Background: Timely and accurate prenatal diagnosis of placenta accreta spectrum (PAS) is pivotal for improving maternal and fetal outcomes. However, the timing of PAS detection and its association with outcomes have rarely been explored. This study examined the association between the gestational week at which PAS was first detected by ultrasound and the clinical characteristics and outcomes of the disorder. Methods: This retrospective cohort study included PAS patients at a tertiary referral center over a 5-year period. Patients who underwent cesarean section with prenatal PAS diagnosis were classified according to the gestational age of the earliest ultrasound PAS detection (<28 weeks or ≥28 weeks). Patient characteristics and outcomes were obtained from the inpatient medical records. Univariate and multivariate robust-error-variance Poisson regression models were used to explore the associations between the timing of ultrasound diagnosis and the risk of intraoperative hemorrhage (≥1500 mL) as well as blood-product transfusion volume (≥800 mL). Results: The study included 166 PAS patients, of whom 39.2% were diagnosed before 28 weeks, and 77.1% delivered at or beyond 34 weeks (median: 35 weeks). Patients with PAS detected before 28 weeks (early detection group) experienced significantly higher intraoperative blood loss volume (median: 1500 mL vs. 800 mL) and red blood cell transfusion volume (median: 586 mL vs. 70 mL). In regression analysis, patients in the early-detection group were significantly more likely to experience blood loss ≥1500 mL and red blood cell transfusion ≥800 mL, and these associations remained significant after adjustment for invasive PAS and hysterectomy. When ultrasound-detection weeks were divided into 6 categories, early detection (<20, 20–24, and 24–28 weeks) was associated with a significantly higher risk of excessive blood loss and increased transfusion volume. Conclusions: PAS detected during the second trimester was associated with more adverse outcomes than cases identified later, highlighting the need for tailored management strategies. The association between gestational age of PAS detection and clinical outcomes warrants further investigation at both clinical and etiological levels.

Placenta Accreta Spectrum (PAS) is a severe obstetric disorder characterized by excessive trophoblast invasion into the uterine myometrium, leading to life-threatening hemorrhage at delivery. While closely monitored, the molecular drivers of its progression remain poorly defined, hindering predictive and therapeutic strategies. Here, we employed longitudinal quantitative proteomics on maternal plasma from five PAS patients across gestation. We identified Keratin 6A (KRT6A) as a key biomarker whose plasma levels increase with PAS progression. Immunohistochemistry confirmed the specific upregulation of KRT6A in trophoblasts at the maternal-fetal interface in PAS. Functional studies demonstrated that KRT6A overexpression significantly enhances the migration and invasion capabilities of trophoblast cell lines in vitro, without affecting proliferation or apoptosis. Integrative bioinformatics analysis linked KRT6A to the activation of the MYC signaling pathway, a known driver of invasiveness. Our data establish KRT6A as a plasma biomarker correlating with PAS severity and a functional regulator of trophoblast invasiveness. These findings suggest a novel mechanism wherein KRT6A-mediated enhancement of trophoblast invasion, potentially via MYC signaling, contributes to PAS pathogenesis. This work provides a potential circulating biomarker for monitoring PAS progression and implicates KRT6A as a candidate therapeutic target for mitigating excessive placental invasion.

Background:Placenta accreta spectrum (PAS) is a leading cause of severe maternal and neonatal complications, yet its risk pathways remain incompletely understood. We aimed to evaluate the association between the number of prior caesarean sections (CS) and adverse maternal and neonatal outcomes in PAS, and to quantify the mediating role of placenta previa (PP) in this relationship. Methods:Based on a retrospective cohort of 231 patients with PAS (61 with no prior CS, 124 with one CS, and 46 with ≥2 CS), we performed multivariate logistic regression to assess associations between CS history and pregnancy outcomes and conducted mediation analysis to estimate the proportion of the CS effect mediated by PP. Results:Patients with ≥2 prior CS had significantly higher rates of second-trimester surgical abortion, percreta, and higher PAS severity scores. While PP, embolisation, blood transfusion, and prolonged hospitalisation were more common in women with any CS history, their frequencies did not increase proportionally with the number of CS. Multivariate analysis demonstrated that a higher number of prior CS was independently associated with increased risks of invasive PAS, massive intraoperative haemorrhage and transfusion, and preterm delivery. Mediation analysis showed that PP contributed to 8.62% of the association between CS history and invasive PAS, 16.93% for transfusion, 32.83% for preterm birth, and 11.40% for neonatal intensive care unit admission. Conclusions:A higher number of previous CS procedures in our sample was associated with higher risks of several adverse maternal outcomes in PAS. Neonatal outcomes, however, were not significantly influenced by the number of prior CS procedures and were more strongly affected by the gestational age at delivery. These relationships were partially mediated by PP, highlighting its important, but incomplete role in the pathway linking prior CS to PAS-related complications.

