Offspring Long-Term Infectious Morbidity following Pregnancies with Cervical Cerclage

Offspring Long-Term Infectious Morbidity following Pregnancies with Cervical Cerclage | 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 Research Article Offspring Long-Term Infectious Morbidity following Pregnancies with Cervical Cerclage Amir SNIR, Polina SCHWARZMAN, Tamar WAINSTOCK, Eyal SHEINER This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8757654/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Apr, 2026 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted 8 You are reading this latest preprint version Abstract Introduction Cervical cerclage is an acceptable procedure in women with cervical insufficiency and known as effective in prevention of preterm delivery. Since the presence of foreign body during pregnancy may change the vaginal microbiom, we aimed to study whether a cervical cerclage is associated with long-term infectious morbidity of the offspring. Study design A population-based cohort study was performed at a tertiary medical center, including all singleton deliveries between the years 1991-2021. Long-term infectious morbidity was compared among offspring after pregnancies with and without cervical cercalge. The diagnoses of infectious morbidities were defined based on ICD-9 codes as recorded in community clinics and hospitalization files. A Kaplan-Meier survival curve was utilized to evaluate the cumulative incidence. A Cox proportional hazards model was used to control for confounders. Results Out of 354,940 offspring included in the analysis, 0.4% (n=1416) were following pregnancies with cervical cerclage. Total infectious morbidity was comparable between the two study groups (OR 1.0, 95% CI 0.9 – 1.1; p = 0.369, Table). Cumulative infectious morbidity was not statistically significant (log-rank test P-value = 0.19, Figure). However, while controlling for confounders such as gestational age and mode of delivery, a significant association between cervical cerclage placement during pregnancy and long term offspring’s infectious morbidities risk reduction was demonstrated (adjusted HR 0.9, 95% CI 0.87 – 0.99, p = 0.036). Conclusion Although cervical cerclage introduces a foreign body and has the theoretical potential to alter the vaginal microbiome, our population based study suggests that cerclage placement during pregnancy might have a protective effect for long-term infectious morbidity of the offspring. These findings support the safety of cerclage in this context. Further investigation regarding the influence of cervical cerclage on vaginal microbiome may be valuable. Figures Figure 1 Introduction Cervical cerclage is a vastly utilized intervention aimed at reducing the risk of preterm birth in women with a history of cervical insufficiency or by certain sonographic or physical exam findings [1]. Cervical cerclage reduces the risk of preterm birth by approximately 20% in these women [2,3]. Cerclage placement in relevant cases is recommended by both the American and the UK Royal College of Obstetricians and Gynecologists [4,5]. Despite its established effectiveness and benefits in reducing preterm births and improving neonatal outcomes, there is a paucity of evidence regarding potential long-term health implications as outcomes beyond the neonatal period is scarcely investigated. In the two Cochrane reviews [6-7] that evaluated the effectiveness of cervical cerclage for preventing preterm birth, no studies were identified assessing long term outcomes, emphasizing the importance that comprehensive research in this area will be conducted. Cervical cerclage, has been studied broadly for its traditional benefits in prolonging gestation and improving neonatal outcomes primarily in the context of mechanical support to the cervix [3]. Emerging evidence suggests that the placement of a cerclage, during pregnancy, may have broader implications, particularly in modulating the maternal and fetal immune environment. A possible immunological modification to the fetal environment may occur due to a maternal immune system interaction with the cervical cerclage as a foreign body. When a cervical cerclage is placed, the maternal immune system may respond by generating a typical foreign body immune reaction to the recognized cervical stich [8,9]. This immune reaction is characterized by a localized inflammation and controlled immune activation, however, it might as well have systemic effects that extend to the developing fetus [10]. Recent studies have been starting to explore the notion that this immune modulation reaction might aid to the maturation of the fetal immune system, potentially reducing the offspring’s susceptibility to infectious diseases. [11,12]. Cervical cerclage possess an additional immunological associated role. During a healthy pregnancy, the cervix protects the uterus and fetus from ascending infection from the vagina and functions as a selective barrier. The cervix shelters the productive lactobacilli while aiding in reducing the amount of pathogens. The cervical mucus plug seals the cervical canal and prevents ascending infection toward the uterus by the vaginal flora [13,14]. Cervical mucus plug irregularities and bacterial vaginosis are associated with an increased risk of preterm birth [15]. It is suggested that cervical cerclage supports the cervical mucosal plug that functions as a barrier to potential ascending infections [16] While the immediate benefits of cervical cerclage in preventing preterm birth are well-documented, the impact on the developing immune system and subsequent susceptibility to infectious diseases in later life remained a topic we aimed to research and debate. Materials and methods A population-based cohort analysis was performed, comparing the occurrence of long-term infectious morbidity in offspring after pregnancies with cervical cerclage versus those who were not. The database consisted of deliveries that took place from 1991 to 2021. The study was conducted at the Soroka University Medical Center (SUMC), a tertiary hospital, which is the only hospital in southern Israel, serving the entire population of the region totaling over one million inhabitants. Thus, the study is based on nonselective population data. The study is approved by the institutional review board (in accordance with the Helsinki Declaration). Infectious morbidity, in accordance with International Classification of Diseases, Ninth Revision (ICD-9) diagnoses) were compared among offspring with and without a placement of cervical cerclage during the pregnancy. Follow-up was conducted up to the age of 18 years. Infectious morbidity cases were identified through diagnoses coded under the International Classification of Diseases, Ninth Revision (ICD-9), extracted from CHS outpatient clinic and hospital records. The infectious disease may have been the main reason for admission or a background disorder in the file. Data were collected from the computerized hospitalization database of SUMC (“Demog-ICD9”), the computerized perinatal database of the obstetrics and gynecology department. The Demog-ICD9 database includes demographic information and ICD-9 codes for all medical diagnoses made during encounters with SUMC in order to ensure maximal integrity and accuracy, experienced medical secretaries routinely review the information before entering it into the database. Coding is performed after assessing medical and perinatal records as well as routine hospital documents. Statistical analysis was performed using SPSS (version 24) and STATA (version 12.0) software. Differences between the groups were assessed using χ 2 test, t test, in accordance with the variable type and its