Exploring feasibility of the Pregnolia System for objective cervical stiffness assessment in different high-risk obstetric groups throughout pregnancy

Cervical remodelling is a complex process that evolves throughout pregnancy and allows the cervix to change from a long, firm and closed structure keeping the developing fetus within the womb, to a dilated passage at the end of labour to enable a vaginal birth. Establishing the extent of cervical remodelling in pregnancy can help clinicians anticipate important pregnancy outcomes such as inadequate cervical remodelling leading to prolonged pregnancy or unsuccessful induction of labour, or premature cervical remodelling contributing to preterm birth. Assessment tools available in clinical practice to evaluate cervical remodelling and predict these outcomes remain limited. The Pregnolia System™ is a novel, point-of-care, cervical assessment tool designed to objectively determine cervical stiffness. Preliminary evidence utilising the device in a limited, low-risk pregnant population demonstrated safety, objectivity and provided baseline data for progressive softening throughout pregnancy. However, application in clinically significant cohorts had not been explored at the outset of this thesis. The work presented in this thesis aimed to assess the feasibility of introducing the Pregnolia System™ as a cervical assessment tool within two clinical obstetric cohorts implicated by cervical remodelling: 1) term pregnancy prior to induction of labour & 2) high-risk women for preterm birth during pregnancy. This work has provided original data regarding acceptability, obtainability and reliability of using the Pregnolia System™ within these clinical obstetric settings. The CASPAR study was an observational, cohort study that recruited 100 term pregnant women and assessed feasibility of the Pregnolia System™ as a pre-induction of labour cervical assessment tool, compared to current routine practice of a digital vaginal examination to establish the Bishop Score. Results are outlined within Chapter Three and demonstrated that the Pregnolia System™ is feasible in this setting. In our acceptability profiling the Pregnolia System™ assessment improved upon the Bishop Score examination in participant discomfort scoring (1.20/10 vs 4.94/10) and 92% would agree to have the assessment again. We identified the speculum examination required to facilitate the Pregnolia System™ as the most uncomfortable part of the assessment, and a potential barrier to wider implementation in future clinical practice. The Pregnolia System™ could achieve triplicate cervical stiffness measurements in 78% of the cohort. Reliability analysis demonstrated that using the first measurement achieved maintained consistency (Cronbach’s Alpha 0.977) whilst improving measurement obtainability to 90% of the cohort. Our recommendation moving forward is to include first measurement achieved with the Pregnolia System™ as final measurement for analysis or clinical correlation in future studies utilising this device. We assessed feasibility within preterm birth cohorts through two further clinical studies; PRECISION & SPRUCE. Results from these two observational studies are described in Chapter Four. The PRECISION feasibility study focused on singleton pregnancies and recruited 55 women high-risk for preterm birth from a dedicated preterm birth clinic. Cervical stiffness assessment using the Pregnolia System™ was undertaken at three study visits during the second trimester, alongside cervical length measurements as part of routine preterm birth surveillance. In terms of acceptability, this high-risk cohort were more challenging to recruit, and we achieved a final recruitment rate of 58% which was 92% of the original target sample size. Of those recruited, participant experience questionnaires confirmed acceptability of the assessment with 68% finding it comparable to the experience of a cervical length scan and in only 10% of subsequent study visits was the assessment tool declined. Comparatively, Pregnolia System™ fidelity was improved in this cohort with triplicate cervical stiffness measurements achieved in 98% of study visits with consistent reliability (Cronbach’s Alpha 0.898). This was the first clinical study undertaken by our research team and an operator learning curve to obtain triplicate measurements was identified when first using the Pregnolia System™ clinically. The SPRUCE study provided gifted cervical stiffness measurements using the Pregnolia System™ from a parallel research team at the study site undertaking a preterm birth study focused within a twin pregnancy cohort. Our twin cervical stiffness results are described in Chapter Four and outline the largest twin pregnancy dataset using the Pregnolia System™ available to date. Findings suggest that cervical stiffness early in the second trimester is similar across twin pregnancies and both high-risk and low-risk singleton pregnancies, providing preliminary data to support universal diagnostic cervical stiffness criteria across the different groups. In conclusion, this comprehensive feasibility assessment of the Pregnolia System™ has confirmed acceptability, obtainability and reliability for cervical stiffness assessment for the purposes in pre induction assessment and asymptomatic, high-risk preterm birth screening. We recommend ongoing application of the device to utilise first measurement obtained rather than triplicate measurements to: maximise obtainability, maintain reliability and theoretically improve acceptability. Although no association between cervical stiffness obtained by the Pregnolia System™ and clinical outcomes could be determined in our studies due to feasibility design, this thesis has provided the foundations required to support future clinical prediction studies to assess utility of the Pregnolia System™ for important clinical outcomes in these cohorts.