A Rare Case Report of Sepsis and Intrauterine Fetal Demise Triggered by Chronic Villitis of Unknown Etiology Following Cervical Cerclage and Its Clinical Implications

A Rare Case Report of Sepsis and Intrauterine Fetal Demise Triggered by Chronic Villitis of Unknown Etiology Following Cervical Cerclage and Its Clinical Implications | 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 Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A Rare Case Report of Sepsis and Intrauterine Fetal Demise Triggered by Chronic Villitis of Unknown Etiology Following Cervical Cerclage and Its Clinical Implications Ping Ni, Sifeng Wang, Wenxia Li, Weitao Yang, Lihui Huang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8351948/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 Cervical cerclage is a common intervention for cervical insufficiency aimed at preventing preterm birth. However, this procedure may be associated with infection risks, such as sepsis, which, although low in incidence, can lead to severe adverse pregnancy outcomes. Chronic villitis of unknown etiology (VUE) is an inflammatory placental disorder, and its association with post-cerclage infection and sepsis has not been fully explored. Case Presentation This case report presents a pregnant woman who underwent cervical cerclage in the second trimester and subsequently developed VUE of unknown etiology, leading to sepsis and ultimately intrauterine fetal death. The patient's clinical symptoms included contractions and signs of infection, but these manifestations were misinterpreted as physiological phenomena of natural labor, resulting in delayed diagnosis. Despite medical interventions, an adverse pregnancy outcome occurred. Conclusion This case highlights the importance of VUE as a potential trigger for sepsis after cervical cerclage, as its symptoms are easily confused with physiological contractions, making early identification difficult. It is recommended to strengthen infection surveillance in perinatal management and establish prevention and early diagnosis protocols for sepsis, with particular consideration of the influence of VUE. Future studies require more case collection and analysis to clarify the relationships between cervical cerclage, VUE, and sepsis, thereby improving maternal and neonatal outcomes. Cervical cerclage Chronic villitis of unknown etiology (VUE) Sepsis Intrauterine fetal death Pregnancy outcome Figures Figure 1 Background Maternal sepsis is a serious obstetric complication caused by infection, particularly common during pregnancy, delivery, abortion, and the postpartum period, and constitutes a significant cause of maternal mortality [1]. Epidemiological data indicate that the incidence of maternal sepsis ranges from 0.002% to 0.04%, accounting for approximately 13% to 25% of maternal deaths [2,3]. Typical manifestations of sepsis include high fever, chills, tachycardia, and hypotension. Precursory symptoms may be infection-induced contractions; however, these can be masked by physiological manifestations like prodromal labor contractions in the peripartum period [4], leading to delays in early diagnosis and treatment. Chronic Villitis of Unknown Etiology (VUE) is an immune-mediated disease associated with maternal immune responses to fetal antigens [5], characterized by lymphohistiocytic infiltration within the villous stroma. The recurrence rate of VUE is estimated to be between 10% and 15% [6], and it is associated with adverse pregnancy outcomes. The clinical features and diagnosis of VUE rely on placental pathological examination [7], but relevant data are scarce, impacting the early diagnosis and management of this condition. This case is a rare instance of maternal sepsis and intrauterine fetal demise in the peripartum period following cervical cerclage, with the etiology ultimately confirmed as VUE. The uniqueness of this case lies in the complex relationship between cervical cerclage, VUE, and sepsis, simultaneously emphasizing the importance of infection surveillance and management during pregnancy post-cerclage. Through the analysis of this case, we have further refined the protocols for the prevention and early recognition of maternal sepsis following cervical cerclage, particularly for women with a history of septic abortion. The findings of this case provide significant experiential and data support for the clinical diagnosis and management of similar cases. Case Presentation A 33-year-old female was admitted at 02:10 AM on September 12, 2022, due to amenorrhea for over 8 months, status post cervical cerclage for over 2 months, and abdominal distension and pain for 8 hours. The patient had irregular menstrual cycles, typically 5-7/45-50 days. Her last menstrual period (LMP) was December 28, 2021, with an estimated date of confinement (EDC) of October 8, 2022. An oral glucose tolerance test (OGTT) performed in the second trimester yielded results of 5.16-11.24-12.18 mmol/L, leading to a diagnosis of "pregnancy with pre-existing diabetes mellitus." She was advised on diet and exercise guidance but did not monitor her blood glucose regularly. On July 1, at 26 weeks and 3 days of gestation, a routine fetal systemic ultrasound revealed painless cervical dilation, leading to a consideration of cervical insufficiency, and the patient was hospitalized. Relevant examinations upon admission showed vaginal secretion cleanliness grade III, normal blood routine, and negative cervical secretion and urine cultures. After vaginal medication treatment, a repeat vaginal secretion routine was normal, and blood glucose monitoring