Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum: A Cross-sectional Study 

Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum: A Cross-sectional Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Help Center Sign In Submit a Preprint Cite Share Download PDF Article Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum: A Cross-sectional Study Nevin Yilmaz, Isil Turan Bakirci, Busra Sahin, Gokhan Bolluk, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4951853/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 08 Feb, 2025 Read the published version in Scientific Reports → Version 1 posted 10 You are reading this latest preprint version Abstract Background This study aimed to assess maternal serum survivin levels in women with placenta previa, with and without placenta accreta spectrum (PAS), to understand its role in abnormal placental adherence and invasion. Methods In this prospective cross-sectional study, we enrolled 84 pregnant women categorized into control (n = 42), placenta previa (n = 24), and PAS (n = 28) groups. Serum survivin levels were quantitatively determined using ELISA, and statistical analyses were performed using ANOVA and post-hoc tests. Results A significant elevation in serum survivin levels was observed in the placenta previa and PAS groups compared to the controls (p < 0.05), suggesting that survivin plays a role in the pathophysiological response to abnormal placental adherence and invasion. Conclusions Elevated serum survivin levels may serve as an early biomarker for the diagnosis and management of placenta previa and PAS, aiding in the planning and timing of surgical interventions and the selection of appropriate surgical centers. Health sciences/Biomarkers Health sciences/Medical research Placenta previa placenta accreta spectrum survivin Figures Figure 1 Introduction The placental attachment process is vital for fetal development and nourishment during pregnancy. It involves a sophisticated network of cellular and molecular mechanisms facilitating the placenta's connection to the uterine lining. Obstetric complications, such as placenta previa and the placenta accreta spectrum (PAS) disorders, pose significant challenges, frequently resulting in considerable maternal and fetal morbidity [ 1 , 2 ] These conditions are primarily characterized by atypical implantation and placental invasion. Placenta previa is identified by the placenta occluding the cervical os, while PAS encompasses various conditions where the placenta inordinately adheres to the uterine wall [ 3 ] The exploration into the molecular underpinnings of placenta previa and PAS has intensified, with the intent to refine diagnostic and therapeutic methods [ 4 , 5 , 6 , 7 ]. Survivin is a pivotal protein influencing cellular longevity and apoptosis [ 8 ]. Known as a cellular life sentinel, it inhibits programmed cell death. Cancer cells have exploited this characteristic to enhance their survivability, promoting tumor growth [ 9 ]. Additionally, survivin, predominantly produced by cytotrophoblast cells, is integral to placental development, with diminished expression in syncytiotrophoblast cells [ 10 ]. Its role in promoting normal cytotrophoblast proliferation during pregnancy is crucial for fetal development. Nonetheless, the function of survivin in pathological pregnancies, such as hydatidiform mole and choriocarcinoma, where its levels increase, and in conditions like preeclampsia, where a decrease is noted, remains controversial [ 11 , 12 ]. While specific studies on circulating survivin during pregnancy are scarce, it is postulated that survivin levels might decline due to heightened apoptotic activity [ 13 ]. The objective of this study was to elucidate the role of survivin in the pathogenesis of placental complications, specifically placenta previa and placenta accreta spectrum (PAS), by examining maternal serum survivin levels across cases of normal placentation, placenta previa, and PAS. Materials and Methods This prospective cross-sectional study was conducted at Kanuni Sultan Suleyman Research Hospital between 2021 and 2022. The cohort included pregnant women within the age range of 18 to 45 years diagnosed with placenta previa and placenta accreta spectrum disorders (PAS). A control group comprised women with physiological pregnancies. Participant recruitment was consecutive, based on admissions to the antenatal clinic or labor ward throughout the study period. The diagnoses of placenta previa and PAS were established using ultrasound imaging. PAS was specifically suspected in cases of anechoic loss of the retroplacental area, prominent placental lacunes, and increased vascularity at the interface of the uterus and bladder. The FIGO staging criteria were applied to diagnose PAS, particularly in patients without prior cesarean section. According to the FIGO criteria, Stage 1 (placenta accreta) involves placental villi directly attached to the myometrium without intervening decidua, Stage 2 (placenta increta) involves placental villi invading the myometrium, and Stage 3 (placenta percreta) involves placental villi penetrating through the myometrium and reaching the uterine serosa or adjacent organs [ 14 ]. For patients who underwent segmental resection and hysterectomy, the resected materials were sent for pathological examination, with specific markings indicating areas suspected of placental invasion. The diagnosis of invasion was confirmed by pathological evaluation. Exclusion criteria encompassed multiple gestations, intrauterine growth restriction, and pre-existing medical conditions such as diabetes, chronic hypertension, and kidney disease. The study protocol adhered to the Declaration of Helsinki and received approval from the Ethics Committee for Human Studies at Kanuni Sultan Suleyman Training and Research Hospital (Approval number: KAEK/2021.05.167). Written informed consent was obtained from all participants, ensuring the maintenance of privacy rights throughout the research. Demographic data gathered included gravidity, age, parity, and medical history. Obstetric and clinical information was also compiled, including gestational age, history of previous cesarean sections, and any comorbidities. Measurement of Serum Survivin Blood samples were collected during hospital admission, specifically within the first hour of admission. The gestational ages of the participants at the time of sample collection ranged from 26 to 40 weeks. This timing was chosen to ensure consistency and to minimize any variations that might affect serum survivin levels. Serum samples were processed and stored at -80°C until further analysis. Serum levels of survivin were quantified using a commercially available ELISA kit following the manufacturer's instructions. The assay was performed in duplicate, and the mean concentration was calculated for each sample. Serum survivin was measured with an enzyme-linked immunosorbent assay method using the commercial kit (Cat No: ab18361, Abcam Inc., UK)). The optical density (OD) was measured spectrophotometrically at a wavelength of 450 nm. The detection range was 93 pg/mL to 9600 pg/mL, and the sensitivity was 7 pg/mL. Statistical Analysis Statistical analyses were performed using IBM SPSS (USA) and GraphPad Prism 7.0 software (GraphPad USA). Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. After the normality test, numeric variables were analyzed with ANOVA with post hoc Tukey test and Kruskal-Wallis ANOVA with post hoc Mann-Whitney test, as appropriate. To control for potential confounders, multivariate analysis was conducted using multiple regression models. This approach allowed us to adjust for variables such as age, parity, and history of cesarean section. Statistical significance was set at p < 0.05. Results Table 1 presents the baseline clinical characteristics of the women with physiological pregnancies, placenta previa, and PAS. The mean age of the PAS group was significantly higher when compared to both the control and placenta previa groups (34.0 ± 4.8 vs. 29.9 ± 5.0 and 31.9 ± 5.1 respectively; p 0.05). The placenta previa group displayed a significantly higher median parity than the control and PAS groups (p 0.05). The rate of multiple cesarean deliveries was notably higher in the PAS group than in the control and placenta previa groups (p < 0.05). The rates of hysterectomy and segmental uterine resection were also higher in the PAS group than those in the placenta previa and control groups. Additionally, we observed a significantly lower median gestational age at delivery in both the PAS and placenta previa groups than in the control group [36 (27–40) vs. 34 (26–40) and 38 (36–40) respectively; p < 0.05]. The median 1- and 5-minute Apgar scores of the PAS group were significantly lower than those of the other groups (p 0.05). The median birth weight of infants born to mothers in the PAS and placenta previa groups was significantly lower than that of infants born to mothers in the control group (p < 0.05). Table 1 Baseline clinical characteristics of control, placenta previa, and PAS groups. Controls (n = 42) Placenta previa (n = 24) PAS (n = 28) Significance Age, years 29.9±5.0 a 31.9±5.1 a 34±4.8 b 0.006 Gravidity 4 (1–6) 3 (1–6) 4 (1–9) 0.058 Parity 2 (1–6) a 1 (0–4) b 2 (0–6) a 0.009 Number of prior cesarean delivery 0 1 2 3 >3 0 13 (31%) 14 (33.3%) 12 (28.5%) 3 (7.2%) 14 (58.3%) 9 (37.5%) 1 (4.2%) 0 0 2 (7.1%) 11 (39.3%) 5 (17.9%) 7 (25%) 3 (10.7%) 0.001 Gestational age at delivery 38 (36–40) a 34 (26–40) b 36 (27–40) b 0.001 APGAR score at 1 minute at 5 minute 7 (2–7) a 9 (6–9) a 6 (2–9) a 9 (5–10) a 6 (1–7) b 9 (4–9) b 0.001 0.001 Birth weight (g) 3085 (2190–4130) 3000 (980–4200) 2830 (1280–3370) 0.013 Obstetrical surgery Cesarean section Cesarean operation with uterine hemostatic suturing Cesarean with hysterectomy Cesarean with segmental uterine resection 42 0 0 0 21 0 2 1 0 9 11 8 Perioperative complications No Bladder injury Re-laparotomy 42 (100%) 0 0 23 (4.2%) 1 (95.8%) 0 22 (67.8) 5 (17.9%) 1 (14.3%) Length of hospital stay (day) 2 (1–3) a 2 (1–17) b 5 (1–37) c 0.001 PAS: Placenta accreta spectrum Data were expressed as mean with standard deviation, median with range, and count (%) as appropriate. When statistically significant differences exist among the study groups, they are coded with letters a, b, and c. The study groups are coded with similar letters when there is no significant difference among the study groups. To address potential confounding factors, we conducted a multivariable regression analysis to explore the relationship between maternal serum survivin levels and various baseline characteristics, including age, gravidity, and parity. The results of the multivariable regression analysis are presented in Table 2 . Table 2 Multivariable regression analysis results Variable Coefficient (β) Standard Error t-value p-value 95% Confidence Interval Constant -161.7580 189.881 -0.852 0.397 -539.048 to 215.532 Age 14.0472 5.920 2.373 0.020 2.285 to 25.809 Gravidity 69.0257 30.690 2.249 0.027 8.046 to 130.006 Parity -61.1950 39.483 -1.550 0.125 -139.647 to 17.257 The analysis indicated that both maternal age and gravidity had significant effects on the serum survivin levels. Specifically, an increase in maternal age and gravidity was associated with higher serum survivin levels (p < 0.05). These findings suggest that the elevated survivin levels observed in the PAS and placenta previa groups are robust and not confounded by these factors. The median duration of hospitalization was significantly longer in the PAS group than that in the placenta previa and control groups. The placenta previa group also had a longer hospitalization duration than the control group (p < 0.05). Figure 1 presents the serum survivin levels in the control, placenta previa, and PAS groups. The median survival of the PAS group was significantly higher than that of the other groups [785 (324.50–1122) vs. 348.3 (173.0-776.4) and 177.9 (87.3–242.0), respectively; p < 0.05]. The median survivin value of the placenta previa group was significantly higher than that of the control group (p < 0.05). Discussion This study demonstrated that women with placenta previa and the placenta accreta spectrum (PAS) exhibit significantly elevated levels of maternal serum survivin compared to those with normal placentation. Survivin plays a pivotal role in modulating cell life span and preventing apoptosis, suggesting its involvement in the pathogenesis of these obstetric complications. Notably, the surge in survivin levels among PAS cases suggests a protective response to mitigate the challenges of abnormal placental attachment and invasion. This mechanism parallels survivin's function in enhancing cancer cell resilience, highlighting its critical role in pathological and physiological contexts 9 . Survivin's dual role in the placenta as an essential promoter of cellular proliferation and an inhibitor of apoptosis underlines a paradoxical contradiction: It is vital for normal placental development while contributing to placental pathologies. Our research supports the notion that survivin's upregulation is necessary for placental establishment; its overexpression may lead to conditions marked by abnormal growth and invasive behavior [ 11 , 12 ]. The decreased survivin levels observed in preeclampsia cases further illuminate this molecule's complex involvement in placental disorders, providing insight into diseases like placenta previa and PAS [ 12 ]. Our findings are consistent with literature that underscores the importance of survivin and related proteins in trophoblast cell proliferation and survival, highlighting the potential of targeting survivin to understand and treat placental dysfunctions [ 10 , 13 , 15 ]. For clinical practice, our study underscores the value of serum survivin as a biomarker for the early detection and management of placental diseases. Recognizing the rise in survivin levels as a harbinger of obstetric complications could lead to more effective interventions. Furthermore, this study contributes to the broader understanding of survivors' multifaceted roles, suggesting that modulating their expression could mitigate adverse outcomes in placental disorders. We also observed a significant age difference among participants, suggesting older mothers are at higher risk of developing PAS, potentially due to age-related uterine changes. The association between multiple cesarean sections and increased PAS risk underscores the need for cautious obstetric management in such cases [ 16 , 17 ]. Surgical intervention rates, like hysterectomy, were also higher in the PAS group, underlining the complexity of managing PAS and the need for early detection. Significant differences were observed in gestational age at delivery and neonatal outcomes between the PAS and placenta previa groups compared to the control group. The PAS and placenta previa groups had earlier deliveries and higher rates of preterm births, along with poorer neonatal outcomes, underscoring the critical need for specialized care. Demographically, the study highlighted the significance of maternal age and history of cesarean deliveries in the prevalence of PAS, reinforcing the need for tailored risk assessments and management plans for at-risk populations. The multivariate regression analysis conducted in our study further strengthens the reliability of our findings. By controlling for maternal