Recombinant fragment of human surfactant protein D to prevent neonatal chronic lung disease (RESPONSE): a protocol for a phase I safety trial in a tertiary neonatal unit.

INTRODUCTION: Chronic respiratory morbidity from bronchopulmonary dysplasia (BPD) remains the most common complication of preterm birth and has consequences for later respiratory, cardiovascular and neurodevelopmental outcomes. The early phases of respiratory illness are characterised by rapid consumption of endogenous surfactant and slow replenishment. Exogenous surfactant is routinely administered to infants born before 28 weeks of gestation as prophylaxis. Endogenous surfactant includes four proteins, known as surfactant proteins (SPs) A, B, C and D. Current bovine-derived and porcine-derived surfactant preparations only contain SPs B and C. SP-D has a key role in lung immune homeostasis as part of the innate immune system. Laboratory studies using recombinant SP-D have demonstrated reduced inflammation, which may be a pathway to reducing the associated morbidity from BPD. RESPONSE uses a recombinant fragment of human SP D (rfhSP-D), in a phase I safety and dose-escalation trial as the first stage in determining its effect in humans. METHODS AND ANALYSIS: This is a single-centre, dose-escalation, phase I safety study aiming to recruit 24 infants born before 30 weeks gestation with respiratory distress syndrome. In addition to routine surfactant replacement therapy, participants will receive three doses of rfhSP-D via endotracheal route at either 1 mg/kg, 2 mg/kg or 4 mg/kg. The study uses a Bayesian continual reassessment method to make dose escalation decisions. Dose-limiting events (DLE) in this trial will be graded according to the published Neonatal Adverse Event Severity Score. The primary outcome of this study is to evaluate the safety profile of rfhSP-D across each dose level based on the profile of DLE to establish the recommended phase 2 dose (RP2D) of rfhSP-D. ETHICS AND DISSEMINATION: The RESPONSE study has received ethical approval from London-Brent NHS Research Health Authority ethics committee. Results from the study will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBERS: ISRCTN17083028, NCT05898633. PROTOCOL VERSION: RESPONSE Protocol V.4.0 24th July 2024.

Job satisfaction and intent to stay in neonatal nursing in England and Wales: a study protocol.

BACKGROUND: Nursing shortages are an ongoing concern for neonatal units, with many struggling to meet recommended nurse to patient ratios. Workforce data underlines the high proportion of neonatal nurses nearing retirement and a reduced number of nurses joining the profession. In order to recommend strategies to increase recruitment and retention to neonatal nursing, we need to understand the current challenges nurses are facing within the profession. The aim of this study is to investigate current job satisfaction, burnout, and intent to stay in neonatal nursing in England and Wales. METHODS: This study has two parts: (1) a systematic review exploring job satisfaction, burnout and intent to stay in neonatal nursing, and any previous interventions undertaken to enhance nurse retention, (2) an online survey of neonatal nurses in England and Wales exploring job satisfaction, burnout and intent to stay in neonatal nursing. We will measure job satisfaction using the McCloskey Mueller Satisfaction Scale (MMSS), burnout using the Copenhagen Burnout Inventory (CBI) and the Nurse Retention Index (NRI) will be used to measure intent to stay. All nurses working in neonatal units in England and Wales will be eligible to participate in the nursing survey. DISCUSSION: Retention of neonatal nurses is a significant issue affecting neonatal units across England and Wales, which can impact the delivery of safe patient care. Exploring job satisfaction and intent to stay will enable the understanding of challenges being faced and how best to support neonatal nurses. Identifying localised initiatives for the geographical areas most at risk of nurses leaving would help to improve nurse retention.

The NeoPACE study: study protocol for the development of a core outcome set for neonatal palliative care.

BACKGROUND: Neonatal death is the leading category of death in children under the age of 5 in the UK. Many babies die following decisions between parents and the neonatal team; when a baby is critically unwell, with the support of healthcare professionals, parents may make the decision to stop active treatment and focus on ensuring their baby has a 'good' death. There is very little evidence to support the clinical application of neonatal palliative care and/or end-of-life care, resulting in variation in clinical provision between neonatal units. Developing core outcomes for neonatal palliative care would enable the development of measures of good practice and enhance our care of families. The aim of this study is to develop a core outcome set with associated tools for measuring neonatal palliative care. METHOD: This study has four phases: (1) identification of potential outcomes through systematic review and qualitative interviews with key stakeholders, including parents and healthcare professionals (2) an online Delphi process with key stakeholders to determine core outcomes (3) identification of outcome measures to support clinical application of outcome use (4) dissemination of the core outcome set for use across neonatal units in the UK. Key stakeholders include parents, healthcare professionals, and researchers with a background in neonatal palliative care. DISCUSSION: Developing a core outcome set will standardise minimum reported outcomes for future research and quality improvement projects designed to determine the effectiveness of interventions and clinical care during neonatal palliative and/or end-of-life care. The core outcome set will provide healthcare professionals working in neonatal palliative and/or end-of-life support with an increased and consistent evidence base to enhance practice in this area. TRIAL REGISTRATION: The study has been registered with the COMET initiative ( https://www.comet-initiative.org/Studies/Details/1470 ) and the systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) (CRD42023451068).

Neonatal organ donation: Retrospective audit into potential donation in a single neonatal unit.