was mostly normal. Following communication, the patient underwent an emergency cervical cerclage on July 6, which proceeded smoothly. Postoperatively, she received cefminox sodium 1g intravenously for infection prophylaxis and vaginal progesterone capsules. The patient experienced no significant discomfort and was discharged on July 11 after signing out. She attended regular outpatient prenatal check-ups post-discharge, with well-controlled blood glucose and normal cervical secretion examinations. Clinical Findings On September 11, 2022, around 18:00, the patient experienced irregular lower abdominal distension and pain without vaginal bleeding or amniotic fluid leakage. She presented to the emergency department and was admitted with a diagnosis of "threatened preterm labor; intrauterine pregnancy at 36 weeks and 5 days, cephalic presentation, live fetus; cervical insufficiency (status post cerclage)." Her pregnancy weight gain was approximately 5 kg. Her obstetrical history was gravida 3, para 1, with a history of a full-term female infant delivery in 2016 who is currently healthy. She had a history of an inevitable abortion in August 2021 at an external hospital, accompanied by high fever during labor, with a positive blood culture for *Escherichia coli*. Admission physical examination revealed: temperature 36.5°C, pulse 120 beats/min, respiration 20 breaths/min, blood pressure 100/70 mmHg, height 157 cm, weight 66 kg. Heart sounds were rapid without murmurs, and lung auscultation showed no significant abnormalities. Abdominal examination revealed irregular uterine contractions, fundal height 33 cm, normal fetal position, fetal heart rate 140 beats/min with regular rhythm. Vaginal digital examination showed a cervical length of 0.5 cm, soft consistency, with the cervical cerclage suture palpable. Diagnostic Assessment Fetal heart monitoring was initiated immediately upon admission, and removal of the cervical cerclage was planned. After transfer to the delivery room, the cerclage suture was successfully removed without cervical laceration. Admission laboratory tests showed: white blood cell count (WBC) 13.20×10^9/L, hemoglobin (HB) 118 g/L, neutrophils (N) 83.80%. After suture removal, the patient went into active labor at 06:20 AM. Vaginal examination under aseptic technique revealed 80% cervical effacement and a relaxed cervical os. Random blood glucose was 7.2 mmol/L. Fetal heart monitoring showed a Category II tracing. Measures including oxygen administration, fluid infusion, and position change for intrauterine resuscitation were performed. Around 07:00 AM, an emergency ultrasound indicated intrauterine fetal demise. After counseling by the on-duty doctor, the patient and family agreed to return to the delivery room. Therapeutic Intervention At 07:30, the patient developed chills and high fever, with a temperature of 39.3°C, pulse 128 beats/min, and blood pressure 103/68 mmHg. Sepsis was suspected. Immediate management included fluid resuscitation, antipyretics, and intravenous infusion of piperacillin sodium and tazobactam sodium for anti-infective therapy. An "orange alert" was activated. At 08:30, reassessment showed temperature 41.0°C, pulse 120-150 beats/min, respiration 30 breaths/min, blood pressure 105/66 mmHg. The patient had mild consciousness disturbance. Laboratory tests showed WBC 9.19×10^9/L, HB 117 g/L, C-reactive protein (CRP) 59.40 mg/L, and a negative influenza test. Considering the severity of sepsis, anti-infective therapy was switched to meropenem 1g intravenously, with continued fluid support. At 10:05, spontaneous rupture of membranes occurred; the amniotic fluid was yellowish with an odor. Amniotic fluid was collected for bacterial culture. At 10:50, full cervical dilation was achieved, and the patient was coached to push. At 11:06, a stillborn male infant weighing 3250g was delivered. A placental swab was taken for bacterial culture. Postpartum vital signs: temperature 37.9°C, pulse 140 beats/min, respiration 22 breaths/min, blood pressure 99/66 mmHg. On postpartum day one, the patient's temperature normalized. Both blood culture and placental swab/amniotic fluid bacterial culture yielded positive results for Escherichia coli, with drug sensitivity indicating susceptibility to meropenem. Urine culture and cervical secretion bacterial culture were negative. The patient continued receiving meropenem for anti-infective therapy postpartum, along with subcutaneous low molecular weight heparin for venous thromboembolism prophylaxis. On postpartum day seven, meropenem was discontinued, and step-down therapy with cefoperazone sulbactam 1g every 8 hours was administered for two days. On postpartum day eight, blood routine was normal, CRP, procalcitonin (PCT), and coagulation function were normal, and repeat blood culture showed no bacterial growth. The patient was eventually discharged without discomfort. Follow-up and Outcomes Placental pathological examination results indicated: 1. Acute chorioamnionitis (Stage III, Grade II); 2. Chronic villitis of unknown etiology, consistent with features of VUE; 3. Chronic deciduitis (basalis); 4. Funisitis. Clinicopathological correlation suggested prominent chronic villitis in this case, consistent with Chronic Villitis of Unknown Etiology (VUE). VUE is considered an immune-related disease associated with adverse pregnancy outcomes and has a high recurrence rate. Clinical follow-up and guidance for high-risk subsequent pregnancies were recommended. Discussion This case report describes sepsis and intrauterine fetal demise triggered by Chronic