Improving uptake of perinatal autopsy

PURPOSE OF REVIEW: Uptake of perinatal autopsy has declined in the West over the past 30 years, largely because of reduced parental acceptance of a traditional invasive autopsy. Several studies have recently investigated the decline to identify the key factors and how they may be mitigated. RECENT FINDINGS: Three main themes were identified that have been found to improve uptake of perinatal autopsy: improved communication, in particular ensuring the consent process was conducted as a conversation with time spent talking through the procedure and allowing time for questions; health professional training to ensure staff discussing autopsy with parents have adequate understanding of the procedure and are able to convey confidence and empathy; and availability of less invasive autopsy, including noninvasive as well as minimally invasive options. These should be offered alongside standard autopsy, which some parents may still prefer. SUMMARY: This review highlights that the discussions that take place, and the options that are available to parents, can profoundly impact whether or not they consent to autopsy investigation. Further research should focus on the impact of offering less invasive options as well as evaluating the training and support materials that have recently been developed

Health professionals’ and coroners’ views on less invasive perinatal and paediatric autopsy: a qualitative study

OBJECTIVE: To assess health professionals’ and coroners’ attitudes towards non-minimally and minimally invasive autopsy in the perinatal and paediatric setting. METHODS: A qualitative study using semistructured interviews. Data were analysed thematically. RESULTS: Twenty-five health professionals (including perinatal/paediatric pathologists and anatomical pathology technologists, obstetricians, fetal medicine consultants and bereavement midwives, intensive care consultants and family liaison nurses, a consultant neonatologist and a paediatric radiologist) and four coroners participated. Participants viewed less invasive methods of autopsy as a positive development in prenatal and paediatric care that could increase autopsy rates. Several procedural and psychological benefits were highlighted including improved diagnostic accuracy in some circumstances, potential for faster turnaround times, parental familiarity with imaging and laparoscopic approaches, and benefits to parents and faith groups who object to invasive approaches. Concerns around the limitations of the technology such not reaching the same levels of certainty as full autopsy, unsuitability of imaging in certain circumstances, the potential for missing a diagnosis (or misdiagnosis) and de-skilling the workforce were identified. Finally, a number of implementation issues were raised including skills and training requirements for pathologists and radiologists, access to scanning equipment, required computational infrastructure, need for a multidisciplinary approach to interpret results, cost implications, equity of access and acceptance from health professionals and hospital managers. CONCLUSION: Health professionals and coroners viewed less invasive autopsy as a positive development in perinatal and paediatric care. However, to inform implementation a detailed health economic analysis and further exploration of parental views, particularly in different religious groups, are required

A pragmatic evidence-based approach to post-mortem perinatal imaging

Post-mortem imaging has a high acceptance rate amongst parents and healthcare professionals as a non-invasive method for investigating perinatal deaths. Previously viewed as a 'niche' subspecialty, it is becoming increasingly requested, with general radiologists now more frequently asked to oversee and advise on appropriate imaging protocols. Much of the current literature to date has focussed on diagnostic accuracy and clinical experiences of individual centres and their imaging techniques (e.g. post-mortem CT, MRI, ultrasound and micro-CT), and pragmatic, evidence-based guidance for how to approach such referrals in real-world practice is lacking. In this review, we summarise the latest research and provide an approach and flowchart to aid decision-making for perinatal post-mortem imaging. We highlight key aspects of the maternal and antenatal history that radiologists should consider when protocolling studies (e.g. antenatal imaging findings and history), and emphasise important factors that could impact the diagnostic quality of post-mortem imaging examinations (e.g. post-mortem weight and time interval). Considerations regarding when ancillary post-mortem image-guided biopsy tests are beneficial are also addressed, and we provide key references for imaging protocols for a variety of cross-sectional imaging modalities

An integrative view of mammalian seasonal neuroendocrinology

This is the peer reviewed version of the following article: Dardente, H., Wood, S.H., Ebling, F. & Sáenz de Miera, C. (2019). An integrative view of mammalian seasonal neuroendocrinology. Journal of neuroendocrinology. Journal of Neuroendocrinology, 31(5), e12729, which has been published in final form at https://doi.org/10.1111/jne.12729. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.Seasonal neuroendocrine cycles that govern annual changes in reproductive activity, energy metabolism and hair growth are almost ubiquitous in mammals that have evolved at temperate and polar latitudes. Changes in nocturnal melatonin secretion regulating gene expression in the pars tuberalis (PT) of the pituitary stalk are a critical common feature in seasonal mammals. The PT sends signal(s) to the pars distalis of the pituitary to regulate prolactin secretion and thus the annual moult cycle. The PT also signals in a retrograde manner via thyroid‐stimulating hormone to tanycytes, which line the ventral wall of the third ventricle in the hypothalamus. Tanycytes show seasonal plasticity in gene expression and play a pivotal role in regulating local thyroid hormone (TH) availability. Within the mediobasal hypothalamus, the cellular and molecular targets of TH remain elusive. However, two populations of hypothalamic neurones, which produce the RF‐amide neuropeptides kisspeptin and RFRP3 (RF‐amide related peptide 3), are plausible relays between TH and the gonadotrophin‐releasing hormone‐pituitary‐gonadal axis. By contrast, the ways by which TH also impinges on hypothalamic systems regulating energy intake and expenditure remain unknown. Here, we review the neuroendocrine underpinnings of seasonality and identify several areas that warrant further research