BACKGROUND: Research has shown that many babies who die in neonatal units could have been potential tissue and/or organ donors. Despite the existence of guidelines supporting its implementation, the incidence of neonatal donation remains rare in the United Kingdom. AIM: The aim of this audit was to retrospectively determine potential eligibility for neonatal tissue and/or organ donation referral in infants who died in a single UK tertiary-level neonatal unit between 2012 and 2021. Cause of death and documentation of any discussions held regarding referral for donation were also explored. STUDY DESIGN: An audit was undertaken to identify all neonatal deaths at a single tertiary-level NICU in London from 2012-2021. Infants who retrospectively could have been referred as potential tissue and/or organ donors were identified using current NHS Blood and Transplant inclusion and exclusion criteria. RESULTS AND CONCLUSION: A significant missed potential for neonatal tissue and/or organ donation referrals was identified, which is likely not just limited to the unit audited. Causes of death were as expected for a tertiary level neonatal unit and centre for therapeutic cooling of babies born with hypoxic perinatal brain injuries. Only one documented conversation was found regarding neonatal donation. RELEVANCE TO CLINICAL PRACTICE: To enable conversations regarding neonatal donation to become a routine part of end-of-life care discussions with families as appropriate, good links between neonatal healthcare professionals and Specialist Nurses in Organ Donation need to be established. This will facilitate the referral of all suitable neonates as potential donors and ensure that neonatal staff feel supported to care for babies identified as potential donors.

Parental experiences of live video streaming technology in neonatal care in England: a qualitative study.

BACKGROUND: The use of bedside cameras in neonatal units facilitates livestreaming of infants to support parental and family bonding when they are unable to be physically present with their baby. This study aimed to explore the experiences of parents of infants previously admitted for neonatal care and who used live video streaming to view their baby in real-time. METHODS: Qualitative semi-structured interviews were conducted after discharge with parents of infants admitted for neonatal care on a tertiary level neonatal unit in the UK in 2021. Interviews were conducted virtually, transcribed verbatim and uploaded into NVivo V12 to facilitate analysis. Thematic analysis by two independent researchers was undertaken to identify themes representing the data. RESULTS: Seventeen participants took part in sixteen interviews. Thematic analysis identified 8 basic themes which were grouped into 3 organizational themes: (1) family integration of the baby including parent-infant, sibling-infant, and wider family-infant attachment facilitated through livestreaming, (2) implementation of the livestreaming service including communication, initial set up of the livestreaming service, and areas for improvement, and (3) parental control including emotional, and situational control. CONCLUSIONS: The use of livestreaming technology can provide parents with opportunities to integrate their baby into their wider family and friendship community and gain a sense of control over their baby's admission for neonatal care. On-going parental education around how to use, and what to expect from, livestreaming technology is required to minimise any potential distress from viewing their baby online.

Cumulative risk factors contributing to hearing loss in preterm infants.

OBJECTIVE: To investigate individual and concomitant risk factors for hearing loss during neonatal care. DESIGN: Case-control study. SETTING: Community. POPULATION: 237 children born <32 weeks of gestation; 57 with hearing loss and 180 with normal hearing born between 2009 and 2013, matched for sex, gestation and year of birth. MAIN OUTCOME MEASURES: Data were abstracted from clinical records for overall risk factors daily for the first 14 days and then weekly until discharge from neonatal care. All infants were screened for the presence of m.1555A>G mutation. RESULTS: Children with hearing loss had lower birth weight for gestational age, more severe neonatal illness, with increased exposure to inotrope, steroid, gentamicin, vancomycin and furosemide, and more frequent physiological risk, elevated bilirubin and creatinine levels and acidosis, but no index child was found to have the m.1555A>G mutation, compared with one among controls. The duration of gentamicin, vancomycin or furosemide administration in the first 14 days was associated with impaired hearing (OR per dose: 1.25; 95% CI 1.14 to 1.38). Multivariate analyses revealed independent risks for hearing loss for each day when there was physiological risk (OR per day 1.15 (1.05 to 1.27)) and each day of medication exposure (OR 1.23 (1.1 to 1.37)). CONCLUSION: Although the relative contribution of underlying illness and medication cannot be identified by this study, cumulative use of ototoxic medication and the presence of physiologic risk factors independently increased the likelihood of hearing loss, warranting close monitoring of coincident therapy throughout neonatal critical care.

Gentamicin, genetic variation and deafness in preterm children.

BACKGROUND: Hearing loss in children born before 32 weeks of gestation is more prevalent than in full term infants. Aminoglycoside antibiotics are routinely used to treat bacterial infections in babies on neonatal intensive care units. However, this type of medication can have harmful effects on the auditory system. In order to avoid this blood levels should be maintained in the therapeutic range. However in individuals with a mitochondrial genetic variant (m.1555A > G), permanent hearing loss can occur even when drug levels are within normal limits. The aim of the study is to investigate the burden that the m.1555A > G mutation represents to deafness in very preterm infants. METHOD: This is a case control study of children born at less than 32 completed weeks of gestation with confirmed hearing loss. Children in the control group will be matched for sex, gestational age and neonatal intensive care unit on which they were treated, and will have normal hearing. Saliva samples will be taken from children in both groups; DNA will be extracted and tested for the mutation. Retrospective pharmacological data and clinical history will be abstracted from the medical notes. Risk associated with gentamicin, m.1555A > G and other co-morbid risk factors will be evaluated using conditional logistic regression. DISCUSSION: If there is an increased burden of hearing loss with m.1555A > G and aminoglycoside use, consideration will be given to genetic testing during pregnancy, postnatal testing prior to drug administration, or the use of an alternative first line antibiotic. Detailed perinatal data collection will also allow greater definition of the causal pathway of acquired hearing loss in very preterm children.