Outcome monitoring and risk stratification after cardiac procedure in neonates, infants, children and young adults born with congenital heart disease: protocol for a multicentre prospective cohort study (Children OMACp).

INTRODUCTION: Congenital heart disease (CHD) represents the most common birth defect, affecting from 0.4% to 1.2% of children born in developed countries. The survival of these patients has increased significantly, but CHD remains one of the major causes of neonatal and childhood death. The aetiology of CHD is complex, with some evidence of both genetic and environmental causes. However, there is still lack of knowledge regarding modifiable risk factors and molecular and genetic mechanisms underlying the development of CHD. This study aims to develop a prospective cohort of patients undergoing cardiac procedures that will bring together routinely collected clinical data and biological samples from patients and their biological mothers, in order to investigate risk factors and predictors of postoperative-outcomes, as well as better understanding the effect of the surgical intervention on the early and long-term outcomes. METHODS AND ANALYSIS: Children OMACp (OMACp, outcome monitoring after cardiac procedure in congenital heart disease) is a multicentre, prospective cohort study recruiting children with CHD undergoing a cardiac procedure. The study aims to recruit 3000 participants over 5 years (2019-2024) across multiple UK sites. Routine clinical data will be collected, as well as participant questionnaires collecting sociodemographic, NHS resource use and quality of life data. Biological samples (blood, urine and surgical waste tissue from patients, and blood and urine samples from biological mothers) will be collected where consent has been obtained. Follow-up outcome and questionnaire data will be collected for 5 years. ETHICS AND DISSEMINATION: The study was approved by the London-Brent Research Ethics Committee on 30 July 2019 (19/SW/0113). Participants (or their parent/guardian if under 16 years of age) must provide informed consent prior to being recruited into the study. Mothers who wish to take part must also provide informed consent prior to being recruited. The study is sponsored by University Hospitals Bristol and Weston Foundation Trust and is managed by the University of Bristol. Children OMACp is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated through peer-reviewed publications, presentation at conference, meetings and through patient organisations and newsletters. TRIAL REGISTRATION NUMBER: ISRCTN17650644.

An evaluation into the use of procalcitonin levels as a biomarker of bacterial sepsis to aid the management of intrapartum pyrexia and chorioamnionitis.

BACKGROUND: Procalcitonin is an established biomarker for bacterial sepsis in the nonpregnant population with better diagnostic and prognostic value for bacterial infections. OBJECTIVE: This study aimed to evaluate whether procalcitonin levels could be used in the diagnosis and management of intrapartum sepsis in women and their neonates suspected of intrapartum bacterial sepsis. STUDY DESIGN: A prospective observational cohort study was conducted at the University Hospitals of Bristol and Weston NHS Foundation Trust. Overall, 117 women and their neonates managed for suspected intrapartum sepsis from June 2020 to October 2020 were included. Procalcitonin levels were measured in addition to routine biomarkers white cell count and C-reactive protein in women and their neonates during the initial septic screen and follow-up blood samples. The placentas underwent detailed histopathology. Maternal and neonatal parameters were used to categorize cases into "high-suspicion bacterial sepsis," "equivocal bacterial sepsis," and "low-suspicion bacterial sepsis." The Kruskal-Wallis test was used to compare categories with biomarker values and placental histology scores. RESULTS: Procalcitonin level was increased in 6 women in the initial septic screen sample, compared with 100 women with an increased C-reactive protein level. There was a significant difference in maternal postnatal procalcitonin results between "high-suspicion bacterial sepsis" and "low-suspicion bacterial sepsis" categories (P=.004). Moreover, 71.2% of placentas showed varying degrees of chorioamnionitis. CONCLUSION: In our cohort of women, 94.6% had normal procalcitonin levels while in labor at the time of the septic screen, consistent with the low number of confirmed bacteremia. The result provided a basis that procalcitonin may complement clinical judgment and interpretation of already used prognostic and diagnostic tests, improving patient care in the management of intrapartum sepsis.

Surgical-PEARL protocol: a multicentre prospective cohort study exploring aetiology, management and outcomes for patients with congenital anomalies potentially requiring surgical intervention.

