Uterine injury during diestrus leads to placental and embryonic defects in future pregnancies in mice†.

Uterine injury from procedures such as Cesarean sections (C-sections) often have severe consequences on subsequent pregnancy outcomes, leading to disorders such as placenta previa, placenta accreta, and infertility. With rates of C-section at ~30% of deliveries in the USA and projected to continue to climb, a deeper understanding of the mechanisms by which these pregnancy disorders arise and opportunities for intervention are needed. Here we describe a rodent model of uterine injury on subsequent in utero outcomes. We observed three distinct phenotypes: increased rates of resorption and death, embryo spacing defects, and placenta accreta-like features of reduced decidua and expansion of invasive trophoblasts. We show that the appearance of embryo spacing defects depends entirely on the phase of estrous cycle at the time of injury. Using RNA-seq, we identified perturbations in the expression of components of the COX/prostaglandin pathway after recovery from injury, a pathway that has previously been demonstrated to play an important role in embryo spacing. Therefore, we demonstrate that uterine damage in this mouse model causes morphological and molecular changes that ultimately lead to placental and embryonic developmental defects.

Trophectoderm grade is associated with the risk of placenta previa in frozen-thawed single-blastocyst transfer cycles.

STUDY QUESTION: Do obstetric and perinatal complications vary according to different blastocyst developmental parameters after frozen-thawed single-blastocyst transfer (SBT) cycles? SUMMARY ANSWER: Pregnancies following the transfer of a blastocyst with a grade C trophectoderm (TE) were associated with an increased risk of placenta previa compared to those with a blastocyst of grade A TE. WHAT IS KNOWN ALREADY: Existing studies investigating the effect of blastocyst morphology grades on birth outcomes have mostly focused on fetal growth and have produced conflicting results, while the risk of obstetric complications has rarely been reported. Additionally, growing evidence has suggested that the appearance of TE cells could serve as the most important parameter for predicting implantation and live birth. Given that the TE ultimately develops into the placenta, it is plausible that this independent predictor may also impact placentation. STUDY DESIGN, SIZE, DURATION: This retrospective cohort study at a tertiary-care academic medical center included 6018 singleton deliveries after frozen-thawed SBT cycles between January 2017 and December 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton pregnancies were grouped into two groups according to blastocyst developmental stage (Days 5 and 6), four groups according to embryo expansion (Stages 3, 4, 5, and 6), three groups according to inner cell mass (ICM) quality (A, B, and C), and three groups according to TE quality (A, B, and C). The main outcomes included pregnancy-induced hypertension, preeclampsia, gestational diabetes mellitus, preterm premature rupture of membrane, placenta previa, placental abruption, placenta accreta, postpartum hemorrhage, preterm birth, low birth weight, small for gestational age, and birth defects. Multivariate logistic regressions were performed to evaluate the effect of blastocyst developmental stage, embryo expansion stage, ICM grade, and TE grade on measured outcomes adjusting for potential confounders. MAIN RESULTS AND THE ROLE OF CHANCE: No association was found between blastocyst developmental stage and obstetric or perinatal outcomes both before and after adjusting for potential confounders, and similar results were found with regard to embryo expansion stage and ICM grade. Meanwhile, the incidence of placenta previa derived from a blastocyst with TE of grade C was higher compared with those derived from a blastocyst with TE of grade A (1.7%, 2.4%, and 4.0% for A, B, and C, respectively, P = 0.001 for all comparisons). After adjusting for potential covariates, TE grade C blastocysts had 2.81 times the likelihood of resulting in placenta previa compared to TE grade A blastocysts (adjusted odds ratio 2.81, 95% CI 1.11-7.09). No statistically significant differences were detected between any other measured outcomes and TE grades both before or after adjustment. LIMITATIONS, REASONS FOR CAUTION: The study is limited by its retrospective, single-center design. Additionally, although the sample size was relatively large for the study group, the sample size for certain subgroups was relatively small and lacked adequate power, particularly the ICM grade C group. Therefore, these results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS: The study extends our knowledge of the potential downstream effect of TE grade on placental abnormalities. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the National Key Research and Development Program of China (2023YFC2705500, 2023YFC2705501, 2023YFC2705505, 2019YFA0802604); National Natural Science Foundation of China (82130046, 82320108009, 82371660, 32300710); Shanghai leading talent program, Innovative research team of high-level local universities in Shanghai (SHSMU-ZLCX20210201, SHSMU-ZLCX20210200, SHSMU-ZLCX20180401), Shanghai Jiaotong University School of Medicine Affiliated Renji Hospital Clinical Research Innovation Cultivation Fund Program (RJPY-DZX-003), Science and Technology Commission of Shanghai Municipality (23Y11901400), Shanghai's Top Priority Research Center Construction Project (2023ZZ02002), and Three-Year Action Plan for Strengthening the Construction of the Public Health System in Shanghai (GWVI-11.1-36). The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels in differentiating placenta accreta spectrum from isolated placenta previa.