distribution. Kaplan-Meier survival curves were used to compare cumulative hospitalization incidences over time, and the differences were analyzed using the log-rank test. To establish an association between infectious diseases and future cumulative hospitalization incidence, while controlling for potential confounders, we used a multivariate Cox proportional hazards model. P -values <0.05 were considered statistically significant. Results During the study period 354,940 offspring met the inclusion criteria. constituted in the analysis, 1,416 of them (0.4%), were following pregnancies with cervical cerclage. These pregnancies exhibited distinct characteristics, including higher rates of gestational diabetes (11.4.9% vs. 4.7.0%) higher rates of preterm delivery in 34-37 gestational weeks (24.9% vs. 6.8%) and in 28-34 gestational weeks (8.6% vs 1.6%), a higher likelihood of cesarean deliveries (29.0% vs. 13.9%), and perinatal mortality (2.3% vs 1.8%). The total infectious morbidity was comparable between the two study groups (OR 1.0, 95% CI 0.9 – 1.1; p = 0.369, Table 2). In addition, cumulative infectious morbidity was not statistically significant (log-rank test P-value = 0.19, Figure). While controlling for confounders such as gestational age and mode of delivery, a significant association between cervical cerclage placement during pregnancy and long term offspring’s infectious morbidities risk reduction was demonstrated (adjusted HR 0.9, 95%CI 0.87 – 0.99, p = 0.036). Discussion This large population-based cohort study evaluated the long-term infectious morbidity in offspring born after pregnancies with cervical cerclage compared to those without. The primary finding demonstrated a statistically significant reduction in the risk of long-term infectious morbidity among children born to mothers who underwent cervical cerclage, after controlling for confounding variables such as gestational age and mode of delivery. While the unadjusted rates of infectious morbidity were similar between the two groups, multivariable analysis revealed a statistically significant protective association. Secondary analysis identified distinct obstetrical characteristics in the cerclage group, including higher rates of gestational diabetes, cesarean delivery, and preterm birth. Cervical cerclage has been extensively studied for its effectiveness in preventing preterm birth, particularly in women with a history of cervical insufficiency or shortened cervical length [2,3,6,7]. Yet, its impact on long-term child health outcomes, especially infectious morbidity, has remained largely unexplored. Our study addresses this gap by suggesting a protective association between cerclage and reduced long-term infection-related hospitalizations in offspring. Previous research primarily emphasized the gestational age extension afforded by cerclage as the primary mechanism for improved neonatal outcomes. It is well established that each additional week of gestation contributes to maturation of the fetal immune system, particularly adaptive immunity, which reduces susceptibility to infections such as respiratory and gastrointestinal illnesses during infancy and early childhood [17–21]. These findings are consistent with our data. however, in our adjusted analysis—where gestational age was accounted for—the protective effect persisted. This indicates that cerclage may exert effects beyond mechanical prolongation of pregnancy. Emerging evidence supports the notion that maternal immune modulation during pregnancy may influence the development of fetal immune competence. Lim et al. (2021) demonstrated that prenatal maternal infection can imprint tissue-specific immunity in offspring, potentially conferring protection or, conversely, vulnerability to postnatal infections depending on the context [10]. Similarly, studies in animal models have shown that maternal inflammation, even when mild, can prime the fetal immune system via cytokine transfer, enhancing neonatal resistance to viral and bacterial pathogens [11,12]. In the context of cervical cerclage, a similar immune-modulatory mechanism may be at play. The suture acts as a foreign body, inciting a localized inflammatory response in the cervix, characterized by increased infiltration of immune cells and secretion of cytokines and chemokines [22,23]. While historically viewed as a potential risk factor for infection, this low-grade, controlled inflammation may paradoxically enhance fetal immune development by promoting hematopoietic stem cell emergence and priming innate immunity [24–26]. Furthermore, observational data suggest that maternal immune activation (MIA) under controlled conditions—such as subclinical infections or mild inflammatory responses—can result in favorable offspring immune outcomes. A recent review by Vidal and Menon (2023) discusses how in utero exposure to inflammatory mediators may lead to the development of a more responsive and adaptable immune system postnatally [27]. Such findings align with our hypothesis that the immunological consequences of cerclage, particularly when not complicated by infection, may be beneficial. In contrast, some studies have raised concerns about cerclage and its potential to disrupt the vaginal microbiota, thereby increasing the risk of ascending infection [28–30]. For instance, research by Xiao et al. (2023) and Vargas et al. (2022) demonstrated that cerclage placement can reduce the dominance of protective Lactobacillus species and increase colonization by pathogenic bacteria. These changes are associated with adverse pregnancy outcomes and may theoretically pose a risk to neonatal health [31,32]. However, such effects may be more pronounced in emergency cerclage or when infection is already present. In our study, the long-term data on offspring suggest that the net impact may still be protective, particularly in carefully selected patients without clinical infection at the time of placement. Moreover, Lindsay Kindinger et al. (2016) reported that the cerclage-associated immune and microbial changes depend on baseline vaginal microbiome composition and local immune status [16]. This supports the need for individualized risk assessment, acknowledging that immune modulation from cerclage may carry heterogeneous effects depending on maternal environment, host response, and microbiome status. In summary, while some published data raise caution regarding potential infection risk linked to microbiome alterations, an emerging body of evidence—particularly from immunological and developmental studies—supports a more nuanced understanding. Controlled maternal immune responses, possibly induced by the presence of a cerclage, may favorably modulate fetal immune development, thus contributing to reduced infectious morbidity in offspring. These findings emphasize the need to reassess the broader implications of cerclage, not just as a mechanical intervention, but as a modulator of the intrauterine immune milieu. This study supports the safety of cervical cerclage, showing that it is not associated with increased long-term infectious morbidity in offspring and may even confer a protective effect. These findings may provide additional reassurance for clinicians and patients when considering cerclage in at-risk pregnancies. To build upon these findings, future prospective studies should explore the biological mechanisms supporting this association. Investigating the impact of cerclage material, placement timing, and procedural technique on immune outcomes may also yield clinically actionable insights. Our study has several limitations. Retrospective studies may have coding errors, despite skilled review. Moreover, potential loss to follow-up are considerations, but