age and gravidity, we confirmed that elevated serum survivin levels observed in the PAS and placenta previa groups were not confounded by these factors. This robust analysis enhances the credibility of serum survivin as a potential biomarker for early detection and management of placental disorders. While this study provides valuable insights into the role of maternal serum survivin levels in the pathogenesis of placenta previa and PAS, several limitations should be acknowledged. First, its cross-sectional design and limited sample size may constrain the generalizability of our findings. Future research should employ longitudinal designs and include broader demographic samples to comprehensively validate the diagnostic and therapeutic utility of survivin. Additionally, we did not perform detailed analysis of survivin expression in the placenta. This analysis could offer deeper insights into the molecular mechanisms underlying placental pathologies such as placenta previa and PAS. Understanding these mechanisms could lead to targeted interventions to mitigate the risks associated with these conditions. Thus, future studies should incorporate placental survivin analysis to enhance our understanding of its role and validate the current findings. Conclusions I n conclusion, our research advocates the use of serum survivin levels as a biomarker for the early detection and management of placental disorders such as placenta previa and PAS. By harnessing the predictive power of survivin levels, clinicians can refine the existing protocols for the early identification and treatment of these conditions, thereby mitigating adverse maternal and neonatal outcomes. Early detection of elevated survivin levels allows for more precise planning regarding the timing and location of delivery, ensuring that high-risk pregnancies are managed in facilities equipped with the necessary resources and specialized surgical expertise. This proactive approach can prevent severe complications, such as massive hemorrhage, uterine rupture, and other life-threatening conditions, by enabling timely intervention. Additionally, it can improve neonatal outcomes by reducing the likelihood of preterm births and associated complications through better management of the delivery timing. Declarations Ethics Approval This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee for Human Studies of Kanuni Sultan Suleyman Training and Research Hospital (Approval number: KAEK/2021.05.167). Conflict of Interest The authors declare that no conflicts of interest could influence the research or the interpretation of its results. We have no financial or personal relationships with individuals or organizations that might bias our work or its outcomes. Informed Consent Written informed consent was obtained from all participants, and their privacy rights were strictly maintained throughout the study. Funding No financial support or external funding was obtained for this research project. Author Contribution Nevin Yilmaz: Study design, data collection, analysis, and writing.Isil Turan Bakirci: Study design, analysis, and writing.Busra Sahin: Data collection, analysis.Gokhan Bolluk: Analysis, and writing.Esra Can: Analysis, and writing.Huri Dedeakayogullari: Analysis.All authors have reviewed and approved the final version of this manuscript and are accountable for the accuracy and integrity of the research. Acknowledgement We would like to express our gratitude to all those who helped us during the writing of this manuscript.Thanks to all the peer reviewers for their opinions and suggestions. Data Availability The datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request. References Obstetric Care Consensus No. Placenta Accreta Spectrum. Obstet. Gynecol. 7 (6). https://doi.org/10.1097/AOG.0000000000002983 (2018). Jauniaux, E., Collins, S. & Burton, G. J. Placenta accreta spectrum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging. Am. J. Obstet. Gynecol. 218 (1), 75–87. https://doi.org/10.1016/j.ajog.2017.05.067 (2018). Silver, R. M. & Barbour, K. D. Placenta accreta spectrum: accreta, increta, and percreta. Obstet. Gynecol. Clin. N. Am. 42 (2), 381–402. https://doi.org/10.1016/j.ogc.2015.01.014 (2015). Balkas, G. & Caglar, T. Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes. Eur. Rev. Med. Pharmacol. Sci. 27 (20), 9955–9961. https://doi.org/10.26355/eurrev_202310_34174 (2023). Shainker, S. A. et al. Placenta accreta spectrum: biomarker discovery using plasma proteomics. Am. J. Obstet. Gynecol. 223 (3), 433. https://doi.org/10.1016/j.ajog.2020.03.019 (2020). .e1-433.e14 Okmen, F. et al. The role of fetal fibronectin and plasminogen activator inhibitor 1 biomarkers in antenatal prediction of placenta accreta spectrum. J. Obstet. Gynaecol. 42 (6), 2008–2012. https://doi.org/10.1080/01443615.2022.2068370 (2022). Uszyński, W. & Uszyński, M. Placenta accreta: epidemiology, molecular mechanism (hypothesis), and some clinical remarks. Ginekol. Pol. 75 (12), 971–978 (2004). Fang, X. L. et al. Overview of role of survivin in cancer: expression, regulation, functions, and its potential as a therapeutic target. J. Drug Target. 1–73. https://doi.org/10.1080/1061186X.2024.2309563 (2024). Turkekul, K. & Erdogan, S. Potent suppression of prostate cancer cell growth and eradication of cancer stem cells by CD44-targeted nanoliposome-quercetin nanoparticles. J. Cancer Prev. 28 (4), 160–174. https://doi.org/10.15430/JCP.2023.28.4.160 (2023). Shiozaki, A. et al. Survivin inhibits apoptosis in cytotrophoblasts. Placenta . 24 (1), 65–76. https://doi.org/10.1053/plac.2002.0860 (2003). Lehner, R., Bobak, J., Kim, N. W., Shroyer, A. L. & Shroyer, K. R. Localization of telomerase hTERT protein and survivin in placenta: relation to placental development and hydatidiform mole. Obstet. Gynecol. 97 (6), 965–970. https://doi.org/10.1016/S0029-7844(01)01131-0 (2001). Li, C. F. et al. Reduced expression of survivin, the inhibitor of apoptosis protein, correlates with severity of preeclampsia. Placenta . 33 (1), 47–51. https://doi.org/10.1016/j.placenta.2011.10.008 (2012). Muschol-Steinmetz, C. et al. B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells. Cell. Cycle . 15 (6), 827–839. https://doi.org/10.1080/15384101.2016.1149273 (2016). Jauniaux, E., Chantraine, F., Silver, R. M. & Langhoff-Roos, J. FIGO consensus guidelines on placenta accreta spectrum disorders: epidemiology. Int. J. Gynaecol. Obstet. 140 (3), 265–273. https://doi.org/10.1002/ijgo.12333 (2018). Fest, S. et al. Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation. Am. J. Reprod. Immunol. 59 (1), 75–83. https://doi.org/10.1111/j.1600-0897.2007.00557.x (2008). Tîrnovanu, M. C. et al. Unexpected dramatic evolution of placenta increta: case report and literature review. J. Personalized Med. 13 (11), 1563. https://doi.org/10.3390/jpm13111563 (2023). Horgan, R. & Abuhamad, A. Placenta accreta spectrum: prenatal diagnosis and management. Obstet. Gynecol. Clin. N. Am. 49 (3), 423–438. https://doi.org/10.1016/j.ogc.2022.02.004 (2022). Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4951853","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":357576463,"identity":"14e4ed53-871e-4d26-bba2-73118940bb0b","order_by":0,"name":"Nevin Yilmaz","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA/ElEQVRIiWNgGAWjYDCCAyDCgIGBjR3EqDgAEXxAlBZmEOPMAQYekGACQS0gANLC2AbRwoBPC9/tswcf8xTcSexj5k78+HPeHTl7scMPgbbYyek2YNcieS4v2ZjH4FliGzPvZgnJbc+MeaTTDIBako3NDmDXYnCGx0xyhsFhkJYNEobbDif2SCeAtBxI3IZbi/lPqJbNPxLngLSkfyCkxYzhA0TLNomDDSAtOfhtkTzDYywB1GIM0mLZcOywMc/tnIIDCQa4/cJ3hsfwQ8Kfw7Lz23s33/xRc1iOfXb65g8fKuzkcGmBAccGNAfjVw4C9oSVjIJRMApGwYgFACkSZAof8oDQAAAAAElFTkSuQmCC","orcid":"","institution":"","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Nevin","middleName":"","lastName":"Yilmaz","suffix":""},{"id":357576464,"identity":"a6d5bd77-269d-42de-a622-67a44f0b5316","order_by":1,"name":"Isil Turan Bakirci","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Isil","middleName":"Turan","lastName":"Bakirci","suffix":""},{"id":357576465,"identity":"e0e4727e-dfca-4a32-b3ed-acd21fbb2aa0","order_by":2,"name":"Busra Sahin","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Busra","middleName":"","lastName":"Sahin","suffix":""},{"id":357576466,"identity":"f63ad768-4639-439d-91ee-b3a5c7e62389","order_by":3,"name":"Gokhan Bolluk","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Gokhan","middleName":"","lastName":"Bolluk","suffix":""},{"id":357576467,"identity":"4931971f-c883-4770-a4dd-afc7525d6f6f","order_by":4,"name":"Esra Can","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Esra","middleName":"","lastName":"Can","suffix":""},{"id":357576468,"identity":"a9ffb55e-fcac-4619-8cde-74dd2fa57525","order_by":5,"name":"Huri Dedeakayogullari","email":"","orcid":"","institution":"","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Huri","middleName":"","lastName":"Dedeakayogullari","suffix":""}],"badges":[],"createdAt":"2024-08-21 13:11:56","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4951853/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4951853/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1038/s41598-025-89384-4","type":"published","date":"2025-02-08T15:57:35+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":66898977,"identity":"0147f3e4-a2c6-4240-bddd-a7b40d21c5a3","added_by":"auto","created_at":"2024-10-17 16:03:03","extension":"jpeg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":190933,"visible":true,"origin":"","legend":"\u003cp\u003eViolin graph of median (25-75% interquartile range) values of serum surviving in the control, placenta previa, and PAS (placenta acreta spectrum) groups. Significances were expressed on the graph.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-4951853/v1/1dacb719d5e7a74ef53dc606.jpeg"},{"id":75930413,"identity":"9f81ab64-90f9-4005-b32a-b94036512234","added_by":"auto","created_at":"2025-02-10 16:11:20","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":777665,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4951853/v1/b647cb6b-a8bf-40d2-948c-f932a2eeb3e4.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum: A Cross-sectional Study ","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe placental attachment process is vital for fetal development and nourishment during pregnancy. It involves a sophisticated network of cellular and molecular mechanisms facilitating the placenta's connection to the uterine lining. Obstetric complications, such as placenta previa and the placenta accreta spectrum (PAS) disorders, pose significant challenges, frequently resulting in considerable maternal and fetal morbidity [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] These conditions are primarily characterized by atypical implantation and placental invasion. Placenta previa is identified by the placenta occluding the cervical os, while PAS encompasses various conditions where the placenta inordinately adheres to the uterine wall [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eThe exploration into the molecular underpinnings of placenta previa and PAS has intensified, with the intent to refine diagnostic and therapeutic methods [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eSurvivin is a pivotal protein influencing cellular longevity and apoptosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Known as a cellular life sentinel, it inhibits programmed cell death. Cancer cells have exploited this characteristic to enhance their survivability, promoting tumor growth [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Additionally, survivin, predominantly produced by cytotrophoblast cells, is integral to placental development, with diminished expression in syncytiotrophoblast cells [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Its role in promoting normal cytotrophoblast proliferation during pregnancy is crucial for fetal development. Nonetheless, the function of survivin in pathological pregnancies, such as hydatidiform mole and choriocarcinoma, where its levels increase, and in conditions like preeclampsia, where a decrease is noted, remains controversial [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. While specific studies on circulating survivin during pregnancy are scarce, it is postulated that survivin levels might decline due to heightened apoptotic activity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe objective of this study was to elucidate the role of survivin in the pathogenesis of placental complications, specifically placenta previa and placenta accreta spectrum (PAS), by examining maternal serum survivin levels across cases of normal placentation, placenta previa, and PAS.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cp\u003eThis prospective cross-sectional study was conducted at Kanuni Sultan Suleyman Research Hospital between 2021 and 2022. The cohort included pregnant women within the age range of 18 to 45 years diagnosed with placenta previa and placenta accreta spectrum disorders (PAS). A control group comprised women with physiological pregnancies. Participant recruitment was consecutive, based on admissions to the antenatal clinic or labor ward throughout the study period.\u003c/p\u003e \u003cp\u003eThe diagnoses of placenta previa and PAS were established using ultrasound imaging. PAS was specifically suspected in cases of anechoic loss of the retroplacental area, prominent placental lacunes, and increased vascularity at the interface of the uterus and bladder. The FIGO staging criteria were applied to diagnose PAS, particularly in patients without prior cesarean section. According to the FIGO criteria, Stage 1 (placenta accreta) involves placental villi directly attached to the myometrium without intervening decidua, Stage 2 (placenta increta) involves placental villi invading the myometrium, and Stage 3 (placenta percreta) involves placental villi penetrating through the myometrium and reaching the uterine serosa or adjacent organs [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. For patients who underwent segmental resection and hysterectomy, the resected materials were sent for pathological examination, with specific markings indicating areas suspected of placental invasion. The diagnosis of invasion was confirmed by pathological evaluation.\u003c/p\u003e \u003cp\u003eExclusion criteria encompassed multiple gestations, intrauterine growth restriction, and pre-existing medical conditions such as diabetes, chronic hypertension, and kidney disease.\u003c/p\u003e \u003cp\u003e The study protocol adhered to the Declaration of Helsinki and received approval from the Ethics Committee for Human Studies at Kanuni Sultan Suleyman Training and Research Hospital (Approval number: KAEK/2021.05.167). Written informed consent was obtained from all participants, ensuring the maintenance of privacy rights throughout the research.\u003c/p\u003e \u003cp\u003eDemographic data gathered included gravidity, age, parity, and medical history. Obstetric and clinical information was also compiled, including gestational age, history of previous cesarean sections, and any comorbidities.