Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum.

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Nevin Yilmaz, Isil Turan Bakirci, Busra Sahin, Gokhan Bolluk, and 2 more This is a preprint; it has not been peer reviewed by a journal.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-4415252/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Placenta previa and placenta accreta spectrum (PAS) are characterized by irregular placental implantation and invasion, which can lead to significant maternal and fetal morbidity. Survivin is a critical protein that affects cellular longevity and apoptosis, and plays a crucial role in placental development during pregnancy. This study aimed to examine the maternal serum survivin levels in patients with normal placentation, placenta previa, and PAS. Methods In this prospective cross-sectional study, we enrolled 84 pregnant women categorized into the control (n=42), placenta previa (n=24), and PAS (n=28) groups. Serum survivin levels were quantitatively determined using ELISA. Results A significant elevation in serum survivin levels was observed in the placenta previa and PAS groups compared to the controls, suggesting a role for survivin in the pathophysiological response to against abnormal placental adherence and invasion. Conclusions Elevated serum survivin level may serve as an early biomarker for diagnosing and managing placenta previa and PAS, underscoring the need for a multidisciplinary approach to managing these complex pregnancy complications. Placenta previa placenta accreta spectrum survivin Figures Figure 1 Introduction Placental attachment is vital for fetal development and nourishment during pregnancy. It involves a sophisticated network of cellular and molecular mechanisms that facilitates the connection of the placenta to the uterine lining. Obstetric complications such as placenta previa and 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, whereas PAS encompasses various conditions in which the placenta inordinately adheres to the uterine wall [ 3 ]. Exploration of 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 an important protein that influences cellular longevity and apoptosis [ 8 ]. Known as the cellular life sentinel, it inhibits programmed cell death. Cancer cells exploit this characteristic to enhance survival and promote tumor growth [ 9 ]. Additionally, survivin, predominantly produced by cytotrophoblasts, 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 such as preeclampsia, where a decrease is noted, remains controversial [ 11 , 12 ]. While specific studies on circulating survivin during pregnancy are scarce, it has been postulated that survivin levels might decline owing to increased apoptotic activity [ 13 ]. This study aimed to delineate the role of survivin in the pathogenesis of placental complications, particularly placenta previa and PAS. We investigated maternal serum survivin levels across normal placentation, placenta previa, and PAS cases, providing insights into the fluctuations in this protein in placenta previa and PAS. Materials and methods Study Population The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee for Human Studies at the Kanuni Sultan Suleyman Training and Research Hospital (approval number: KAEK/2021.05.167). Written informed consent was obtained from all the participants to ensure the maintenance of their privacy rights throughout the study. This prospective cross-sectional study was conducted at Kanuni Sultan Suleyman Research Hospital between 2021 and 2022. The cohort included pregnant women aged range of 18 to 45 years diagnosed with placenta previa and PAS. The control group comprised women with physiological pregnancies. Participant recruitment was based on admissions to the antenatal clinic or labor ward during the study period. Exclusion criteria included multiple gestations, intrauterine growth restriction, and pre-existing medical conditions, such as diabetes, chronic hypertension, and kidney disease. Obstetric and clinical information was obtained from an electronic medical record system. 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. Measurement of Serum Survivin Blood samples were collected during hospitalization. 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 levels were measured using an enzyme-linked immunosorbent assay with a 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 93–9600 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 using ANOVA with a post hoc Tukey test and Kruskal-Wallis ANOVA with post hoc Mann-Whitney test, as appropriate. 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). Similarly, the median gravidity, miscarriage history, and body mass index between the study groups (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). Although statistical analyses could not be conducted, obstetric and perinatal complications were more prevalent in the placenta previa and PAS groups than in the control group. The rates of hysterectomy and segmental uterine resection were also higher in 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). 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). 