Neonatal health care costs of very preterm babies in England: a retrospective analysis of a national birth cohort.

OBJECTIVES: Babies born between 27+0 and 31+6 weeks of gestation represent the largest group of very preterm babies requiring National Health Service (NHS) care; however, up-to-date, cost figures for the UK are not currently available. This study estimates neonatal costs to hospital discharge for this group of very preterm babies in England. DESIGN: Retrospective analysis of resource use data recorded within the National Neonatal Research Database. SETTING: Neonatal units in England. PATIENTS: Babies born between 27+0 and 31+6 weeks of gestation in England and discharged from a neonatal unit between 2014 and 2018. MAIN OUTCOME MEASURES: Days receiving different levels of neonatal care were costed, along with other specialised clinical activities. Mean resource use and costs per baby are presented by gestational age at birth, along with total costs for the cohort. RESULTS: Based on data for 28 154 very preterm babies, the annual total costs of neonatal care were estimated to be £262 million, with 96% of costs attributable to routine daily care provided by units. The mean (SD) total cost per baby of this routine care varied by gestational age at birth; £75 594 (£34 874) at 27 weeks as compared with £27 401 (£14 947) at 31 weeks. CONCLUSIONS: Neonatal healthcare costs for very preterm babies vary substantially by gestational age at birth. The findings presented here are a useful resource to stakeholders including NHS managers, clinicians, researchers and policymakers.

Exploring variation in quality of care and clinical outcomes between neonatal units: a novel use for the UK National Neonatal Audit Programme (NNAP).

Neonatology is a relatively new specialty, in which much of the practice remains non-evidence based. Variation in the quality of care delivered is recognised but measuring this is challenging. One possible indicator of this is variation in practice. For more than a decade, the National Neonatal Audit Project (NNAP) has described variation in practice between UK neonatal units in relation to its annually reviewed audit measures. These are based on evidence based national standards or developed by a consensus method and have become de facto measures defining good quality of neonatal healthcare within the UK. In this article we explore the practicality of using the NNAP to look for associations between quality of care and outcomes. This would not be to validate the measures but could help towards a better understanding of the reasons underlying recognised variation in outcomes, even between neonatal units of the same designation.

Reducing risks for infant mortality in the Midlands, UK: a qualitative study identifying areas for improvement in the delivery of key public health messages in the perinatal period.

BACKGROUND: The Midlands has amongst the highest rates of neonatal and infant mortality in the UK. A public health parent education and empowerment programme, aimed at reducing key risks associated with this mortality was established and evaluated in the region. This was undertaken in an attempt to identify areas for optimal delivery of the public health messages around reducing risks for neonatal and infant mortality. METHOD: Qualitatively assessment, using the software package Dedoose®, was undertaken. This involved analysis of reflections by the programme trainers, after the delivery of their training sessions to parents, families and carers, between 01 January and 31 December 2021. These were intended to capture insights from the trainers on parent, family, carer and staff perspectives, perceptions/misperceptions around reducing risks for infant mortality. Potential areas for improvement in delivery of the programme were identified from this analysis. RESULTS: A total of 323 programmes, comprising 524 parents, family members and carers were offered the programme. Analysis of 167 reflections around these interactions and those of staff (n = 29) are reported. The programme was positively received across parents, families, carers and staff. Four overall themes were identified: (a) reach and inclusion, (b) knowledge, (c) practical and emotional support and (d) challenges for delivery of the programme. Recommendations for improved delivery of the programme were identified, based on qualitative analysis. CONCLUSION: This novel approach to empowerment and education around neonatal public health messaging is a valuable tool for parents, families, carers and staff in the Midlands. Key practical recommendations for enhancing delivery of these critical public health messages were identified from this qualitative research. These are likely to be of value in other parts of the UK and globally.

Neonatal BCG: a time for change.