OBJECTIVE: Our study aimed to differentiate patients with placenta accreta spectrum (PAS) from those with placenta previa (PP) using maternal serum levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-alpha (TNF-alpha), interleukin-4 (IL-4), and IL-10. METHODS: The case group consisted of 77 patients with placenta previa, and the control group consisted of 90 non-previa pregnant women. Of the pregnant women in the case group, 40 were diagnosed with PAS in addition to placenta previa and 37 had placenta previa with no invasion. The maternal serum VEGF, TNF-alpha, IL-4, and IL-10 levels were compared between the case and control groups. Then the success of these markers in differentiating between PP and PAS was evaluated. RESULTS: We found the VEGF, TNF-alpha, and IL-4 levels to be higher and the IL-10 level to be lower in the case group compared to the control group (p < 0.001). We observed a statistically significantly lower IL-10 level in the patients with PAS than those with PP (p = 0.029). In the receiver operating characteristic analysis, the optimal cut-off of IL-10 in the detection of PAS was 0.42 ng/mL). In multivariate analysis, the risk of PAS was significant for IL-10 (odds ratio (OR) 0.45, 95 % confidence interval (CI) 0.25-0.79, p = 0.006) and previous cesarean section (OR 2.50, 95 % Cl 1.34-4.66, p = 0.004). The model's diagnostic sensitivity and specificity, including previous cesarean section, preoperative hemoglobin (Hb), TNF-alpha, and IL-10 were 75 % and 72.9 %, respectively. CONCLUSION: The study showed that the IL-10 level was lower in patients with PAS than in those with PP. A statistical model combining risk factors including previous cesarean section, preoperative Hb, TNF-alpha, and IL-10 may improve clinical diagnosis of PAS in placenta previa cases. Cytokines may be used as additional biomarkers to the clinical risk factors in the diagnosis of PAS.

Real-time ultrasound demonstration of uterine isthmus contractions during pregnancy.

BACKGROUND: Asymptomatic isthmic contractions are a frequent physiological phenomenon in pregnancy, sometimes triggered by bladder voiding. They can interfere with proper cervical length assessment and may lead to false images of placenta previa. However, there is limited research on the prevalence and characteristics of these contractions. OBJECTIVE: This study aimed to determine the prevalence and characteristics of isthmic contractions after bladder voiding in the second trimester of pregnancy, to evaluate their effect on cervical length assessment, and to propose a new method for the objective assessment of the presence and intensity of isthmic contractions. STUDY DESIGN: In this prospective observational study, long videos of the uterine cervix were recorded in 30 singleton pregnancies during the second trimester of pregnancy after bladder voiding. Isthmic length and cervicoisthmic length changes were assessed over time. The isthmic length was measured using a new approach, which involved calculating the distance from the base of the cervix to the internal os, including the isthmus. RESULTS: Isthmic contractions were observed in 43% of pregnant women (95% confidence interval, 26%-62%) after bladder voiding. The median time for complete isthmus relaxation was 19.7 minutes (95% confidence interval, 15.0 to not available). No substantial differences in maternal characteristics were found between individuals with and without contractions. The proposed method for measuring isthmic length provided an objective assessment of the presence and intensity of isthmic contractions. A cutoff of 18 mm in isthmic length allowed for the distinction of pregnant women presenting a contraction. In addition, the study identified a characteristic undulatory pattern in the relaxation of the isthmus in half of the cases with contractions. CONCLUSION: Isthmic contractions are a common occurrence after bladder voiding in the second trimester of pregnancy and may interfere with proper cervical length assessment. We recommend performing cervical assessment at least 20 minutes after bladder voiding to reduce the risk of bias in cervical length measurement and to avoid false images of placenta previa. The new method for measuring isthmic length provides an objective way to assess the presence and intensity of isthmic contractions. Further research is needed to understand the role of isthmic contractions in the physiology of pregnancy and birth.

Validity of ICD-10 diagnosis codes for placenta accreta spectrum disorders.

BACKGROUND: The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life-threatening pregnancy complication that is increasing in incidence. OBJECTIVE: We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD-10 and assess contributing factors to incorrect code assignments. METHODS: We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD-10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard. RESULTS: Among 22,345 patients, 104 (0.46%) had an ICD-10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD-10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD-10 codes for placenta accreta spectrum subtypes- accreta, increta and percreta-were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features. CONCLUSION: These findings from a quaternary obstetric centre suggest that ICD-10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases.

Determinants of emergency Cesarean delivery in pregnancies complicated by placenta previa with or without placenta accreta spectrum disorder: analysis of ADoPAD cohort.