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 Miscarriage 0 (0–2) 0 (0–3) 0 (0–5) 0.680 BMI (kg/m 2 ) 25.37 (20.0-184.6) 27.11 (21.26–29.62) 28.63 (22.89–34.37) 0.926 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 Obstetric complications No Gestational diabetes Preeclampsia 41 (97.6%) 0 1 (2.4%) 22 (91.7%) 0 2 (8.3%) 24 (85.7%) 1 (3.6%) 3 (10.7%) Neonatal morbidities Asphyxia Prematurity TTN No 1 (2.4%) 2 (4.8%) 0 39 (92.9) 0 1 (4.2%) 3 (12.5%) 20 (83.3%) 0 4 (13.8%) 7 (25.5%) 17 (60.7%) 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 Hemoglobin (g/dL) Preoperative Postoperative 11.7 (7.9–14.6) 10.6 (7.5–13.8) 10.8 (8.0-14.3) 9.6 (7.2–14.4) 12 (8.6–13.3) 9.9 (7.5–12.4) 0.531 0.178 Hematocrit (%) Preoperative Postoperative 36.3 (26.7–43.8) 32.9 (25–42) 33.1 (23.6–44.7) 29.3 (21.5–40.1) 35.7 (25-42.2) 30.8 (22.6–37.3) 0.323 0.092 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 2 (1–3) a 2 (1–17) b 5 (1–37) c 0.001 Red blood cell transfusion, units No 1 unit 2 units 3 units >3 units 41 (97.6%) 0 1 (2.4%) 0 0 20 (83.4%) 1 (4.1%) 0 0 3 (12.5%) 21 (75.2%) 2 (7.1%) 1 (3.5%) 3 (10.7%) 1 (3.5%) PAS: Placenta accreta spectrum TTN: Transient Tachypnea of the Newborn 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. Figure 1 shows the serum survival values 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 survival 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 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 in PAS suggests a protective response to mitigate the challenges of abnormal placental attachment and invasion. This mechanism parallels the function of survivin in enhancing cancer cell resilience, highlighting its critical role in pathological and physiological contexts [ 9 ]. The dual role of survivin in the placenta as an essential promoter of cellular proliferation and an inhibitor of apoptosis underlines a paradoxical contradiction: survivin is vital for normal placental development while contributing to placental pathologies. Our research supports the notion that upregulation of survivin is necessary for placental establishment, and that 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 the complex involvement of this molecule in placental disorders, providing insight into diseases such as placenta previa and PAS [ 12 ]. Our findings are consistent with the literature, which 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 dysfunction [ 10 , 13 , 14 ]. In clinical practice, our study underscores the value of serum survivin as a biomarker for 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 a 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 the participants, suggesting that older mothers are at a higher risk of developing PAS, potentially because of age-related uterine changes. The association between multiple cesarean sections increased PAS risk underscores the need for cautious obstetric management in such cases [ 15 , 16 ]. Despite the small sample size, trends indicated more obstetric/perinatal complications in the PAS and placenta previa groups than in the controls, highlighting the need for careful management [ 17 ]. Surgical intervention rates, such as hysterectomy, were also higher in the PAS group, underlining the complexity of PAS management and need for early detection. Significant differences were observed in gestational age at delivery and neonatal outcomes between the PAS and placenta previa groups and 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, this study highlights 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. Compared to controls, the trend towards higher obstetric and perinatal complications in PAS and placenta previa groups calls for vigilant clinical attention and a multidisciplinary care approach to optimize maternal and neonatal outcomes [ 18 ]. Limitations However, the study's cross-sectional design and limited sample size may restrict the generalizability of the findings. Future research should employ a longitudinal designs and broader demographic sampling to comprehensively validate the diagnostic and therapeutic utility of survivors. Moreover, exploring the molecular mechanisms that regulate survivin expression in the placenta could reveal targeted interventions and mitigate the risks associated with placental diseases. Conclusion In conclusion, our research advocates for a multidisciplinary approach for managing complex pregnancies, emphasizing the necessity of continuous exploration of the role of survivin in placental pathology. By harnessing the predictive power of survivin levels, clinicians can refine existing protocols for the early identification and treatment of placenta previa and PAS, thereby mitigating adverse maternal and neonatal outcomes. Declarations Availability of data and materials The data analyzed during the study are available from the corresponding author upon request. Funding No financial or external funding was received for this study. 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 can influence the research or interpretation of results. We have no financial or personal relationships with individuals or organizations that may bias our work or its outcomes. Authors’ Contributions 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 Bulut: Analysis. All authors have reviewed and approved the final version of this manuscript and are accountable for the accuracy and integrity of the research. Informed Consent Written informed consent was obtained from all participants and their privacy rights were maintained throughout the study. References Obstetric Care Consensus No. Obstet Gynecol. 