The CASPAR study. A feasibility cohort study using the Pregnolia System for objective cervical stiffness assessment prior to primiparous induction of labour.

Objective To determine if the Pregnolia System (PS) for cervical stiffness (CS) assessment is feasible for an induction of labour (IOL) cohort and to inform whether a definitive, IOL outcome prediction study is justified. Design Single-centre, prospective, observational, feasibility study. Setting Liverpool Women’s Hospital (Liverpool, UK) IOL suite. Population 100 primiparous, term pregnant women with intact membranes undergoing IOL. Methods Participants underwent a CS assessment using the PS and routine Bishop score (BS) before IOL commenced. Participants completed an acceptability questionnaire. Decision for IOL was as per clinical team and unit policy. Clinical outcomes were collected from electronic records after delivery. Main Outcome Measures Feasibility outcomes; recruitment rate, acceptability profile and assessment tool fidelity in this cohort. Clinical outcomes; exploring associations between PS CS results and IOL outcomes of interest. Results Recruitment was good at 68% (100/148). Reliability analysis of completed CS assessments showed internal consistency to be excellent (Cronbach’s Alpha 0.967). The PS assessment had a lower discomfort score compared to Bishops Score assessment (mean difference 3.73). Both cervical assessment tools had poor diagnostic capability for outcomes following induction of labour including vaginal delivery (PS AUC 0.466 95%CI 0.340, 0.593, BS AUC 0.621 95% CI 0.497-0.745) and failed IOL caesarean section (PS AUC 0.563 95%CI 0.354, 0.780, BS AUC 0.463, 95% CI 0.239-0.687). Conclusion This novel study confirms feasibility of the PS for pre-induction cervical assessment. However, it could not determine clinical utility in this cohort due to study design for feasibility outcomes. The CASPAR study. A feasibility cohort study using the Pregnolia System for objective cervical stiffness assessment prior to primiparous induction of labour. Elizabeth Medford 1,2, Steven Lane 2, Angharad Care 1,2, Andrew Sharp 1,2 . 1 Liverpool Women’s Hospital, NHS Foundation Trust, Crown Street, Liverpool UK. 2 University of Liverpool, UK. Correspondance to; E Medford [email protected]

To determine if the Pregnolia System (PS) for cervical stiffness (CS) assessment is feasible for an induction of labour (IOL) cohort and to inform whether a definitive, IOL outcome prediction study is justified. Design Single-centre, prospective, observational, feasibility study. Setting Liverpool Women’s Hospital (Liverpool, UK) IOL suite. Population 100 primiparous, term pregnant women with intact membranes undergoing IOL.

Participants underwent a CS assessment using the PS and routine Bishop score (BS) before IOL commenced. Participants completed an acceptability questionnaire. Decision for IOL was as per clinical team and unit policy. Clinical outcomes were collected from electronic records after delivery. Main Outcome Measures Feasibility outcomes; recruitment rate, acceptability profile and assessment tool fidelity in this cohort. Clinical outcomes; exploring associations between PS CS results and IOL outcomes of interest.

Recruitment was good at 68% (100/148). Reliability analysis of completed CS assessments showed internal consistency to be excellent (Cronbach’s Alpha 0.967). The PS assessment had a lower discomfort score compared to Bishops Score assessment (mean difference 3.73). Both cervical assessment tools had poor diagnostic capability for outcomes following induction of labour including vaginal delivery (PS AUC 0.466 95%CI 0.340, 0.593, BS AUC 0.621 95% CI 0.497-0.745) and failed IOL caesarean section (PS AUC 0.563 95%CI 0.354, 0.780, BS AUC 0.463, 95% CI 0.239-0.687).