"The communication and support from the health professional is incredibly important": A qualitative study exploring the processes and practices that support parental decision-making about postmortem examination

Background Consent rates for postmortem (PM) examination in the perinatal and paediatric setting have dropped significantly in the United Kingdom, the United States, and the Western Europe. We explored the factors that act as facilitators or barriers to consent and identified processes and practices that support parental decision‐making. Methods A qualitative study conducted with bereaved parents, parent advocates, and health care professionals in the United Kingdom. Analysis was conducted on 439 free‐tect comments within a cross‐sectional survey, interviews with a subset of 20 survey respondents and 25 health professionals, and a focus group with five parent advocates. Results Three broad parental decision‐making groups were identified: 1, “Not open to postmortem examination”; 2, “Consent regardless of concerns”; and 3, “Initially undecided.” Decisional drivers that were particularly important for this “undecided” group were “the initial approach,” “adjustment and deliberation,” “detailed discussion about the procedure,” and “formal consent.” The way in which these were managed by health care staff significantly impacted whether those parents' consented to PM, particularly for those who are ambivalent about the procedure. Conclusions We propose a set of recommendations to improve the way PM counselling and consent is managed. Adopting such measures is likely to lead to improved family experience and more consistent and high‐quality discussion regarding PM

Factors Affecting Uptake of Postmortem Examination in the Prenatal, Perinatal and Paediatric Setting; a Systematic Review

BACKGROUND: Postmortem examination is the single most useful investigation in providing information to parents about why their baby or child died. Despite this, uptake remains well below the recommended 75%. OBJECTIVE: To address the question 'what are the barriers and motivators to perinatal, prenatal and paediatric PM examination?' SEARCH STRATEGY: Key databases including Pubmed and CINAHL; Cochrane library, websites of relevant patient organisations, hand search of key journals, first and last authors and references. SELECTION CRITERIA: Peer reviewed qualitative, quantitative or mixed methods research examining factors affecting uptake or decline of perinatal or paediatric post-mortem examination. DATA COLLECTION AND ANALYSIS: Narrative synthesis; findings were compared across studies to examine interrelations. MAIN RESULTS: Seven major themes describing barriers to postmortem uptake were identified: Dislike of invasiveness, practicalities of the procedure, organ retention issues, protective parenting, communication and understanding, religion and culture and professional or organisational barriers. Six major themes related to factors which facilitated parental consent were identified: desire for information, contributing to research, coping and well-being, respectful care, minimally invasive options and policy and practice. There were a number of themes in the literature that reflected best practice. CONCLUSION: Findings highlight the need for better health professional education and the fact some concerns may be mitigated if less invasive methods of post-mortem were routinely available. New consent packages and codes of practice may have a positive impact on perception of examination after death. The landscape is changing; further research is necessary to assess the impact on postmortem uptake rates. This article is protected by copyright. All rights reserved

Paw Morphology in the Domestic Guinea Pig (Cavia porcellus) and Brown Rat (Rattus norvegicus).

Mammals have adapted to different habitats, food types and modes of locomotion, which are reflected in a diverse range of paw morphologies. While the behaviour of rats and guinea pigs is well-defined, especially in terms of their locomotor and foraging behaviours, the anatomy of their foot pads has not yet been explored and compared. This study investigated adaptations in paw morphology in the domestic guinea pig (Cavia porcellus) and the brown rat (Rattus norvegicus). We predicted that rat paws would display adaptations associated with paw dexterity for handling prey items and climbing; whereas guinea pig paws would support mechanical pressure absorption for a herbivorous, sedentary and terrestrial lifestyle. Using histology techniques and scanning electron microscope, we show that rat paws have many small, deformable pads that are relatively spaced out to enable movement. The pads are clustered towards the anterior of the foot, which coincides with where the most force occurs during locomotion, as rats walk on their toes and towards the front of their paw. Guinea pigs had fewer and larger pads and the posterior pad of the forepaw was textured and contained cartilage, which may act to reduce friction and compression during standing and locomotion. We suggest that differences in paw morphology in rat and guinea pig are associated with loading during locomotion as well as paw mobility. Examining paw morphology and movement abilities in more species will give further insights in to the evolution of locomotor adaptations and paw dexterity in rodents. This article is protected by copyright. All rights reserved