The BCG vaccination programme in the UK is risk based and has usually been given to eligible babies soon after birth. On advice from the Joint Committee on Vaccination and Immunisation, NHS England and Improvement recently revised the timing of this vaccination to 28 days after birth or soon thereafter. In this article, we highlight the change in timing of vaccination, the rationale and barriers to BCG uptake that this change may pose.

Nutrition and Immunity in Perinatal Hypoxic-Ischemic Injury.

Perinatal hypoxia ischaemia (PHI), acute and chronic, may be associated with considerable adverse outcomes in the foetus and neonate. The molecular and cellular mechanisms of injury and repair associated with PHI in the perinate are not completely understood. Increasing evidence is mounting for the role of nutrients and bioactive food components in immune development, function and repair in PHI. In this review, we explore current concepts around the neonatal immune response to PHI with a specific emphasis on the impact of nutrition in the mother, foetus and neonate.

Managerial thinking in neonatal care: a qualitative study of place of care decision-making for preterm babies born at 27-31 weeks gestation in England.

OBJECTIVES: Preterm babies born between 27 and 31 weeks of gestation in England are usually born and cared for in either a neonatal intensive care unit or a local neonatal unit-with such units forming part of Operational Delivery Networks. As part of a national project seeking to optimise service delivery for this group of babies (OPTI-PREM), we undertook qualitative research to better understand how decisions about place of birth and care are made and operationalised. DESIGN: Qualitative analysis of ethnographic observation data in neonatal units and semi-structured interviews with neonatal staff. SETTING: Six neonatal units across two neonatal networks in England. Two were neonatal intensive care units and four were local neonatal units. PARTICIPANTS: Clinical staff (n=15) working in neonatal units, and people present in neonatal units during periods of observation. RESULTS: In the context of real-world neonatal practice, with multiple (and rapidly-evolving) uncertainties relating to mothers, babies and unit/network capacity, 'best place of care' protocols were only one element of much more complex decision-making processes. Staff often made judgements from a less-than-ideal starting point, and were forced to respond to evolving clinical and organisational factors. In particular, we report that managerial considerations relating to demand and capacity organised decision-making; demand and capacity management was time-consuming and generated various pressures on families, and tensions between staff. CONCLUSIONS: Researchers and policymakers should take account of the organisational context within which place of care decisions are made. The dominance of demand and capacity management considerations is likely to limit the impact of other improvement interventions, such as initiatives to integrate families into the neonatal care provision. Demand and capacity management is an important element of neonatal care that may be overlooked, but significantly organises how care is delivered.

Surrogate decision making in crisis.

Care of the critically ill newborn includes support for the birth mother/parents with regular updates around the clinical condition of the baby, and involvement in discussions around complex decision-making issues . Discussions around continuation or discontinuation of life-sustaining are challenging even in the most straightforward of cases, but what happens when the birth mother is critically unwell? Such cases can lead to uncertainty around who should assume the parental role for these difficult discussions . In this round table discussion, we explore the ethical, moral and legal uncertainties raised by coincident severe maternal and neonatal illness in the context of surrogacy.

Optimising frontline learning and engagement between consultant-led neonatal teams in the West Midlands: a survey on the utility of an augmented simulation training technique.