This novel study confirms feasibility of the PS for pre-induction cervical assessment. However, it could not determine clinical utility in this cohort due to study design for feasibility outcomes. Funding Pregnolia AG provided the device for use in this study and provided financial aid to fund a Clinical research Fellow to undertake this research. Pregnolia AG had no role in the study design, decision to publish or preparation of the manuscript. 1. Introduction Induction of labour (IOL) is a common obstetric intervention affecting over one third of pregnant women in England.(1) Although subjective and only weakly predictive of delivery outcomes, the Bishop score is still used in UK practice to determine whether cervical preparation is required.(2-5) The Pregnolia System (PS) is a novel cervical assessment tool that provides cervical stiffness (CS) results through a vacuum-aspiration technique. (6, 7) The assessment requires a speculum examination to visualise the cervix and allow placement of the sterile device probe directly to the anterior lip of the cervix (Figure 1). A foot-pump is activated, and the control unit generates a negative pressure which displaces the underlying cervical epithelium into the device probe tip. Once adequate tissue displacement is achieved, the device automatically releases the pressure and detaches from the cervix whilst generating a final closing pressure, termed the Cervical Stiffness Index (CSI, mbar). One complete assessment requires consecutive, triplicate measurements as per manufacturer guidance. The higher the stiffness of the tissue, the higher the CSI result. (7, 8) Figure 1. The Pregnolia System- vaginal probe and control unit with foot pump. A small study involving an unselected, pregnant cohort demonstrated that the PS provided safe, objective, quantitative CS results.(7, 8) Using silicone cervical models, the PS has demonstrated improved reliability and reduced inter-observer variability over digital palpation of the cervix which could be extrapolated as a comparison to the Bishop score.(6) However, there is very limited data available using the PS within clinical obstetric settings.(9, 10) Current research is mainly focused towards preterm birth (PTB) risk stratification following preliminary evidence showing the PS detects cervical softening before cervical length shortening.(7, 11, 12) Formal assessment of this novel device as a pre-induction cervical assessment tool has not yet been extensively investigated. The objective of this study was to formally explore the feasibility of using the PS for pre-induction cervical assessment. This study aimed to: 1) determine recruitment rate, 2) verify acceptability within the IOL cohort, 3) establish fidelity of CS triplicate measurements and 4) inform application of triplicate measurements in clinical practice. Clinical outcomes regarding labour and delivery were collected to allow provisional exploration of associations between pre-induction PS CS assessments and clinical outcomes of interest. This was to inform hypothesis development for future definitive studies, if the PS assessment was proven to be feasible in this cohort. All candidate clinical measures were compared with the Bishop score recorded concurrently at each study visit, which served as the reference standard. 2. Methods 2.1 Study Design and Population This feasibility study was a single site, prospective, cohort study of 100 primiparous women with a term, singleton pregnancy, with intact membranes, undergoing IOL at the Liverpool Women’s Hospital (LWH) in the UK. Need for IOL was determined by their clinical team. Participants were recruited at time of attendance for IOL. After providing informed consent, participants underwent CS assessment using the PS, followed by their routine pre-induction digital vaginal examination to assess the Bishop score. Participants then completed a questionnaire regarding their experience of cervical assessment with the PS. In all cases IOL was performed as per unit policy. Clinical outcomes were collected from electronic hospital records following delivery. (See Supporting Information Figure 1) The Liverpool Babies patient and public involvement (PPI) group, was a fundamental contributor to study design and ensured the study addressed a research question that was important to the cohort and involved study procedures that were acceptable to women undergoing IOL. A 12 month-follow up focus group allowed for results to be disseminated to participants and provided feedback to the study team to inform further research in this cohort. 2.2 Study outcomes Clear feasibility outcomes were outlined as part of the published study protocol.(13) These aim to establish the ability to recruit to a study within the IOL cohort using this novel cervical assessment tool, determine acceptability of the PS in this population and setting, and assess the PS ability to achieve reliable CS triplicate measurements in this cohort and infer appropriate clinical application of the results. Induction and delivery clinical outcomes have been collected to identify any preliminary associations for clinical utility of the PS in this obstetric clinical setting. Together, these outcomes can inform if a further, definitive, outcome prediction study in this cohort is justified. 