Placenta Accreta Spectrum (PAS): Diagnosis, Clinical Presentation, Therapeutic Approaches, and Clinical Outcomes.

Placenta accreta spectrum (PAS) refers to the abnormal adhesion of the placenta to the myometrium, with varying degrees of severity. Placenta accreta involves adhesion to the myometrium, placenta increta invades the myometrium, and placenta percreta extends through the serosa to adjacent organs. The condition is linked to deficient decidualization in scarred uterine tissue, and the risk increases when placenta previa is present and with each prior cesarean delivery. Other risk factors include advanced maternal age, IVF, short intervals between cesareans, and smoking. PAS incidence has risen due to the increase in cesarean deliveries. Placenta previa combined with PAS significantly raises the risk of severe peripartum bleeding, often necessitating a cesarean section with a total hysterectomy. Recognizing PAS prepartum is essential, with sonographic indicators including intraplacental lacunae and uterovesical hypervascularization. However, PAS can be present without sonographic signs, making clinical risk factors crucial for diagnosis. Effective management requires a multidisciplinary approach and proper infrastructure. This presentation covers PAS cases treated at University Hospital Freiburg, detailing patient conditions, diagnostic methods, treatments and outcomes.

Placenta Accreta Spectrum: A Comprehensive Review of Guidelines.

Importance: Placenta accreta spectrum (PAS) represents a range of disorders characterized by abnormal placental invasion and is associated with severe maternal morbidity and mortality. Objective: The aim of this study was to review and compare the most recently published major guidelines on the diagnosis and management of this potentially life-threatening obstetric complication. Evidence Acquisition: A descriptive review of guidelines from the American College of Obstetricians and Gynecologists, the Royal Australian and New Zealand College of Obstetricians and Gynecologists, the International Society for Abnormally Invasive Placenta, the Royal College of Obstetricians and Gynecologists, the International Federation of Gynecology and Obstetrics, and the Society of Obstetricians and Gynecologists of Canada on PAS disorders was carried out. Results: There is a consensus among the reviewed guidelines regarding the definition and the diagnosis of PAS using specific sonographic signs. In addition, they all agree that the use of magnetic resonance imaging should be limited to the evaluation of the extension to pelvic organs in case of placenta percreta. Moreover, American College of Obstetricians and Gynecologists, Royal College of Obstetricians and Gynecologists, International Federation of Gynecology and Obstetrics, and the Society of Obstetricians and Gynecologists of Canada agree that screening for PAS disorders should be based on clinical risk factors along with sonographic findings. Regarding management, they all highlight the importance of a multidisciplinary team approach and recommend delivery by elective cesarean section at a tertiary center with experienced staff and appropriate resources. Routine preoperative ureteric stenting and occlusion of pelvic arteries are universally not recommended. Moreover, hysterectomy following the delivery of the fetus, expectant management with placenta left in situ, and conservative management in case of focal disease and desired fertility are all considered as acceptable treatment options. The reviewed guidelines also suggest some measures for intraoperative and postoperative hemorrhage control and recommend prophylactic administration of antibiotics. Methotrexate after expectant management is unanimously discouraged. On the other hand, there is no common pathway with regard to the optimal timing of delivery, the recommended mode of anesthesia, the preferred skin incision, and the effectiveness of the delayed hysterectomy approach. Conclusions: PAS disorders are mainly iatrogenic conditions with a constantly rising incidence and potentially devastating consequences for both the mother and the neonate. Thus, the development of uniform international practice protocols for effective screening, diagnosis, and management seems of paramount importance and will hopefully drive favorable pregnancy outcomes.

Customizing EV-CATCHER to Purify Placental Extracellular Vesicles from Maternal Plasma to Detect Placental Pathologies.