2018;132(6):e259–75. https://doi.org/10.1097/AOG.0000000000002983 . 7: Placenta Accreta Spectrum. Jauniaux E, Collins S, Burton GJ. Placenta accreta spectrum: pathophysiology and evidence-based anatomy for prenatal ultrasound imaging. Am J Obstet Gynecol. 2018;218(1):75–87. https://doi.org/10.1016/j.ajog.2017.05.067 . Silver RM, Barbour KD. Placenta accreta spectrum: accreta, increta, and percreta. Obstet Gynecol Clin N Am. 2015;42(2):381–402. https://doi.org/10.1016/j.ogc.2015.01.014 . Balkaş G, Çaglar 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. 2023;27(20):9955–61. https://doi.org/10.26355/eurrev_202310_34174 . 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Muschol-Steinmetz C, Jasmer B, Kreis N-N, Steinhäuser K, Ritter A, Rolle U, Yuan J, Louwen F. B-cell lymphoma 6 promotes proliferation and survival of trophoblastic cells. Cell Cycle (Georgetown Tex). 2016;15(6):827–39. https://doi.org/10.1080/15384101.2016.1149273 . Fest S, Brachwitz N, Schumacher A, Zenclussen ML, Khan F, Wafula PO, Casalis PA, Fill S, Costa S-D, Mor G, Volk H-D, Lode HN, Zenclussen AC. (2008). Supporting the hypothesis of pregnancy as a tumor: survivin is upregulated in normal pregnant mice and participates in human trophoblast proliferation. American Journal of Reproductive Immunology (New York, N.Y.: 1989) , 59 (1), 75–83. https://doi.org/10.1111/j.1600-0897.2007.00557.x . Tîrnovanu MC, Tîrnovanu VG, Toma B, Toma L, Țarcă E, Stătescu L, Tîrnovanu ȘtefanD, Ungureanu C, Trandafirescu MF, Bernic J, Cojocaru E. (2023). Unexpected Dramatic Evolution of Placenta Increta: Case Report and Literature Review. In Journal of personalized medicine (Vol. 13, Issue 11). https://doi.org/10.3390/jpm13111563 . Horgan R, Abuhamad A. Placenta Accreta Spectrum: Prenatal Diagnosis and Management. Obstet Gynecol Clin N Am. 2022;49(3):423–38. https://doi.org/10.1016/j.ogc.2022.02.004 . Fonseca A, de Ayres D. Maternal morbidity and mortality due to placenta accreta spectrum disorders. Best Pract Res Clin Obstet Gynecol. 2021;72:84–91. https://doi.org/10.1016/j.bpobgyn.2020.07.011 . Toussia-Cohen S, Castel E, Friedrich L, Mor N, Ohayon A, Levin G, Meyer R. Neonatal outcomes in pregnancies complicated by placenta accreta- a matched cohort study. Arch Gynecol Obstet. 2024. https://doi.org/10.1007/s00404-023-07353-6 . Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board 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-4415252","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":304982409,"identity":"980fd27f-e641-4d64-8232-bae7998c5220","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,"prefix":"","firstName":"Nevin","middleName":"","lastName":"Yilmaz","suffix":""},{"id":304982410,"identity":"45f122c9-d5f4-44fa-b082-62a15d3de2d0","order_by":1,"name":"Isil Turan Bakirci","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Isil","middleName":"Turan","lastName":"Bakirci","suffix":""},{"id":304982411,"identity":"a7cd737a-0d57-440c-8adf-6a262b131bc9","order_by":2,"name":"Busra Sahin","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Busra","middleName":"","lastName":"Sahin","suffix":""},{"id":304982412,"identity":"97c4b30d-f6aa-4862-b83b-a91b502b2634","order_by":3,"name":"Gokhan Bolluk","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Gokhan","middleName":"","lastName":"Bolluk","suffix":""},{"id":304982413,"identity":"d61e5457-5355-4e2a-be49-77ec2c51f57f","order_by":4,"name":"Esra Can","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Esra","middleName":"","lastName":"Can","suffix":""},{"id":304982414,"identity":"6daa0b00-7ea0-4b4a-a7f7-4e6341b9413e","order_by":5,"name":"Huri Bulut","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Huri","middleName":"","lastName":"Bulut","suffix":""}],"badges":[],"createdAt":"2024-05-13 20:53:19","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4415252/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4415252/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":57728747,"identity":"f68a1875-61e4-4252-97ed-7e52058a4215","added_by":"auto","created_at":"2024-06-04 21:48:51","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-4415252/v1/fbcb2abb45c5454ca1162113.jpeg"},{"id":62882398,"identity":"66a2d742-a44a-4c99-9ab8-26a4c959e127","added_by":"auto","created_at":"2024-08-20 15:03:57","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":610229,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4415252/v1/ffa45dc1-1759-4d3a-acaa-9d4ed2e5f663.