OBJECTIVES: To investigate the rate and outcome of emergency Cesarean delivery (CD) in women with placenta previa with or without placenta accreta spectrum disorders (PAS) and to elucidate the diagnostic accuracy of ultrasound in predicting emergency CD. METHODS: This was a secondary analysis of a multicenter prospective study involving 16 referral hospitals in Italy (ADoPAD study). Inclusion criteria were women with placenta previa minor (< 20 mm from the internal cervical os) or placenta previa major (covering the os), aged ≥ 18 years, who underwent transabdominal and transvaginal ultrasound assessment at ≥ 26 + 0 weeks of gestation. The primary outcome was the occurrence of emergency CD, defined as the need for immediate surgical intervention performed for emergency maternal or fetal indication, including active labor, cumulative maternal bleeding > 500 mL, severe and persistent vaginal bleeding such that maternal hemodynamic stability could not be achieved or maintained, or category-III fetal heart rate tracing unresponsive to resuscitative measures. The primary outcome was reported separately in the population of women with placenta previa and no PAS confirmed after birth and in those with PAS. The secondary aim was to report on the strength of association and to test the diagnostic accuracy of ultrasound in predicting emergency CD. Univariate, multivariate and diagnostic accuracy analyses were used to analyze the data. RESULTS: A total of 450 women, including 97 women with placenta previa and PAS and 353 with placenta previa only, were analyzed. In women with placenta previa and PAS, emergency CD was required in 20.6% (95% CI, 14-30%), and 60.0% (12/20) delivered before 34 weeks of gestation. The mean gestational age at delivery was 32.3 ± 2.7 weeks in women undergoing emergency CD and 34.9 ± 1.8 weeks in those undergoing elective CD (P < 0.001). Women undergoing emergency CD had a higher median estimated blood loss (2500 (interquartile range (IQR), 1350-4500) vs 1100 (IQR, 625-2500) mL; P = 0.012), mean units of blood transfused (7.3 ± 8.8 vs 2.5 ± 3.4; P = 0.02) and more frequent placement of a mechanical balloon (50.0% vs 16.9%; P = 0.002) compared with those undergoing elective CD. On univariate analysis, the presence of interrupted retroplacental space, interrupted bladder line and placental lacunae was more common in women not experiencing emergency CD. No comprehensive multivariate analysis could be performed in this subgroup of women. Ultrasound signs of PAS, including presence of interrupted retroplacental space, interrupted bladder line and placental lacunae, were not predictive of emergency CD. In women with placenta previa but no PAS, emergency CD was required in 31.2% (95% CI, 26.6-36.2%), and 32.7% (36/110) delivered before 34 weeks of gestation. The mean gestational age at delivery was lower in women undergoing emergency CD compared with those undergoing elective CD (34.2 ± 2.9 vs 36.7 ± 1.6 weeks; P < 0.001). Pregnancies complicated by emergency CD were associated with a lower birth weight (2330 ± 620 vs 2800 ± 480 g; P < 0.001) and had a higher risk of need for blood transfusion (22.7% vs 10.7%; P = 0.003) compared with those who underwent elective CD. On multivariate analysis, only placental thickness (odds ratio (OR), 1.02 (95% CI, 1.00-1.03); P = 0.046) and cervical length < 25 mm (OR, 3.89 (95% CI, 1.33-11.33); P = 0.01) were associated with emergency CD. However, a short cervical length showed low diagnostic accuracy for predicting emergency CD in these women. CONCLUSION: Emergency CD occurred in about 20% of women with placenta previa and PAS and 30% of those with placenta previa only and was associated with worse maternal outcome compared with elective intervention. Prenatal ultrasound is not predictive of the risk of emergency CD in women with these disorders. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of preoperative ultrasound signs associated with bladder injury during complex Cesarean delivery: case-control study.

OBJECTIVE: Intraoperative hemorrhage and peripartum hysterectomy are the main complications in patients presenting with a low-lying placenta or placenta previa undergoing repeat Cesarean delivery (CD). Patients with a high probability of placenta accreta spectrum (PAS) at birth also have a higher risk of intraoperative urologic injury. The aim of this study was to evaluate the ultrasound signs and intraoperative features associated with these injuries. METHODS: This was a retrospective case-control study of consecutive singleton pregnancies included in a prospective cohort of patients with a history of at least one prior CD and diagnosed prenatally with an anterior low-lying placenta or placenta previa at 32-36 weeks' gestation. All patients underwent investigational preoperative transabdominal and transvaginal ultrasound examination within 48 h prior to delivery. Ultrasound anomalies of uterine contour and uteroplacental vascularity, and gross anomalies of the lower uterine segment (LUS) and surrounding pelvic tissue at delivery, were recorded using a standardized protocol, which included evaluation of the extent of uterine contour anomalies. The diagnosis of PAS was established when one or more placental lobules could not be separated digitally from the uterine wall at delivery or during the gross examination of the hysterectomy or partial myometrial resection specimens, and was confirmed by histopathology. Data were compared between cases complicated by intraoperative bladder injury and controls from the same cohort matched at a 1:3 ratio by parity and the number of prior CDs using conditional logistic regression. RESULTS: There were 16 (9.4%) patients with an intraoperative bladder injury in a cohort of 170 managed by the same multidisciplinary team during the study period. There were no patients diagnosed with ureteric or bladder trigone damage. There were 14 (87.5%) patients with a bladder injury that had histopathologic evidence of PAS at birth, including 11 (68.8%) cases described on microscopic examination as placenta increta and three (18.8%) as placenta creta. There was a significant (P = 0.03) difference between cases and controls in the distribution of intraoperative LUS vascularity, whereby the higher the number of enlarged vessels, the higher the odds of bladder injury. Multivariable regression analysis revealed that both gestational age at delivery and LUS remodeling on transabdominal ultrasound were associated with bladder injury. A higher gestational age was associated with a lower risk of injury. A higher LUS remodeling grade on transabdominal ultrasound was associated with an increased risk of bladder injury. Patients with Grade-3 remodeling (involving > 50% of the LUS) had 9-times higher odds of a bladder injury compared to patients with Grade-1 remodeling (involving < 30% of the LUS). CONCLUSIONS: Preoperative ultrasound examination is useful in the evaluation of the risk of intraoperative bladder injury in patients with a history of prior CD presenting with a low-lying placenta or placenta previa. The larger the remodeling of the LUS on transabdominal ultrasound, the higher the risk of adverse urologic events. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Prenatal detection of placenta accreta spectrum using a sonographic checklist.