their effects likely apply similarly to both groups. Our study’s major strength stems from the fact that our medical center is the sole tertiary hospital in the southern region of Israel. That, combined with free essential health insurance provided to each citizen of Israel, makes it safe to assume that if a woman gave birth to a child in SUMC, the child would reach SUMC when in need of major medical assistance. Furthermore, the incorporation of data from our tertiary hospital and outpatient clinics, which collectively address most healthcare needs in the entire region, reinforces the reliability of our findings. Conclusion The findings in our study supports the protective role of cervical cerclage in reducing long-term infectious morbidity in offspring. Although cervical cerclage introduces a foreign body and has the theoretical potential to alter the vaginal microbiome, our population based study suggests that cerclage placement during pregnancy might have a protective effect for long-term infectious morbidity of the offspring. These findings support the safety of cerclage in this context. Further investigation regarding the influence of cervical cerclage on immunological interactions may be valuable. Declarations Conflict of interest statement : The authors report no conflict of interest. Financial support : This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors . Paper presentation information : The abstract of this study was presented during the 44rd Annual Pregnancy Meeting™, held February 10-14, 2024, at the Gaylord National Resort & Convention Center in National Harbor, MD (Submission ID: 1601423) . References Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75–84. Berghella V, Rafael TJ, Szychowski JM, Rust OA, Owen J. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol. 2011;117(3):663–671. Alfirevic Z, Stampalija T, Roberts D, Jorgensen AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;(4):CD008991. American College of Obstetricians and Gynecologists. Practice Bulletin No. 142: Cerclage for the Management of Cervical Insufficiency. Obstet Gynecol. 2014;123(2 Pt 1):372–379. doi:10.1097/01.AOG.0000443276.68274.cc Shennan A, To M. RCOG Green-top Guideline No. 60. Royal College of Obstetricians and Gynaecologists. 2011. Alfirevic Z, Stampalija T, Roberts D, Jorgensen A. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;(4):CD008991. Rafael TJ, Berghella V, Alfirevic Z. Cervical stitch (cerclage) for preventing preterm birth in multiple pregnancy. Cochrane Database Syst Rev. 2014;(10):CD009166. Moawad GN, Tyan P, Bracke T, et al. Systematic review of transabdominal cerclage placed via laparoscopy for the prevention of preterm birth. J Minim Invasive Gynecol. 2018;25(2):277–286. Debbs RH, DeLa Vega GA, Pearson S, et al. Transabdominal cerclage after comprehensive evaluation of women with previous unsuccessful transvaginal cerclage. Am J Obstet Gynecol. 2007;197(3):317.e1–317.e4. Lim AI, et al. Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring. Science. 2021;373(6555):eabf3002. Gleditsch DD, Shornick LP, Van Steenwinckel J, et al. Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model. Pediatr Res. 2014;76(1):33–40. Mukherjee S, Allen RM, Lukacs NW, et al. STAT3-mediated IL-17 production by postseptic T cells exacerbates viral immunopathology of the lung. Shock. 2012;38(5):515–523. Witkin SS. The vaginal microbiome, vaginal anti-microbial defence mechanisms, and the clinical challenge of reducing infection-related preterm birth. BJOG. 2015;122(2):213–218. Lacroix G, Gouyer V, Gottrand F, Desseyn JL. The cervicovaginal mucus barrier. Int J Mol Sci. 2020;21(21):8266. Leitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):375–390. Kindinger LM, et al. Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage. Sci Transl Med. 2016;8(350):350ra102. Melville JM, Moss TJM. The immune consequences of preterm birth. Front Mol Neurosci. 2013;7:79. Miller JE, Hammond GC, Strunk T, et al. Association of gestational age and growth measures at birth with infection-related admissions to hospital throughout childhood: a population-based, data-linkage study from Western Australia. Lancet Infect Dis. 2016;16(8):952–961. Davidesko S, Wainstock T, Sheiner E, Pariente G. Long-term infectious morbidity of premature infants: is there a critical threshold? J Clin Med. 2020;9(9):3008. Padeh E, Wainstock T, Sheiner E, et al. Gestational age and the long-term impact on children's infectious urinary morbidity. Arch Gynecol Obstet. 2019;299(2):385–392. Imterat M, Wainstock T, Moran-Gilad J, et al. The association between gestational age and otitis media during childhood: a population-based cohort analysis. J Dev Orig Health Dis. 2019;10(2):214–220. Cai S, Wu Y, Zeng L, Ding Y. Effects of vaginal microecology and immunity on the pregnancy outcome of cervical cerclage. BMC Womens Health. 2022;22(1):167. Fang J, Lin Y, Chen Z, et al. The association of inflammatory markers with maternal-neonatal outcome after cervical cerclage. J Inflamm Res. 2023;16:245–255. Apostol AC, López DA, Lebish EJ, et al. Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity. bioRxiv. Published May 8, 2022. doi:10.1101/2022.05.08.491095 Espin-Palazon R, Weijts B, Mulero V, Traver D. Proinflammatory signals as fuel for the fire of hematopoietic stem cell emergence. Trends Cell Biol. 2018;28(1):58–66. Mariani SA, Li Z, Rice S, et al. Pro-inflammatory aorta-associated macrophages are involved in embryonic development of hematopoietic stem cells. Immunity. 2019;50(6):1439–1452.e5. Vidal MS Jr, Menon R. In utero priming of fetal immune activation: myths and mechanisms. J Reprod Immunol. 2023;157:103922. Quinn M. Final report of the MRC/RCOG randomised controlled trial of cervical cerclage. Br J Obstet Gynaecol. 1993;100(12):1154–1155. Xiao Y, Huang S, Yu W, et al. Effects of emergency/nonemergency cervical cerclage on the vaginal microbiome of pregnant women with cervical incompetence. Front Cell Infect Microbiol. 2023;13:1072960. Vargas M, Yañez F, Elias A, et al. Cervical pessary and cerclage placement for preterm birth prevention and cervicovaginal microbiome changes. Acta Obstet Gynecol Scand. 2022;101(12):1403–1413. Tables Table 1. Maternal and obstetrical outcomes, according to pregnancies with or without cervical cerclage Maternal Characteristic/Pregnancy Outcome Cerclage n = 1416 No Cerclage n = 354940 OR P Value Cesarean delivery (%) 29.0 13.9 2.5 (2.2 – 2.8) < 0.001 Low birth weight (%) 18.7 6.9 3.1 (2.7 – 3.5) < 0.001 GDM (%) 11.4 4.7 2.6 (2.2 – 3.0) < 0.001 Hypertensive disease (%) 6.0 4.7 1.3 (1.0 – 1.6) 0.02 Perinatal mortality (%) 2.3 0.8 3.0 (2.1 – 4.2) < 0.001 SGA (%) 4.6 3.3 07 (0.5 – 0.9) 0.02 Preterm delivery 34–37 weeks’ gestation (%) 24.9 6.8 4.5 (4.0 – 5.1) < 0.001 Preterm delivery 28–34 weeks’ gestation (%) 8.6 1.6 5.8 (4.8 – 7.0) < 0.001 Placental Abruption (%) 0.7 0.5 1.7 (1.0 – 3.0) 0.032 Table 2. Offspring long-term infectious morbidity after pregnancy with and without cervical cerclage Infectious Morbidity No Cerclage n = 354940 Cerclage n = 1416 OR (95% CI) P Value Respiratory infections 176546 (51.6) 730 (49.7) 1.1 (.09 – 1.2) 0.173 Viral infections 11450 (3.2) 42 (3.0) 0.9 (0.7 – 1.2) 0.581 Ophthalmic infections 6197 (1.7) 25 (1.8) 1.0 (0.7 – 1.5) 0.955 Skin infections 15672 (4.4) 63 (4.4) 1.0 (0.8 – 1.3) 0.951 Bacterial infections 5171 (3.0) 20 (3.2) 0.9 (0.7 – 1.2) 0.889 Neonatal infections 4637 (1.5) 21 (1.3) 1.1 (0.7 – 1.7) 0.559 Bacteremia/Septicemia 3181 (0.9) 11 (0.8) 0.9 (0.5 – 1.6) 0.634 Central nervous system infections 1849 (0.6) 8 (0.5) 1.0 (0.5 – 2.1) 0.818 Ear, nose and throat infections 23028 (6.5) 110 (7.8) 1.2 (0.9 – 1.4) 0.051 Gastrointestinal infections 10494 (3.0) 