Villitis of Unknown Etiology (VUE) following cervical cerclage. Chronic villitis is a group of rare but devastating gestational syndromes [ 8 ]. It is considered an immune-mediated placental disease, potentially related to maternal immune responses to fetal antigens. It is characterized by lymphohistiocytic infiltration within the villous stroma [9,10]. High-grade VUE is associated with various adverse pregnancy outcomes, including high rates of first-trimester miscarriage, severe fetal growth restriction, and late intrauterine fetal demise. It is linked to fetal central nervous system injury and carries a high recurrence risk (25–50%) [ 11 ]. Literature suggests an increased incidence of VUE in male fetuses with statistical significance. A retrospective study from Saudi Arabia [ 12 ] indicated a higher prevalence of fetal and maternal inflammatory responses in placentas from male infants compared to female infants, suggesting differences in placental inflammatory responses based on neonatal sex. This characteristic is further supported by the present case, where the patient's first pregnancy resulted in a normal female neonate, while the subsequent two pregnancies complicated by VUE involved male fetuses, suggesting a possible correlation. Furthermore, early identification and monitoring of maternal sepsis are crucial. Early symptoms of obstetric sepsis can be insidious and masked by physiological changes [ 13 ]. In this case, after the patient developed contractions, the cervical cerclage was urgently removed. As the contractions were initially considered physiological due to spontaneous labor onset, antibiotics were not administered. Shortly thereafter, high fever developed, followed by intrauterine fetal demise. This underscores the need to strengthen the early identification and monitoring of infections in pregnant women. Literature suggests that the rate of puerperal bloodstream infection is significantly higher in those who undergo cervical cerclage compared to those who do not (P < 0.005), with Escherichia coli being a common pathogen [ 14 ]. Escherichia coli is a Gram-negative bacterium widely present in intestinal mucosal barrier tissues and is the most common pathogen causing sepsis [15]. In this case, the positive culture for Escherichia coli aligns with relevant literature findings. Strict aseptic technique during cervical cerclage placement and removal, along with timely identification of infectious pathogens and rational antibiotic use, are essential, especially for women with a history of septic abortion, to reduce the incidence of postoperative infections [ 16 ]. This case also has certain limitations. VUE cases are relatively rare. Although this study provides lessons for the clinical management of sepsis, the sample size is small and constitutes a single case report, which cannot fully reflect the general patterns of the disease. Therefore, future research should involve the collection and analysis of more cases to more comprehensively evaluate the relationship between cervical cerclage, VUE, and sepsis, aiming to improve perinatal maternal and neonatal outcomes through early diagnosis and treatment. Conclusion This case highlights that chronic villitis of unknown etiology (VUE) can serve as a critical precipitant for maternal sepsis and intrauterine fetal demise following cervical cerclage. The diagnostic challenge lies in the non-specific, insidious nature of early infective signs, which may be obscured by physiological changes in pregnancy, leading to delayed intervention. Key clinical implications include: 1.Enhanced vigilance for subclinical infections in cerclage patients, particularly when contractions occur;2. Prophylactic antibiotic consideration upon cerclage removal if infection is suspected;3. Aseptic rigor during both placement and removal procedures to reduce iatrogenic risks. The recurrence risk of VUE (25–50%) and its possible association with male fetal sex observed in this case necessitate further investigation into etiopathogenetic mechanisms. Although limited by the inherent constraints of a single-case report, these findings underscore the imperative for multicenter collaborations to aggregate cases, validate these observations, and develop evidence-based protocols for early detection and management of cerclage-associated sepsis, ultimately improving perinatal outcomes. Abbreviations VUE villitis of unknown etiology CRP C-reactive protein Declarations 1.Ethics and Consent to Participate declarations The study was approved by the Medical Ethics Committee of Changsha Maternal and Child Health Care Hospital, No. EC-20250430-04. 2. Funding :There was no Funding. 3. Consent to Publish declaration Written informed consent has been obtained and all the data in the article have been approved. 4. Data Availability declaration All data generated or analysed during this study are included in this published article (and its supplementary information files) 5. Author Contribution declaration All authors of this study have read and approved the final manuscript for submission and are accountable for all aspects of the research. The specific contributions are as follows: Ping Ni: Contributed to Investigation, Data Curation, and Writing the original draft. Sifeng Wang: Contributed to Conceptualization, Methodology, Validation, and Form al Analysis. Wenxia Li: Contributed to Data Curation, Formal Analysis, and Literature Investigation. Weitao Yang: Contributed to Pathological Investigation and Diagnosis, and provided key Resources (pathological evidence). Lihui Huang: Contributed to Supervision, Project Administration, Funding Acquisition, and Reviewing & Editing the final manuscript. Corresponding author: Lihui Huang. 