Elizabeth S. Draper

Background: Patient and Public Involvement and Engagement (PPIE) is increasingly recognised as essential to the relevance, feasibility, and impact of paediatric intensive/critical care research. However, reporting of PPIE processes and outcomes, particularly in child health studies, remains limited, often lacking detail on sustained involvement and its influence across the research lifecycle. Case study: This case study presents the PPIE approach embedded within the OCEANIC Study, a multi-centre longitudinal mixed-methods investigation into the outcomes and support needs of children and families following paediatric intensive care unit (PICU) discharge. The study uniquely sustained engagement with a Children, Young People and Parent Advisory Group (CYPPAG) over eight years, aligning with the National Institute for Health and Care Research (NIHR) standards for public involvement. We detail the strategies used to foster inclusive, respectful, and impactful collaboration, including co-development of study materials, iterative feedback on recruitment and retention strategies, and involvement in qualitative data interpretation and dissemination. The advisory group’s contributions shaped study design, enhanced recruitment, and informed dissemination, including co-authorship and conference presentations. PPIE impact was explored qualitatively through CYPPAG feedback, tracking of study changes informed by the CYPPAG, and ongoing reflection within the research team. Conclusion: The OCEANIC Study demonstrates the feasibility and value of longitudinal, embedded PPIE in paediatric critical care research. It offers a novel model for sustained advisory group involvement, evidencing how meaningful collaboration can improve research relevance, rigour, and reach. This case study provides actionable insights for researchers seeking to integrate PPIE across the research continuum and highlights the therapeutic and empowering impact of involvement for contributors.

Background: The optimal target for systemic oxygenation in critically ill children is unknown. Liberal oxygenation is widely practised but is associated with harm in observational studies. Objectives: To evaluate the clinical and cost-effectiveness of a conservative oxygenation target of peripheral oxygen saturation 88–92% compared with peripheral oxygen saturation > 94% in critically ill children admitted to paediatric intensive care unit as an emergency. Design and setting: A pragmatic, open, multicentre, parallel-group, randomised clinical trial conducted in 15 National Health Service paediatric intensive care units and associated emergency transport services across England and Scotland. Participants: Children aged > 38 weeks corrected gestational age and < 16 years, enrolled within 6 hours of being accepted for admission to paediatric intensive care unit as an emergency; receiving invasive mechanical ventilation with supplemental oxygen; and in face-to-face contact with paediatric intensive care unit or emergency transport services staff. Interventions: Adjustment of ventilator and inspired oxygen settings aiming to achieve peripheral oxygen saturation 88–92% (conservative oxygenation) or peripheral oxygen saturation > 94% (liberal oxygenation) during invasive mechanical ventilation. Main outcome measures: Primary outcomes: duration of organ support at 30 days, with death by day 30 ranked as the worst outcome (clinical effectiveness) and incremental costs, quality-adjusted life-years and net monetary benefit at 12 months (cost-effectiveness). Secondary outcomes: incremental costs at 30 days; mortality at paediatric intensive care unit discharge, 30 days, 90 days and 12 months; time to liberation from ventilation; duration of organ support; length of paediatric intensive care unit and hospital stay; functional status at paediatric intensive care unit discharge; and health-related quality of life at 12 months. Results: Two thousand and forty children were randomised between 1 September 2020 and 15 May 2022. Consent was obtained for 1872 (94%) – 939 to the conservative and 933 to the liberal oxygenation group – who were included in the primary analysis. Duration of organ support or death in the first 30 days was lower in the conservative oxygenation group [probabilistic index 0.53, 95% confidence interval 0.50 to 0.55; p = 0.04 Wilcoxon rank-sum test, adjusted odds ratio 0.84 (95% confidence interval 0.72 to 0.99)]. Both components of the composite primary outcome and secondary outcomes favoured conservative oxygenation. Average costs at 30 days strongly indicated lower costs with conservative oxygenation. Longer-term estimated incremental costs and quality-adjusted life-years were lower and net monetary benefit marginally favoured conservative oxygenation but with wide uncertainty [incremental costs −£879 (95% confidence interval −9036 to 7278); quality-adjusted life-years 0.001 (−0.010 to 0.011); net monetary benefit £894 (95% confidence interval −7290 to 9078)]. Limitations: Exclusion of two large paediatric intensive care unit populations, due to a lack of equipoise and the number of participants excluded because of not being able to obtain deferred consent. Future work: Future work should focus on identification of the mechanisms underlying the observed benefit; trials of intermediate or lower peripheral oxygen saturation values in individuals at higher risk; and identification of individualised treatment effects in relation to oxygen therapy. Conclusions: A conservative oxygenation target resulted in a greater probability of a better outcome in terms of duration of organ support at 30 days or death. Longer-term survival and health-related quality of life were consistent with the primary outcome. While conservative oxygenation is likely to reduce costs in the short term, longer-term cost-effectiveness was surrounded with wide uncertainty. Funding: This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number NIHR127547.

