Title: Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic autopsy examination; Feasibility study
Funder: Department of Health and Social Care

Abstract: Extensive literature indicates that Perinatal and Paediatric post-mortem examination (autopsy) provides additional information in around one third of cases, (whilst also providing important governance, audit and other roles in the remainder), with significant implications for genetic counselling, management of future pregnancies or other family members. However, for the majority of parents for whom the findings of a post-mortem examination may be beneficial, traditional standard open autopsy is unacceptable, with no alternative currently offered. Uptake of consented perinatal and paediatric post-mortem examinations in the United Kingdom is only 15-45% depending on patient group. The option of less invasive autopsy based on post-mortem magnetic resonance imaging (PMMRI), has recently been addressed in 400 cases, with reported high (>90%) concordance between the less invasive approach and full traditional autopsy. Nevertheless, in many cases, especially paediatric deaths, diagnosis could only be made following specific investigation of tissue samples. To address this issue whilst ensuring that the approach is acceptable to parents, the minimally invasive perinatal autopsy (MIA) has been developed based on a combination of PM MRI and endoscopic assisted tissue sampling. This feasibility study will provide data regarding the potential applicability, usefulness and acceptability of MIA in this clinical setting using a variety of methods including; 1 Analysis of existing perinatal autopsy data. This will include analysis of National perinatal mortality statistics, retrospective review of a unique, large, catalogued autopsy database from a specialist perinatal autopsy centre (containing >4500 cases), and retrospective review of a single centre experience of MIA. These findings will determine the patient groups for which MIA with tissue sampling would be most applicable, will provide information to allow extrapolation of potential usefulness and feasibility in clinical care nationally, and will provide pilot data regarding the utility of MIA in real clinical practice. 2-Assessment of patient and public acceptability. Using several methods we will assess the acceptability of MIA with and without tissue sampling for patients and the public in order to inform potential uptake of the technique for subsequent performance of a larger clinical trial or evaluation of implementation into clinical practice. Approaches will include several established methods within the field of qualitative healthcare research including; use of structured questionnaires, interviews with parents and public, and performance of focus groups to ensure inclusion of a range of demographic, clinical, ethnic and religious groups. The study will recruit parents from two specialist UK centres. Based on these findings, trajectory to either a clinical trial to formally assess MIA with endoscopic guided tissue sampling, or a formal implementation and cost-effectiveness study, will be produced including design options and estimates of sample size. The applicants and the associated centre have an outstanding, Internationally recognised track record in this area, have expertise in performance of both less invasive perinatal autopsy and qualitative healthcare research in the perinatal period (with associated parental anxieties), and are intimately acquainted with the philosophy and strategy of NIHR, therefore are uniquely placed to carry out this project.

Lay abstract: The death of a baby or child, either during the pregnancy (miscarriage/stillbirth), after birth (infant death), following termination of pregnancy for abnormality (ToP), or in childhood, leaves parents with important questions such as ‘why did this happen?’, ‘what are the chances of it happening again?’ and ‘will it affect anyone else in the family?’. For many of these questions, answers can only be provided by carrying out a post-mortem or autopsy examination, which gives answers in 30-50% of cases. Autopsy often involves a large procedure like an operation in which all parts of the body can be examined in detail, including the internal organs, which requires a large incision to be made on the body. For a range of reasons, including moral and religious, the majority of parents do not currently agree to an autopsy being carried out: the most common reason given is dislike of the large incision being made on the body and feeling that the child has suffered enough, in addition to concerns regarding organ removal and retention. Recently, it has been shown that the information needed to answer the parents' questions can be obtained without needing a standard autopsy. This alternative approach involves careful examination of the medical notes, performing a special type of imaging called MRI (like an detailed X Ray) of the baby, and carrying out tests that do not require any cuts to be made to the baby, such as blood tests and examining the placenta for example. This approach has been shown to obtain the necessary information in up to 90% of cases, depending on the circumstances, but is not suitable for ALL types of death, since in some cases further special tests are needed which require tissue samples. Instead of a large incision, it is now possible to take these samples by using a ‘keyhole surgery’ approach through a much smaller incision. The aim of this study is therefore to work out how many, and which types of patient, may be suitable for this alternative autopsy approach, and most importantly to find out how parents and families feel about it, specifically whether they feel it would be more acceptable than standard autopsy. If so, the data obtained would be used to decide whether a large study comparing the standard to the new approach is required, and how such a large study should be performed.

Research activity codes: 8.1 ORGANISATION AND DELIVERY OF SERVICES
Health categories: GENERIC HEALTH RELEVANCE;REPRODUCTIVE HEALTH AND CHILDBIRTH