8. Competing Interests : There are no competing interests. References Claudia Nieuwoudt, Sarah E White, R Phillips Heine, et al.Maternal Sepsis.Clinical obstetrics and gynecology 2024 Sep 01;67(3):589-604 doi:10.1097/GRF.0000000000000881 Ryan EE, Brar N, Allard G, et al. Clinical Features of SARS-CoV-2 Infection During Pregnancy and Associated Placental Pathologies. Int J Gynecol Pathol. 2024;43(1):15-24. doi:10.1097/PGP.0000000000000948 Wang Y, Tang C, Li Y, Hu W. Puerperal septic shock complicated with symmetrical peripheral gangrene: A case report. Medicine (Baltimore). 2024;103(13):e37571. doi:10.1097/MD.0000000000037571 Choice S, Sherman A, Holder K, Harrington E. Gram-negative sepsis caused by a rare pathogen Phytobacter ursingii. BMJ Case Rep. 2024;17(4). Published 2024 Apr 16. doi:10.1136/bcr-2023-258384 Freedman AA, Goldstein JA, Miller GE, Borders A, Keenan-Devlin L, Ernst LM. Seasonal Variation of Chronic Villitis of Unknown Etiology. Pediatr Dev Pathol. 2020;23(4):253-259. doi:10.1177/1093526619892353 Scott HM, Mehta R, Branda ME, et al. Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease. Reprod Sci. 2024;31(4):997-1005. doi:10.1007/s43032-023-01402- Rose SJ, Nguyen EM, Branda ME, et al. Maternal Factors and Placental Pathologies Associated with a Diagnosis of Chronic Villitis. Am J Perinatol. 2024;41(S 01):e3351-e3362. doi:10.1055/a-2223-3348 Cornish EF, McDonnell T, Williams DJ. Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome. Front Immunol. 13:825075. Published 2022 None. doi:10.3389/fimmu.2022.825075 [9] Sato Y. Inflammatory lesions in placental pathology. J Obstet Gynaecol Res. 2022;48(1):58-65. doi:10.1111/jog.14932 Lothert PK, Fedyshyn B, Girard S, Chakraborty R, Norgan AP, Enninga EAL. Spatial proteomics reveals phenotypic and functional differences in T cell and macrophage subsets during villitis of unknown etiology. Sci Rep. 2024;14(1):914. Published 2024 Jan 9. doi:10.1038/s41598-024-51545-2 [11] Mekinian A, Kolanska K, Cheloufi M, et al. Chronic Villitis of unknown etiology (VUE): Obstetrical features, outcome and treatment. J Reprod Immunol. 148:103438. doi:10.1016/j.jri.2021.103438 Waleed Aldahmash, Khaldoon Aljerian, Saleh Alwasel; Prevalence of Fetal Inflammatory Response Syndrome and Villitis of Unknown Etiology in the Placenta of Saudi Women and Their Association with Baby SexLife (Basel, Switzerland) 2024 Jan 02;14(1) doi:10.3390/life14010079 Zhao M, Feng J, Tang L. Competing endogenous RNAs in lung cancer. Cancer Biol Med. 2021;18(1):1-20. doi:10.20892/j.issn.2095-3941.2020.0203 Dueholm M, Lundorf E.Transvaginal ultrasound or MRI for diagnosis of adenomyosis[J].Curr Opin Obstet Gyne- col,2007,19(6):505-512 Du M, Liu X, Ji X, et al. Berberine alleviates enterotoxigenic Escherichia coli-induced intestinal mucosal barrier function damage in a piglet model by modulation of the intestinal microbiome. Front Nutr. 11:1494348. Published 2024 None. doi:10.3389/fnut.2024.1494348 Li Y, Zu X, Hu X, Zhao C, Mo M, Fan B. Competing endogenous RNA network analysis reveals pivotal ceRNAs in bladder urothelial carcinoma. Transl Androl Urol. 2021;10(2):797-808. doi:10.21037/tau-20-1167 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-8351948","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":578335414,"identity":"0fffd1e0-f0c1-4a45-8b9e-f4f51e687dbb","order_by":0,"name":"Ping Ni","email":"","orcid":"","institution":"Changsha Hospital for Maternal \u0026 Child Health Care Affiliated to Hunan Normal University","correspondingAuthor":false,"prefix":"","firstName":"Ping","middleName":"","lastName":"Ni","suffix":""},{"id":578335416,"identity":"1e431564-2561-40ea-a39c-4dd5865ebc15","order_by":1,"name":"Sifeng Wang","email":"","orcid":"","institution":"Changsha Hospital 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1","display":"","copyAsset":false,"role":"figure","size":41196,"visible":true,"origin":"","legend":"\u003cp\u003ePlacental pathological examination results\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-8351948/v1/0c6bc822d6aed0189568c31a.jpg"},{"id":101943344,"identity":"357e578a-506c-4f15-a86e-e75aa7a73591","added_by":"auto","created_at":"2026-02-05 09:41:41","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":430064,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8351948/v1/62ff0732-a73d-48c7-8d0d-15921a031c9c.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A Rare Case Report of Sepsis and Intrauterine Fetal Demise Triggered by Chronic Villitis of Unknown Etiology Following Cervical Cerclage and Its Clinical Implications","fulltext":[{"header":"Background","content":"\u003cp\u003eMaternal sepsis is a serious obstetric complication caused by infection, particularly common during pregnancy, delivery, abortion, and the postpartum period, and constitutes a significant cause of maternal mortality [1]. Epidemiological data indicate that the incidence of maternal sepsis ranges from 0.002% to 0.04%, accounting for approximately 13% to 25% of maternal deaths [2,3]. Typical manifestations of sepsis include high fever, chills, tachycardia, and hypotension. Precursory symptoms may be infection-induced contractions; however, these can be masked by physiological manifestations like prodromal labor contractions in the peripartum period [4], leading to delays in early diagnosis and treatment. Chronic Villitis of Unknown Etiology (VUE) is an immune-mediated disease associated with maternal immune responses to fetal antigens [5], characterized by lymphohistiocytic infiltration within the villous stroma. The recurrence rate of VUE is estimated to be between 10% and 15% [6], and it is associated with adverse pregnancy outcomes. The clinical features and diagnosis of VUE rely on placental pathological examination [7], but relevant data are scarce, impacting the early diagnosis and management of this condition.