Background:The gut microbiota of pregnant women changes dynamically throughout gestation, adapting to the physiological changes of pregnancy. At the same time, dysbacteriosis is involved in the pathophysiological processes of pregnancy-related diseases. Research on gut microbiota and gestational diabetes mellitus (GDM) is relatively extensive, and targeting the gut microbiota may improve maternal health. Dietary supplements such as prebiotics improve metabolic immune function in pregnant women by stimulating the growth of beneficial bacteria and promoting the production of short-chain fatty acids (SCFAs). Previous animal studies suggest that prebiotic preparations derived from galactooligosaccharides (GOS) in human milk are superior to other prebiotics. Objective:This study aims to explore the systemic effects of GOS targeting the gut microbiota on the levels of metabolism, immunity, and circulating SCFAs. Materials and methods:(1) A total of 135 pregnant women with available delivery outcomes and matched BMI were included in the analysis. From the first trimester (T1), the GOS group and the control group received GOS and fructooligosaccharide (FOS) preparations, respectively. Before the intervention (T1) and after the intervention (T2), blood samples were collected from pregnant women for LC-MS metabolomic analysis and targeted detection of short-chain fatty acids. At the same time, clinical information, metabolic indicators, and the GDM incidence rate were compared between groups, and subgroup analyses were conducted for overweight and obese participants. Statistical analyses included the t-test, the nonparametric Wilcoxon test, and the χ 2 test. Correlation analysis was conducted using Fisher's exact test and Pearson's coefficient. (2) In order to examine the correlation between targeted gut microbiota intervention and phenotypic changes, 52 pregnant women who provided stool samples before and after the intervention (i.e., T1 and T2) were analyzed. The 16S rRNA V3-V4 variable region was sequenced on the Illumina HiSeq 2,500 platform, and QIIME was used for bioinformatics analysis. The correlations among differential flora, glycolipid metabolism, inflammatory factors, and metabolites were analyzed. Results:(1) Non-target metabolites identified several metabolites with inter-group differences: cyclamate, reserpic acid, and phenylbenzimidazole sulfonic acid were relatively higher in the GOS group. Pathway analysis indicated enrichment in butyrate, propionate, and other SCFA-related metabolic pathways, as well as in cysteine and methionine metabolism. (2) The targeted metabolites of SCFAs were further analyzed, and the effects of the intervention on SCFAs were compared. After GOS intervention, the levels of acetic acid, propionic acid, butyric acid, and hexanoic acid all increased (p < 0.01). Among overweight and obese pregnant women with GDM, GOS increased the levels of butyric acid and hexanoic acid (p < 0.05). At T2, compared with the control group, hexanoic acid levels in the GOS group increased significantly (p < 0.01). Correlation analysis with clinical glucose and lipid metabolism indices showed that hexanoic acid was negatively correlated with total cholesterol (TCHO) (r = -0.415, p < 0.001) and LDL (r = -0.347, p < 0.01). (3) The relative abundance of different flora was correlated with glycolipid metabolism indices and inflammatory factors. The relative abundance of Dorea showed a negative correlation trend with TCHO and LDL. Additionally, the relative abundance of different flora was also correlated with circulating SCFAs. The relative abundance of Dorea and Paraprevotella showed a positive correlation trend with hexanoic acid. Conclusion:GOS preparations containing ingredients derived from human milk may target the gut microbiota to promote the production of hexanoic acid, thereby improving lipid metabolism and inflammation, and may be beneficial for overweight and obese people with GDM.