Placenta Accreta Spectrum (PAS) is a life-threatening condition in which placental trophoblastic cells abnormally invade the uterus, often up to the uterine serosa and, in extreme cases, tissues beyond the uterine wall. Currently, there is no clinical assay for the non-invasive detection of PAS, and only ultrasound and MRI can be used for its diagnosis. Considering the subjectivity of visual assessment, the detection of PAS necessitates a high degree of expertise and, in some instances, can lead to its misdiagnosis. In clinical practice, up to 50% of pregnancies with PAS remain undiagnosed until delivery, and it is associated with increased risk of morbidity/mortality. Although many studies have evaluated the potential of fetal biomarkers circulating in maternal blood, very few studies have evaluated the potential of circulating placental extracellular vesicles (EVs) and their miRNA contents for molecular detection of PAS. Thus, to purify placental EVs from maternal blood, we customized our robust ultra-sensitive immuno-purification assay, termed EV-CATCHER, with a monoclonal antibody targeting the membrane Placental Alkaline Phosphatase (PLAP) protein, which is unique to the placenta and present on the surface of placental EVs. Then, as a pilot evaluation, we compared the miRNA expression profiles of placental EVs purified from the maternal plasma of women diagnosed with placenta previa (controls, n = 16); placenta lying low in uterus but not invasive) to those of placental EVs purified from the plasma of women with placenta percreta (cases, n = 16), PAS with the highest level of invasiveness. Our analyses reveal that miRNA profiling of PLAP+ EVs purified from maternal plasma identified 40 differentially expressed miRNAs when comparing these two placental pathologies. Preliminary miRNA pathway enrichment and gene ontology analysis of the top 14 upregulated and top nine downregulated miRNAs in PLAP+ EVs, purified from the plasma of women diagnosed with placenta percreta versus those diagnosed with placenta previa, suggests a potential role in control of cellular invasion and motility that will require further investigation.

Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

BACKGROUND: Placenta accreta spectrum is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in the outcomes of patients with placenta accreta spectrum. OBJECTIVE: This study aimed to investigate health inequities in maternal and neonatal outcomes of pregnancies with placenta accreta spectrum. STUDY DESIGN: This multicentered retrospective cohort study included patients with a histopathological diagnosis of placenta accreta spectrum at 4 regional perinatal centers between January 1, 2013, and June 30, 2022. Maternal race and ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. The primary outcome was a composite adverse maternal outcome: transfusion of ≥4 units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury, or mortality. The secondary outcomes were a composite adverse neonatal outcome (Apgar score of <7 at 1 minute, morbidity, or mortality), gestational age at placenta accreta spectrum diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race and ethnicity with maternal and neonatal outcomes. RESULTS: A total of 408 pregnancies with placenta accreta spectrum were included. In 218 patients (53.0%), the diagnosis of placenta accreta spectrum was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, body mass index, income, and parity, there was no difference in composite adverse maternal outcomes among the racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team, and cesarean hysterectomy were similar among groups. CONCLUSION: In our multicentered placenta accreta spectrum cohort, race and ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis, or planned multidisciplinary care. This study hypothesized that a comparable incidence of individual risk factors for perinatal morbidity and geographic proximity reduces potential inequities that may exist in a larger population.

Management of placenta accreta spectrum in low- and middle-income countries.

Placenta accreta spectrum (PAS) can be associated massive intra- and post-operative hemorrhage which when not controlled can lead to maternal death. Important advances have occurred in understanding the pathophysiology and therapeutic options for this condition. The prevalence of PAS at birth is direct association with the cesarean delivery (CD) rate in the corresponding population and is increasing worldwide. Limited health infrastructure in low- and middle-income countries increases the morbidity and mortality of patients with PAS at birth. In many cases, obstetricians working in limited resources settings cannot follow some of the international guideline's recommendations and have to opt for low-cost management procedures. In this review, we describe the particularities of managing PAS care in low- and middle-income countries from of prenatal evaluation of patients at risk of PAS at birth, therapeutic options, and inter-institutional collaboration. We also propose a management protocol based on training of the local obstetric teams rather than on sophisticated technological resources that are almost never available in low-resource scenarios.

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.

First-trimester screening for placenta accreta spectrum.

In recent years, there has been a significant rise in cases of placenta accreta spectrum, a group of life-threatening placental disorders that can arise during childbirth. Early detection plays a crucial role in facilitating meticulous delivery planning, ultimately leading to a reduction in mortality and morbidity rates and improved overall outcomes. Although third-trimester ultrasound has traditionally been the primary method for prenatal screening for placenta accreta spectrum, it often falls short in identifying cases or diagnosis is too late for optimal delivery planning. Emerging evidence has highlighted the option of early detection of placenta accreta spectrum indicators during the first trimester of pregnancy. This comprehensive review delves into our current knowledge of sonographic assessment of the uterine cervicoisthmic complex in the first trimester, examining the location and appearance of cesarean scars and exploring first-trimester screening strategies, ultimately paving the way for improved maternal and neonatal outcomes.