BACKGROUND: In England, neonatal care is delivered in operational delivery networks, comprising a combination of the Neonatal Intensive Care (NICU), Local-Neonatal (LNU) or Special-Care Units (SCU), based on their ability to care for babies with different degrees of illness or prematurity. With the development of network care pathways, the most premature and sickest are mostly triaged for delivery in services linked to NICU. This has created anxiety for teams in LNU and SCU. Less exposure to sicker babies has resulted in limited opportunities to maintain expertise for when these babies unexpectedly deliver at their centre and thereafter require transfer for care, to NICU. Simultaneously, LNU and SCU teams develop skills in the care of the less ill and premature baby which would also be of benefit to NICU teams. A need for mutual learning through inter-unit multidirectional collaborative learning and engagement (hereafter also called neonatal networking) between teams of different designations emerged. Here, neonatal networking is defined as collaboration, shared clinical learning and developing an understanding of local systems strengths and challenges between units of different and similar designations. We describe the responses to the development of a clinical and systems focussed platform for this engagement between different teams within our neonatal ODN. METHOD: An interactive 1-day programme was developed in the West Midlands, focussing on a non-hierarchical, equal partnership between neonatal teams from different unit designations. It utilised simulation around clinical scenarios, with a slant towards consultant engagement. Four groups rotating through four clinical simulation scenarios were developed. Each group participated in a clinical simulation scenario, led by a consultant and supported by nurses and doctors in training together with facilitators, with a further ~two consultants, as observers within the group. All were considered learners. Consultant candidates took turns to be participants and observers in the simulation scenarios so that at the end of the day all had led a scenario. Each simulation-clinical debrief session was lengthened by a further ~ 20 min, during which freestyle discussion with all learners occurred. This was to promote further bonding, through multidirectional sharing, and with a systems focus on understanding the strengths and challenges of practices in different units. A consultant focus was adopted to promote a long-term engagement between units around shared care. There were four time points for this neonatal networking during the course of the day. Qualitative assessment and a Likert scale were used to assess this initiative over 4 years. RESULTS: One hundred fifty-five individuals involved in frontline neonatal care participated. Seventy-seven were consultants, supported by neonatal trainees, staff grade doctors, clinical fellows, advanced neonatal nurse practitioners and nurses in training. All were invited to participate in the survey. The survey response rate was 80.6%. Seventy-nine percent felt that this learning strategy was highly relevant; 96% agreed that for consultants this was appropriate adult learning. Ninety-eight percent agreed that consultant training encompassed more than bedside clinical management, including forging communication links between teams. Thematic responses suggested that this was a highly useful method for multi-directional learning around shared care between neonatal units. CONCLUSION: Simulation, enhanced with systems focussed debrief, appeared to be an acceptable method of promoting multidirectional learning within neonatal teams of differing designations within the WMNODN.

T Lymphocytes, Multi-Omic Interactions and Bronchopulmonary Dysplasia.

Bronchopulmonary dysplasia (BPD) remains a significant clinical challenge in neonatal medicine. BPD is clearly a multifactorial disease with numerous antenatal and postnatal components influencing lung development. Extremely immature infants are born in the late canalicular or early saccular stage and usually receive intensive care until the early alveolar stage of lung development, resulting in varying magnitudes of impairment of alveolar septation, lung fibrosis, and abnormal vascular development. The interactions between T lymphocytes, the genome and the epigenome, the microbiome and the metabolome, as well as nutrition and therapeutic interventions such as the exposure to oxygen, volutrauma, antibiotics, corticosteroids, caffeine and omeprazole, play an important role in pathogenesis and disease progression. While our general understanding of these interactions thanks to basic research is improving, this knowledge is yet to be translated into comprehensive prevention and clinical management strategies for the benefit of preterm infants developing BPD and later during infancy and childhood suffering from the disease itself and its sequelae. In this review, we summarise existing evidence on the interplay between T lymphocytes, lung multi-omics and currently used therapeutic interventions in BPD, and highlight avenues for potential future immunology related research in the field.

Effecting a national implementation project through distributed leadership in the West Midlands: rising to the spread challenge.

We describe the utility and impact of a distributed leadership model to implement a National Health Service (NHS) England Academic Health Sciences national quality improvement programme, in the West Midlands. This model was adopted to address the inherent difficulties of implementing change in practice in a large geographical region with a diverse population of health service personnel. We report on the inclusion of a senior trainee as part of the implementation team, supported by a multidisciplinary clinical consultant team, with equal agency in decision making, acting as mentors and activators in the background.

Non-specific effects of BCG vaccination on neutrophil and lymphocyte counts of healthy neonates from a developed country.