The early colonization and establishment of the microbiome in newborns is a crucial step in the development of the immune system and host metabolism. However, the exact timing of initial microbial colonization remains a subject of ongoing debate. While numerous studies have attempted to determine the presence or absence of intrauterine bacteria, the majority of them have drawn conclusions based on sequencing data from maternal or infant samples taken at a single time point. In this study, we aimed to investigate the microbial population in amniotic fluid (AF) from the second trimester until the time of delivery using multiple microbiological methods. AF samples were collected during the second trimester (19–21 gestational weeks) and at the time of delivery. Cohort 1 included 51 women who underwent the term and elective cesarean section, with both their second trimester and delivery AF samples (n = 55, respectively) analyzed. Cohort 2 contained 22 women who experienced infection-related adverse pregnancy outcomes (including preterm birth, histological chorioamnionitis, and stillbirth), with only their second trimester AF samples (n = 24) examined. Additionally, multiple procedural negative controls and technical positive controls were applied to this study to remove potential contamination. Microbial profiles were assessed through cultivation, quantitative real-time polymerase chain reaction, 16S ribosomal RNA gene sequencing, and cytokine analysis. In cohort 1, the bacterial load and community structure in the second trimester AF samples were indistinguishable from negative controls. Although marginally higher bacterial loads and different bacterial communities were observed in the delivery AF samples compared to negative controls, these bacterial DNA were not considered biologically functional due to the absence of maternal inflammatory responses. In cohort 2, the bacterial load and community structure of the second trimester AF samples differed significantly from those of negative controls, with Ureaplasma and Lactobacillus identified as the most prevalent genera against negative controls. Our study demonstrates that no microorganisms were detected in the AF of healthy pregnancies from the second trimester to the delivery. The presence of Ureaplasma and Lactobacillus in the second trimester AF may be associated with infection-related adverse pregnancy outcomes.

Gut microbiome dysbiosis is associated with gestational diabetes mellitus (GDM), and its modulation represents a promising approach for enhancing glycemic control. In this study, we aimed to discover specific alterations in the gut microbiome through lifestyle management. We performed metagenome sequencing on fecal samples and measured short-chain fatty acid (SCFA) in plasma samples from 27 well-controlled GDM pregnancies before and after glycemic control. At the same time, 38 normal glucose tolerance (NGT) samples served as controls. Additionally, we employed two-sample Mendelian Randomization (MR) to validate our findings against Genome-Wide Association Study (GWAS) database. Our dynamic analysis revealed Bifidobacterium genus increased in GDM patients after intervention. The MR analysis confirmed that the family of Bifidobacteriaceae (OR 0.929, 95

INTRODUCTION:Placenta accreta spectrum (PAS) is a serious condition associated with severe postpartum hemorrhage, leading to emergency hysterectomy. Research has predominantly focused on clinical diagnosis and the prevention of adverse maternal outcomes, but the underlying pathological mechanisms remain poorly understood, partly due to the limitations of animal models. METHODS:In this study, we conducted up to three cesarean sections (CS) on full-term pregnant mice, since a history of multiple CS is an independent risk factor for PAS. We evaluated pregnancy outcomes, placental development, morphology, trophoblast invasion, and angiogenesis at the maternal-fetal interface to assess the impact of repeated CS. RESULTS:Following repeated CS, the model mice displayed adverse pregnancy outcomes, including placental dysplasia, incomplete remodeling of spiral arteries, deep trophoblast invasion at the maternal-fetal interface, and reduced placental perfusion. Additionally, the mice exhibited abnormal fetal development, imbalances in angiogenic and anti-angiogenic both within the placenta and in peripheral blood. CONCLUSION:The pathological phenotypes of placenta and adverse pregnancy outcomes observed in mice with a history of three CSs closely resemble the clinical features of PAS. This model offers a valuable tool for studying the pathogenesis of PAS and could serve as a foundation for the development of early prevention strategies.