Value of early pregnancy ultrasound combined with ultrasound score in the evaluation of placenta accreta in scar uterus: A retrospective cohort study.

The objective of this study is to investigate the value of early pregnancy ultrasound combined with ultrasound score (USS) for the evaluation of placenta accreta (PA) in scar uteri. Thirty cases of PA in scar uteri diagnosed by ultrasound at our hospital between June 2021 and June 2022 were selected retrospectively (observation group). In addition, 30 patients had placenta attached to the anterior wall of the uterus and covered the internal orifice of the cervix; however, no PA was selected in the same period (control group). The results of surgical pathology and ultrasound examination in the first trimester of pregnancy (11-14 weeks of pregnancy, fetal top hip length 4.5-8.4 cm) were analyzed. Ultrasonic image characteristics of the 2 groups were scored using an ultrasonic scoring scale. The ultrasonic signs and ultrasonic scores of the 2 groups were analyzed. The diagnostic value of ultrasound and USS for PA in the scarred uterus alone and in combination was analyzed based on the gold standard of surgical and pathological results. The rich blood flow signal at the junction of the uterine serosa and bladder, the rate of blood flow in the cavity of the placental parenchyma, the thinning rate of the myometrium after placenta, and the abnormal rate of the low echo area after placenta in the observation group were significantly higher than those in the control group (P < .05). The USS of the observation group was significantly higher than that of the control group (P < .05). The sensitivity (93.33%) and accuracy (95.00%) of the combined examinations were significantly higher than those of ultrasound (70.00% and 83.33%, respectively) (P < .05). The sensitivity and accuracy of combined examination were slightly higher than those of USS examination (83.33% and 90.00%), but the difference was not statistically significant (P > .05). There was no significant difference between the specificity of combined examination (93.33%) and ultrasound (96.67%) and USS (96.67%) (P > .05). Early pregnancy ultrasound and USS evaluation have high application value in the diagnosis and evaluation of early scar uterine PA. The combination of the 2 methods can further improve the sensitivity and accuracy of diagnosis.

Placenta Invasion Anomaly without Placenta Previa in the First Trimester of Pregnancy and its Conservative Management: A Case Presentation.

Diagnosing placenta accreta spectrum (PAS) is rather difficult in the first trimester of pregnancy. Especially if the localization of the placenta is not in and around the cervical canal, this may not attract the attention of obstetricians. Early diagnosis can decrease bleeding during curettage or miscarriage, but there are no guidelines regarding its diagnosis in the first trimester. In addition, there is insufficient evidence-based knowledge in the literature on the management and treatment of PAS without placenta previa. In this article, conservative treatment without hysterectomy of a patient diagnosed with PAS in first trimester was presented.

Determination of biomarker candidates for the placenta accreta spectrum by plasma proteomic analysis.

Placenta accreta spectrum (PAS) presents a significant obstetric challenge, associated with considerable maternal and fetal-neonatal morbidity and mortality. Nevertheless, it is imperative to acknowledge that a noteworthy subset of PAS cases remains undetected until the time of delivery, thereby contributing to an augmented incidence of morbidity among the affected individuals. The delayed identification of PAS not only hinders timely intervention but also exacerbates the associated health risks for both the maternal and fetal outcomes. This underscores the urgency to innovate strategies for early PAS diagnosis. In this study, we aimed to explore plasma proteins as potential diagnostic biomarkers for PAS. Integrated transcriptome and proteomic analyses were conducted to establish a novel diagnostic approach. A cohort of 15 pregnant women diagnosed with PAS and delivering at Inonu University Faculty of Medicine between 01/04/2021 and 01/01/2023, along with a matched control group of 15 pregnant women without PAS complications, were enrolled. Plasma protein identification utilized enzymatic digestion and liquid chromatography-tandem mass spectrometry techniques. Proteomic analysis identified 228 plasma proteins, of which 85 showed significant differences (P < 0.001) between PAS and control cases. We refined this to a set of 20 proteins for model construction, resulting in a highly accurate classification model (96.9% accuracy). Notable associations were observed for proteins encoded by P01859 (Immunoglobulin heavy constant gamma 2), P02538 (Keratin type II cytoskeletal 6A), P29622 [Kallistatin (also known as Serpin A4)], P17900 (Ganglioside GM2 activator Calmodulin-like protein 5), and P01619 (Immunoglobulin kappa variable 3-20), with fold changes indicating their relevance in distinguishing PAS from control groups. In conclusion, our study has identified novel plasma proteins that could serve as potential biomarkers for early diagnosis of PAS in pregnant women. Further research and validation in larger PAS cohorts are necessary to determine the clinical utility and reliability of these proteomic biomarkers for diagnosing PAS.