\u003c/p\u003e\n\u003cp\u003eThis case is a rare instance of maternal sepsis and intrauterine fetal demise in the peripartum period following cervical cerclage, with the etiology ultimately confirmed as VUE. The uniqueness of this case lies in the complex relationship between cervical cerclage, VUE, and sepsis, simultaneously emphasizing the importance of infection surveillance and management during pregnancy post-cerclage. Through the analysis of this case, we have further refined the protocols for the prevention and early recognition of maternal sepsis following cervical cerclage, particularly for women with a history of septic abortion. The findings of this case provide significant experiential and data support for the clinical diagnosis and management of similar cases.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 33-year-old female was admitted at 02:10 AM on September 12, 2022, due to amenorrhea for over 8 months, status post cervical cerclage for over 2 months, and abdominal distension and pain for 8 hours. The patient had irregular menstrual cycles, typically 5-7/45-50 days. Her last menstrual period (LMP) was December 28, 2021, with an estimated date of confinement (EDC) of October 8, 2022. An oral glucose tolerance test (OGTT) performed in the second trimester yielded results of 5.16-11.24-12.18 mmol/L, leading to a diagnosis of \"pregnancy with pre-existing diabetes mellitus.\" She was advised on diet and exercise guidance but did not monitor her blood glucose regularly.\u003c/p\u003e\n\u003cp\u003eOn July 1, at 26 weeks and 3 days of gestation, a routine fetal systemic ultrasound revealed painless cervical dilation, leading to a consideration of cervical insufficiency, and the patient was hospitalized. Relevant examinations upon admission showed vaginal secretion cleanliness grade III, normal blood routine, and negative cervical secretion and urine cultures. After vaginal medication treatment, a repeat vaginal secretion routine was normal, and blood glucose monitoring was mostly normal. Following communication, the patient underwent an emergency cervical cerclage on July 6, which proceeded smoothly. Postoperatively, she received cefminox sodium 1g intravenously for infection prophylaxis and vaginal progesterone capsules. The patient experienced no significant discomfort and was discharged on July 11 after signing out. She attended regular outpatient prenatal check-ups post-discharge, with well-controlled blood glucose and normal cervical secretion examinations.\u003c/p\u003e\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n\n"},{"header":"Clinical Findings","content":"\u003cp\u003eOn September 11, 2022, around 18:00, the patient experienced irregular lower abdominal distension and pain without vaginal bleeding or amniotic fluid leakage. She presented to the emergency department and was admitted with a diagnosis of \u0026quot;threatened preterm labor; intrauterine pregnancy at 36 weeks and 5 days, cephalic presentation, live fetus; cervical insufficiency (status post cerclage).\u0026quot; Her pregnancy weight gain was approximately 5 kg. Her obstetrical history was gravida 3, para 1, with a history of a full-term female infant delivery in 2016 who is currently healthy. She had a history of an inevitable abortion in August 2021 at an external hospital, accompanied by high fever during labor, with a positive blood culture for *Escherichia coli*.\u003c/p\u003e\n\u003cp\u003eAdmission physical examination revealed: temperature 36.5\u0026deg;C, pulse 120 beats/min, respiration 20 breaths/min, blood pressure 100/70 mmHg, height 157 cm, weight 66 kg. Heart sounds were rapid without murmurs, and lung auscultation showed no significant abnormalities. Abdominal examination revealed irregular uterine contractions, fundal height 33 cm, normal fetal position, fetal heart rate 140 beats/min with regular rhythm. Vaginal digital examination showed a cervical length of 0.5 cm, soft consistency, with the cervical cerclage suture palpable.\u003c/p\u003e\n\u003cp\u003eDiagnostic Assessment\u003c/p\u003e\n\u003cp\u003eFetal heart monitoring was initiated immediately upon admission, and removal of the cervical cerclage was planned. After transfer to the delivery room, the cerclage suture was successfully removed without cervical laceration. Admission laboratory tests showed: white blood cell count (WBC) 13.20\u0026times;10^9/L, hemoglobin (HB) 118 g/L, neutrophils (N) 83.80%. After suture removal, the patient went into active labor at 06:20 AM. Vaginal examination under aseptic technique revealed 80% cervical effacement and a relaxed cervical os. Random blood glucose was 7.2 mmol/L. Fetal heart monitoring showed a Category II tracing. Measures including oxygen administration, fluid infusion, and position change for intrauterine resuscitation were performed. Around 07:00 AM, an emergency ultrasound indicated intrauterine fetal demise.\u003c/p\u003e\n\u003cp\u003eAfter counseling by the on-duty doctor, the patient and family agreed to return to the delivery room.