TO THE EDITORS: We read the Letter regarding our study from our friend Jingmei Ma, which mainly discussed the difference and the possible reasons for the incidence of postpartum hemorrhage between our study1 and Sentilhes' study2. Thanks for your attention. We agree with the opinion that the smaller sample maybe the main reason that IPI was not found to be associated with recurrent PAS and PPH. We expected a multicenter study with larger samples to find the relationship and the actual influencing factors. Letter to Editor regarding ' Subsequent pregnancy outcomes and risk factors following conservative treatment for placenta accreta spectrum: A retrospective cohort study': Interpregnancy interval: Attention should be given after conservative treatment of placenta accreta spectrumAmerican Journal of Obstetrics & Gynecology MFMPreviewTO THE EDITORS: We read with interest the article published in October 2023 by Huidan Zhao et al., which focused on the investigation of the clinical outcomes and risk factors for subsequent pregnancies among patients with placenta accreta spectrum (PAS) who had undergone conservative treatment[1]. This retrospective, single center study found that the recurrence of PAS after conservative management of previous PAS was 22.7%, and the postpartum hemorrhage rate was 9.1%. We noted that the incidence of postpartum hemorrhage (9.1%) was different from the retrospective, national multicenter study published by Lo ̈ıc Sentilhes et al in 2010, which concluded that the postpartum hemorrhage rate was 19.0% (95% CI, 5.4–41.9%) after conservative management of previous PAS[2]. Full-Text PDF

To editor: The disorders associated with placenta accreta spectrum (PAS) are potentially severe obstetric complications that should be managed by expert centers with substantial resources to provide both preoperative and intraoperative assessments and then prearrange a multidisciplinary team with an appropriate delivery plan. Placenta accreta spectrum was first described in 1937 as “attempts to remove the placenta led to major postpartum hemorrhage that required emergency or secondary hysterectomy to control bleeding.”1 In 1966, Luke et al2 classified this condition into placenta creta (or vera, adherenta), increta, and perceta based on the depth of placenta villi adhesion or invasion, as determined by pathological features. Although infrequent, there have been significant advances in the global evolution of the strategies used to manage PAS, especially over the last decade. From epidemiological variance to diagnostic standardization Previous research identified a correlation between an increasing trend of PAS with previous cesarean section, as well as repeated surgical abortion.3,4 A study carried out in the United States reported that by the end of 2017, 1 of 313 cesarean deliveries had PAS.3 Ming et al4 analyzed data from the China Labor and Delivery Survey in 2015 and 2016 and identified a higher prevalence of PAS than in other countries, with a substantial variance by geographic regions. These authors showed that the highest prevalence of PAS was recorded in the northwest of China (3.93%; 95% confidence interval [CI]: 2.51%–5.51%), followed by the southwest (3.63%; 95% CI: 2.22%–5.05%) and the south (3.24%; 95% CI: 1.93%–4.67%); the northeast of China had the lowest prevalence of PAS (0.99%; 95% CI: 0.55%–1.48%). The elevated global prevalence of PAS has become a significant cause for concern.4,5 Although the variable characteristics of PAS could potentially be explained by differences in maternal characteristics, it became very evident that there was an urgent need to develop consistent terminology and diagnostic criteria that are essential for study bias analysis. In 2018, the International Federation of Gynecology and Obstetrics (FIGO) classified PAS disorders by different pathological forms, considering both clinical and pathological standards.6 This consensus underlined the importance of histopathological examination in PAS disorders if we are to improve screening, diagnosis, and management.7 In alignment with the recommendations provided by a group of Chinese experts, adhering to the FIGO guidelines is emphasized for maintaining consistency in terminology, including the grading system. Furthermore, endorsing the pathological examination of each PAS placenta is essential to mitigate heterogeneity and methodological bias. The three categories of PAS are illustrated as follows8: Grade 1: Abnormally adherent placenta; characterized by villi adhering directly to the myometrium without a decidual interface Grade 2: Abnormally invasive placentation; involves villi invading into the myometrium Grade 3: Abnormally invasive placentation; entails villi invading the entire thickness of the uterine wall, either reaching the serosa or extending beyond. Cases within this category are further classified into: grade 3a, confined to