IRES-Mediated Translation of Utrophin A Is Enhanced by Glucocorticoid Treatment in Skeletal Muscle Cells

Glucocorticoids are currently the only drug treatment recognized to benefit Duchenne muscular dystrophy (DMD) patients. The nature of the mechanisms underlying the beneficial effects remains incompletely understood but may involve an increase in the expression of utrophin. Here, we show that treatment of myotubes with 6α−methylprednisolone-21 sodium succinate (PDN) results in enhanced expression of utrophin A without concomitant increases in mRNA levels thereby suggesting that translational regulation contributes to the increase. In agreement with this, we show that PDN treatment of cells transfected with monocistronic reporter constructs harbouring the utrophin A 5′UTR, causes an increase in reporter protein expression while leaving levels of reporter mRNAs unchanged. Using bicistronic reporter assays, we further demonstrate that PDN enhances activity of an Internal Ribosome Entry Site (IRES) located within the utrophin A 5′UTR. Analysis of polysomes demonstrate that PDN causes an overall reduction in polysome-associated mRNAs indicating that global translation rates are depressed under these conditions. Importantly, PDN causes an increase in the polysome association of endogenous utrophin A mRNAs and reporter mRNAs harbouring the utrophin A 5′UTR. Additional experiments identified a distinct region within the utrophin A 5′UTR that contains the inducible IRES activity. Together, these studies demonstrate that a translational regulatory mechanism involving increased IRES activation mediates, at least partially, the enhanced expression of utrophin A in muscle cells treated with glucocorticoids. Targeting the utrophin A IRES may thus offer an important and novel therapeutic avenue for developing drugs appropriate for DMD patients

Minimally invasive autopsy for fetuses and children based on a combination of post-mortem MRI and endoscopic examination: a feasibility study

BACKGROUND: Less invasive perinatal and paediatric autopsy methods, such as imaging alongside targeted endoscopy and organ biopsy, may address declining consent rates for traditional autopsy, but their acceptability and accuracy are not known. OBJECTIVES: The aims of this study were to provide empirical data on the acceptability and likely uptake for different types of autopsy among key stakeholders (study 1); and to analyse existing autopsy data sources to provide estimates of the potential efficacy of less invasive autopsy (LIA) and its projected utility in clinical practice (study 2). REVIEW METHODS: Study 1: this was a mixed-methods study. Parents were involved in research design and interpretation of findings. Substudy 1: a cross-sectional survey of 859 parents who had experienced miscarriage, termination of pregnancy for fetal anomaly, stillbirth, infant or child death, and interviews with 20 responders. Substudy 2: interviews with 25 health professionals and four coroners. Substudy 3: interviews with 16 religious leaders and eight focus groups, with 76 members of the Muslim and Jewish community. Study 2: a retrospective analysis of national data in addition to detailed information from an existing in-house autopsy database of > 5000 clinical cases that had undergone standard autopsy to determine the proportion of cases by clinical indication group for which tissue sampling of specific internal organs significantly contributed to the diagnosis. RESULTS: Substudy 1: 91% of participants indicated that they would consent to some form of LIA, 54% would consent to standard autopsy, 74% to minimally invasive autopsy (MIA) and 77% to non-invasive autopsy (NIA). Substudy 2: participants viewed LIA as a positive development, but had concerns around the limitations of the technology and de-skilling the workforce. Cost implications, skills and training requirements were identified as implementation challenges. Substudy 3: religious leaders agreed that NIA was religiously permissible, but MIA was considered less acceptable. Community members indicated that they might consent to NIA if the body could be returned for burial within 24 hours. Study 2: in 5-10% of cases of sudden unexplained death in childhood and sudden unexplained death in infants, the final cause of death is determined by routine histological sampling of macroscopically normal organs, predominantly the heart and lungs, and in this group routine histological sampling therefore remains an important aspect of investigation. In contrast, routine histological examination of macroscopically normal organs rarely (< 0.5%) provides the cause of death in fetal cases, making LIA and NIA approaches potentially highly applicable. LIMITATIONS: A key limitation of the empirical research is that it is hypothetical. Further research is required to determine actual uptake. Furthermore, because of the retrospective nature of the autopsy data set, findings regarding the likely contribution of organ sampling to final diagnosis are based on extrapolation of findings from historical autopsies, and prospective data collection is required to validate the conclusions. CONCLUSIONS: LIA is viable and acceptable (except for unexplained deaths), and likely to increase uptake. Further health economic, performance and implementation studies are required to determine the optimal service configuration required to offer this as routine clinical care. FUNDING: The National Institute for Health Research Health Technology Assessment programme