\u003c/p\u003e\n\u003cp\u003eTherapeutic Intervention\u003c/p\u003e\n\u003cp\u003eAt 07:30, the patient developed chills and high fever, with a temperature of 39.3\u0026deg;C, pulse 128 beats/min, and blood pressure 103/68 mmHg. Sepsis was suspected. Immediate management included fluid resuscitation, antipyretics, and intravenous infusion of piperacillin sodium and tazobactam sodium for anti-infective therapy. An \u0026quot;orange alert\u0026quot; was activated.\u003c/p\u003e\n\u003cp\u003eAt 08:30, reassessment showed temperature 41.0\u0026deg;C, pulse 120-150 beats/min, respiration 30 breaths/min, blood pressure 105/66 mmHg. The patient had mild consciousness disturbance. Laboratory tests showed WBC 9.19\u0026times;10^9/L, HB 117 g/L, C-reactive protein (CRP) 59.40 mg/L, and a negative influenza test. Considering the severity of sepsis, anti-infective therapy was switched to meropenem 1g intravenously, with continued fluid support.\u003c/p\u003e\n\u003cp\u003eAt 10:05, spontaneous rupture of membranes occurred; the amniotic fluid was yellowish with an odor. Amniotic fluid was collected for bacterial culture.\u003c/p\u003e\n\u003cp\u003eAt 10:50, full cervical dilation was achieved, and the patient was coached to push. At 11:06, a stillborn male infant weighing 3250g was delivered. A placental swab was taken for bacterial culture.\u003c/p\u003e\n\u003cp\u003ePostpartum vital signs: temperature 37.9\u0026deg;C, pulse 140 beats/min, respiration 22 breaths/min, blood pressure 99/66 mmHg.\u003c/p\u003e\n\u003cp\u003eOn postpartum day one, the patient\u0026apos;s temperature normalized. Both blood culture and placental swab/amniotic fluid bacterial culture yielded positive results for Escherichia coli, with drug sensitivity indicating susceptibility to meropenem. Urine culture and cervical secretion bacterial culture were negative. The patient continued receiving meropenem for anti-infective therapy postpartum, along with subcutaneous low molecular weight heparin for venous thromboembolism prophylaxis. On postpartum day seven, meropenem was discontinued, and step-down therapy with cefoperazone sulbactam 1g every 8 hours was administered for two days. On postpartum day eight, blood routine was normal, CRP, procalcitonin (PCT), and coagulation function were normal, and repeat blood culture showed no bacterial growth. The patient was eventually discharged without discomfort.\u003c/p\u003e\n\u003cp\u003eFollow-up and Outcomes\u003c/p\u003e\n\u003cp\u003ePlacental pathological examination results indicated:\u003c/p\u003e\n\u003cp\u003e1. \u0026nbsp;Acute chorioamnionitis (Stage III, Grade II);\u003c/p\u003e\n\u003cp\u003e2. \u0026nbsp;Chronic villitis of unknown etiology, consistent with features of VUE;\u003c/p\u003e\n\u003cp\u003e3. \u0026nbsp;Chronic deciduitis (basalis);\u003c/p\u003e\n\u003cp\u003e4. \u0026nbsp;Funisitis.\u003c/p\u003e\n\u003cp\u003eClinicopathological correlation suggested prominent chronic villitis in this case, consistent with Chronic Villitis of Unknown Etiology (VUE). VUE is considered an immune-related disease associated with adverse pregnancy outcomes and has a high recurrence rate. Clinical follow-up and guidance for high-risk subsequent pregnancies were recommended.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case report describes sepsis and intrauterine fetal demise triggered by Chronic Villitis of Unknown Etiology (VUE) following cervical cerclage. Chronic villitis is a group of rare but devastating gestational syndromes [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It is considered an immune-mediated placental disease, potentially related to maternal immune responses to fetal antigens. It is characterized by lymphohistiocytic infiltration within the villous stroma [9,10]. High-grade VUE is associated with various adverse pregnancy outcomes, including high rates of first-trimester miscarriage, severe fetal growth restriction, and late intrauterine fetal demise. It is linked to fetal central nervous system injury and carries a high recurrence risk (25\u0026ndash;50%) [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Literature suggests an increased incidence of VUE in male fetuses with statistical significance. A retrospective study from Saudi Arabia [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e12\u003c/span\u003e] indicated a higher prevalence of fetal and maternal inflammatory responses in placentas from male infants compared to female infants, suggesting differences in placental inflammatory responses based on neonatal sex. This characteristic is further supported by the present case, where the patient's first pregnancy resulted in a normal female neonate, while the subsequent two pregnancies complicated by VUE involved male fetuses, suggesting a possible correlation.\u003c/p\u003e \u003cp\u003eFurthermore, early identification and monitoring of maternal sepsis are crucial. Early symptoms of obstetric sepsis can be insidious and masked by physiological changes [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In this case, after the patient developed contractions, the cervical cerclage was urgently removed. As the contractions were initially considered physiological due to spontaneous labor onset, antibiotics were not administered. Shortly thereafter, high fever developed, followed by intrauterine fetal demise. This underscores the need to strengthen the early identification and monitoring of infections in pregnant women. Literature suggests that the rate of puerperal bloodstream infection is significantly higher in those who undergo cervical cerclage compared to those who do not (P\u0026thinsp;\u0026lt;\u0026thinsp;0.005), with Escherichia coli being a common pathogen [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Escherichia