INTRODUCTION: The European Working Group for Abnormally Invasive Placenta proposed a checklist of ultrasound features for the antenatal detection of placenta accreta spectrum (PAS). This study aims to assess the performance of the checklist in identifying histopathologically confirmed PAS cases in a cohort with a high pre-test probability of PAS, and identify if particular features are associated with PAS. MATERIAL AND METHODS: This is a prospective multi-site cohort study conducted between 2018 and 2023. Consecutive patients who underwent ultrasound assessment for suspicion of PAS were included, and the sonographic checklist was completed at the time of ultrasound. Cases were defined as PAS where they had intraoperative findings as described by the International Federation of Gynecology and Obstetrics (FIGO) grading, and histopathological findings for hysterectomy and myometrial resection cases. All non-PAS cases in this study had placenta previa and at least one prior cesarean delivery. RESULTS: Seventy-eight participants met inclusion criteria, of whom 63 (80.7%) were diagnosed with PAS. Cesarean hysterectomy was performed in 49 cases (62.8%). Overall, third-trimester ultrasound performed at a median gestational age of 32 weeks (IQR 30-34 weeks) had a sensitivity of 0.84 (95% CI 0.73 to 0.92) and specificity of 0.73 (95% CI 0.45 to 0.92) for detecting PAS, with a positive and negative likelihood ratio of 3.15 (95% CI 1.35 to 7.35) and 0.22 (95% CI 0.11 to 0.41), respectively. Features most associated with PAS were abnormal placental lacunae (Odds Ratio [OR] 5.40 [95% CI 1.61 to 18.03] and myometrial thinning OR 6.87 [95% CI 1.93 to 24.4]). While many of the ultrasound features seen in PAS were also present in cases of placenta previa with prior Cesarean section, the median (IQR) number of features present in PAS cases was significantly higher than in the non-PAS placenta previa group (six features [3-8] vs. two features [0-3] p = 0.001). No case of non-PAS placenta previa had more than five features present. CONCLUSIONS: The use of a standardized sonographic checklist had a high sensitivity and good specificity for the detection of PAS in this prospective cohort of well-classified PAS cases.

Cesarean hysterectomy in pregnancies complicated with placenta previa accreta: a retrospective hospital-based study.

BACKGROUND: Placenta previa accreta (PPA) is a severe obstetric condition that can cause massive postpartum hemorrhage and transfusion. Cesarean hysterectomy is necessary in some severe cases of PPA to stop the life-threatening bleeding, but cesarean hysterectomy can be associated with significant surgical blood loss and major complications. The current study is conducted to investigate the potential risk factors of excessive blood loss during cesarean hysterectomy in women with PPA. METHODS: This is a retrospective study including singleton pregnancies after 28 weeks of gestation in women with placenta previa and pathologically confirmed placenta accreta spectrum who received hysterectomy during cesarean sections. A total of 199 women from January 2012 to August 2023 were included in this study and were divided into Group 1 (estimated surgical blood loss (EBL) ≤ 3500 mL, n = 103) and Group 2 (EBL > 3500 mL, n = 96). The primary outcome was defined as an EBL over 3500 mL. Baseline characteristics and surgical outcomes were compared between the two groups. A multivariate logistic regression model was applied to find potential risk factors of the primary outcome. RESULTS: Massive surgical blood loss was prevalent in our study group, with a median EBL of 3500 mL. The multivariate logistic analysis showed that emergency surgery (OR 2.18, 95% CI 1.08-4.41, p = 0.029), cervical invasion of the placenta (OR 2.70, 95% CI 1.43-5.10, p = 0.002), and intraoperative bladder injury (OR 5.18, 95% CI 2.02-13.28, p = 0.001) were all associated with the primary outcome. Bilateral internal iliac arteries balloon occlusion (OR 0.57, 95% CI 0.34-0.97) and abdominal aortic balloon occlusion (OR 0.33, 95% CI 0.19-0.56) were negatively associated with the primary outcome. CONCLUSIONS: Emergency surgery, cervical invasion of the placenta, and intraoperative bladder injury were potential risk factors for additional EBL during cesarean hysterectomy in women with PPA. Future prospective studies are needed to confirm the effect of intra-arterial balloon occlusion in cesarean hysterectomy of PPA.