48 (3.4) 1.1 (0.9 – 1.5) 0.337 Total infectious morbidity 195557 (56.3) 797 (55.1) 1.0 (0.9 – 1.1) 0.369 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Apr, 2026 Read the published version in Archives of Gynecology and Obstetrics → Version 1 posted Reviewers agreed at journal 07 Feb, 2026 Reviewers agreed at journal 07 Feb, 2026 Reviewers agreed at journal 05 Feb, 2026 Reviewers agreed at journal 04 Feb, 2026 Reviewers invited by journal 04 Feb, 2026 Editor assigned by journal 03 Feb, 2026 Submission checks completed at journal 03 Feb, 2026 First submitted to journal 01 Feb, 2026 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-8757654","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":587351432,"identity":"885cfddc-37f2-458a-84bf-aceb8087c340","order_by":0,"name":"Amir SNIR","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAtUlEQVRIiWNgGAWjYLCCBAYbIMnYeIAULWkgLQ0kaGFgOAwmidPCP+34swcP95y3W9t+GGhLjU00QS0St3PMDRKe3U7ediYRqOVYWm4DQT23c9gkEg7cTjY7ANTC2HCYsBb52+nPgFrOJZudf0ikFoPbCWZALQfszG4Qa4vh7RyQluQEsxtAWxKI8Ysc0GGSPw7Y2ZudT3/44EONDRHeh4JEsMoEYpWDgD0pikfBKBgFo2CEAQAXxUmFnEb+vAAAAABJRU5ErkJggg==","orcid":"","institution":"Soroka University Medical Center, Ben-Gurion University of the Negev","correspondingAuthor":true,"prefix":"","firstName":"Amir","middleName":"","lastName":"SNIR","suffix":""},{"id":587351433,"identity":"ebc84f99-9828-4f09-9f98-33ebf701a04c","order_by":1,"name":"Polina SCHWARZMAN","email":"","orcid":"","institution":"Soroka University Medical Center, Ben-Gurion University of the Negev","correspondingAuthor":false,"prefix":"","firstName":"Polina","middleName":"","lastName":"SCHWARZMAN","suffix":""},{"id":587351434,"identity":"4005c052-8701-4f13-9ee4-d1cdac06607b","order_by":2,"name":"Tamar WAINSTOCK","email":"","orcid":"","institution":"Ben-Gurion University of the Negev","correspondingAuthor":false,"prefix":"","firstName":"Tamar","middleName":"","lastName":"WAINSTOCK","suffix":""},{"id":587351435,"identity":"1f8e34b6-a2bf-4acd-8ba8-b286019a7a18","order_by":3,"name":"Eyal SHEINER","email":"","orcid":"","institution":"Soroka University Medical Center, Ben-Gurion University of the Negev","correspondingAuthor":false,"prefix":"","firstName":"Eyal","middleName":"","lastName":"SHEINER","suffix":""}],"badges":[],"createdAt":"2026-02-01 16:24:53","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8757654/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8757654/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00404-026-08431-1","type":"published","date":"2026-04-27T15:58:21+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":102172934,"identity":"8542cba6-220d-4585-bc5e-3cd51e58e522","added_by":"auto","created_at":"2026-02-09 05:09:56","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":24579,"visible":true,"origin":"","legend":"\u003cp\u003eCumulative incidence of hospitalization with infectious morbidity in offspring according to presence of cervical cerclage during pregnancy or not.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8757654/v1/0fde54f3bdc0fee8dad266f8.png"},{"id":108437932,"identity":"2b4835dd-e232-4cfc-907d-e3bf629c3fbc","added_by":"auto","created_at":"2026-05-04 16:04:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":241612,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8757654/v1/fad74019-ce49-40dd-ad46-4052fcd93d16.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Offspring Long-Term Infectious Morbidity following Pregnancies with Cervical Cerclage","fulltext":[{"header":"Introduction","content":"\u003cp\u003eCervical cerclage is a vastly utilized intervention aimed at reducing the risk of preterm birth in women with a history of cervical insufficiency or by certain sonographic or physical exam findings [1]. Cervical cerclage\u0026nbsp;reduces the risk of preterm birth by approximately 20% in these women [2,3]. Cerclage placement in relevant cases is recommended by both the American and the UK Royal College of Obstetricians and Gynecologists [4,5].\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eDespite its established effectiveness and benefits in reducing preterm births and improving neonatal outcomes, there is a paucity of evidence regarding potential long-term health implications as outcomes beyond the neonatal period is scarcely investigated. In the two Cochrane reviews [6-7] that evaluated the effectiveness of cervical cerclage for preventing preterm birth, no studies were identified assessing long term outcomes, emphasizing the importance that comprehensive research in this area will be conducted.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCervical cerclage, has been studied broadly for its traditional benefits in prolonging gestation and improving neonatal outcomes primarily in the context of mechanical support to the cervix [3]. Emerging evidence suggests that the placement of a cerclage, during pregnancy, may have broader implications, particularly in modulating the maternal and fetal immune environment. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eA possible immunological modification to the fetal environment may occur due to a maternal immune system interaction with the cervical cerclage as a foreign body. \u0026nbsp;When a cervical cerclage is placed, the maternal immune system may respond by generating a typical foreign body immune reaction to the recognized cervical stich [8,9]. This immune reaction is characterized by a localized inflammation and controlled immune activation, however, it might as well have systemic effects that extend to the developing fetus [10]. Recent studies have been starting to explore the notion that this immune modulation reaction might aid to the maturation of the fetal immune system, potentially reducing the offspring’s susceptibility to infectious diseases. [11,12].\u003c/p\u003e\n\u003cp\u003eCervical cerclage possess an additional immunological associated role. During a healthy pregnancy, the cervix protects the uterus and fetus from ascending infection from the vagina and functions as a\u0026nbsp;selective barrier. The cervix shelters the productive lactobacilli while aiding in reducing the amount of pathogens. The cervical mucus plug seals the cervical canal and prevents ascending infection toward the uterus by the vaginal flora [13,14]. Cervical mucus plug irregularities and bacterial vaginosis are associated with an increased risk of preterm birth [15]. \u0026nbsp;It is suggested that\u0026nbsp;cervical cerclage supports the cervical mucosal plug that functions as a barrier to potential ascending infections [16]\u003c/p\u003e\n\u003cp\u003eWhile the immediate benefits of cervical cerclage in preventing preterm birth are well-documented, the impact on the developing immune system and subsequent susceptibility to infectious diseases in later life remained a topic we aimed to research and debate.\u003c/p\u003e"},{"header":"Materials and methods ","content":"\u003cp\u003eA population-based cohort analysis was performed, comparing the occurrence of\u0026nbsp;long-term infectious morbidity in offspring after pregnancies with cervical cerclage versus those who were not. The database consisted of deliveries that took place from 1991 to 2021.