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum.","fulltext":[{"header":"Introduction","content":"\u003cp\u003ePlacental attachment is vital for fetal development and nourishment during pregnancy. It involves a sophisticated network of cellular and molecular mechanisms that facilitates the connection of the placenta to the uterine lining. Obstetric complications such as placenta previa and 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, whereas PAS encompasses various conditions in which the placenta inordinately adheres to the uterine wall [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eExploration of 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 an important protein that influences cellular longevity and apoptosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Known as the cellular life sentinel, it inhibits programmed cell death. Cancer cells exploit this characteristic to enhance survival and promote tumor growth [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Additionally, survivin, predominantly produced by cytotrophoblasts, 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 such as 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 has been postulated that survivin levels might decline owing to increased apoptotic activity [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis study aimed to delineate the role of survivin in the pathogenesis of placental complications, particularly placenta previa and PAS. We investigated maternal serum survivin levels across normal placentation, placenta previa, and PAS cases, providing insights into the fluctuations in this protein in placenta previa and PAS.\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003e The study protocol adhered to the Declaration of Helsinki and was approved by the Ethics Committee for Human Studies at the Kanuni Sultan Suleyman Training and Research Hospital (approval number: KAEK/2021.05.167). Written informed consent was obtained from all the participants to ensure the maintenance of their privacy rights throughout the study.\u003c/p\u003e \u003cp\u003eThis prospective cross-sectional study was conducted at Kanuni Sultan Suleyman Research Hospital between 2021 and 2022. The cohort included pregnant women aged range of 18 to 45 years diagnosed with placenta previa and PAS. The control group comprised women with physiological pregnancies. Participant recruitment was based on admissions to the antenatal clinic or labor ward during the study period. Exclusion criteria included multiple gestations, intrauterine growth restriction, and pre-existing medical conditions, such as diabetes, chronic hypertension, and kidney disease.\u003c/p\u003e \u003cp\u003eObstetric and clinical information was obtained from an electronic medical record system. 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.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of Serum Survivin\u003c/h2\u003e \u003cp\u003eBlood samples were collected during hospitalization. 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 levels were measured using an enzyme-linked immunosorbent assay with a 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\u0026ndash;9600 pg/mL, and the sensitivity was 7 pg/mL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" 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 using ANOVA with a post hoc Tukey test and Kruskal-Wallis ANOVA with post hoc Mann-Whitney test, as appropriate. Statistical significance was set at p\u0026lt; 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). Similarly, the median gravidity, miscarriage history, and body mass index between the study groups (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). Although statistical analyses could not be conducted, obstetric and perinatal complications were more prevalent in the placenta previa and PAS groups than in the control group.\u003c/p\u003e \u003cp\u003eThe rates of hysterectomy and segmental uterine resection were also higher in 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\u003eRegarding preoperative and postoperative parameters, the study groups displayed similar median hemoglobin and hematocrit values (p\u0026thinsp;\u0026gt;\u0026thinsp;0.05). 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\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\u003eMiscarriage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0\u0026ndash;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0 (0\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.680\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI (kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25.37 (20.0-184.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.11 (21.26\u0026ndash;29.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e28.63 (22.89\u0026ndash;34.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.926\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\u003eObstetric complications\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003eGestational diabetes\u003c/p\u003e \u003cp\u003ePreeclampsia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (97.6%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (91.7%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e2 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e24 (85.7%)\u003c/p\u003e \u003cp\u003e1 (3.6%)\u003c/p\u003e \u003cp\u003e3 (10.7%)\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\u003eNeonatal morbidities\u003c/p\u003e \u003cp\u003eAsphyxia\u003c/p\u003e \u003cp\u003ePrematurity\u003c/p\u003e \u003cp\u003eTTN\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003cp\u003e2 (4.8%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e39 (92.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1 (4.2%)\u003c/p\u003e \u003cp\u003e3 (12.5%)\u003c/p\u003e \u003cp\u003e20 (83.