and including the uterine serosa; grade 3b, involving urinary bladder invasion; and grade 3c, featuring invasion of other pelvic tissues/organs As with other obstetric complications, the management of PAS could be improved by applying high-quality prenatal assessments by ultrasound or magnetic resonance imaging; the application of this strategy could identify high-risk pregnancies. Expert opinions from China recommended scoring systems that integrate maternal risk factors with ultrasound features to further stratify the severity of PAS.9 In 2019, the International Society for Placenta Accreta Spectrum (IS-PAS) delivered its own “evidence-based guidelines.” Together with Peking University First Hospital, the IS-PAS organized the 2020 Online International Workshop on PAS; the published minutes arising from this meeting emphasized the need for consistency for each classification of PAS. In particular, this meeting highlighted the need to consider the underdiagnosis and overdiagnosis of PAS, even when applying standard descriptors from two-dimensional and color Doppler ultrasound manifestations.10 Combined with the information provided by prenatal imaging, a pathological diagnosis could be used as the gold standard for diagnosis PAS, thus avoiding confirmation bias by the surgeon. Considering that undergoing multiple cesarean sections can lead to a lasting impairment of the lower uterine segment wall and the formation of dense pelvic adhesions, it is important to be mindful of potential false-positive diagnoses of PAS. This includes considering features commonly found in pregnancies with a history of previous cesarean sections. A prospective study was conducted to assess the influence of cesarean scarring on the perinatal diagnosis of PAS. The study11 used a 1:1 ratio for prenatally diagnosed PAS and non-PAS cases, aiming to identify a distinctive ultrasound descriptor for accurate pathological diagnosis. During surgery, distinctive features such as large areas of uterine dehiscence, a densely tangled bed of vessels, and multiple vessels running laterally and craniocaudally in the uterine serosa were not identified as specific to PAS. Unsurprisingly, the authors also reported that a loss of the clear zone and myometrial thinning were common features observed in cases without PAS. A more specific presentation includes a higher placental lacunae grade, hypervascularity of the uterovesical/subplacental area, as well as the presence of bridging vessels and lacunae feeder vessels. Following the publication of the FIGO guidelines in 2018, an expert panel then recommended specific classification and reporting guidelines for the pathological diagnosis of PAS disorders.12 These pathological guidelines focused on the delivered placenta, total or partial hysterectomy, curettage to retain the products of conception, terminology, and reporting elements, as well as distinct nomenclature for hysterectomy and delivered placentas, thus providing detailed guidance for PAS. The role of clinical evaluation in the selection of surgical strategy In terms of surgical options, both nonconservative (hysterectomy) and conservative strategies7 should be considered on an individual basis. Given the fact that there is a low probability of detecting PAS during prenatal assessments, it can only be diagnosed fully at delivery. However, taking into account clinical and pathological evidence, in many cases, the approach taken for surgical treatment could be determined by an experienced surgeon. From a public health perspective, the diagnosis of relatively rare disorders represents a significant challenge as these conditions are associated with a high frequency of missed diagnoses and multiple treatment options; this situation calls for individualized management, especially in middle- or low-income countries or regions. In a previous study, Aryananda et al13 described the outcomes of 29 unexpected cases of PAS in resource-poor hospitals; of these cases, some did not undergo cesarean delivery; in other cases, the placenta was left in situ or partially removed following cesarean delivery, and some cases underwent postcesarean hysterectomy. Patients who experienced deferred or delayed cesarean delivery were associated with lower rates of maternal morbidity; in addition, five maternal deaths were recorded that were attributed to the lack of accessibility to telemedicine.13 The authors stated that access to telemedicine in these low-resource countries could have avoided maternal death and led to a far better prognosis. Considering that PAS cases may be identified during cesarean delivery, operating teams could benefit from a telemedicine approach. This approach allows for the assessment of options such as “open-close abdominal surgery or leaving the placenta in situ” with experienced teams. In 2023, the Colombian consensus of the PAS development group14 released a “treatment