\u003c/p\u003e\n\u003cp\u003eThe study was conducted at the Soroka University Medical Center (SUMC), a tertiary hospital, which is the only hospital in southern Israel, serving the entire population of the region totaling over one million inhabitants. Thus, the study is based on nonselective population data. The study is approved by the institutional review board (in accordance with the Helsinki Declaration). Infectious morbidity, in accordance with International Classification of Diseases, Ninth Revision (ICD-9) diagnoses) were compared among offspring with and without a placement of cervical cerclage during the pregnancy. Follow-up was conducted up to the age of 18 years. Infectious morbidity cases were identified through diagnoses coded under the International Classification of Diseases, Ninth Revision (ICD-9), extracted from CHS outpatient clinic and hospital records. The infectious disease may have been the main reason for admission or a background disorder in the file. \u0026nbsp;Data were collected from the computerized hospitalization database of SUMC (\u0026ldquo;Demog-ICD9\u0026rdquo;), the computerized perinatal database of the obstetrics and gynecology department. The Demog-ICD9 database includes demographic information and ICD-9 codes for all medical diagnoses made during encounters with SUMC in order to ensure maximal integrity and accuracy, experienced medical secretaries routinely review the information before entering it into the database. Coding is performed after assessing medical and perinatal records as well as routine hospital documents.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eStatistical analysis was performed using SPSS (version 24) and STATA (version 12.0) software. Differences between the groups were assessed using \u0026chi;\u003csup\u003e2\u003c/sup\u003e test, \u003cem\u003et\u003c/em\u003e test, in accordance with the variable type and its distribution. Kaplan-Meier survival curves were used to compare cumulative hospitalization incidences over time, and the differences were analyzed using the log-rank test. To establish an association between infectious diseases and future cumulative hospitalization incidence, while controlling for potential confounders, we used a multivariate Cox proportional hazards model. \u003cem\u003eP\u003c/em\u003e-values \u0026lt;0.05 were considered statistically significant.\u003cstrong\u003e\u003cbr\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eDuring the study period\u0026nbsp;354,940 offspring\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003emet the inclusion criteria. constituted in the analysis, 1,416 of them (0.4%), were following pregnancies with cervical cerclage.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThese pregnancies exhibited distinct characteristics, including higher rates of\u0026nbsp;gestational diabetes (11.4.9% vs. 4.7.0%) higher rates of preterm delivery in 34-37 gestational weeks (24.9% vs. 6.8%) and in 28-34 gestational weeks (8.6% vs 1.6%), a higher likelihood of cesarean deliveries (29.0% vs. 13.9%), and perinatal mortality (2.3% vs 1.8%).\u003c/p\u003e\n\u003cp\u003eThe total infectious morbidity was comparable between the two study groups (OR 1.0, 95% CI\u0026nbsp;0.9 \u0026ndash; 1.1; p = 0.369, Table 2). In addition, cumulative infectious morbidity was\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003enot statistically significant (log-rank test P-value = 0.19, Figure). While controlling for confounders such as gestational age and mode of delivery, a significant association between cervical cerclage placement during pregnancy and long term offspring\u0026rsquo;s infectious morbidities \u003cstrong\u003erisk reduction\u003c/strong\u003e was demonstrated (adjusted HR 0.9, 95%CI 0.87 \u0026ndash; 0.99, \u003cem\u003ep\u003c/em\u003e = 0.036).\u0026nbsp;\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis large population-based cohort study evaluated the long-term infectious morbidity in offspring born after pregnancies with cervical cerclage compared to those without. The primary finding demonstrated a statistically significant reduction in the risk of long-term infectious morbidity among children born to mothers who underwent cervical cerclage, after controlling for confounding variables such as gestational age and mode of delivery. While the unadjusted rates of infectious morbidity were similar between the two groups, multivariable analysis revealed a statistically significant protective association. Secondary analysis identified distinct obstetrical characteristics in the cerclage group, including higher rates of gestational diabetes, cesarean delivery, and preterm birth.\u003c/p\u003e\n\u003cp\u003eCervical cerclage has been extensively studied for its effectiveness in preventing preterm birth, particularly in women with a history of cervical insufficiency or shortened cervical length [2,3,6,7]. Yet, its impact on long-term child health outcomes, especially infectious morbidity, has remained largely unexplored. Our study addresses this gap by suggesting a protective association between cerclage and reduced long-term infection-related hospitalizations in offspring.\u003c/p\u003e\n\u003cp\u003ePrevious research primarily emphasized the gestational age extension afforded by cerclage as the primary mechanism for improved neonatal outcomes. It is well established that each additional week of gestation contributes to maturation of the fetal immune system, particularly adaptive immunity, which reduces susceptibility to infections such as respiratory and gastrointestinal illnesses during infancy and early childhood [17\u0026ndash;21]. These findings are consistent with our data. however, in our adjusted analysis\u0026mdash;where gestational age was accounted for\u0026mdash;the protective effect persisted. This indicates that cerclage may exert effects beyond mechanical prolongation of pregnancy.\u003c/p\u003e\n\u003cp\u003eEmerging evidence supports the notion that maternal immune modulation during pregnancy may influence the development of fetal immune competence. Lim et al. (2021) demonstrated that prenatal maternal infection can imprint tissue-specific immunity in offspring, potentially conferring protection or, conversely, vulnerability to postnatal infections depending on the context [10]. Similarly, studies in animal models have shown that maternal inflammation, even when mild, can prime the fetal immune system via cytokine transfer, enhancing neonatal resistance to viral and bacterial pathogens [11,12].\u003c/p\u003e\n\u003cp\u003eIn the context of cervical cerclage, a similar immune-modulatory mechanism may be at play. The suture acts as a foreign body, inciting a localized inflammatory response in the cervix, characterized by increased infiltration of immune cells and secretion of cytokines and chemokines [22,23]. While historically viewed as a potential risk factor for infection, this low-grade, controlled inflammation may paradoxically enhance fetal immune development by promoting hematopoietic stem cell emergence and priming innate immunity [24\u0026ndash;26].\u003c/p\u003e\n\u003cp\u003eFurthermore, observational data suggest that maternal immune activation (MIA) under controlled conditions\u0026mdash;such as subclinical infections or mild inflammatory responses\u0026mdash;can result in favorable offspring immune outcomes. A recent review by Vidal and Menon (2023) discusses how in utero exposure to inflammatory mediators may lead to the development of a more responsive and adaptable immune system postnatally [27]. Such findings align with our hypothesis that the immunological consequences of cerclage, particularly when not complicated by infection, may be beneficial.\u003c/p\u003e\n\u003cp\u003eIn contrast, some studies have raised concerns about cerclage and its potential to disrupt the vaginal microbiota, thereby increasing the risk of ascending infection [28\u0026ndash;30]. For instance, research by Xiao et al. (2023) and Vargas et al. (2022) demonstrated that cerclage placement can reduce the dominance of protective Lactobacillus species and increase colonization by pathogenic bacteria. These changes are associated with adverse pregnancy outcomes and may theoretically pose a risk to neonatal health [31,32]. However, such effects may be more pronounced in emergency cerclage or when infection is already present. In our study, the long-term data on offspring suggest that the net impact may still be protective, particularly in carefully selected patients without clinical infection at the time of placement.