Association between endometriosis and perinatal complications: a case-control study.

BACKGROUND: Recently, a history of endometriosis has been reported to be associated with several perinatal complications. However, it is unknown whether pre-pregnancy treatment for endometriosis reduces perinatal complications. In this study, we aimed to clarify the association between endometriosis and perinatal complications and investigate whether there is a significant difference in the incidence of placenta previa depending on the degree of surgical completion of endometriosis before pregnancy. METHODS: This case-control study included 2781 deliveries at the Hirosaki University Hospital between January 2008 and December 2019. The deliveries were divided into a case group with a history of endometriosis (n = 133) and a control group without endometriosis (n = 2648). Perinatal outcomes and complications were compared between the case and control groups using a t-test and Fisher's exact test. Multiple logistic regression models were used to identify the risk factors for placenta previa. Additionally, we examined whether the degree of surgical completion of endometriosis before pregnancy was associated with the risk of placenta previa. RESULTS: Patients with a history of endometriosis had a significantly higher risk of placenta previa (crude odds ratio, 2.66; 95% confidence interval, 1.37‒4.83). Multiple logistic regression analysis showed that a history of endometriosis was a significant risk factor for placenta previa (adjusted odds ratio, 2.30; 95% confidence interval, 1.22‒4.32). In addition, among patients with revised American Society for Reproductive Medicine stage III-IV endometriosis, the incidence of placenta previa was significantly lower in patients who underwent complete surgery (3/51 patients, 5.9%) than in those who did not (3/9 patients, 33.3%) (p = 0.038). CONCLUSIONS: A history of endometriosis is an independent risk factor for placenta previa. Given the limitations of this study, further research is needed to determine the impact of endometriosis surgery on perinatal complications.

Prevalence of fetal anomalies, stillbirth, neonatal morbidity, or mortality in pregnancies complicated by placenta accreta spectrum disorders.

INTRODUCTION: Placenta accreta spectrum disorders (PAS) lead to major complications in pregnancy. While the maternal morbidity associated with PAS is well known, there is less information regarding neonatal morbidity in this setting. The aim of this study is to describe the neonatal outcomes (fetal malformations, neonatal morbidity, twin births, stillbirth, and neonatal death), using an international multicenter database of PAS cases. MATERIAL AND METHODS: This was a prospective, multicenter cohort study based on prospectively collected cases, using the international multicenter database of the International Society for PAS, carried out between January 2020 and June 2022 by 23 centers with experience in PAS care. All PAS cases were included, regardless of whether singleton or multiple pregnancies and were managed in each center according to their own protocols. Data were collected via chart review. Local Ethical Committee approval and Data Use Agreements were obtained according to local policies. RESULTS: There were 315 pregnancies eligible for inclusion, with 12 twin pregnancies, comprising 329 fetuses/newborns; 2 cases were excluded due to inconsistency of data regarding fetal abnormalities. For the calculation of neonatal morbidity and mortality, all elective pregnancy terminations were excluded, hence 311 pregnancies with 323 newborns were analyzed. In our cohort, 3 neonates (0.93%) were stillborn; of the 320 newborns delivered, there were 10 cases (3.13%) of neonatal death. The prevalence of major congenital malformations was 4.64% (15/323 newborns), most commonly, cardiovascular, central nervous system, and gastrointestinal tract malformations. The overall prevalence of major neonatal morbidity in pregnancies complicated by PAS was 47/311 (15.1%). There were no stillbirths, neonatal deaths, or fetal malformations in reported twin gestations. CONCLUSIONS: Although some outcomes may be too rare to detect within our cohort and data should be interpreted with caution, our observational data supports reassuring neonatal outcomes for women with PAS.

Obstetric blood transfusion in placenta previa patients with prenatal anemia: a retrospective study.

BACKGROUND: The appropriate use of obstetric blood transfusion is crucial for patients with placenta previa and prenatal anemia. This retrospective study aims to explore the correlation between prenatal anemia and blood transfusion-related parameters in this population. METHODS: We retrieved the medical records of consecutive participants who were diagnosed with placenta previa and underwent cesarean section in our hospital. We compared the baseline demographics and clinical characteristics of patients with and without anemia. The correlation between prenatal anemia and obstetric blood transfusion-related parameters was evaluated using multivariate regression analysis. RESULTS: A total of 749 patients were enrolled, with a mean prenatal hemoglobin level of 10.87 ± 1.37 g/dL. Among them, 54.87% (391/749) were diagnosed with anemia. The rate of obstetric blood transfusion was significantly higher in the anemia group (79.54%) compared to the normal group (44.41%). The median allogeneic red blood cell transfusion volume in the anemia group was 4.00 U (IQR 2.00-6.00), while in the normal group, it was 0.00 U (IQR 0.00-4.00). The prenatal hemoglobin levels had a non-linear relationship with intraoperative allogeneic blood transfusion rate, massive blood transfusion rate, red blood cell transfusion units, and fresh plasma transfusion volume in patients with placenta previa, with a threshold of 12 g/dL. CONCLUSIONS: Our findings suggest that prenatal anemia is associated with a higher rate of blood transfusion-related parameters in women with placenta previa when the hemoglobin level is < 12 g/dL. These results highlight the importance of promoting prenatal care in placenta previa patients with a high requirement for blood transfusion.