consensus in a resource-limited setting,” addressing six dimensions: the pathway for PAS care, roles at different levels of care, organization of interdisciplinary teams at reference hospitals, training teams, surgical treatment, and management without prenatal diagnosis. This document emphasizes the significance of developing a training program and therapeutic options based on the insights of local experts. It addresses specific challenges that may be encountered in such settings and outlines potential solutions, including collaboration between different hospitals and the utilization of telemedicine. Simultaneously, overcoming administrative barriers in the health system is crucial for facilitating communication between patients and physicians. Subsequently, the same group developed a training system for conservative surgeries that aimed to reduce transfusion and vascular intervention.15 Based on a unique intraoperative staging and PAS topography classification, it was possible to select cases that were suitable for one-step conservative surgery. The three main selection criteria were developed for one-step conservative surgery: (1) the absence of vesicouterine fibrosis, (2) the presence of at least 2 cm of healthy myometrium above the cervix, and (3) more than 50% of the axial uterine circumference. The second criterion, relating to patients with cervix or uterine segment involvement, was in accordance with our own study in which we identified an association between PAS complicated with placenta previa and severe maternal morbidity.16 With 3793 PAS cases recorded in the National Inpatient Sample Database, it is clear that we need to develop specific interventions to alleviate maternal and surgical morbidities for this particular subgroup of PAS patients. With further investigation and validation, it should be possible for surgeons to stratify cases of PAS in an objective manner while also protecting fertility requirements. The program is inspiring as the feasibility of conservative treatment has been a hot topic given the inconsistency of guidelines worldwide.17 In China, the PAS Referral Center applies a range of different surgical procedures.18–20 For individuals desiring fertility preservation, a conservative strategy involving block resection with subsequent reconstruction should be contemplated. In addition to the surgical procedure outlined in the FIGO 2018 guideline, modifications to Chandraharan's Triple P procedure have been proposed by Wei et al.18 In this adaptation, adherence to “perioperative placental localization” and “placental nonseparation” is maintained. However, the second step involving “pelvic devascularization” with interventional radiology has been replaced by bundling the lower uterine segment with a Foley catheter because of the absence of radiological services. Etiological investigations have shed new light on the prediction and prevention of severe outcomes in PAS patients Jauniaux et al1 described how the combined analysis of ultrasound imaging and pathological features can provide new insight into PAS. By analyzing histopathological features, these authors showed how extravillous trophoblast (EVT) cells can reach the large uterine artery and that the placental villi can separate from the scarred myometrium by thick fibrinoid deposition at the level of the Rohr layer within and around the cesarean scar; this condition presents as edema and myofiber disarray.21 These authors further hypothesized that deep EVT invasion was unlike the metastasis of a tumor; rather, such invasion related to the high-velocity maternal blood flow entering the intervillous space directly from the radial artery, and that this process could represent the main driver of PAS pathogenesis. The thick deposition of fibrinoids in PAS may be indicative of abnormal fibrinolysis functionality. Guo et al investigated the feasibility of routine coagulation testing prior to delivery and verified the association between prothrombin time, d-dimer, and fibrin degradation product with blood loss volume in severe PAS cases, which is the most common form of severe maternal morbidity.22 The IS-PAS referred to these findings in their review of hemostatic considerations in PAS23 and recommended the provision of prepartum and intrapartum coagulation testing, including complete blood count, fibrinogen levels, standard coagulation parameters, and d-dimers. In contrast, conservative management strategies may leave the placenta untouched; however, the coagulation activity induced by local trophoblasts may increase the consumption of fibrinogen and increase the levels of d-dimer, thus increasing the risk of secondary hemorrhage. With our growing understanding of the placenta, PAS etiology, and prenatal imaging, it has become clear that biomarkers may have potential value for predicting PAS. However, to date, there are no established biomarkers for