INTRODUCTION: Congenital anomalies affect over 2% of pregnancies. Surgical advances have reduced mortality and improved survival for patients with congenital anomalies potentially requiring surgical (CAPRS) intervention. However, our understanding of aetiology, diagnostic methods, optimal management, outcomes and prognostication is limited. Existing birth cohorts have low numbers of individual heterogenous CAPRS. The Surgical Paediatric congEnital Anomalies Registry with Long term follow-up (Surgical-PEARL) study aims to establish a multicentre prospective fetal, child and biological parent cohort of CAPRS. METHODS AND ANALYSIS: From 2022 to 2027, Surgical-PEARL aims to recruit 2500 patients with CAPRS alongside their biological mothers and fathers from up to 15 UK centres. Recruitment will be antenatal or postnatal dependent on diagnosis timing and presentation to a recruitment site. Routine clinical data including antenatal scans and records, neonatal intensive care unit (NICU) records, diagnostic and surgical data and hospital episode statistics will be collected. A detailed biobank of samples will include: parents' blood and urine samples; amniotic fluid if available; children's blood and urine samples on admission to NICU, perioperatively or if the child has care withdrawn or is transferred for extracorporeal membrane oxygenation; stool samples; and surplus surgical tissue. Parents will complete questionnaires including sociodemographic and health data. Follow-up outcome and questionnaire data will be collected for 5 years. Once established we will explore the potential of comparing findings in Surgical-PEARL to general population cohorts born in the same years and centres. ETHICS AND DISSEMINATION: Ethical and health research authority approvals have been granted (IRAS Project ID: 302251; REC reference number 22/SS/0004). Surgical-PEARL is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated widely through peer-reviewed publication, conference presentations and through patient organisations and newsletters. TRIAL REGISTRATION NUMBER: ISRCTN12557586.

Fifteen-minute consultation: Drowning in children.

Drowning is a significant cause of childhood morbidity and mortality globally. The underlying mechanisms vary with child development and most are modifiable to public health promotion strategies. This article serves to highlight some of the specific considerations for the clinical management of drowning in children, both prehospital and by the in-hospital paediatric resuscitation team. This includes changes to standard advanced paediatric life support in the presence of hypothermia.

Social and behavioural factors in Non-suspicious unexpected death in infancy; experience from metropolitan police project indigo investigation.

BACKGROUND: Risk factors for Sudden Unexpected Death in Infancy (SUDI) are well described, and such cases are now investigated according to standard protocols. In London, Project Indigo of the Metropolitan Police provides a unique, detailed framework for such data collection. We investigate such data to provide a contemporary account of SUDI in a large city and further link data to publically available datasets to investigate interactions with social factors. METHODS: Retrospective analysis of data routinely collected by the Metropolitan Police Service in all cases of non-suspicious SUDI deaths in London during a six year period. RESULTS: SUDI deaths are associated with markers of social deprivation in London. A significant proportion of such deaths are associated with potentially modifiable risk factors such as cigarette smoking and co-sleeping, such behaviour also being associated with social factors, including accommodation issues. CONCLUSIONS: Routinely collected data provide valuable insight into patterns and associations of mortality, with SUDI remaining a significant issue in London. Risk factors include social disadvantage, which may manifest in part by affecting behavioural patterns such as co-sleeping and public health interventions to reduce rates require significant social modification.

Brain weight in sudden unexpected death in infancy: experience from a large single-centre cohort.

AIMS: Published reports of brain weight in sudden infant death syndrome (SIDS) are contradictory, although several have concluded that brain weight is increased in SIDS compared with controls or reference data. This is important as, if brain weight is significantly different, it may be of diagnostic use or provide insights into the aetiology of SIDS. The aim of this study was to use a large series of well-characterized sudden unexpected infant deaths from a single centre to provide definitive data regarding this issue. METHODS: A retrospective review identified 1100 infants who had died suddenly and undergone a comprehensive autopsy at Great Ormond Street Hospital between 1996 and 2011. They were split into two groups: those in whom death could be explained and those whose deaths remained unexplained despite full investigation (SIDS/unexplained sudden unexpected death in infancy). RESULTS: There were 1100 cases of whom 573 (52%) were unexplained and 527 (48%) explained. Multiple regression analysis, which adjusted for sex, age and post-mortem interval, showed no difference in the ratio of brain weight : body weight between those infants dying of explained causes and those in whom no cause could be found. This finding remained true when restricting analysis to those with macroscopically normal brains. CONCLUSIONS: In this large series of infants dying of both explained and unexplained causes, brain weight, once corrected for body weight, did not vary consistently with the cause of death. Brain weight cannot be used as a diagnostic indicator of the cause of death or to inform hypothetical models of the pathogenesis of SIDS.

Potentially preventable infant and child deaths identified at autopsy; findings and implications.