\u003c/p\u003e \u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of Serum Survivin\u003c/h2\u003e \u003cp\u003eBlood samples were collected during hospital admission, specifically within the first hour of admission. The gestational ages of the participants at the time of sample collection ranged from 26 to 40 weeks. This timing was chosen to ensure consistency and to minimize any variations that might affect serum survivin levels. Serum samples were processed and stored at -80\u0026deg;C until further analysis. Serum levels of survivin were quantified using a commercially available ELISA kit following the manufacturer's instructions. The assay was performed in duplicate, and the mean concentration was calculated for each sample. Serum survivin was measured with an enzyme-linked immunosorbent assay method using the commercial kit (Cat No: ab18361, Abcam Inc., UK)). The optical density (OD) was measured spectrophotometrically at a wavelength of 450 nm. The detection range was 93 pg/mL to 9600 pg/mL, and the sensitivity was 7 pg/mL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analyses were performed using IBM SPSS (USA) and GraphPad Prism 7.0 software (GraphPad USA). Descriptive statistics were used to summarize the demographic and clinical characteristics of the study population. After the normality test, numeric variables were analyzed with ANOVA with post hoc Tukey test and Kruskal-Wallis ANOVA with post hoc Mann-Whitney test, as appropriate. To control for potential confounders, multivariate analysis was conducted using multiple regression models. This approach allowed us to adjust for variables such as age, parity, and history of cesarean section. Statistical significance was set at p\u0026thinsp;\u0026lt;\u0026thinsp;0.05.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the baseline clinical characteristics of the women with physiological pregnancies, placenta previa, and PAS. The mean age of the PAS group was significantly higher when compared to both the control and placenta previa groups (34.0\u0026thinsp;\u0026plusmn;\u0026thinsp;4.8 vs. 29.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.0 and 31.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.1 respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05) while the mean ages of the control and placenta previa groups exhibited no significant difference (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThe placenta previa group displayed a significantly higher median parity than the control and PAS groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Conversely, the median parity of the control and PAS groups did not differ significantly (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The rate of multiple cesarean deliveries was notably higher in the PAS group than in the control and placenta previa groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eThe rates of hysterectomy and segmental uterine resection were also higher in the PAS group than those in the placenta previa and control groups. Additionally, we observed a significantly lower median gestational age at delivery in both the PAS and placenta previa groups than in the control group [36 (27\u0026ndash;40) vs. 34 (26\u0026ndash;40) and 38 (36\u0026ndash;40) respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05]. The median 1- and 5-minute Apgar scores of the PAS group were significantly lower than those of the other groups (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). In contrast, the median 1- and 5-minute Apgar scores for the control and placenta previa groups did not exhibit significant differences (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). The median birth weight of infants born to mothers in the PAS and placenta previa groups was significantly lower than that of infants born to mothers in the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline clinical characteristics of control, placenta previa, and PAS groups.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eControls (n\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePlacenta previa (n\u0026thinsp;=\u0026thinsp;24)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePAS (n\u0026thinsp;=\u0026thinsp;28)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eSignificance\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, years\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e29.9\u0026plusmn;5.0\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31.9\u0026plusmn;5.1\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e34\u0026plusmn;4.8\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1\u0026ndash;6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (1\u0026ndash;9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.058\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1\u0026ndash;6)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0\u0026ndash;4)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (0\u0026ndash;6)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.009\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNumber of prior cesarean delivery\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e3\u003c/p\u003e \u003cp\u003e\u0026gt;3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e13 (31%)\u003c/p\u003e \u003cp\u003e14 (33.3%)\u003c/p\u003e \u003cp\u003e12 (28.5%)\u003c/p\u003e \u003cp\u003e3 (7.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14 (58.3%)\u003c/p\u003e \u003cp\u003e9 (37.5%)\u003c/p\u003e \u003cp\u003e1 (4.2%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (7.1%)\u003c/p\u003e \u003cp\u003e11 (39.3%)\u003c/p\u003e \u003cp\u003e5 (17.9%)\u003c/p\u003e \u003cp\u003e7 (25%)\u003c/p\u003e \u003cp\u003e3 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGestational age at delivery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e38 (36\u0026ndash;40)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (26\u0026ndash;40)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (27\u0026ndash;40)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAPGAR score\u003c/p\u003e \u003cp\u003eat 1 minute\u003c/p\u003e \u003cp\u003eat 5 minute\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (2\u0026ndash;7)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e9 (6\u0026ndash;9)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (2\u0026ndash;9)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e9 (5\u0026ndash;10)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (1\u0026ndash;7)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003cp\u003e9 (4\u0026ndash;9)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBirth weight (g)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3085 (2190\u0026ndash;4130)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3000 (980\u0026ndash;4200)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2830 (1280\u0026ndash;3370)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.013\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObstetrical surgery\u003c/p\u003e \u003cp\u003eCesarean section\u003c/p\u003e \u003cp\u003eCesarean operation with uterine hemostatic suturing\u003c/p\u003e \u003cp\u003eCesarean with hysterectomy\u003c/p\u003e \u003cp\u003eCesarean with segmental uterine resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e2\u003c/p\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e9\u003c/p\u003e \u003cp\u003e11\u003c/p\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePerioperative complications\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eBladder injury\u003c/p\u003e \u003cp\u003eRe-laparotomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42 (100%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e23 (4.2%)\u003c/p\u003e \u003cp\u003e1 (95.8%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (67.8)\u003c/p\u003e \u003cp\u003e5 (17.9%)\u003c/p\u003e \u003cp\u003e1 (14.