coli is a Gram-negative bacterium widely present in intestinal mucosal barrier tissues and is the most common pathogen causing sepsis [15]. In this case, the positive culture for Escherichia coli aligns with relevant literature findings. Strict aseptic technique during cervical cerclage placement and removal, along with timely identification of infectious pathogens and rational antibiotic use, are essential, especially for women with a history of septic abortion, to reduce the incidence of postoperative infections [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e16\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThis case also has certain limitations. VUE cases are relatively rare. Although this study provides lessons for the clinical management of sepsis, the sample size is small and constitutes a single case report, which cannot fully reflect the general patterns of the disease. Therefore, future research should involve the collection and analysis of more cases to more comprehensively evaluate the relationship between cervical cerclage, VUE, and sepsis, aiming to improve perinatal maternal and neonatal outcomes through early diagnosis and treatment.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case highlights that chronic villitis of unknown etiology (VUE) can serve as a critical precipitant for maternal sepsis and intrauterine fetal demise following cervical cerclage. The diagnostic challenge lies in the non-specific, insidious nature of early infective signs, which may be obscured by physiological changes in pregnancy, leading to delayed intervention.\u003c/p\u003e \u003cp\u003eKey clinical implications include: 1.Enhanced vigilance for subclinical infections in cerclage patients, particularly when contractions occur;2. Prophylactic antibiotic consideration upon cerclage removal if infection is suspected;3. Aseptic rigor during both placement and removal procedures to reduce iatrogenic risks.\u003c/p\u003e \u003cp\u003eThe recurrence risk of VUE (25\u0026ndash;50%) and its possible association with male fetal sex observed in this case necessitate further investigation into etiopathogenetic mechanisms. Although limited by the inherent constraints of a single-case report, these findings underscore the imperative for multicenter collaborations to aggregate cases, validate these observations, and develop evidence-based protocols for early detection and management of cerclage-associated sepsis, ultimately improving perinatal outcomes.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eVUE \u0026nbsp;villitis of unknown etiology\u003c/p\u003e\n\u003cp\u003eCRP \u0026nbsp;C-reactive protein\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003e1.Ethics and Consent to Participate declarations\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study was approved by the Medical Ethics Committee of\u003c/p\u003e\n\u003cp\u003eChangsha Maternal and Child Health Care Hospital, No. EC-20250430-04.\u003c/p\u003e\n\u003cp\u003e2. \u003cstrong\u003eFunding\u0026nbsp;\u003c/strong\u003e:There was no Funding.\u003c/p\u003e\n\u003cp\u003e3. \u003cstrong\u003eConsent to Publish declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent has been obtained and all the data in the article have been approved.\u003c/p\u003e\n\u003cp\u003e4. \u003cstrong\u003eData Availability declaration\u003c/strong\u003eAll data generated or analysed during this study are included in this published article (and its supplementary information files)\u003c/p\u003e\n\u003cp\u003e5.\u003cstrong\u003e\u0026nbsp;Author Contribution declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll authors of this study have read and approved the final manuscript for submission and are accountable for all aspects of the research. The specific contributions are as follows:\u003c/p\u003e\n\u003cp\u003ePing Ni: Contributed to Investigation, Data Curation, and Writing the original draft.\u003c/p\u003e\n\u003cp\u003eSifeng Wang: Contributed to Conceptualization, Methodology, Validation, and Form al Analysis.\u003c/p\u003e\n\u003cp\u003eWenxia Li: Contributed to Data Curation, Formal Analysis, and Literature Investigation.\u003c/p\u003e\n\u003cp\u003eWeitao Yang: Contributed to Pathological Investigation and Diagnosis, and provided key Resources (pathological evidence).\u003c/p\u003e\n\u003cp\u003eLihui Huang: Contributed to Supervision, Project Administration, Funding Acquisition, and Reviewing \u0026amp; Editing the final manuscript.\u003c/p\u003e\n\u003cp\u003eCorresponding author: Lihui Huang.\u003c/p\u003e\n\u003cp\u003e8. \u003cstrong\u003eCompeting Interests\u0026nbsp;\u003c/strong\u003e: There are no competing interests.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eClaudia Nieuwoudt, Sarah E White, R Phillips Heine, et al.Maternal Sepsis.Clinical obstetrics and gynecology 2024 Sep 01;67(3):589-604 doi:10.1097/GRF.0000000000000881\u003c/li\u003e\n\u003cli\u003eRyan EE, Brar N, Allard G, et al. Clinical Features of SARS-CoV-2 Infection During Pregnancy and Associated Placental Pathologies. Int J Gynecol Pathol. 2024;43(1):15-24. doi:10.1097/PGP.0000000000000948 \u003c/li\u003e\n\u003cli\u003eWang Y, Tang C, Li Y, Hu W. Puerperal septic shock complicated with symmetrical peripheral gangrene: A case report. Medicine (Baltimore). 2024;103(13):e37571. doi:10.1097/MD.0000000000037571 \u003c/li\u003e\n\u003cli\u003eChoice S, Sherman A, Holder K, Harrington E. Gram-negative sepsis caused by a rare pathogen \u0026lt;i\u0026gt;Phytobacter ursingii\u0026lt;/i\u0026gt;. BMJ Case Rep. 2024;17(4). Published 2024 Apr 16. doi:10.1136/bcr-2023-258384\u003c/li\u003e\n\u003cli\u003eFreedman AA, Goldstein JA, Miller GE, Borders A, Keenan-Devlin L, Ernst LM. Seasonal Variation of Chronic Villitis of Unknown Etiology. Pediatr Dev Pathol. 