2.3 Statistical Analysis For feasibility outcomes, recruitment rate, acceptability data and obtaining triplicate results were represented as descriptive statistics, primarily with frequency of observations (percentages), but also generating mean (SD) and median (IQR) as appropriate. Further acceptability profiling involved comparison of Likert-scale discomfort scores by generating mean differences and 95% confidence intervals (CI). Internal consistency of the device for triplicate measurements was analysed using Cronbach’s alpha (CA) with a value ≥0.9 denoting excellent internal consistency. For clinical outcomes baseline characteristics of the participants were compared using descriptive statistics, however formal hypothesis testing has not been performed due to the feasibility design of this study and the lack of a formal sample size calculation. The sample size was designed for feasibility outcomes and not powered for testing statistical significance between differences in clinical outcomes. Preliminary exploration of associations between PS CS results and continuous clinical outcomes has been performed using scatter plots and generating correlation coefficients (R value). Preliminary diagnostic performance of the PS CS results for categorical clinical outcomes has been demonstrated through received operating characteristic (ROC) curves with area under the curve (AUC) and 95% CIs being calculated. Associations and diagnostic performance for Bishop Score and clinical outcomes has been shown for comparison. All data was analysed using SPSS 29.01. 3 Results 3.1 Feasibility Outcomes 3.1.1 Recruitment Rate 148 women were approached for inclusion in the study with 100 agreeing to participate, achieving a recruitment rate of 68% (100/148). 97 participants completed the study visit (Supporting Information Figure 2). There were no dropouts following recruitment and no participants were lost to follow up. 3.1.2 Acceptability Profile Of the 48 eligible patients who declined study participation, the majority declined due to the requirement for an additional speculum to facilitate the study procedure (n=28, 58%). The remaining group either declined due to general anxiety surrounding the IOL process and found study involvement too overwhelming at that time (n=10, 21%), or they had a general disinterest towards any additional research involvement (n=10, 21%). 90 participants (90%) completed the post-study procedure questionnaire. The Bishop score had the highest mean discomfort score (4.93/10), whereas the PS had the lowest (1.20/10). The discomfort score for the PS was significantly lower than both the speculum examination (mean difference 3.15, 95% CI 2.58–3.73) and the Bishop score (mean difference 3.73, 95% CI 3.09–4.37) (Supporting Information Table 1 & Figure 3). However, the PS requires the use of a speculum to facilitate the assessment and cannot be completed independently to a speculum examination. Therefore, the speculum discomfort score can be taken as the most noticeable part of the overall PS CS assessment. Despite this, the speculum discomfort score still improves upon the BS discomfort score (4.35/10 vs 4.93/10). Acceptability of the PS appeared good: 69% (n=62) of the participants did not notice the device taking a measurement during the speculum examination, and 92% (n=83) indicated they would agree to use the tool again (Supporting Information Figure 3). Of those women who had experienced a smear test before (n=61), almost all (n=59, 97%) of them felt having the PS assessment was better than or similar to having a smear. This is a very comparable gynaecological examination given the inherent requirement of a speculum for a smear assessment. Overall participants found the PS assessment, including the speculum, the most tolerable cervical assessment tool prior to their induction of labour (n=47, 52%). At the 12-month follow-up focus group, 10 participants confirmed the PS cervical assessment tool was acceptable to them and reiterated the importance and need for more information regarding predicting outcomes of IOL to assist with their decision- making. 3.1.3 Pregnolia System Fidelity 3.1.3.1 Triplicate Measurement obtainability Two participants were not eligible for PS assessment at the time of the study procedure. At least one CS measurement was achieved in 88 participants of the remaining 98 eligible participants (90%). 76 participants (78%) who underwent PS cervical assessment achieved full triplicate measurements for analysis as per study protocol. 14% of the eligible participants did not achieve triplicate measurements due to increased mucus and secretions not allowing an adequate seal to be achieved with the Pregnolia probe for vacuum aspiration. A variety of other reasons accounting for the remainder are outlined in Supporting Information Table 2. 