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of hospital stay (day)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (1\u0026ndash;3)\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1\u0026ndash;17)\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (1\u0026ndash;37)\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003ePAS: Placenta accreta spectrum\u003c/p\u003e \u003cp\u003eData were expressed as mean with standard deviation, median with range, and count (%) as appropriate. When statistically significant differences exist among the study groups, they are coded with letters a, b, and c. The study groups are coded with similar letters when there is no significant difference among the study groups.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eTo address potential confounding factors, we conducted a multivariable regression analysis to explore the relationship between maternal serum survivin levels and various baseline characteristics, including age, gravidity, and parity. The results of the multivariable regression analysis are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariable regression analysis results\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCoefficient (β)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eStandard Error\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e95% Confidence Interval\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConstant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-161.7580\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e189.881\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-0.852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.397\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-539.048 to 215.532\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.0472\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.920\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.373\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.020\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.285 to 25.809\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGravidity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e69.0257\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30.690\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.249\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.046 to 130.006\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eParity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e-61.1950\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39.483\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.550\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-139.647 to 17.257\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe analysis indicated that both maternal age and gravidity had significant effects on the serum survivin levels. Specifically, an increase in maternal age and gravidity was associated with higher serum survivin levels (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). These findings suggest that the elevated survivin levels observed in the PAS and placenta previa groups are robust and not confounded by these factors.\u003c/p\u003e \u003cp\u003eThe median duration of hospitalization was significantly longer in the PAS group than that in the placenta previa and control groups. The placenta previa group also had a longer hospitalization duration than the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e presents the serum survivin levels in the control, placenta previa, and PAS groups. The median survival of the PAS group was significantly higher than that of the other groups [785 (324.50\u0026ndash;1122) vs. 348.3 (173.0-776.4) and 177.9 (87.3\u0026ndash;242.0), respectively; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05]. The median survivin value of the placenta previa group was significantly higher than that of the control group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis study demonstrated that women with placenta previa and the placenta accreta spectrum (PAS) exhibit significantly elevated levels of maternal serum survivin compared to those with normal placentation. Survivin plays a pivotal role in modulating cell life span and preventing apoptosis, suggesting its involvement in the pathogenesis of these obstetric complications. Notably, the surge in survivin levels among PAS cases suggests a protective response to mitigate the challenges of abnormal placental attachment and invasion. This mechanism parallels survivin's function in enhancing cancer cell resilience, highlighting its critical role in pathological and physiological contexts\u003csup\u003e9\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eSurvivin's dual role in the placenta as an essential promoter of cellular proliferation and an inhibitor of apoptosis underlines a paradoxical contradiction: It is vital for normal placental development while contributing to placental pathologies. Our research supports the notion that survivin's upregulation is necessary for placental establishment; its overexpression may lead to conditions marked by abnormal growth and invasive behavior [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The decreased survivin levels observed in preeclampsia cases further illuminate this molecule's complex involvement in placental disorders, providing insight into diseases like placenta previa and PAS [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our findings are consistent with literature that underscores the importance of survivin and related proteins in trophoblast cell proliferation and survival, highlighting the potential of targeting survivin to understand and treat placental dysfunctions [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. For clinical practice, our study underscores the value of serum survivin as a biomarker for the early detection and management of placental diseases. Recognizing the rise in survivin levels as a harbinger of obstetric complications could lead to more effective interventions. Furthermore, this study contributes to the broader understanding of survivors' multifaceted roles, suggesting that modulating their expression could mitigate adverse outcomes in placental disorders.\u003c/p\u003e \u003cp\u003eWe also observed a significant age difference among participants, suggesting older mothers are at higher risk of developing PAS, potentially due to age-related uterine changes. The association between multiple cesarean sections and increased PAS risk underscores the need for cautious obstetric management in such cases [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Surgical intervention rates, like hysterectomy, were also higher in the PAS group, underlining the complexity of managing PAS and the need for early detection. Significant differences were observed in gestational age at delivery and neonatal outcomes between the PAS and placenta previa groups compared to the control group. The PAS and placenta previa groups had earlier deliveries and higher rates of preterm births, along with poorer neonatal outcomes, underscoring the critical need for specialized care.\u003c/p\u003e \u003cp\u003eDemographically, the study highlighted the significance of maternal age and history of cesarean deliveries in the prevalence of PAS, reinforcing the need for tailored risk assessments and management plans for at-risk populations.\u003c/p\u003e \u003cp\u003eThe multivariate regression analysis conducted in our study further strengthens the reliability of our findings. By controlling for maternal age and gravidity, we confirmed that elevated serum survivin levels observed in the PAS and placenta previa groups were not confounded by these factors. This robust analysis enhances the credibility of serum survivin as a potential biomarker for early detection and management of placental disorders.