2020;23(4):253-259. doi:10.1177/1093526619892353\u003c/li\u003e\n\u003cli\u003eScott HM, Mehta R, Branda ME, et al. Effect of Anti-TNF Biologic Exposure During Pregnancy on Villitis of Unknown Etiology Diagnoses in Patients with Autoimmune Disease. Reprod Sci. 2024;31(4):997-1005. doi:10.1007/s43032-023-01402- \u003c/li\u003e\n\u003cli\u003eRose SJ, Nguyen EM, Branda ME, et al. Maternal Factors and Placental Pathologies Associated with a Diagnosis of Chronic Villitis. Am J Perinatol. 2024;41(S 01):e3351-e3362. doi:10.1055/a-2223-3348 \u003c/li\u003e\n\u003cli\u003eCornish EF, McDonnell T, Williams DJ. Chronic Inflammatory Placental Disorders Associated With Recurrent Adverse Pregnancy Outcome. Front Immunol. 13:825075. Published 2022 None. doi:10.3389/fimmu.2022.825075\u003c/li\u003e\n\u003cli\u003e[9] Sato Y. Inflammatory lesions in placental pathology. J Obstet Gynaecol Res. 2022;48(1):58-65. doi:10.1111/jog.14932\u003c/li\u003e\n\u003cli\u003eLothert PK, Fedyshyn B, Girard S, Chakraborty R, Norgan AP, Enninga EAL. Spatial proteomics reveals phenotypic and functional differences in T cell and macrophage subsets during villitis of unknown etiology. Sci Rep. 2024;14(1):914. Published 2024 Jan 9. doi:10.1038/s41598-024-51545-2\u003c/li\u003e\n\u003cli\u003e[11] Mekinian A, Kolanska K, Cheloufi M, et al. Chronic Villitis of unknown etiology (VUE): Obstetrical features, outcome and treatment. J Reprod Immunol. 148:103438. doi:10.1016/j.jri.2021.103438 \u003c/li\u003e\n\u003cli\u003eWaleed Aldahmash, Khaldoon Aljerian, Saleh Alwasel; Prevalence of Fetal Inflammatory Response Syndrome and Villitis of Unknown Etiology in the Placenta of Saudi Women and Their Association with Baby SexLife (Basel, Switzerland) 2024 Jan 02;14(1) doi:10.3390/life14010079\u003c/li\u003e\n\u003cli\u003eZhao M, Feng J, Tang L. Competing endogenous RNAs in lung cancer. Cancer Biol Med. 2021;18(1):1-20. doi:10.20892/j.issn.2095-3941.2020.0203\u003c/li\u003e\n\u003cli\u003eDueholm M, Lundorf E.Transvaginal ultrasound or MRI for diagnosis of adenomyosis[J].Curr Opin Obstet Gyne- col,2007,19(6):505-512 \u003c/li\u003e\n\u003cli\u003eDu M, Liu X, Ji X, et al. Berberine alleviates enterotoxigenic \u0026lt;i\u0026gt;Escherichia coli\u0026lt;/i\u0026gt;-induced intestinal mucosal barrier function damage in a piglet model by modulation of the intestinal microbiome. Front Nutr. 11:1494348. Published 2024 None. doi:10.3389/fnut.2024.1494348 \u003c/li\u003e\n\u003cli\u003eLi Y, Zu X, Hu X, Zhao C, Mo M, Fan B. Competing endogenous RNA network analysis reveals pivotal ceRNAs in bladder urothelial carcinoma. Transl Androl Urol. 2021;10(2):797-808. doi:10.21037/tau-20-1167\u003c/li\u003e\n\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":"Cervical cerclage, Chronic villitis of unknown etiology (VUE), Sepsis, Intrauterine fetal death, Pregnancy outcome","lastPublishedDoi":"10.21203/rs.3.rs-8351948/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8351948/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eCervical cerclage is a common intervention for cervical insufficiency aimed at preventing preterm birth. However, this procedure may be associated with infection risks, such as sepsis, which, although low in incidence, can lead to severe adverse pregnancy outcomes. Chronic villitis of unknown etiology (VUE) is an inflammatory placental disorder, and its association with post-cerclage infection and sepsis has not been fully explored.\u003c/p\u003e\u003ch2\u003eCase Presentation\u003c/h2\u003e \u003cp\u003eThis case report presents a pregnant woman who underwent cervical cerclage in the second trimester and subsequently developed VUE of unknown etiology, leading to sepsis and ultimately intrauterine fetal death. The patient's clinical symptoms included contractions and signs of infection, but these manifestations were misinterpreted as physiological phenomena of natural labor, resulting in delayed diagnosis. Despite medical interventions, an adverse pregnancy outcome occurred.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis case highlights the importance of VUE as a potential trigger for sepsis after cervical cerclage, as its symptoms are easily confused with physiological contractions, making early identification difficult. It is recommended to strengthen infection surveillance in perinatal management and establish prevention and early diagnosis protocols for sepsis, with particular consideration of the influence of VUE. Future studies require more case collection and analysis to clarify the relationships between cervical cerclage, VUE, and sepsis, thereby improving maternal and neonatal outcomes.\u003c/p\u003e","manuscriptTitle":"A Rare Case Report of Sepsis and Intrauterine Fetal Demise Triggered by Chronic Villitis of Unknown Etiology Following Cervical Cerclage and Its Clinical Implications","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-23 00:41:27","doi":"10.21203/rs.3.rs-8351948/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":"ccd814c2-ea68-4a5b-9b81-90bc04054016","owner":[],"postedDate":"January 23rd, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-04T18:40:17+00:00","versionOfRecord":[],"versionCreatedAt":"2026-01-23 00:41:27","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8351948","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8351948","identity":"rs-8351948","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}