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e4 (13.8%)\u003c/p\u003e \u003cp\u003e7 (25.5%)\u003c/p\u003e \u003cp\u003e17 (60.7%)\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\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\u003eHemoglobin (g/dL)\u003c/p\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003cp\u003ePostoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.7 (7.9\u0026ndash;14.6)\u003c/p\u003e \u003cp\u003e10.6 (7.5\u0026ndash;13.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.8 (8.0-14.3)\u003c/p\u003e \u003cp\u003e9.6 (7.2\u0026ndash;14.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12 (8.6\u0026ndash;13.3)\u003c/p\u003e \u003cp\u003e9.9 (7.5\u0026ndash;12.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.531\u003c/p\u003e \u003cp\u003e0.178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematocrit (%)\u003c/p\u003e \u003cp\u003ePreoperative\u003c/p\u003e \u003cp\u003ePostoperative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36.3 (26.7\u0026ndash;43.8)\u003c/p\u003e \u003cp\u003e32.9 (25\u0026ndash;42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.1 (23.6\u0026ndash;44.7)\u003c/p\u003e \u003cp\u003e29.3 (21.5\u0026ndash;40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.7 (25-42.2)\u003c/p\u003e \u003cp\u003e30.8 (22.6\u0026ndash;37.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.323\u003c/p\u003e \u003cp\u003e0.092\u003c/p\u003e \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\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\" colname=\"c1\"\u003e \u003cp\u003eRed blood cell transfusion, units\u003c/p\u003e \u003cp\u003eNo\u003c/p\u003e \u003cp\u003e1 unit\u003c/p\u003e \u003cp\u003e2 units\u003c/p\u003e \u003cp\u003e3 units\u003c/p\u003e \u003cp\u003e\u0026gt;3 units\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41 (97.6%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e1 (2.4%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (83.4%)\u003c/p\u003e \u003cp\u003e1 (4.1%)\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e0\u003c/p\u003e \u003cp\u003e3 (12.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21 (75.2%)\u003c/p\u003e \u003cp\u003e2 (7.1%)\u003c/p\u003e \u003cp\u003e1 (3.5%)\u003c/p\u003e \u003cp\u003e3 (10.7%)\u003c/p\u003e \u003cp\u003e1 (3.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\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\u003eTTN: Transient Tachypnea of the Newborn\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\u003eFigure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e shows the serum survival values 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 survival 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 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 in PAS suggests a protective response to mitigate the challenges of abnormal placental attachment and invasion. This mechanism parallels the function of survivin in enhancing cancer cell resilience, highlighting its critical role in pathological and physiological contexts [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe dual role of survivin in the placenta as an essential promoter of cellular proliferation and an inhibitor of apoptosis underlines a paradoxical contradiction: survivin is vital for normal placental development while contributing to placental pathologies. Our research supports the notion that upregulation of survivin is necessary for placental establishment, and that 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 the complex involvement of this molecule in placental disorders, providing insight into diseases such as placenta previa and PAS [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Our findings are consistent with the literature, which 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 dysfunction [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In clinical practice, our study underscores the value of serum survivin as a biomarker for 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 a 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 the participants, suggesting that older mothers are at a higher risk of developing PAS, potentially because of age-related uterine changes. The association between multiple cesarean sections increased PAS risk underscores the need for cautious obstetric management in such cases [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Despite the small sample size, trends indicated more obstetric/perinatal complications in the PAS and placenta previa groups than in the controls, highlighting the need for careful management [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Surgical intervention rates, such as hysterectomy, were also higher in the PAS group, underlining the complexity of PAS management and need for early detection. Significant differences were observed in gestational age at delivery and neonatal outcomes between the PAS and placenta previa groups and 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, this study highlights 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. Compared to controls, the trend towards higher obstetric and perinatal complications in PAS and placenta previa groups calls for vigilant clinical attention and a multidisciplinary care approach to optimize maternal and neonatal outcomes [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e "},{"header":"Limitations","content":"\u003cp\u003eHowever, the study's cross-sectional design and limited sample size may restrict the generalizability of the findings. Future research should employ a longitudinal designs and broader demographic sampling to comprehensively validate the diagnostic and therapeutic utility of survivors. Moreover, exploring the molecular mechanisms that regulate survivin expression in the placenta could reveal targeted interventions and mitigate the risks associated with placental diseases.