Risk factors of severe postpartum hemorrhage in pregnant women with placenta previa or low-lying placenta: a retrospective cohort study.

BACKGROUND: The severe postpartum hemorrhage (SPPH) leads to dangerous maternal conditions, and its rate is still increasing and the trend in related risk factors is changing. Placenta-related problems remain the high-risk factor for SPPH. The object is to investigate the prevalence and the risk factors of the severe postpartum hemorrhage in pregnant women with placenta previa or low-lying placenta. METHOD: A retrospective analysis of pregnant women with placenta previa or low-lying placenta after 28 weeks gestation from May 2018 to May 2023 in the Peking Union Medical College Hospital was conducted. The primary outcome was severe postpartum hemorrhage defined as blood loss ≥ 1000 mL within 24 h of childbirth, or with signs or symptoms of low blood volume requiring transfusion of ≥ 4U of red blood cells. Univariate and multivariate logistic regression were used to identify potential risk factors of severe postpartum hemorrhage and receiver operating curve to evaluate the prediction performance. RESULTS: Of the 14,964 women, 201 met the inclusive criteria. SPPH rate was 1.3% overall and 18.9% in women with placenta previa or low-lying placenta. Weight (aOR = 0.93, 95%CI 0.87-0.99), increta or percreta placenta (aOR = 7.93, 95%CI 2.53-24.77) were the risk factors. The area under the ROC curve was 0.69(95%CI 0.59-0.80) for increta or percreta placenta alone, and 0.72(95%CI 0.62-0.82) for the combination of times of cesarean sections and anterior placenta. CONCLUSIONS: Placenta accreta spectrum was the key independent risk factor of SPPH in women with placenta previa or low-lying placenta. Antenatal risk assessment of SPPH in these population is highly desirable and optimal intervention could be planned.

Evaluation of maternal serum protein biomarkers in the prenatal evaluation of placenta accreta spectrum: A systematic scoping review.

INTRODUCTION: Placenta accreta spectrum (PAS) is an increasingly commonly reported condition due to the continuous increase in the rate of cesarean deliveries (CD) worldwide; however, the prenatal screening for pregnant patients at risk of PAS at birth remains limited, in particular when imaging expertise is not available. MATERIAL AND METHODS: Two major electronic databases (MEDLINE and Embase) were searched electronically for articles published in English between October 1992 and January 2023 using combinations of the relevant medical subject heading terms and keywords. Two independent reviewers selected observational studies that provided data on one or more measurement of maternal blood-specific biomarker(s) during pregnancies with PAS at birth. PRISMA Extension for Scoping Review (PRISMA-ScR) was used to extract data and report results. RESULTS: Of the 441 reviewed articles, 29 met the inclusion criteria reporting on 34 different biomarkers. 14 studies were retrospective and 15 prospective overall including 18 251 participants. Six studies had a cohort design and the remaining a case-control design. Wide clinical heterogeneity was found in the included studies. In eight studies, the samples were obtained in the first trimester; in five, the samples were collected on hospital admission for delivery; and in the rest, the samples were collected during the second and/or third trimester. CONCLUSIONS: Measurements of serum biomarkers, some of which have been or are still used in screening for other pregnancy complications, could contribute to the prenatal evaluation of patients at risk of PAS at delivery; however, important evidence gaps were identified for suitable cutoffs for most biomarkers, variability of gestational age at sampling and the potential overlap of the marker values with other placental-related complications of pregnancy.

Placental volume as a novel sign for identifying placenta accreta spectrum in pregnancies with complete placenta previa.

BACKGROUND: Placenta accreta spectrum (PAS) carries an increased risk of maternal-fetal mortality and morbidity, and magnetic resonance imaging (MRI) features for PAS have been used for preoperative identification. This study aims to investigate the role of placental volume evaluated by MRI in identifying PAS in pregnant women with complete placenta previa. METHODS: Totally 163 cases of complete placenta previa pregnant women with a history of cesarean section underwent MRI for suspected PAS were included. We categorized the patients into two groups according to the presence or absence of PAS, and the maternal-fetal perinatal outcomes and placental volume analyzed by 3D Slice software were compared. RESULTS: There were significantly more gravidity, parity, and number of previous cesarean delivery in the PAS group (P < 0.05). Significant differences were also found between the two groups with respect to the following baseline characteristics: gestational age at delivery, intraoperative blood loss, blood transfusion, and neonatal birth weight (P < 0.05). Of 163 women in the study, 7 (4.294%) required cesarean hysterectomy for high-grade PAS or pernicious bleeding during cesarean section, and PAS was confirmed with histologic confirmation in 6 (85.714%) cases. The placental volume in PAS group was greater than that in the non-PAS group (P < 0.05). With a threshold of more than 887 cm3, the sensitivity and specificity in identifying PAS were 85.531% and 83.907% respectively, with AUC 0.908 (95% CI: 0.853-0.948). CONCLUSIONS: Placental volume may be a promising indicator of PAS in complete placenta previa patients with a history of cesarean section.