BCG vaccination is known to reduce neonatal mortality from infections in a pathogen-agnostic manner. In this observational study we report on whether an emergency granulopoietic response is elicited in term babies from a developed country following BCG vaccination. We studied a cohort of neonates re-admitted to the hospital from home for feeding support separated into 2 groups dependent on whether they had received BCG vaccination. Clinical data including gender, weight, gestational age, method of feeding and full blood count results were retrieved retrospectively. While lymphocyte counts increase following BCG vaccination irrespective of gender and in proportion with the time elapsed after vaccination, the increase in neutrophil counts, is only observed in boys. This increase appears to be temporary. Our results confirm the presence of emergency granulopoiesis following BCG vaccination in a neonatal cohort from a developed country. However, this effect appears to be gender-specific and is present only in boys.

The impact of level of neonatal care provision on outcomes for preterm babies born between 27 and 31 weeks of gestation, or with a birth weight between 1000 and 1500 g: a review of the literature.

OBJECTIVE: There is evidence that birth and care in a maternity service associated with a neonatal intensive care unit (NICU) is associated with improved survival in preterm babies born at <27 weeks of gestation. We conducted a systematic review to address whether similar gains manifested in babies born between 27+0 and 31+6 weeks (hereafter 27 and 31 weeks) of gestation, or in those with a birth weight between 1000 and 1500 g. METHODS: We searched Embase, Medline and CINAHL databases for studies comparing outcomes for babies born between 27 and 31 weeks or between 1000 and 1500 g birth weight, based on designation of the neonatal unit where the baby was born or subsequently cared for (NICU vs non-NICU setting). A modified QUIPS (QUality In Prognostic Studies) tool was used to assess quality. RESULTS: Nine studies compared outcomes for babies born between 27 and 31 weeks of gestation and 11 studies compared outcomes for babies born between 1000 and 1500 g birth weight. Heterogeneity in comparator groups, birth locations, gestational age ranges, timescale for mortality reporting, and description of morbidities facilitated a narrative review as opposed to a meta-analysis. CONCLUSION: Due to paucity of evidence, significant heterogeneity and potential for bias, we were not able to answer our question-does place of birth or care affect outcomes for babies born between 27 and 31 weeks? This supports the need for large-scale research to investigate place of birth and care for babies born in this gestational age range.

Optimising neonatal service provision for preterm babies born between 27 and 31 weeks gestation in England (OPTI-PREM), using national data, qualitative research and economic analysis: a study protocol.

INTRODUCTION: In England, for babies born at 23-26 weeks gestation, care in a neonatal intensive care unit (NICU) as opposed to a local neonatal unit (LNU) improves survival to discharge. This evidence is shaping neonatal health services. In contrast, there is no evidence to guide location of care for the next most vulnerable group (born at 27-31 weeks gestation) whose care is currently spread between 45 NICU and 84 LNU in England. This group represents 12% of preterm births in England and over onr-third of all neonatal unit care days. Compared with those born at 23-26 weeks gestation, they account for four times more admissions and twice as many National Health Service bed days/year. METHODS: In this mixed-methods study, our primary objective is to assess, for babies born at 27-31 weeks gestation and admitted to a neonatal unit in England, whether care in an NICU vs an LNU impacts on survival and key morbidities (up to age 1 year), at each gestational age in weeks. Routinely recorded data extracted from real-time, point-of-care patient management systems held in the National Neonatal Research Database, Hospital Episode Statistics and Office for National Statistics, for January 2014 to December 2018, will be analysed. Secondary objectives are to assess (1) whether differences in care provided, rather than a focus on LNU/NICU designation, drives gestation-specific outcomes, (2) where care is most cost-effective and (3) what parents' and clinicians' perspectives are on place of care, and how these could guide clinical decision-making. Our findings will be used to develop recommendations, in collaboration with national bodies, to inform clinical practice, commissioning and policy-making. The project is supported by a parent advisory panel and a study steering committee. ETHICS AND DISSEMINATION: Research ethics approval has been obtained (IRAS 212304). Dissemination will be through publication of findings and development of recommendations for care. TRIAL REGISTRATION NUMBER: NCT02994849 and ISRCTN74230187.