3.1.3.2 Triplicate Measurement reliability When analysing overall sequential triplicate measurements by the median value, the first CS result (CSI 1: 51mbar, IQR 45) was consistently the highest, with each subsequent measurement demonstrating reduced values (CSI 2: 41mbar, IQR 45, CSI 3: 39mbar, IQR 43). This confirmed the expected trend of consecutive measurements due to the viscoelastic nature of cervical tissue.(14) Given the established difference in CSI between sequential measurements in a triplicate set, we compared different combinations of PS CS measurements in our reliability analysis to inform clinical application of the decreasing results. Overall, the PS has excellent internal consistency for CS measurements, regardless of which combination of the triplicate results was used (CA >0.9 throughout) (Table 1). These results support the use of the first CS result obtained as the final CS value for clinical application. Table 1. Reliability analysis of the Pregnolia System for triplicate cervical stiffness measurements using Cronbach’s Alpha Note. CSI1- 1 st attempted measurement of sequential triplicate measurements, CSI2- 2 nd attempted measurement of sequential triplicate measurements, CSI3- 3 rd attempted measurement of sequential triplicate measurements, Min- minimum result obtained, Max- maximum result obtained, 1 st CSI achieved- first measurement to be successfully obtained during full assessment, Mean and median included if ≥ 2 measurements available from CSI1, 2 & 3. 3.2 Exploring Clinical Utility Baseline characteristics for the cohort are detailed in Table 2. Participant demographics were similar when comparing by mode of delivery. A greater proportion of IOL for reduced fetal movements (RFM)(22.5% vs 9%) and maternal medical disease (10% vs 5%) resulted in caesarean section, whereas all IOL for fetal concern resulted in vaginal delivery (10% vs 0%). Participants that required additional cervical ripening methods (i.e. Propess & Prostin) resulted in an increased proportion delivered by caesarean section (22.5% vs 5%). Women who achieved a vaginal delivery following IOL had a shorter interval from rupture of membranes until delivery (709±423 vs 917±440), shorter duration of oxytocin usage (452±387 vs 703±402) and shorter duration of 1 st and 2 nd stages of labour (265±226 vs 359±218, 100±75 vs 171±96). This feasibility study protocol was able to collect outcome data to fulfil the core outcome set for trials on IOL. (Supporting information Table 3) The ability of PS (AUC 0.466, 95%CI 0.340-0.593) and Bishop score (AUC 0.621, 95%CI 0.497-0.745) to predict vaginal delivery following IOL was poor, as an AUC ≤0.5 indicates no better performance than chance (Figure 2). Identifying those women who subsequently require a caesarean delivery after a failed IOL was determined to be a key clinical outcome of interest following IOL. Both PS & Bishop score were poor predictive cervical assessment tools for this outcome (PS AUC 0.563, 95%CI 0.354-0.780 & Bishop score 0.463, 95%CI 0.239-0.687). Similarly, there was no signal of diagnostic prowess for PS CS or Bishop score for other IOL outcomes of clinical interest including achieving active labour, achieving full dilatation, spontaneous rupture of membranes, not requiring oxytocin and requiring more than one cervical ripening method (Supporting Information Figure 4 and Table 4). There was no clear association found between PS CS and duration of ruptured membranes (R= 0.042), duration of oxytocin (R=-0.104), interval from onset of induction to delivery (R=0.081) or length of active 1 st stage of labour (R=-0.215). (Supporting Information Figure 5.) Table 2. Demographic, induction and labour characteristics for the CASPAR study population. | Caesarean section n=40 | Vaginal Delivery n=57 | || | Age (years) | 29±5.5 | 29±6.5 | 29+4.7 | | Booking BMI | 27±5.9 | 28±6.9 | 26±5.0 | | Ethnicity White Black Asian Mixed Other | 76 (78%) 6 (6%) 11 (11%) 3 (3%) 1 (1%) | 30 (75%) 3 (7.5%) 5 (12.5%) 1 (2.5%) 1 (2.5%) | 46 (81%) 3 (5.3%) 6 (10.5%) 2 (3.5%) 0 | | IMD decile 1 2 | 44 (45%) 13 (13%) | 20 (50%) 7 (17.5%) | 24 (42%) 6 (11%) | | Indication for induction Post dates Reduced Fetal Movements Large for Gestational Age Maternal Request Advanced Maternal Age Maternal medical disease Gestation Diabetes Pre-eclampsia/Pregnancy Induced Hypertension Fetal concern Other | 38 (39%) 14 (14%) 13 (13%) 3 (3%) 2 (2%) 7 (7%) 9 (9%) 4 (4%) 6 (6%) 1 (1%) | 13 (32.5%) 9 (22.5%) 5 (12.5%) 2 (5%) 2 (5%) 4 (10%) 4 (10%) 1 (2.5%) 0 0 | 25 (44%) 5 (9%) 8 (14%) 1 (2%) 0 3 (5%) 5 (9%) 3 (5%) 6 (10%) 1 (2%) | | Gestation at induction (weeks+days ) 37+0- 37+6 38+0-38+6 39+0-39+6 40+0-40+6 ≥41+0 | 40+0 (2+1) 7 (7%) 19 (20%) 22 (23%) 16 (16%) 33 (34%) | 39+5 (2+0) 4 (10%) 5 (12.5%) 13 (32.5%) 7 (17.5%) 11 (27.5%) | 40+1 (2+2) 3 (5%) 14 (24%) 9 (16%) 9 (16%) 22 (39%) | | Cervical ripening method Propess only Propess + Prostin Balloon Nil required | 77 (79%) 12 (12%) 0 8 (8%) | 28 (70%) 9 (22.5%) 0 3(7.5%) | 49 (86%) 3 (5%) 0 5 (9%) | | Rupture of membranes Spontaneous Artificial Unable to ARM ARM not indicated Missing | 22 (23%) 68 (70%) 