\u003c/p\u003e \u003cp\u003eWhile this study provides valuable insights into the role of maternal serum survivin levels in the pathogenesis of placenta previa and PAS, several limitations should be acknowledged. First, its cross-sectional design and limited sample size may constrain the generalizability of our findings. Future research should employ longitudinal designs and include broader demographic samples to comprehensively validate the diagnostic and therapeutic utility of survivin.\u003c/p\u003e \u003cp\u003eAdditionally, we did not perform detailed analysis of survivin expression in the placenta. This analysis could offer deeper insights into the molecular mechanisms underlying placental pathologies such as placenta previa and PAS. Understanding these mechanisms could lead to targeted interventions to mitigate the risks associated with these conditions. Thus, future studies should incorporate placental survivin analysis to enhance our understanding of its role and validate the current findings.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003e \u003cb\u003eI\u003c/b\u003en conclusion, our research advocates the use of serum survivin levels as a biomarker for the early detection and management of placental disorders such as placenta previa and PAS. By harnessing the predictive power of survivin levels, clinicians can refine the existing protocols for the early identification and treatment of these conditions, thereby mitigating adverse maternal and neonatal outcomes. Early detection of elevated survivin levels allows for more precise planning regarding the timing and location of delivery, ensuring that high-risk pregnancies are managed in facilities equipped with the necessary resources and specialized surgical expertise. This proactive approach can prevent severe complications, such as massive hemorrhage, uterine rupture, and other life-threatening conditions, by enabling timely intervention. Additionally, it can improve neonatal outcomes by reducing the likelihood of preterm births and associated complications through better management of the delivery timing.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e \u003ch2\u003eEthics Approval\u003c/h2\u003e \u003cp\u003e This study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee for Human Studies of Kanuni Sultan Suleyman Training and Research Hospital (Approval number: KAEK/2021.05.167).\u003c/p\u003e \u003c/p\u003e \u003cp\u003e \u003cstrong\u003eConflict of Interest\u003c/strong\u003e \u003cp\u003eThe authors declare that no conflicts of interest could influence the research or the interpretation of its results. We have no financial or personal relationships with individuals or organizations that might bias our work or its outcomes.\u003c/p\u003e \u003c/p\u003e\u003cp\u003e \u003ch2\u003eInformed Consent\u003c/h2\u003e \u003cp\u003e Written informed consent was obtained from all participants, and their privacy rights were strictly maintained throughout the study.\u003c/p\u003e \u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e \u003cp\u003eNo financial support or external funding was obtained for this research project.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eNevin Yilmaz: Study design, data collection, analysis, and writing.Isil Turan Bakirci: Study design, analysis, and writing.Busra Sahin: Data collection, analysis.Gokhan Bolluk: Analysis, and writing.Esra Can: Analysis, and writing.Huri Dedeakayogullari: Analysis.All authors have reviewed and approved the final version of this manuscript and are accountable for the accuracy and integrity of the research.\u003c/p\u003e\u003ch2\u003eAcknowledgement\u003c/h2\u003e\u003cp\u003eWe would like to express our gratitude to all those who helped us during the writing of this manuscript.Thanks to all the peer reviewers for their opinions and suggestions.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available due to privacy and ethical restrictions but are available from the corresponding author on reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eObstetric Care Consensus No. Placenta Accreta Spectrum. \u003cem\u003eObstet. Gynecol.\u003c/em\u003e \u003cb\u003e7\u003c/b\u003e (6). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1097/AOG.0000000000002983\u003c/span\u003e\u003cspan address=\"10.1097/AOG.0000000000002983\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJauniaux, E., Collins, S. \u0026amp; Burton, G. J. Placenta accreta spectrum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging. \u003cem\u003eAm. J. Obstet. Gynecol.\u003c/em\u003e \u003cb\u003e218\u003c/b\u003e (1), 75\u0026ndash;87. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajog.2017.05.067\u003c/span\u003e\u003cspan address=\"10.1016/j.ajog.2017.05.067\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSilver, R. M. \u0026amp; Barbour, K. D. Placenta accreta spectrum: accreta, increta, and percreta. \u003cem\u003eObstet. Gynecol. Clin. N. Am.\u003c/em\u003e \u003cb\u003e42\u003c/b\u003e (2), 381\u0026ndash;402. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ogc.2015.01.014\u003c/span\u003e\u003cspan address=\"10.1016/j.ogc.2015.01.014\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2015).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBalkas, G. \u0026amp; Caglar, T. Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes. \u003cem\u003eEur. Rev. Med. Pharmacol. Sci.\u003c/em\u003e \u003cb\u003e27\u003c/b\u003e (20), 9955\u0026ndash;9961. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.26355/eurrev_202310_34174\u003c/span\u003e\u003cspan address=\"10.26355/eurrev_202310_34174\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShainker, S. A. et al. Placenta accreta spectrum: biomarker discovery using plasma proteomics. \u003cem\u003eAm. J. Obstet. Gynecol.\u003c/em\u003e \u003cb\u003e223\u003c/b\u003e (3), 433. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ajog.2020.03.019\u003c/span\u003e\u003cspan address=\"10.1016/j.ajog.2020.03.019\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2020). \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e.e1-433.e14\u003c/span\u003e\u003cspan address=\"http://.e1-433.e14\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOkmen, F. et al. The role of fetal fibronectin and plasminogen activator inhibitor 1 biomarkers in antenatal prediction of placenta accreta spectrum. \u003cem\u003eJ. Obstet. Gynaecol.\u003c/em\u003e \u003cb\u003e42\u003c/b\u003e (6), 2008\u0026ndash;2012. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/01443615.2022.2068370\u003c/span\u003e\u003cspan address=\"10.1080/01443615.2022.2068370\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUszyński, W. \u0026amp; Uszyński, M. Placenta accreta: epidemiology, molecular mechanism (hypothesis), and some clinical remarks. \u003cem\u003eGinekol. Pol.\u003c/em\u003e \u003cb\u003e75\u003c/b\u003e (12), 971\u0026ndash;978 (2004).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFang, X. L. et al. Overview of role of survivin in cancer: expression, regulation, functions, and its potential as a therapeutic target. \u003cem\u003eJ. Drug Target.\u003c/em\u003e 1\u0026ndash;73. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/1061186X.2024.2309563\u003c/span\u003e\u003cspan address=\"10.1080/1061186X.2024.2309563\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2024).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurkekul, K. \u0026amp; Erdogan, S. Potent suppression of prostate cancer cell growth and eradication of cancer stem cells by CD44-targeted nanoliposome-quercetin nanoparticles. \u003cem\u003eJ. Cancer Prev.\u003c/em\u003e \u003cb\u003e28\u003c/b\u003e (4), 160\u0026ndash;174. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.15430/JCP.2023.28.4.160\u003c/span\u003e\u003cspan address=\"10.15430/JCP.2023.28.4.160\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShiozaki, A. et al. Survivin inhibits apoptosis in cytotrophoblasts. \u003cem\u003ePlacenta\u003c/em\u003e. \u003cb\u003e24\u003c/b\u003e (1), 65\u0026ndash;76. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1053/plac.2002.0860\u003c/span\u003e\u003cspan address=\"10.1053/plac.2002.0860\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2003).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLehner, R., Bobak, J., Kim, N. W., Shroyer, A. L. \u0026amp; Shroyer, K. R. Localization of telomerase hTERT protein and survivin in placenta: relation to placental development and hydatidiform mole. \u003cem\u003eObstet. Gynecol.\u003c/em\u003e \u003cb\u003e97\u003c/b\u003e (6), 965\u0026ndash;970. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/S0029-7844(01)01131-0\u003c/span\u003e\u003cspan address=\"10.1016/S0029-7844(01)01131-0\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2001).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLi, C. F. et al. Reduced expression of survivin, the inhibitor of apoptosis protein, correlates with severity of preeclampsia. \u003cem\u003ePlacenta\u003c/em\u003e. \u003cb\u003e33\u003c/b\u003e (1), 47\u0026ndash;51. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.placenta.2011.10.008\u003c/span\u003e\u003cspan address=\"10.1016/j.placenta.2011.10.008\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2012).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMuschol-Steinmetz, C. et al. B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells. \u003cem\u003eCell. Cycle\u003c/em\u003e. \u003cb\u003e15\u003c/b\u003e (6), 827\u0026ndash;839. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1080/15384101.2016.1149273\u003c/span\u003e\u003cspan address=\"10.1080/15384101.2016.1149273\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2016).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJauniaux, E., Chantraine, F., Silver, R. M. \u0026amp; Langhoff-Roos, J. FIGO consensus guidelines on placenta accreta spectrum disorders: epidemiology. \u003cem\u003eInt. J. Gynaecol. Obstet.\u003c/em\u003e \u003cb\u003e140\u003c/b\u003e (3), 265\u0026ndash;273. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1002/ijgo.12333\u003c/span\u003e\u003cspan address=\"10.1002/ijgo.12333\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2018).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFest, S. et al. Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation. \u003cem\u003eAm. J. Reprod. Immunol.\u003c/em\u003e \u003cb\u003e59\u003c/b\u003e (1), 75\u0026ndash;83. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1111/j.1600-0897.2007.00557.x\u003c/span\u003e\u003cspan address=\"10.1111/j.1600-0897.2007.00557.x\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2008).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eT\u0026icirc;rnovanu, M. C. et al. Unexpected dramatic evolution of placenta increta: case report and literature review. \u003cem\u003eJ. Personalized Med.\u003c/em\u003e \u003cb\u003e13\u003c/b\u003e (11), 1563. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.3390/jpm13111563\u003c/span\u003e\u003cspan address=\"10.3390/jpm13111563\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHorgan, R. \u0026amp; Abuhamad, A. Placenta accreta spectrum: prenatal diagnosis and management. \u003cem\u003eObstet. Gynecol. Clin. N. Am.\u003c/em\u003e \u003cb\u003e49\u003c/b\u003e (3), 423\u0026ndash;438. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1016/j.ogc.2022.02.004\u003c/span\u003e\u003cspan address=\"10.1016/j.ogc.2022.02.004\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e (2022).\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Placenta previa, placenta accreta spectrum, survivin","lastPublishedDoi":"10.21203/rs.3.rs-4951853/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4951853/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThis study aimed to assess maternal serum survivin levels in women with placenta previa, with and without placenta accreta spectrum (PAS), to understand its role in abnormal placental adherence and invasion.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this prospective cross-sectional study, we enrolled 84 pregnant women categorized into control (n\u0026thinsp;=\u0026thinsp;42), placenta previa (n\u0026thinsp;=\u0026thinsp;24), and PAS (n\u0026thinsp;=\u0026thinsp;28) groups. Serum survivin levels were quantitatively determined using ELISA, and statistical analyses were performed using ANOVA and post-hoc tests.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eA significant elevation in serum survivin levels was observed in the placenta previa and PAS groups compared to the controls (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05), suggesting that survivin plays a role in the pathophysiological response to abnormal placental adherence and invasion.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eElevated serum survivin levels may serve as an early biomarker for the diagnosis and management of placenta previa and PAS, aiding in the planning and timing of surgical interventions and the selection of appropriate surgical centers.\u003c/p\u003e","manuscriptTitle":"Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum: A Cross-sectional Study ","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-10-17 16:02:58","doi":"10.21203/rs.3.rs-4951853/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-11-11T06:03:15+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-11-10T13:28:04+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-10-14T19:27:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"221991775257963378321986016164974239916","date":"2024-10-07T14:31:08+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"335060145287897278952821230192786738101","date":"2024-09-22T16:36:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-09-20T15:32:00+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-09-15T13:00:17+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2024-08-30T10:51:12+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-08-29T11:22:39+00:00","index":"","fulltext":""},{"type":"submitted","content":"Scientific Reports","date":"2024-08-21T13:10:32+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"scientific-reports","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"scirep","sideBox":"Learn more about [Scientific Reports](http://www.nature.com/srep/)","snPcode":"","submissionUrl":"","title":"Scientific Reports","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Scientific Reports","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1a78713b-2f57-4304-9415-dd63957f601e","owner":[],"postedDate":"October 17th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[{"id":38036764,"name":"Health sciences/Biomarkers"},{"id":38036765,"name":"Health sciences/Medical research"}],"tags":[],"updatedAt":"2025-02-10T16:02:13+00:00","versionOfRecord":{"articleIdentity":"rs-4951853","link":"https://doi.org/10.1038/s41598-025-89384-4","journal":{"identity":"scientific-reports","isVorOnly":false,"title":"Scientific Reports"},"publishedOn":"2025-02-08 15:57:35","publishedOnDateReadable":"February 8th, 2025"},"versionCreatedAt":"2024-10-17 16:02:58","video":"","vorDoi":"10.1038/s41598-025-89384-4","vorDoiUrl":"https://doi.org/10.1038/s41598-025-89384-4","workflowStages":[]},"version":"v1","identity":"rs-4951853","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4951853","identity":"rs-4951853","version":["v1"]},"buildId":"zQwnuV7TCBrMSSSToR1PI","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}