\u003c/p\u003e\n\u003cp\u003eMoreover, Lindsay Kindinger et al. (2016) reported that the cerclage-associated immune and microbial changes depend on baseline vaginal microbiome composition and local immune status [16]. This supports the need for individualized risk assessment, acknowledging that immune modulation from cerclage may carry heterogeneous effects depending on maternal environment, host response, and microbiome status.\u003c/p\u003e\n\u003cp\u003eIn summary, while some published data raise caution regarding potential infection risk linked to microbiome alterations, an emerging body of evidence\u0026mdash;particularly from immunological and developmental studies\u0026mdash;supports a more nuanced understanding. Controlled maternal immune responses, possibly induced by the presence of a cerclage, may favorably modulate fetal immune development, thus contributing to reduced infectious morbidity in offspring. These findings emphasize the need to reassess the broader implications of cerclage, not just as a mechanical intervention, but as a modulator of the intrauterine immune milieu.\u003c/p\u003e\n\u003cp\u003eThis study supports the safety of cervical cerclage, showing that it is not associated with increased long-term infectious morbidity in offspring and may even confer a protective effect. These findings may provide additional reassurance for clinicians and patients when considering cerclage in at-risk pregnancies. To build upon these findings, future prospective studies should explore the biological mechanisms supporting this association. Investigating the impact of cerclage material, placement timing, and procedural technique on immune outcomes may also yield clinically actionable insights.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study has several limitations. Retrospective studies may have coding errors, despite skilled review. Moreover, potential loss to follow-up are considerations, but their effects likely apply similarly to both groups. \u0026nbsp;\u003c/p\u003e\n\u003cp\u003eOur study\u0026rsquo;s major strength stems from the fact that our medical center is the sole tertiary hospital in the southern region of Israel. That, combined with free essential health insurance provided to each citizen of Israel, makes it safe to assume that if a woman gave birth to a child in SUMC, the child would reach SUMC when in need of major medical assistance. Furthermore, the incorporation of data from our tertiary hospital and outpatient clinics, which collectively address most healthcare needs in the entire region, reinforces the reliability of our findings.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThe findings in our study supports the protective role of cervical cerclage in reducing long-term infectious morbidity in offspring. \u0026nbsp;Although cervical cerclage introduces a foreign body and has the theoretical potential to alter the vaginal microbiome, our population based study suggests that cerclage placement during pregnancy might have a protective effect for long-term infectious morbidity of the offspring. These findings support the safety of cerclage in this context. Further investigation regarding the influence of cervical cerclage on immunological interactions may be valuable.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflict of interest statement\u003c/strong\u003e: The authors report no conflict of interest.\u003cspan dir=\"RTL\"\u003e\u0026nbsp;\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial support\u003c/strong\u003e: This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePaper presentation information\u003c/strong\u003e: The abstract of this study was presented during the 44rd Annual Pregnancy Meeting\u0026trade;, held February 10-14, 2024, at the\u0026nbsp;Gaylord National Resort \u0026amp; Convention Center\u0026nbsp;in\u0026nbsp;National Harbor, MD (Submission ID:\u0026nbsp;1601423)\u003cspan dir=\"RTL\"\u003e.\u003c/span\u003e\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eGoldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75\u0026ndash;84.\u003c/li\u003e\n\u003cli\u003eBerghella V, Rafael TJ, Szychowski JM, Rust OA, Owen J. Cerclage for short cervix on ultrasonography in women with singleton gestations and previous preterm birth: a meta-analysis. Obstet Gynecol. 2011;117(3):663\u0026ndash;671.\u003c/li\u003e\n\u003cli\u003eAlfirevic Z, Stampalija T, Roberts D, Jorgensen AL. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;(4):CD008991. \u003c/li\u003e\n\u003cli\u003eAmerican College of Obstetricians and Gynecologists. Practice Bulletin No. 142: Cerclage for the Management of Cervical Insufficiency. Obstet Gynecol. 2014;123(2 Pt 1):372\u0026ndash;379. doi:10.1097/01.AOG.0000443276.68274.cc\u003c/li\u003e\n\u003cli\u003eShennan A, To M. RCOG Green-top Guideline No. 60. Royal College of Obstetricians and Gynaecologists. 2011.\u003c/li\u003e\n\u003cli\u003eAlfirevic Z, Stampalija T, Roberts D, Jorgensen A. Cervical stitch (cerclage) for preventing preterm birth in singleton pregnancy. Cochrane Database Syst Rev. 2012;(4):CD008991.\u003c/li\u003e\n\u003cli\u003eRafael TJ, Berghella V, Alfirevic Z. Cervical stitch (cerclage) for preventing preterm birth in multiple pregnancy. Cochrane Database Syst Rev. 2014;(10):CD009166.\u003c/li\u003e\n\u003cli\u003eMoawad GN, Tyan P, Bracke T, et al. Systematic review of transabdominal cerclage placed via laparoscopy for the prevention of preterm birth. J Minim Invasive Gynecol. 2018;25(2):277\u0026ndash;286.\u003c/li\u003e\n\u003cli\u003eDebbs RH, DeLa Vega GA, Pearson S, et al. Transabdominal cerclage after comprehensive evaluation of women with previous unsuccessful transvaginal cerclage. Am J Obstet Gynecol. 2007;197(3):317.e1\u0026ndash;317.e4.\u003c/li\u003e\n\u003cli\u003eLim AI, et al. Prenatal maternal infection promotes tissue-specific immunity and inflammation in offspring. Science. 2021;373(6555):eabf3002.\u003c/li\u003e\n\u003cli\u003eGleditsch DD, Shornick LP, Van Steenwinckel J, et al. Maternal inflammation modulates infant immune response patterns to viral lung challenge in a murine model. Pediatr Res. 2014;76(1):33\u0026ndash;40.\u003c/li\u003e\n\u003cli\u003eMukherjee S, Allen RM, Lukacs NW, et al. STAT3-mediated IL-17 production by postseptic T cells exacerbates viral immunopathology of the lung. Shock. 2012;38(5):515\u0026ndash;523.\u003c/li\u003e\n\u003cli\u003eWitkin SS. The vaginal microbiome, vaginal anti-microbial defence mechanisms, and the clinical challenge of reducing infection-related preterm birth. BJOG. 2015;122(2):213\u0026ndash;218.\u003c/li\u003e\n\u003cli\u003eLacroix G, Gouyer V, Gottrand F, Desseyn JL. The cervicovaginal mucus barrier. Int J Mol Sci. 2020;21(21):8266.\u003c/li\u003e\n\u003cli\u003eLeitich H, Kiss H. Asymptomatic bacterial vaginosis and intermediate flora as risk factors for adverse pregnancy outcome. Best Pract Res Clin Obstet Gynaecol. 2007;21(3):375\u0026ndash;390. \u003c/li\u003e\n\u003cli\u003eKindinger LM, et al. Relationship between vaginal microbial dysbiosis, inflammation, and pregnancy outcomes in cervical cerclage. Sci Transl Med. 2016;8(350):350ra102.\u003c/li\u003e\n\u003cli\u003eMelville JM, Moss TJM. The immune consequences of preterm birth. Front Mol Neurosci. 2013;7:79.