Anaemia and red blood cell transfusion in women with placenta accreta spectrum: an analysis of 38,060 cases.

Placenta accreta spectrum (PAS) has become a significant life-threatening issue due to its increased incidence and associated morbidity and mortality. Pregnancy is often associated with states of anaemia, and severe maternal haemorrhage represents a major risk factor for red blood cell (RBC) transfusion. The present study retrospectively analyzed the prevalence of anaemia, transfusion requirements and outcome in women with PAS. Using data from the German Statistical Office pregnant patients with deliveries hospitalized between January 2012 and December 2021 were included. Primary outcome was the prevalence of anemia and administration of RBCs. Secondary outcome were complications in women with PAS who received RBC transfusion. In total 6,493,606 pregnant women were analyzed, of which 38,060 (0.59%) were diagnosed with PAS. The rate of anaemia during pregnancy (60.36 vs. 23.25%; p < 0.0001), postpartum haemorrhage (47.08 vs. 4.41%; p < 0.0001) and RBC transfusion rate (14.68% vs. 0.72%; p < 0.0001) were higher in women with PAS compared to women without PAS. Women with PAS who had bleeding and transfusion experienced significantly more peripartum complications than those who did not. A multiple logistic regression revealed that the probability for RBC transfusion in all pregnant women was positively associated with anaemia (OR 21.96 (95% CI 21.36-22.58)). In women with PAS, RBC transfusion was positively associated with the presence of renal failure (OR 11.27 (95% CI 9.35-13.57)) and congestive heart failure (OR 6.02 (95% CI (5.2-7.07)). Early anaemia management prior to delivery as well as blood conservation strategies are crucial in women diagnosed with PAS.

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.

Pregnancy-specific beta-1-glycoprotein 6 is a potential novel diagnostic biomarker of placenta accreta spectrum.

Early diagnosis is essential for the safer perinatal management of placenta accreta spectrum (PAS). We used transcriptome analysis to investigate diagnostic maternal serum biomarkers and the mechanisms of PAS development. We analyzed eight formalin-fixed paraffin-embedded placental specimens from two placenta increta and three placenta percreta cases who underwent cesarean hysterectomy at Sapporo Medical University Hospital between 2013 and 2019. Invaded placental regions were isolated from the uterine myometrium and RNA was extracted. The transcriptome difference between normal placenta and PAS was analyzed by microarray analysis. The PAS group showed markedly decreased expression of placenta-specific genes such as LGALS13 and the pregnancy-specific beta-1-glycoprotein (PSG) family. Term enrichment analysis revealed changes in genes related to cellular protein catabolic process, female pregnancy, autophagy, and metabolism of lipids. From the highly dysregulated genes in the PAS group, we investigated the expression of PSG family members, which are secreted into the intervillous space and can be detected in maternal serum from the early stage of pregnancy. The gene expression level of PSG6 in particular was progressively decreased from placenta increta to percreta. The PSG family, especially PSG6, is a potential biomarker for PAS diagnosis.

Modified one-step conservative uterine surgery (MOSCUS) versus cesarean hysterectomy in the management of placenta accreta spectrum: A single-center retrospective analysis based on 619 Vietnamese pregnant women.