The relationship between cervical length and area measurements evaluated by MRI and the amount of hemorrhage in PAS cases.

BACKGROUND: Placenta accreta spectrum often leads to massive hemorrhage and even maternal shock and death. This study aims to identify whether cervical length and cervical area measured by magnetic resonance imaging correlate with massive hemorrhage in patients with placenta accreta spectrum. METHODS: The study was conducted at our hospital, and 158 placenta previa patients with placenta accreta spectrum underwent preoperative magnetic resonance imaging examination were included. The cervical length and cervical area were measured and evaluated their ability to identify massive hemorrhage in patients with placenta accreta spectrum. RESULTS: The cervical length and area in patients with massive hemorrhage were both significantly smaller than those in patients without massive hemorrhage. The results of multivariate analysis show that cervical length and cervical area were significantly associated with massive hemorrhage. In all patients, a negative linear was found between cervical length and amount of blood loss (r =-0.613), and between cervical area and amount of blood loss (r =-0.629). Combined with cervical length and cervical area, the sensitivity, specificity, and the area under the curve for the predictive massive hemorrhage were 88.618%, 90.209%, and 0.890, respectively. CONCLUSION: The cervical length and area might be used to recognize massive hemorrhage in placenta previa patients with placenta accreta spectrum.

Incorporation of vasa previa screening into a routine anomaly scan: A single center cohort study.

INTRODUCTION: Vasa previa (VP), defined as unprotected fetal vessels traversing the membranes over the cervix, is associated with a high perinatal mortality when undiagnosed prenatally. Conversely, prenatal diagnosis with ultrasound and cesarean delivery before the membranes rupture is associated with excellent outcomes. However, controversy exists regarding screening for VP. In the UK, routine screening for VP is not recommended. The objective of this study was to report the incidence of VP and our experience in the detection of VP with a universal screening protocol at the time of the second-trimester fetal anomaly scan with third-trimester confirmation in an unselected population of pregnancies. MATERIAL AND METHODS: We performed a single-center historical cohort study of all pregnant women who underwent routine second-trimester anomaly screening scans at West Middlesex University Hospital, London, UK, between 2012 and 2016. Over 5 years, every patient undergoing routine anomaly screening was evaluated for VP using a systematic protocol during their 20-week anomaly scan. Suspected cases of VP were rescanned in the third trimester by specialist sonographers with an interest in VP. The primary outcomes were the incidence and detection of VP. RESULTS: During the study period, 24 690 anatomy scans were performed. A total of 64 patients were identified as having potential VP at the second-trimester anomaly screening scan, of which 19 were confirmed by the specialist sonographer in the third trimester and at delivery. The screen positive rate was 0.26% (95% confidence interval [CI] 0.20%-0.32%). VP at birth was found in 19/24690 births (1:1299 [95% CI: 1:832-1:2030] births). Universal screening for VP using our protocol had a sensitivity of 100% and a specificity of 99.78% (95% CI: 99.72%-99.84%). The false-positive rate of the second-trimester screen was 0.18% (95% CI: 0.13-0.24). There were no false positives or false negatives at delivery. Of the 19 patients with confirmed VP, 17 had scheduled cesarean deliveries, and two required emergency deliveries due to antepartum hemorrhage. One baby died, giving a perinatal mortality of 5%. CONCLUSIONS: VP complicates approximately 1:1300 pregnancies. Routine screening for VP yielded a 100% detection rate. We suggest the inclusion of structured VP assessment in standard fetal anomaly screening programs.

Nomogram based on clinical characteristics and ultrasound indicators for predicting severe postpartum hemorrhage in patients with anterior placenta previa combined with previous cesarean section: a retrospective case-control study.

