001/1.000). The ratio between the distance of the two umbilical cords insertion points and the placental maximum diameter in the spontaneous twin anemia polycythemia sequence group was significantly larger than in the two control groups (0.78 [0.49-0.99] vs 0.64 [0.32-1.00] vs 0.55 [0.05-1.00], P = .033/<.001/.138). CONCLUSIONS: In spontaneous twin anemia polycythemia sequence placentas, the number of superficial vascular anastomoses is lower, their diameter is smaller and the distance between the two umbilical cord insertion points is longer.

Placental characteristics in different types of selective fetal growth restriction in monochorionic diamniotic twins.

INTRODUCTION: This study aimed to explore the differences in placental characteristics among three types of selective fetal growth restriction (sFGR) in monochorionic diamniotic twin pregnancies. MATERIAL AND METHODS: A total of 123 placentas with sFGR between April 2013 and October 2019 were retrospectively analyzed after dye injection. Placental characteristics were compared among the three types. RESULTS: The gestational age at diagnosis and delivery was less in sFGR II and III than in sFGR I (22.9 [21.7-33.6], 23.3 [20.0-26.1] and 25.7 [19.0-35.0] weeks, p < 0.001; 32.3 [31.6-35.1], 34.1 [29.9-34.7] and 35.5 [34.0-37.0] weeks, p < 0.001). The birthweight discordance ratio was less in sFGR I than in sFGR II (0.28 [0.14-0.43] and 0.30 [0.23-0.37], p < 0.001). The prevalence of a thick artery-artery anastomosis was higher in sFGR III than in sFGR I or II (81.8%, 44.9% and 48.6%, p = 0.010). The placental territory discordance ratio was higher in sFGR II and III than in sFGR I (0.60 [0.17-0.88], 0.60 [0.01-0.80] and 0.50 [0.01-0.71], p = 0.001). CONCLUSIONS: Compared with sFGR I, the earlier onset time of sFGR II and III might be due to their higher placental territory discordance. The prevalence of thick artery-artery anastomoses was expected to be higher in sFGR III than in sFGR I or II.