Neonatal nurse staffing and delivery of clinical care in the SSBC Newborn Network.

OBJECTIVE: To measure nursing workload and timely completion of essential tasks in relation to the staffing levels recommended by the British Association of Perinatal Medicine (BAPM) in Staffordshire, Shropshire and Black Country Newborn Network. METHODS: A prospective observational study was conducted measuring the time taken by selected nurses to undertake the necessary tasks for babies receiving different levels of care in the Network's six constituent neonatal units. An independent observer was used. The unit and individual's workload was evaluated against BAPM standards. Delays in essential predetermined tasks were recorded. The impact on quantity of care given and on the number of delayed tasks were compared between those with the recommended workload or less and those overstretched. RESULTS: Between October 2008 and February 2009, 89 nurses were observed caring for 244 neonates over 534 h. 54% of nursing shifts failed to meet BAPM standards. Nurses with workload greater than the BAPM-recommended levels demonstrated a 28% decrease in median time spent on clinical care per baby. 92 (17%) essential tasks were delayed >1 h or not done. Delays/omissions were more likely when BAPM standards were not met (53% vs 40%, p=0.049). In nursing observations without delays/omissions, accommodating for adequate nursing breaks and working in the same area, nurses could cater for no more than 1.2, 1.5 and 2.7 babies in intensive care, high dependency care and special care, respectively. CONCLUSION: Understaffing leads to measurable problems including delays to essential treatment and reduced clinical care. BAPM standards are not aspirational and should be regarded as a minimum. Further research on optimising nursing care efficiency with limited nursing resources is necessary.

Unique acquisition of cytotoxic T-lymphocyte escape mutants in infant human immunodeficiency virus type 1 infection.

The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.

Adaptive evolution in perinatal HIV-1.

The immune-viral dynamics of the transmission of HIV-1 from mother to child are poorly understood, despite 20 years of research. Here we review evidence that the maternal immune response against HIV-1 can select forms of the virus that evade immunity and when transmitted have negative consequences in the child. Moreover, recent studies indicate that when wild-type virus is transmitted, an early immune response in the child can lead to the selection of viral escape forms in the first few months of life. These data suggest that adaptive immune surveillance in both mother and child contributes to the pathogenesis of early perinatal HIV-1. These observations augment our general understanding of the processes that determine the evolution of HIV-1 as it passes from one host to another.

CD8 epitope escape and reversion in acute HCV infection.

In the setting of acute hepatitis C virus (HCV) infection, robust HCV-specific CD8+ cytotoxic T lymphocyte (CTL) responses are associated with initial control of viremia. Despite these responses, 70-80% of individuals develop persistent infection. Although viral escape from CD8 responses has been illustrated in the chimpanzee model of HCV infection, the effect of CD8 selection pressure on viral evolution and containment in acute HCV infection in humans remains unclear. Here, we examined viral evolution in an immunodominant human histocompatibility leukocyte antigen (HLA)-B8-restricted NS3 epitope in subjects with acute HCV infection. Development of mutations within the epitope coincided with loss of strong ex vivo tetramer and interferon gamma enzyme-linked immunospot responses, and endogenous expression of variant NS3 sequences suggested that the selected mutations altered processing and presentation of the variant epitope. Analysis of NS3 sequences from 30 additional chronic HCV-infected subjects revealed a strong association between sequence variation within this region and expression of HLA-B8, supporting reproducible allele-specific selection pressures at the population level. Interestingly, transmission of an HLA-B8-associated escape mutation to an HLA-B8 negative subject resulted in rapid reversion of the mutation. Together, these data indicate that viral escape from CD8+ T cell responses occurs during human HCV infection and that acute immune selection pressure is of sufficient magnitude to influence HCV evolution.