BACKGROUND: Placental accreta spectrum disorders (PAS) are a high-risk group for severe postpartum hemorrhage (SPPH), with the incidence of PAS increasing annually. Given that cesarean section and anterior placenta previa are the primary risk factors for PAS, therefore, our study aims to investigate the predictive value of clinical characteristics and ultrasound indicators for SPPH in patients with anterior placenta previa combined with previous cesarean section, providing a theoretical basis for early prediction of SPPH. METHODS: A total of 450 patients with anterior placenta previa combined with previous cesarean section were retrospectively analyzed at Shengjing Hospital affiliated with China Medical University between January 2018 and March 2022. Clinical data and ultrasound indicators were collected. Patients were categorized into SPPH (blood loss >2000mL, 182 cases) and non-SPPH (blood loss ≤ 2000mL, 268 cases) groups based on the blood loss within 24 h postpartum. The population was randomly divided into training and validation cohorts at a 7:3 ratio. LASSO and multifactorial logistic regression analyses were utilized to identify independent risk factors for SPPH. Accordingly, a nomogram prediction model was constructed, the predictive performance was assessed using receiver operating characteristic (ROC) curves, calibration curves and decision curve analysis (DCA). RESULTS: Among the 450 patients, 182 experienced SPPH (incidence rate, 40.44%). Preoperative systemic immune-inflammatory index, preoperative D-dimer level, preoperative placenta accreta spectrum ultrasound scoring system (PASUSS) score, and one-step-conservative surgery were identified as independent risk factors for SPPH in patients with anterior placenta previa combined with previous cesarean section. A nomogram was constructed based on these factors. The areas under the ROC curves for the training and validation cohorts were 0.844 (95%CI: 0.801-0.888) and 0.863 (95%CI: 0.803-0.923), respectively. Calibration curves and DCA indicated that this nomogram demonstrated good predictive accuracy. CONCLUSIONS: This nomogram presents an effective and convenient prediction model for identifying SPPH in patients with anterior placenta previa combined with previous cesarean section. It can guide surgical planning and improve prognosis.

A new step-wise surgical technique of knapsack-like uterine compression sutures for intractable postpartum hemorrhage in cesarean section.

BACKGROUND: Intractable postpartum hemorrhage (PPH) during cesarean section has been a significant concern for obstetricians. We aimed to explore the effectiveness and safety of a new type of uterine compression suture, the step-wise surgical technique of knapsack-like sutures for treating intractable PPH caused by uterine atony and placenta factors in cesarean section. METHODS: The step-wise surgical technique of knapsack-like sutures was established on the basis of the artful combination of vertical strap-like sutures and an annular suture-ligation technique. This novel surgical technique was applied to 34 patients diagnosed with PPH during cesarean section due to severe uterine atony and placental factors in our department. The hemostatic effects, clinical outcomes and follow-up visit results were all reviewed and analyzed. RESULTS: This new uterine compression suture successfully stopped bleeding in 33 patients, and the effective rate was 97.06%. Only 1 patient failed and was changed to use bilateral uterine arterial embolization and internal iliac artery embolization. The follow-up visits indicated that 33 patients restored menstruation except for 1 who was diagnosed with amenorrhea. The gynecological ultrasound tests of all the patients suggested good uterine involutions, and they had no obvious complaints such as hypogastralgia. CONCLUSIONS: This step-wise surgical technique of knapsack-like uterine compression sutures can compress the uterus completely. It is a technique that can conserve the uterus and fertility function without special equipment in caesarean section for PPH, with the characteristics of being safe, simple and stable (3 S) with rapid surgery, reliable hemostasis and resident doctor to operation (3R).

Differentiating placenta accreta spectrum from scar dehiscence with underlying, non-adherent placenta: A systematic review of scoring systems and primary data analysis.

INTRODUCTION: Accurate discrimination between placenta accreta spectrum (PAS) and scar dehiscence with underlying non-adherent placenta is challenging both on prenatal ultrasound and intraoperatively. This can lead to overdiagnosis of PAS and unnecessarily aggressive management of scar dehiscence which increases the risk of morbidity. Several scoring systems have been published which combine clinical and ultrasound information to help diagnose PAS in women at high risk. This research aims to provide insights into the reliability and utility of existing accreta scoring systems in differentiating these two closely related but different conditions to contribute to improved clinical decision making and patient outcomes. MATERIAL AND METHODS: A literature search was performed in four electronic databases. The references of relevant articles were also assessed. The articles were then evaluated according to the predefined inclusion criteria. Primary data for testing each scoring system were obtained retrospectively from two hospitals with specialized PAS services. Each scoring system was used to evaluate the predicted outcome of each case. RESULTS: The literature review yielded 15 articles. Of these, eight did not have a clearly described diagnostic criteria for accreta, hence were excluded. Of the remaining seven studies, one was excluded due to unorthodox diagnostic criteria and two were excluded as they differed from the other systems hindering comparison. Four scoring systems were therefore tested with the primary data. All the scoring systems demonstrated higher scores for high-grade PAS compared to scar dehiscence (p < 0.001) with an excellent Area Under the receiver operator characteristic Curve ranging from 0.82 (95% CI 0.71-0.92) to 0.87 (95% CI 0.79-0.96) in differentiating between these two conditions. However, no statistically significant differences were noted between the low-grade PAS and scar dehiscence on all scoring systems. CONCLUSIONS: Most published scoring systems have no clearly defined diagnostic criteria. Scoring systems can differentiate between scar dehiscence with underlying non-adherent placenta from high-grade PAS with excellent diagnostic accuracy, but not for low-grade PAS. Hence, relying solely on these scoring systems may lead to errors in estimating the risk or extent of the condition which hinders preoperative planning.