PAS that are available for clinical practice24; this is due to the involvement of multiple biological processes, including placental function, angiogenesis, coagulation, oxidative stress, and inflammation. To identify specific biomarkers, it is critical that we acquire accurate clinicopathological evidence for patients with PAS. Although challenging, cohort studies could trace the dynamic trends of PAS subgroups associated with severe morbidity. Our current ability to diagnose PAS could be further improved by applying the advantages afforded by new technologies.25,26 For example, Afshar et al25 reported a nanostructure-embedded microchip that was able to enrich clustered circulating trophoblasts from the maternal blood during early pregnancy to distinguish PAS from non-PAS with an area under the receiver operating characteristic curve of 0.924. In another study, Shainker et al26 used an aptamer-based proteomics platform to identify a unique plasma protein signature for PAS; this signature was confirmed by enzyme-linked immunosorbent assays. In vivo and in vitro verifications are also important, as single-cell sequencing27 and placenta villi organoids28 provide the opportunity in the field. Although there is a need to identify noninvasive biomarkers for the severity of PAS, the current clinical screening modalities for PAS are not conclusive. Besides the proteomic analysis with maternal plasma, the molecular and cellular investigations to reveal the mechanism underlining the topographic classification of PAS presented during operation could be realized with single-cell sequencing and placenta villi organoids. With accumulative data of single-cell sequencing on both healthy and pathological placenta, clues of the injured or dysfunctional cells could be yielded, including preeclampsia, preterm birth, and PAS. In the PAS placenta, in the absence of normal decidual cells, the abrupt differentiation of progenitor cytotrophoblast interacted with ADIRF+ (adipogenesis regulatory factor) and DES+ (desmin) maternal stromal cells. The pathway from healthy to injured could be further verified with in vitro models. The placental villi organoids from early, late, or diseased pregnancies contain cytotrophoblasts with capabilities to differentiate into EVTs, along with the stromal and immune cells. Taking advantage of the findings from cell atlases, a deeper investigation of the pathogenesis and therapeutics of PAS could be achieved. Conclusion As PAS is a high-risk obstetric complication with a wide range of clinical presentations, its management is challenging for the crucial demand of multidisciplinary expert team. With the new insights in understanding the pathogenesis, the management of PAS has been standardized according to the stratification of individual condition. Taking consideration of all perspectives of the stakeholders, including the patients and physicians from referral centers or a lower level of hospitals, the academic society should update the recommendations with a standardized prospective study design with sustainable evidence. Editor Note Huixia Yang and Jingmei Ma are editorial board members of Maternal-Fetal Medicine. The article was subject to the journal's standard procedures, with peer review handled independently of the editors and the associated research groups.

The establishment of human gut microbiota in early life is closely associated with both short- and long-term infant health. Delivery mode and feeding pattern are two important determinants of infant gut microbiota. In this longitudinal cohort study, we examined the interplay between the delivery mode and feeding pattern on the dynamics of infant gut microbiota from 6 weeks to 6 months post-delivery in 139 infants. We also assessed the relationship between infant respiratory infection susceptibility and gut microbial changes associated with delivery mode and feeding pattern. At 6 weeks postpartum, the composition and structure of gut microbiota of cesarean section-delivered (CSD) infants differed from those of vaginally delivered (VD) infants, with decreased Bacteroides and Escherichia-Shigella and increased Klebsiella, Veillonella, and Enterococcus. At 6 months postpartum, these delivery mode-induced microbial shifts were restored by exclusive breastfeeding, resulting in similar gut microbial profiles between VD and CSD infants who were exclusively breastfed (P = 0.57) and more variable gut microbial profiles between VD and CSD infants who were mixed fed (P < 0.001). We identified that the VD-associated genera were enriched in healthy infants, while the CSD-associated genera were enriched in infants who suffered from respiratory infections. Our findings indicate that exclusive breastfeeding may play a health-promoting role by reducing infant respiratory infection susceptibility through the restoration of gut microbiota perturbations caused by cesarean section.