\u003c/li\u003e\n\u003cli\u003eMiller JE, Hammond GC, Strunk T, et al. Association of gestational age and growth measures at birth with infection-related admissions to hospital throughout childhood: a population-based, data-linkage study from Western Australia. Lancet Infect Dis. 2016;16(8):952\u0026ndash;961.\u003c/li\u003e\n\u003cli\u003eDavidesko S, Wainstock T, Sheiner E, Pariente G. Long-term infectious morbidity of premature infants: is there a critical threshold? J Clin Med. 2020;9(9):3008.\u003c/li\u003e\n\u003cli\u003ePadeh E, Wainstock T, Sheiner E, et al. Gestational age and the long-term impact on children\u0026apos;s infectious urinary morbidity. Arch Gynecol Obstet. 2019;299(2):385\u0026ndash;392.\u003c/li\u003e\n\u003cli\u003eImterat M, Wainstock T, Moran-Gilad J, et al. The association between gestational age and otitis media during childhood: a population-based cohort analysis. J Dev Orig Health Dis. 2019;10(2):214\u0026ndash;220. \u003c/li\u003e\n\u003cli\u003eCai S, Wu Y, Zeng L, Ding Y. Effects of vaginal microecology and immunity on the pregnancy outcome of cervical cerclage. BMC Womens Health. 2022;22(1):167.\u003c/li\u003e\n\u003cli\u003eFang J, Lin Y, Chen Z, et al. The association of inflammatory markers with maternal-neonatal outcome after cervical cerclage. J Inflamm Res. 2023;16:245\u0026ndash;255.\u003c/li\u003e\n\u003cli\u003eApostol AC, L\u0026oacute;pez DA, Lebish EJ, et al. Prenatal inflammation perturbs fetal hematopoietic development and causes persistent changes to postnatal immunity. bioRxiv. Published May 8, 2022. doi:10.1101/2022.05.08.491095\u003c/li\u003e\n\u003cli\u003eEspin-Palazon R, Weijts B, Mulero V, Traver D. Proinflammatory signals as fuel for the fire of hematopoietic stem cell emergence. Trends Cell Biol. 2018;28(1):58\u0026ndash;66. \u003c/li\u003e\n\u003cli\u003eMariani SA, Li Z, Rice S, et al. Pro-inflammatory aorta-associated macrophages are involved in embryonic development of hematopoietic stem cells. Immunity. 2019;50(6):1439\u0026ndash;1452.e5. \u003c/li\u003e\n\u003cli\u003eVidal MS Jr, Menon R. In utero priming of fetal immune activation: myths and mechanisms. J Reprod Immunol. 2023;157:103922.\u003c/li\u003e\n\u003cli\u003eQuinn M. Final report of the MRC/RCOG randomised controlled trial of cervical cerclage. Br J Obstet Gynaecol. 1993;100(12):1154\u0026ndash;1155.\u003c/li\u003e\n\u003cli\u003eXiao Y, Huang S, Yu W, et al. Effects of emergency/nonemergency cervical cerclage on the vaginal microbiome of pregnant women with cervical incompetence. Front Cell Infect Microbiol. 2023;13:1072960.\u003c/li\u003e\n\u003cli\u003eVargas M, Ya\u0026ntilde;ez F, Elias A, et al. Cervical pessary and cerclage placement for preterm birth prevention and cervicovaginal microbiome changes. Acta Obstet Gynecol Scand. 2022;101(12):1403\u0026ndash;1413.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1.\u0026nbsp;\u003c/strong\u003e\u003cstrong\u003eMaternal and obstetrical outcomes, according to pregnancies with or without cervical cerclage\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eMaternal Characteristic/Pregnancy Outcome\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCerclage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 1416\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Cerclage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 354940\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003eCesarean delivery (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e29.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e13.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e2.5 (2.2 \u0026ndash; 2.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003eLow birth weight (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e18.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e6.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e3.1 (2.7 \u0026ndash; 3.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003eGDM (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e11.4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e2.6 (2.2 \u0026ndash; 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003eHypertensive disease (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e6.0\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e4.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e1.3 (1.0 \u0026ndash; 1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003ePerinatal mortality (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e2.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e0.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e3.0 (2.1 \u0026ndash; 4.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003eSGA (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e4.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e3.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e07 (0.5 \u0026ndash; 0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e0.02\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003ePreterm delivery 34\u0026ndash;37 weeks\u0026rsquo; gestation (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e24.9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e6.8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e4.5 (4.0 \u0026ndash; 5.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003ePreterm delivery \u0026nbsp;28\u0026ndash;34 weeks\u0026rsquo; gestation (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e8.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e1.6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e5.8 (4.8 \u0026ndash; 7.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e\u0026lt; 0.001\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 30.1917%;\"\u003e\n \u003cp\u003ePlacental Abruption (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e0.7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.8914%;\"\u003e\n \u003cp\u003e0.5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.1278%;\"\u003e\n \u003cp\u003e1.7 (1.0 \u0026ndash; 3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 13.8978%;\"\u003e\n \u003cp\u003e0.032\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Offspring long-term infectious morbidity after pregnancy with and without cervical cerclage\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"640\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eInfectious Morbidity\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNo Cerclage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 354940\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCerclage\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003en = 1416\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eOR\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(95% CI)\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e\u003cstrong\u003eP Value\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eRespiratory infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e176546 (51.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e730 (49.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.1 (.09 \u0026ndash; 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.173\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eViral infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e11450 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e42 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e0.9 (0.7 \u0026ndash; 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.581\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eOphthalmic infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e6197 (1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e25 (1.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.0 (0.7 \u0026ndash; 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.955\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eSkin infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e15672 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e63 (4.