OBJECTIVES: To compare maternal outcome measures in surgical management of placenta accreta spectrum (PAS)-the modified one-step conservative uterine surgery (MOSCUS), a new approach at Tu Du Hospital in Vietnam, versus cesarean hysterectomy, and to identify factors that appear to contribute to the successful outcome of the MOSCUS. METHODS: This retrospective study was conducted at Tu Du Hospital in southern Vietnam between January 2019 and December 2020. The study enrolled all pregnant women at more than 28 weeks of pregnancy with a diagnosis of PAS who underwent either a cesarean hysterectomy or a uterus-preserving approach using the MOSCUS method. RESULTS: The prevalence of PAS at our single tertiary referral hospital was 0.4% (619 PAS cases/132 518 births) in 2 years. Among 296 patients, the surgical time duration, estimated blood loss, and red blood cell transfusion in the MOSCUS group (n = 217) were all significantly less than in the cesarean hysterectomy group (n = 79) (152.72 ± 42.23 vs 185.13 ± 58.22 min, 1000 vs 1500 mL, and 500 vs 710 mL, respectively). Intraoperatively, the rate of visceral injuries in the hysterectomy group was higher than that in the MOSCUS group (P < 0.001). However, the rate of postoperative infection was higher in the MOSCUS group than in the cesarean hysterectomy group (P = 0.012). Of a total of 217 cases managed using the MOSCUS management, 24 required a secondary hysterectomy; the success rate was 88.9% (95% confidence interval [CI] 84.3%-93.1%). Some of the primary factors associated with the success of MOSCUS included maternal age less than 35 years, planned surgery, severity of PAS, and estimated blood loss during surgery (odds ratio [OR] 5.16, 95% CI 1.96-13.59; OR 3.05, 95% CI 1.08-8.62; OR 3.62, 95% CI 1.19-10.98; and OR 49.66, 95% CI 11.16-221.02, respectively; P < 0.05). CONCLUSION: MOSCUS is an acceptable alternative to cesarean hysterectomy in many patients diagnosed with PAS. This new surgical management of PAS resulted in the preservation of the uterus, and a favorable outcome in nearly 9 out of 10 pregnant women. We believe that MOSCUS can be safely offered for the management of PAS in referral hospital settings.

Placenta accreta spectrum care infrastructure: an evidence-based review of needed resources supporting placenta accreta spectrum care.

The incidence of placenta accreta spectrum, the deeply adherent placenta with associated increased risk of maternal morbidity and mortality, has seen a significant rise in recent years. Therefore, there has been a rise in clinical and research focus on this complex diagnosis. There is international consensus that a multidisciplinary coordinated approach optimizes outcomes. The composition of the team will vary from center to center; however, central themes of complex surgical experts, specialists in prenatal diagnosis, critical care specialists, neonatology specialists, obstetrics anesthesiology specialists, blood bank specialists, and dedicated mental health experts are universal throughout. Regionalization of care is a growing trend for complex medical needs, but the location of care alone is just a starting point. The goal of this article is to provide an evidence-based framework for the crucial infrastructure needed to address the unique antepartum, delivery, and postpartum needs of the patient with placenta accreta spectrum. Rather than a clinical checklist, we describe the personnel, clinical unit characteristics, and breadth of contributing clinical roles that make up a team. Screening protocols, diagnostic imaging, surgical and potential need for critical care, and trauma-informed interaction are the basis for comprehensive care. The vision from the author group is that this publication provides a semblance of infrastructure standardization as a means to ensure proper preparation and readiness.

Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes.

OBJECTIVE: Our work aims to determine whether there is an association between first-trimester serum pregnancy-associated plasma protein A (PAPP-A) multiples of the median (MoM) value and placenta previa with or without placenta accreta spectrum disorders (PAS) in women. PATIENTS AND METHODS: A retrospective analysis was performed on 267 patients who had first-trimester screening test results for aneuploidy, including nonadherent placenta previa (n=106), placenta previa with PAS (n=60), and control group (healthy pregnant women with previous cesarean section and normal placental location, n=101). To assess the significant difference between these groups, PAPP-A MoMs were compared. RESULTS: The median PAPP-A MoM of 1.96 in placenta previa with PAS was significant (>0.88) in nonadherent placenta previa and 0.89 in the control group (p<0.001). Serum PAPP-A was found to be significantly associated with the severity of bleeding, such that patients with severe bleeding of 1,500 mL or more (n=54) had a higher mean PAPP-A MoM (1.93±0.69; p<0.001). Furthermore, the mean PAPP-A MoM was found to be 1.96±0.74 in the hysterectomy group and 0.89±0.47 in the conservative management group, and the difference was found to be significantly higher (p<0.001). CONCLUSIONS: Elevated PAPP-A values in the first trimester of pregnancy may be a useful marker for identifying women at higher risk of PAS and adverse outcomes.