ObjectiveThis study aims to evaluate the importance of the gestational age at diagnosis and the types of cesarean scar pregnancy (CSP) for treatment outcomes and to identify the optimal treatment based on both the gestational age at diagnosis and the CSP type.MethodsA retrospective cohort study included 223 pregnant women diagnosed with CSP at Peking University First Hospital, Beijing, China, between 2014 and 2018. All CSP cases underwent ultrasound-guided vacuum aspiration followed by supplementary curettage. Adjuvant treatment modalities included intramuscular injection of systemic methotrexate, uterine artery embolization, and hysteroscopy before ultrasound-guided vacuum aspiration. Linear regression was used to determine the relationship between intraoperative blood loss and gestational age at diagnosis, CSP type, highest β-human chorionic gonadotropin level, and management procedures.ResultsNone of the patients required blood transfusions or hysterectomies. Patients presenting at <8, 8–10, and >10 weeks had median estimated blood loss of 5, 10, and 35 ml, respectively. Patients with type I CSP, type II CSP, and type III CSP had median blood loss of 5, 5 and 10 ml, respectively. Multivariate linear regression analysis demonstrated that the gestational age at diagnosis (p < 0.001) and type of CSP (p = 0.023) were independent predictors of intraoperative estimated blood loss. For type I CSP patients, ultrasound-guided vacuum aspiration followed by supplementary curettage alone was performed in 15 of 34 (44.1%) patients, including 12/27 (44.4%) diagnosed at <8 weeks, 2/6 (33.3%) at 8–10 weeks, and 1/1 for >10 weeks. In type II CSP patients, fewer cases were managed by ultrasound-guided vacuum aspiration followed by supplementary curettage alone as the gestational age at diagnosis increased [18/96 (18.8%) for <8 weeks, 7/41 (17.1%) for 8–10 weeks, none for >10 weeks]. Most type III CSP patients (41/45, 91.1%) needed treatments in addition to the ultrasound-guided vacuum aspiration regardless of the gestational age at diagnosis. All CSP patients were treated successfully and did not require readmission or further medical interventions.ConclusionGestational age at diagnosis of CSP and its type show a strong correlation with estimated blood loss during ultrasound-guided vacuum aspiration. With careful management, CSPs may be treated at any gestational week, regardless of their type, with minimal intraoperative bleeding.

胎盘植入性疾病（placenta accreta spectrum，PAS）指胎盘绒毛滋养细胞浸润并侵入子宫深肌层，分娩时胎盘难以自然剥离，导致产后出血等严重并发症的一类疾病。PAS的临床诊断依赖影像学指征及危险因素。现已明确体外受精移植（ in vitro fertilization，IVF）是PAS的独立危险因素 ［1］。2022年12月，《美国妇产科杂志?母胎医学》（ American Journal of Obstetrics & Gynecology MFM）刊出了一篇文献，评估IVF伴PAS者（IVF-PAS）与自然受孕伴PAS者（N-PAS）的妊娠特征和分娩结局 ［2］。

TO THE EDITORS: We read with interest the article published in October 2023 by Huidan Zhao et al., which focused on the investigation of the clinical outcomes and risk factors for subsequent pregnancies among patients with placenta accreta spectrum (PAS) who had undergone conservative treatment[1]. This retrospective, single center study found that the recurrence of PAS after conservative management of previous PAS was 22.7%, and the postpartum hemorrhage rate was 9.1%. We noted that the incidence of postpartum hemorrhage (9.1%) was different from the retrospective, national multicenter study published by Lo ̈ıc Sentilhes et al in 2010, which concluded that the postpartum hemorrhage rate was 19.0% (95% CI, 5.4–41.9%) after conservative management of previous PAS[2]. Reply to ' Interpregnancy interval: Attention should be given after conservative treatment of placenta accreta spectrum'American Journal of Obstetrics & Gynecology MFMPreviewTO THE EDITORS: We read the Letter regarding our study from our friend Jingmei Ma, which mainly discussed the difference and the possible reasons for the incidence of postpartum hemorrhage between our study1 and Sentilhes’ study2. Thanks for your attention. We agree with the opinion that the smaller sample maybe the main reason that IPI was not found to be associated with recurrent PAS and PPH. We expected a multicenter study with larger samples to find the relationship and the actual influencing factors. Full-Text PDF

胎盘植入性疾病（placenta accreta spectrum disorders，PAS）是指胎盘组织过度侵入子宫肌层的一组疾病，与子宫内膜损伤有关，随着有剖宫产史者再次妊娠比例增加，PAS发病率也在增加。既往美国对PAS孕妇临床常规采用子宫切除术以降低产妇的病死率，近年来，国际范围内广泛的经验分享和观点碰撞使得保守治疗PAS成为热点问题。