3 (3%) 3 (3%) 1 (1%) | 8 (20%) 26 (65%) 3 (7.5%) 3 (7.5%) 0 | 14 (25%) 42 (74%) 0 0 1 (1%) | | Interval from rupture of membranes to delivery (mins) | 788±438 | 917±440 | 709±423 | | Oxytocin required Yes No Not indicated | 72 (74%) 19 (20%) 6 (6%) | 30 (75%) 4 (10%) 6 (15%) | 42 (74%) 15 (26%) 0 | | Duration of oxytocin* (mins) N=90 | 543±408 | 703±402 | 452±387 | | Induction onset to delivery (hrs) | 41±18 | 39±14 | 41±22 | | Established in active labour Yes No | 78 (80%) 19 (20%) | 21 (53%) 19 (47%) | 57 (100%) 0 | | Length of active 1 st stage * (mins) N=48 | 274±225 | 359±218 | 265±226 | | Achieved full dilatation Yes No | 61 (63%) 36 (37%) | 4 (10%) 36 (90%) | 57 (100%) 0 | | Length of 2 nd stage* (mins) N=56 | 105±78 | 171±96 | 100±75 | Note. Continuous variables represented as Mean ±SD if normally distributed, and median (IQR) if not-normally distributed. Categorical variables represented as number (%). *missing information from electronic maternity clinical records, number included as N Figure 2. ROC curves to demonstrate predictive ability of Pregnolia System and Bishop’s Score for IOL outcomes; a) Vaginal Delivery b) Failed IOL. a ) b ) 4 Discussion 4.1 Main Findings and Interpretation The CASPAR study demonstrates that use of the PS as a CS assessment tool at the time of IOL is feasible. However, it’s utility for IOL clinical outcome associations could not be demonstrated adequately in this cohort due to the feasibility study design. An adequate recruitment rate of 68% was achieved, which is comparable to other IOL studies where recruitment varies from 27% to 89%.(9, 15-17) Considering our study explores introduction of a novel assessment tool for this population, this recruitment rate reflects the acceptability of this tool for cervical assessment in this setting. This is the first study to fully assess participant experience and perception of the assessment tool when using the PS for cervical assessment as part of IOL. Participants preferred the CS assessment tool over the current reference standard of pre-induction cervical assessment using the Bishop score. From participant questionnaire results we recommend describing the assessment as “similar to or better than having a smear test” with over half of women being unable to feel the stiffness test taking place during their speculum examination. Our comparison discomfort scores for the stiffness assessment and Bishop score are supported by similar findings in a smaller preliminary study from Belgium, although our larger cohort allows for statistical significance in the comparison between assessment tools for discomfort.(9) Our study also captures perceptions regarding speculum examination at term gestation, with 58% declining participation due to the requirement for a speculum and a comparatively high discomfort score for the speculum examination for those that took part in the study (4.35/10). Although the PS is very well tolerated in our cohort, the inherent requirement for a speculum examination to facilitate use of the PS is an ongoing potential barrier to implementation of this study across wider obstetric cohorts and within clinical practice. This study has fully assessed the obtainability of triplicate measurements at term gestation. There have been limited previous clinical studies using the PS at this point in pregnancy (7, 9). Our study has highlighted a number of challenges in achieving triplicate measurements in this cohort of patients, mostly due to difficulty with achieving an appropriate seal between the Pregnolia probe and the cervix secondary to increased vaginal secretions, mucus or discharge at this point in pregnancy. Salaets et al. (9) found an 11% prevalence of difficulty with vaginal mucus during use of the PS but did not fully explain how this may have impacted upon triplicate results and the final cohort used for analysis. Badir et al. (7) included the 1 st measurement only in their reported analysis and didn’t comment on obtainability of triplicate measurements. In the CASPAR study we have found a 14% prevalence of issues achieving an adequate seal for triplicate measurements, however only 5% prevented no measurements at all. We were able to achieve at least one CS reading in 90% of our cohort, but triplicate measurements in only 78%. The protocol requirement for triplicate measurements excludes 12% of the cohort with at least one available CS measurement. If this rule was applied clinically, it would mean 12% of the patients having this assessment performed prior to IOL would obtain results that could not be used. In comparison 100% of participants or patients can achieve a documented Bishop score. By combining our obtainability and reliability findings, we were able to challenge the requirement for triplicate measurements when using the PS in either a study protocol or clinical setting. Our reliability analysis shows that despite observing differences in sequential measurements on each participant, the results remained strongly correlated and consistent across different combinations (e.g., first, second and third; highest vs lowest; first measurement achieved vs. mean of all available). Given the observed difficulty obtaining triplicate results in the entire cohort, but ability to achieve at least one CS measurement, the reliability analysis supports the recommendation to use first CS measurement achieved during the assessment with the PS as the final CS result for that participant. This would improve the proportion of women with a meaningful result from 78% to 90%. Needing only one CS measurement will also reduce the duration required for CS assessment and therefore reduce speculum placement duration. This could potentially improve other factors that affect acquisition of results during this study procedure, such as tolerability of speculum and participant experience. 