PURPOSE: The purpose of the study was to determine the proportion of pediatric deaths investigated by HM Coronial autopsy which were potentially preventable deaths due to treatable natural disease, and what implications such findings may have for health policies to reduce their occurrence. METHODS: A retrospective study of 1779 autopsies of individuals between 7 days and 14 years of age requested by HM Coroner, taking place in one specialist pediatric autopsy center, was undertaken. Cases were included if they involved a definite natural disease process in which appropriate recognition and treatment was likely to have affected their outcome. Strict criteria were used and cases were excluded where the individual had any longstanding condition which might have predisposed them to, or altered the recognition of, acute illness, or its response to therapy. RESULTS: Almost 8% (134/1779) of the study group were potentially preventable deaths as a result of natural disease, the majority occurring in children younger than 2 years of age. Most individuals reported between 1 and 7 days of symptoms before their death, and the majority had sought medical advice during this period, including from general practitioners within working hours, and hospital emergency departments. Of those who had sought medical attention, around one-third had done so more than once (28%, 15/53). Sepsis and pneumonia accounted for the majority of deaths (46 and 34% respectively), with all infections (sepsis, pneumonia and meningitis) accounting for 110/134 (82%). CONCLUSION: Around 10% of pediatric deaths referred to HM Coroner are potentially preventable, being the result of treatable natural acute illnesses. In many cases medical advice had been sought during the final illness. The results highlight how a review of autopsy data can identify significant findings with the potential to reduce mortality, and the importance of centralized investigation and reporting of pediatric deaths.

The value of postmortem experience in undergraduate medical education: current perspectives.

The autopsy has traditionally been used as a tool in undergraduate medical education, but recent decades have seen a sharp decline in their use for teaching. This study reviewed the current status of the autopsy as a teaching tool by means of systematic review of the medical literature, and a questionnaire study involving UK medical schools. Teachers and students are in agreement that autopsy-based teaching has many potential benefits, including a deeper knowledge of basic clinical sciences, medical fallibility, end of life issues, audit and the "hidden curriculum". The reasons underlying the decline in teaching are complex, but include the decreasing autopsy rate, increasing demands on teachers' time, and confusion regarding the law in some jurisdictions. Maximal use of autopsies for teaching may be achieved by involvement of anatomical pathology technologists and trainee pathologists in teaching, the development of alternative teaching methods using the principles of the autopsy, and clarification of the law. Students gain most benefit from repeated attendance at autopsies, being taught by enthusiastic teachers, when they have been effectively prepared for the esthetic of dissection and the mortuary environment.

Immersion-related deaths in infants and children: autopsy experience from a specialist center.

PURPOSE: To investigate the demographics, circumstances and autopsy findings in infants and children dying following immersion. METHODS: A retrospective review of a pediatric autopsy database at a specialist center over a 16-year period (1995-2010) was undertaken to identify deaths between 7 days and 16 years of age in whom death occurred following immersion. RESULTS: 28 infants and children died following immersion during the study period. 82 % were aged <4 years, with peak age of death between 1 and 2 years. Immersion occurred at home in a bath or private pool in 70 % of cases. There was a lack of direct supervision in all but two cases where the information was recorded (91 %); one of these cases occurred in a public swimming lesson, and in the other the carer was incapacitated. Autopsy findings were non-specific. Facial or subconjunctival petechial hemorrhages were a feature of 18 % of cases. There was increased lung weight, or histological pulmonary edema/intra-alveolar hemorrhage in all but one case. CONCLUSIONS: The data suggest that the majority of pediatric immersion-related deaths were potentially preventable with appropriate supervision. The findings strongly support the role of education regarding adequate carer supervision of infants and children while bathing, particularly in children with underlying conditions such as epilepsy. As private pools and "hot tubs" become more common in the UK and other jurisdictions, specific recommendations such as fencing pools will need to be included in advice to carers. So-called 'dry drowning" appears to be an uncommon mechanism of death in this age group.

Reference ranges for organ weights of infants at autopsy: results of >1,000 consecutive cases from a single centre.

BACKGROUND: Infancy is the most common period for childhood death, including both neonatal deaths from obstetric or medical complications and sudden unexpected infant deaths. The weighing of organs at autopsy is an established process and is recommended in current protocols. However, minimal contemporary data is available regarding reference ranges for organ weights of infants. METHODS: Organ weight data for consecutive infant autopsies over a 14 year period performed at a single tertiary centre, including >1,000 cases, were examined in order to provide up to date reference ranges across this age range, using linear regression modelling and the standard LMS method. RESULTS: 1,525 infant autopsies were analysed, of which 1,190 were subsequently used in the creation of linear regression models prior to performance of the LMS method. Organ weight charts were produced for the 5th, 25th, 50th, 75th and 95th centiles for the heart, lungs, liver, spleen, kidneys, pancreas, thymus gland and adrenal glands. CONCLUSION: This study provides the largest single centre contemporary dataset of infant autopsies allowing provision of up-to-date 'normal' ranges for all major organ weights across this age range.

