Title: Developing and Testing a Clinical Grade Magnetic Impedance Spectroscopy Device for Cervical Assessment to Predict Preterm Birth.
Funder: Department of Health and Social Care

Abstract: We developed the MIS device to improve on the Mark V EIS probe that demonstrated lower cervical resistivity values in mid-trimester in preterm-delivered women [1]. The Mark 1 MIS device measures tissue electrical conductivity without the need for surface electrodes as required for EIS. The system induces and senses magnetic field perturbation of tissue to determine its electrical conductivity. The device is equipped with improved ergonomics, better application of the probe to the cervix, and enhanced data acquisition. It has an inbuilt ferrite core that shields out potentially confounding signals generated by surrounding vaginal tissue (see supporting documentation for technical details). The technical plan. We will improve the device to take repeated cervical measurements by: Enhancing device specifications supported by further computational modeling Improving the electronics that drive the apparatus Investigate strategies to reduce system drift during measurements: holding the probe at body temperature, mechanically moving the probe ferrite assembly to chop the signal, construct the system using extremely low thermal expansion parts. Develop additional techniques to ensure that the probe is held correctly in consistent relationship to the cervix. This will include new software to give the operator feedback and improve visualisation. Whilst developing the current MIS apparatus, we have been simultaneously generating technical files that will facilitate formal applications during this proposed project to the MHRA to provide regulatory approvals towards CE Marking, preparatory to larger scale multicentre clinical trials. Proposed pilot clinical studies. We will obtain pilot data to determine whether cervical resistivity by MIS predicts PTB, and apply for regulatory approvals towards a larger scale multicentre clinical trial: we will measure cervical resistivity by MIS, compared to transvaginal ultrasound cervical length (TVUS CL) and quantitative cervicovaginal fluid fetal fibronectin (fFN), in 60 pregnant women at high risk of PTB but no symptoms of preterm labour (at 20-22 weeks and at 26-28 weeks gestation), and 60 women presenting to the labour ward (at 20-34 weeks) with symptoms of, but not in established (uterine contractions less than 3 in 10 mins, cervix The research plan. The research project will be undertaken in three work packages (WP) over 36 months. WP1 (duration 30 months, M1-30, Lead TJH) will involve optimizing device hardware and software, culminating in an application for MHRA clinical evaluation by 18 months. WP2 (duration 30 months, M1-30, Lead DA) will overlap with WP1 and ensure the derivation of preliminary data that will a) inform the MHRA application for regulatory approvals and b) enable further optimization of the probe hardware and software, followed by studies of the clinical cohorts detailed above. WP3 (duration 18 months, M19-36, Lead SW/SD/DA). We will analyse the data obtained, supervised by SW (statistician), undertake a cost-effectiveness analysis of the clinical device prototype (Lead SD), and develop a multicentre study grant application to assess MIS in prenatal screening for PTB. Analysis plan. We will compare the area under the ROC curves for tissue resistivity by MIS, TVUS CL, and fFN at study time points, for PTB (primary outcome: delivery 0.8, and also, improve the predictive value of TVUS CL/fibronectin. The project milestones and deliverables are detailed below and in the attached Gantt chart.

Lay abstract: Every year, globally, about 15 million babies are born preterm (before 37 weeks). This number is rising[3]. Preterm birth (PTB) complications are the leading cause of death among children under 5 years of age, responsible for nearly 1 million deaths annually. PTB poses a strain on scarce health resources: each very premature baby costs tens of thousands of pounds in newborn care. One in 4 babies born before 28 weeks develop neurological impairment, a parent often having to give up work to care for an affected child. The prediction and prevention of PTB remain challenging because current methods, such as measuring the cervix by ultrasound, have limited accuracy. If a technique that reliably predicts PTB could be developed, there are care measures that can be employed to delay birth to reduce long-term disability/impairment. We have been studying whether we can detect the changes in cervical tissue structure and composition that precede PTB by using very low current Electrical Impedance Spectroscopy(EIS). We recently showed that women at high risk of PTB (history of previous PTB), who deliver preterm, including delivery before 28 weeks gestation, have lower cervical resistance" in mid-pregnancy than those who deliver at term. With NIHR funding, we have developed a new device, based on a technique called magnetic impedance spectroscopy (MIS), that should address limitations of the EIS device for assessing PTB risk. We now want to refine the new MIS device by minimising the signals it receives from other tissues around the cervix and making its measurements at internal body temperature more stable. We will also conduct clinical experiments to test whether it predicts PTB better than the previous EIS device, and check whether pregnant women find its use acceptable. This information will allow us to obtain UK regulatory approval to test the device in larger trials."

Research activity codes: 4.2 EVALUATION OF MARKERS AND TECHNOLOGIES;4.1 DISCOVERY AND PRECLINICAL TESTING OF MARKERS AND TECHNOLOGIES
Health categories: REPRODUCTIVE HEALTH AND CHILDBIRTH