4.2 Strengths and Limitations The study design was pragmatic to its clinical setting to assess its’ direct potential for implementation in future clinical practice. Data collection methods were robust and able to meet the requirements of the core outcome set for trials on IOL, again reflecting the ability of the study protocol to be upscaled to a larger definitive trial design. PPI group involvement took place throughout the study from protocol writing to dissemination of results and ensured the focus of study outcomes were centred to the patient’s needs. This study is limited by its size. Although this cohort size was adequate for ascertaining feasibility, which was the primary objective, it was not powered for clinical outcome associations and can therefore not confirm clinical utility of the PS for CS assessments in the IOL population. However, our confirmation of feasibility and acceptability can inform, appropriately powered, larger, studies that could answer the question of predictive acumen for IOL clinical outcomes. 4.3 Conclusion This is the first study to explore the feasibility of using the PS for CS assessments in the IOL clinical setting. Our findings support the ability to adequately recruit to a clinical study using this new device within an NHS setting, confirms acceptability of this cervical assessment tool at the time of IOL in this population and provides clinical data to recommend the use of single CS measurements taken using the PS to improve measurement obtainability in this cohort. These findings confirm feasibility of the PS for cervical assessment prior to IOL in term, primiparous women. At this time, no associations between pre-induction CS assessment with the PS and outcomes of IOL have been demonstrated. Importantly, we also found no association between pre-induction Bishop score and IOL outcomes. 4.4 Practical Recommendations (clinical and research) This feasibility study has confirmed that first time mothers facing the prospect of IOL want to know if the IOL process will achieve a vaginal delivery. Women were prepared to undergo a novel cervical assessment tool at the time of their IOL to try and answer this question. This confirms that predicting the mode of delivery following IOL is still a valid and relevant concern for our term obstetric population as well as having value for the organisation of hospital services. Further research within this field needs to keep this outcome at the centre of the question the research is going to answer. We feel the feasibility of this device in this setting has been proven by the CASPAR study. If any further studies using the PS were conducted, it would need to be powered to give a definitive answer for the clinical outcomes associated with IOL. We would also recommend using the first CS measurements obtained using the PS as the final result for each participant. Contribution to Authorship Elizabeth Medford : conceptualization, methodology, validation, formal analysis, data curation, writing- original draft, visualisation, project administration. Steven lane : methodology, formal analysis, writing- review and editing. Angharad Care : conceptualisation, methodology, writing- review and editing, funding acquisition, project administration, supervision. Andrew Sharp conceptualisation, methodology, writing- reviewing and editing, project administration, supervision. Acknowledgments We would like to thank all the women who participated in this study and the staff at Liverpool Women’s Hospital who helped facilitate this study. The terms “women” and “mother” are used in this manuscript to refer to all those who are pregnant and give birth. The authors acknowledge that not all people who are pregnant and give birth will identify themselves as women. Ethics Approval This study received approval from the Seasonal Research Ethics Committee, UK (23/LO/0627). All study participants have given written informed consent prior to entry to the study and were aware that participation is completely voluntary. Conflicts of Interest The authors declare no conflicts of interest. Pregnolia AG provided the device for use in this study and provided financial aid to fund a Clinical research Fellow to undertake this research. Pregnolia AG had no role in the study design, decision to publish or preparation of the manuscript.