Sudden unexpected infant deaths associated with car seats.

The purpose of this study was to investigate the frequency, circumstances, demographics, and causes of death of infants dying while seated in car safety seats. A retrospective review of a pediatric autopsy database at a specialist center over a 16-year period was undertaken to identify any infant deaths (aged <1 year), in whom death occurred while seated in a car safety seat. Fourteen car seat-associated deaths were identified from a total of 1,465 coronial infant autopsies (0.96 %). Four involved infants were being appropriately transported in the car seat, all of whom had a medical underlying cause of death (one infection and three congenital heart disease). The majority (10 cases; 70 %) occurred while car seats were being inappropriately used, outside of the car, including as an alternative to a cot or high-chair. Five of these infants died of explained causes, but four deaths remained unexplained after autopsy, and in one no cause of death was available. There were no cases of previously healthy infants dying unexpectedly in a car seat when it was being used appropriately, and in this series there were no cases of traumatic death associated with car seats, either during road traffic accidents, or from falling or being suspended from a car seat. Infant deaths in car seats are rare. These data support the recommendation that car seats be used only for transport and not as alternatives for cots or high-chairs. More research is required to investigate the effect of travel in car seats on infants with underlying conditions. There appears to be no increased risk of unexpected deaths of healthy infants transported appropriately in car seats.

Fatal aspiration of foreign bodies in infants and children.

PURPOSE: To investigate the frequency, circumstances, demographics and autopsy findings of infants and children dying as a result of foreign body aspiration. METHODS: Retrospective review of autopsy cases in children aged between seven days and 18 years, at one specialist centre over a 16-year period, in which death was the result of aspiration of a foreign body. RESULTS: Ten cases were identified out of a total autopsy population of 2165. Only one individual had an underlying diagnosis potentially contributing to aspiration. All but one case involved aspiration of food, with grapes being a feature of four cases. In cases with a prolonged survival interval, autopsy demonstrated bronchopneumonia and hypoxic-ischaemic encephalopathy. In the remaining cases autopsy findings were non-specific. CONCLUSIONS: Fatal aspiration of a foreign body is rare in this population. The cases involve normal children who aspirate food, particularly grapes. There are typically minimal, non-specific findings at autopsy.

Medical student attitudes to the autopsy and its utility in medical education: a brief qualitative study at one UK medical school.

Attending postmortems enables students to learn anatomy and pathology within a clinical context, provides insights into effects of treatment and introduces the reality that patients die. Rates of clinical autopsies have declined and medical schools have cut obligatory autopsy sessions from their curricula making it difficult to assess medical student perceptions of, and attitudes towards, the educational value of autopsy. Our aim was to investigate these perceptions by designing a brief qualitative study comprising nominal technique and focus group discussions with Cambridge Graduate Course students, all of whom had attended autopsies. Three general themes emerged from the focus group discussions: the value of autopsy as a teaching tool and ways the experience could be improved, the initial impact of the mortuary and the autopsy itself, and the "emerging patient"-an emotional continuum running from cadaver to autopsy subject and living patient. Educational benefits of autopsy-based teaching included greater understanding of anatomy and physiology, greater appreciation of the role of other health care professionals and an enhanced appreciation of psycho-social aspects of medical practice. Students suggested improvements for ameliorating the difficult emotional consequences of attendance. We conclude that autopsy-based teaching represents a low-cost teaching technique which is highly valued by students and has application to many diverse medical specialties and skills. However, careful preparation and organization of sessions is required to maximize potential educational benefits and reduce any negative emotional impact.

Myocardial necrosis and infarction in newborns and infants.

PURPOSE: This study aimed to investigate the incidence, and underlying associations, of myocardial necrosis occurring in infants undergoing autopsy. METHODS: An autopsy database containing anonymized details of all infant autopsies conducted at Great Ormond Street Hospital between January 1996 and December 2010 was searched to identify all infants with myocardial necrosis. The characteristics of the necrosis and any underlying associations were reviewed. RESULTS: Myocardial necrosis was recorded in 187 autopsies out of a total of 1,637 (11.4%), and was localized to the papillary muscles, subendocardial region, or trabeculae in 50.8% of cases. The most common associations were congenital heart disease, perinatal asphyxia, coronary artery abnormalities, or sepsis. Three cases of apparently idiopathic myocardial infarction were identified and are described in detail. CONCLUSIONS: Myocardial necrosis is relatively common in infants who die and undergo autopsy, and is most commonly associated with congenital heart disease and perinatal asphyxia. Myocardial infarction can occur in infancy in the absence of any apparent underlying cause: the etiology of these cases is unclear.