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, our research advocates for a multidisciplinary approach for managing complex pregnancies, emphasizing the necessity of continuous exploration of the role of survivin in placental pathology. By harnessing the predictive power of survivin levels, clinicians can refine existing protocols for the early identification and treatment of placenta previa and PAS, thereby mitigating adverse maternal and neonatal outcomes.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data analyzed during the study are available from the corresponding author upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo financial or external funding was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis 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\n\u003cp\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that no conflicts of interest can influence the research or interpretation of results. We have no financial or personal relationships with individuals or organizations that may bias our work or its outcomes.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNevin Yilmaz: Study design, data collection, analysis, and writing.\u003c/p\u003e\n\u003cp\u003eIsil Turan Bakirci: Study design, analysis, and writing.\u003c/p\u003e\n\u003cp\u003eBusra Sahin: Data collection, analysis.\u003c/p\u003e\n\u003cp\u003eGokhan Bolluk: Analysis, and writing.\u003c/p\u003e\n\u003cp\u003eEsra Can: Analysis, and writing.\u003c/p\u003e\n\u003cp\u003eHuri Bulut: Analysis.\u003c/p\u003e\n\u003cp\u003eAll 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\n\u003cp\u003e\u003cstrong\u003eInformed Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from all participants and their privacy rights were maintained throughout the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eObstetric Care Consensus No. Obstet Gynecol. 2018;132(6):e259\u0026ndash;75. \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. 7: Placenta Accreta Spectrum.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJauniaux E, Collins S, Burton GJ. 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Arch Gynecol Obstet. 2024. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1007/s00404-023-07353-6\u003c/span\u003e\u003cspan address=\"10.1007/s00404-023-07353-6\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Placenta previa, placenta accreta spectrum, survivin","lastPublishedDoi":"10.21203/rs.3.rs-4415252/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4415252/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePlacenta previa and placenta accreta spectrum (PAS) are characterized by irregular placental implantation and invasion, which can lead to significant maternal and fetal morbidity. Survivin is a critical protein that affects cellular longevity and apoptosis, and plays a crucial role in placental development during pregnancy. This study aimed to examine the maternal serum survivin levels in patients with normal placentation, placenta previa, and PAS.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this prospective cross-sectional study, we enrolled 84 pregnant women categorized into the control (n=42), placenta previa (n=24), and PAS (n=28) groups. Serum survivin levels were quantitatively determined using ELISA.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA significant elevation in serum survivin levels was observed in the placenta previa and PAS groups compared to the controls, suggesting a role for survivin in the pathophysiological response to against abnormal placental adherence and invasion.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eElevated serum survivin level may serve as an early biomarker for diagnosing and managing placenta previa and PAS, underscoring the need for a multidisciplinary approach to managing these complex pregnancy complications.\u003c/p\u003e","manuscriptTitle":"Assessment of Serum Survivin in Women with Placenta Previa and Accreta Spectrum.","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-06-04 21:48:46","doi":"10.21203/rs.3.rs-4415252/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"1a78713b-2f57-4304-9415-dd63957f601e","owner":[],"postedDate":"June 4th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-08-20T14:55:50+00:00","versionOfRecord":[],"versionCreatedAt":"2024-06-04 21:48:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4415252","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4415252","identity":"rs-4415252","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}