1. England N. NHS Maternity Statistics, England, 2023-24. . In: Health. Do, editor. 2023-24.2. (NICE) NIfHaCE. Inducing Labour NG207. 2021.3. Faltin-Traub EF, Boulvain M, Faltin DL, Extermann P, Irion O. Reliability of the Bishop score before labour induction at term. Eur J Obstet Gynecol Reprod Biol. 2004;112(2):178-81.4. Kolkman DG, Verhoeven CJ, Brinkhorst SJ, van der Post JA, Pajkrt E, Opmeer BC, Mol BW. The Bishop score as a predictor of labor induction success: a systematic review. Am J Perinatol. 2013;30(8):625-30.5. Meier K, Parrish J, D’Souza R. Prediction models for determining the success of labor induction: A systematic review. Acta Obstet Gynecol Scand. 2019;98(9):1100-12.6. Badir S, Bernardi L, Feijo Delgado F, Quack Loetscher K, Hebisch G, Hoesli I. Aspiration technique-based device is more reliable in cervical stiffness assessment than digital palpation. BMC Pregnancy Childbirth. 2020;20(1):391.7. Badir S, Mazza E, Zimmermann R, Bajka M. Cervical softening occurs early in pregnancy: characterization of cervical stiffness in 100 healthy women using the aspiration technique. Prenat Diagn. 2013;33(8):737-41.8. Badir S, Bajka M, Mazza E. A novel procedure for the mechanical characterization of the uterine cervix during pregnancy. J Mech Behav Biomed Mater. 2013;27:143-53.9. Salaets E, Richter J. Prediction of duration of labor based on biomechanical measurements of the cervix: A preliminary study. Eur J Obstet Gynecol Reprod Biol. 2020;244:25-30.10. Stone J, House M. Measurement of cervical softness before cerclage placement with an aspiration-based device. Am J Obstet Gynecol MFM. 2023;5(4):100881.11. Breuking S, Oudijk MA, van Eekelen R, de Boer MA, Pajkrt E, Hermans F. Assessment of cervical softening and the prediction of preterm birth (STIPP): protocol for a prospective cohort study. BMJ Open. 2023;13(11):e071597.12. Medford E, Lane S, Sharp A, Care A. The PRECISION study protocol: Can cervical stiffness in the second trimester predict preterm birth in high-risk singleton pregnancies? A feasibility, cohort study. PLoS One. 2025;20(2):e0316297.13. Medford E, Lane S, Merriel A, Sharp A, Care A. The CASPAR study protocol. Can cervical stiffness predict successful vaginal delivery after induction of labour? a feasibility, cohort study. PLoS One. 2025;20(1):e0311324.14. AG P. Pregnolia System Cervical Stiffness Assessment Instructions for Use. In: AG P, editor. wwwpregnoliacom/instructions2022.15. Grobman WA, Rice MM, Reddy UM, Tita ATN, Silver RM, Mallett G, et al. Labor Induction versus Expectant Management in Low-Risk Nulliparous Women. N Engl J Med. 2018;379(6):513-23.16. Walker KF, Bugg GJ, Macpherson M, McCormick C, Grace N, Wildsmith C, et al. Randomized Trial of Labor Induction in Women 35 Years of Age or Older. N Engl J Med. 2016;374(9):813-22.17. Abdullah ZHA, Chew KT, Velayudham VRV, Yahaya Z, Jamil AAM, Abu MA, et al. Pre-induction cervical assessment using transvaginal ultrasound versus Bishops cervical scoring as predictors of successful induction of labour in term pregnancies: A hospital-based comparative clinical trial. PLoS One. 2022;17(1):e0262387. Information & Authors Information Version history Copyright This work is licensed under a Non Exclusive No Reuse License. Collection

Authors Metrics & Citations Metrics Article Usage 228views 120downloads Citations Download citation Elizabeth Medford, Steven Lane, Angharad Care, et al. The CASPAR study. A feasibility cohort study using the Pregnolia System for objective cervical stiffness assessment prior to primiparous induction of labour.. Authorea. 07 November 2025. DOI: https://doi.org/10.22541/au.176249360.02315657/v1 DOI: https://doi.org/10.22541/au.176249360.02315657/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.