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.0 (0.8 \u0026ndash; 1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.951\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eBacterial infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e5171 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e20 (3.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e0.9 (0.7 \u0026ndash; 1.2)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.889\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eNeonatal infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e4637 (1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e21 (1.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.1 (0.7 \u0026ndash; 1.7)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.559\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 24.805%;\"\u003e\n \u003cp\u003eBacteremia/Septicemia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e3181 (0.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e11 (0.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e0.9 (0.5 \u0026ndash; 1.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.634\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.805%;\"\u003e\n \u003cp\u003eCentral nervous system infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e1849 (0.6)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e8 (0.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.0 (0.5 \u0026ndash; 2.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.818\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.805%;\"\u003e\n \u003cp\u003eEar, nose and throat infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e23028 (6.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e110 (7.8)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.2 (0.9 \u0026ndash; 1.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.051\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.805%;\"\u003e\n \u003cp\u003eGastrointestinal infections\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e10494 (3.0)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e48 (3.4)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.1 (0.9 \u0026ndash; 1.5)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.337\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 24.805%;\"\u003e\n \u003cp\u003eTotal infectious morbidity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 22.1529%;\"\u003e\n \u003cp\u003e195557 (56.3)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 20.5928%;\"\u003e\n \u003cp\u003e797 (55.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 17.6287%;\"\u003e\n \u003cp\u003e1.0 (0.9 \u0026ndash; 1.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 14.8206%;\"\u003e\n \u003cp\u003e0.369\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-8757654/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8757654/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eIntroduction\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCervical cerclage is an acceptable procedure in women with cervical insufficiency and known as effective in prevention of preterm delivery. \u003cstrong\u003e\u0026nbsp;\u003c/strong\u003eSince the presence of foreign body during pregnancy may change the vaginal microbiom, we aimed to study whether a cervical cerclage is associated with long-term infectious morbidity of the offspring.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eStudy design\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eA population-based cohort study was performed at a tertiary medical center, including all singleton deliveries between the years 1991-2021. Long-term infectious morbidity was compared among offspring after pregnancies with and without cervical cercalge. The diagnoses of infectious morbidities were defined based on ICD-9 codes as recorded in community clinics and hospitalization files. A Kaplan-Meier survival curve was utilized to evaluate the cumulative incidence. A Cox proportional hazards model was used to control for confounders.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eOut of 354,940 offspring included in the analysis, 0.4% (n=1416) were following pregnancies with cervical cerclage. Total infectious morbidity was comparable between the two study groups (OR 1.0, 95% CI 0.9 – 1.1; p = 0.369, Table). Cumulative infectious morbidity was\u003cstrong\u003e \u003c/strong\u003enot statistically significant (log-rank test P-value = 0.19, Figure). However, while controlling for confounders such as gestational age and mode of delivery, a significant association between cervical cerclage placement during pregnancy and long term offspring’s infectious morbidities\u0026nbsp; \u003cstrong\u003erisk reduction\u003c/strong\u003e was demonstrated (adjusted HR 0.9, 95% CI 0.87 – 0.99, \u003cem\u003ep\u003c/em\u003e = 0.036).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAlthough cervical cerclage introduces a foreign body and has the theoretical potential to alter the vaginal microbiome, our population based study suggests that cerclage placement during pregnancy might have a protective effect for long-term infectious morbidity of the offspring. These findings support the safety of cerclage in this context. Further investigation regarding the influence of cervical cerclage on vaginal microbiome may be valuable.\u003c/p\u003e","manuscriptTitle":"Offspring Long-Term Infectious Morbidity following Pregnancies with Cervical Cerclage","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-09 05:08:14","doi":"10.21203/rs.3.rs-8757654/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"reviewerAgreed","content":"104603500482059711620595876972010551279","date":"2026-02-07T07:49:50+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"21991754338453851714825670349293869710","date":"2026-02-07T06:15:55+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325317470548882668075020541082866152837","date":"2026-02-05T14:19:25+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"174192029413722239938650565585409422330","date":"2026-02-04T19:32:18+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-02-04T17:30:08+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-02-03T20:36:34+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-02-03T12:14:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Gynecology and Obstetrics","date":"2026-02-01T16:14:06+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-gynecology-and-obstetrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"arch","sideBox":"Learn more about [Archives of Gynecology and Obstetrics](https://www.springer.com/journal/404)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/arch/default.aspx","title":"Archives of Gynecology and Obstetrics","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"c3e3c074-d121-4784-93ff-289bc806cadb","owner":[],"postedDate":"February 9th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T16:03:52+00:00","versionOfRecord":{"articleIdentity":"rs-8757654","link":"https://doi.org/10.1007/s00404-026-08431-1","journal":{"identity":"archives-of-gynecology-and-obstetrics","isVorOnly":false,"title":"Archives of Gynecology and Obstetrics"},"publishedOn":"2026-04-27 15:58:21","publishedOnDateReadable":"April 27th, 2026"},"versionCreatedAt":"2026-02-09 05:08:14","video":"","vorDoi":"10.1007/s00404-026-08431-1","vorDoiUrl":"https://doi.org/10.1007/s00404-026-08431-1","workflowStages":[]},"version":"v1","identity":"rs-8757654","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8757654","identity":"rs-8757654","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}