Aim: To investigate, for preterm babies born between 27⁺⁰ and 31⁺⁶ weeks gestation in England, optimal place of birth and early care. Design: Mixed methods. Setting: National Health Service neonatal care, England. Methods: To investigate whether birth and early care in neonatal intensive care units (tertiary units) compared to local neonatal units (non-tertiary units) influenced gestation-specific survival and other major outcomes, we analysed data from the National Neonatal Research Database, for 29,842 babies born between 27⁺⁰ and 31⁺⁶ weeks gestation and discharged from neonatal care between 1 January 2014 and 31 December 2018. We utilised an instrumental variable (maternal excess travel time between local neonatal units and neonatal intensive care units) to control for unmeasured differences. Sensitivity analyses excluded postnatal transfers within 72 hours of birth and multiple births. Outcome measures were death in neonatal care, infant mortality, necrotising enterocolitis, retinopathy of prematurity, severe brain injury, bronchopulmonary dysplasia, and receipt of breast milk at discharge. We also analysed outcomes by volume of neonatal intensive care activity. We undertook a health economic analysis using a cost-effectiveness evaluation from a National Health Service perspective and using additional lives saved as a measure of benefit, explored differences in quality of care in high compared with low-performing units and performed ethnographic qualitative research. Results: The safe gestational age cut-off for babies to be born between 27⁺⁰ and 31⁺⁶ weeks and early care at either location was 28 weeks. We found no effect on mortality in neonatal care (mean difference −0.001; 99% confidence interval −0.011 to 0.010; p = 0.842) or in infancy (mean difference −0.002; 99% confidence interval −0.014 to 0.009; p = 0.579) (n = 18,847), including after sensitivity analyses. A significantly greater proportion of babies in local neonatal units had severe brain injury (mean difference −0.011; 99% confidence interval −0.022 to −0.001; p = 0.007) with the highest mean difference in babies born at 27 weeks (−0.040). Those transferred in the first 72 hours were more likely to have severe brain injury. For 27 weeks gestation, birth in centres with neonatal intensive care units reduced the risk of severe brain injury by 4.2% from 11.9% to 7.7%. The number needed to treat was 25 (99% confidence interval 10 to 59) indicating that 25 babies at 27 weeks would have to be delivered in a neonatal intensive care unit to prevent one severe brain injury. For babies born at 27 weeks gestation, birth in a high-volume unit (> 1600 intensive care days/year) reduced the risk of severe brain injury from 0.242 to 0.028 [99% confidence interval 0.035 to 0.542; p = 0.003; number needed to treat = 4 (99% confidence interval 2 to 29)]. Estimated annual total costs of neonatal care were £262 million. The mean (standard deviation) cost per baby varied from £75,594 (£34,874) at 27 weeks to £27,401 (£14,947) at 31 weeks. Costs were similar between neonatal intensive care units and local neonatal units for births at 27⁺⁰ to 29⁺⁶ weeks gestation, but higher for local neonatal units for those born at 30⁺⁰ to 31⁺⁶ weeks. No difference in additional lives saved were observed between the settings. These results suggested that neonatal intensive care units are likely to represent value for money for the National Health Service. However, careful interpretation of this results should be exercised due to the ethical and practical concerns around the reorganisation of neonatal care for very preterm babies from local neonatal units to neonatal intensive care units purely on the grounds of cost savings. We identified a mean reduction in length of stay (1 day; 95% confidence interval 1.029 to 1.081; p < 0.001) in higher-performing units, based on adherence to evidence- and consensus-based measures. Staff reported that decision-making to optimise capacity for babies was an important part of their work. Parents reported valuing their baby’s development, homecoming, continuity of care, inclusion in decision-making, and support for their emotional and physical well-being. Conclusions: Birth and early care for babies ≥ 28 weeks is safe in both neonatal intensive care units and local neonatal units in England. For anticipated births at 27 weeks, antenatal transfer of mothers to centres colocated with neonatal intensive care units should be supported. When these inadvertently occur in centres with local neonatal units, clinicians should risk assess decisions for postnatal transfer, taking patient care requirements, staff skills and healthcare resources into consideration and counselling parents regarding the increased risk of severe brain injury associated with transfer. Study registration: This study is registered as Current Controlled Trials NCT02994849 and ISRCTN74230187. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme (NIHR award ref: 15/70/104) and is published in full in Health and Social Care Delivery Research; Vol. 13, No. 12. See the NIHR Funding and Awards website for further award information.

Objective: Extremes of prepregnancy maternal BMI increase neonatal mortality and morbidity at term. They also increase the risk of extremely preterm (EP, i.e., <27 weeks' gestational age) births. However, the association between maternal BMI and outcomes for EP babies is poorly understood.Methods: We used a cross‐country design, bringing together the following three population‐based, prospective, national EP birth cohorts: EXPRESS (Sweden, 2004–2007); EPICure 2 (UK, 2006); and EPIPAGE 2 (France, 2011). We included all singleton births at 22 to 26 weeks' gestational age with a live fetus at maternal hospital admission. Our exposure was maternal prepregnancy BMI, i.e., underweight, reference, overweight, or obesity. Odds ratios (OR) for survival without severe neonatal morbidity to hospital discharge according to maternal BMI were calculated using logistic regression.Results: A total of 1396 babies were born to mothers in the reference group, 140 to those with underweight, 719 to those with overweight, 556 to those with obesity, and 445 to those with missing BMI information. There was no difference in survival without major neonatal morbidity (reference, 22%; underweight, 26%, OR, 1.31, 95% CI: 0.82–2.08; overweight, 23%, OR, 1.00, 95% CI: 0.77–1.29; obesity, 19%, OR, 0.94, 95% CI: 0.70–1.25).Conclusions: No associations were seen between maternal BMI and outcomes for EP babies.

Objective To investigate SARS-CoV-2 vaccine uptake and effectiveness in children and young people (CYP) with life-limiting neurodisability. Design We undertook a retrospective cohort study using national hospital data in England from 21 December 2020 to 2 September 2022 to describe SARS-CoV-2 vaccination uptake, and then examined COVID-19 hospitalisation, paediatric intensive care unit (PICU) admission and death following SARS-CoV-2 infection by vaccination status using Cox regression models. Patients CYP aged 5–17 with life-limiting neurodisability. Results We identified 38 067 CYP with life-limiting neurodisability; 13 311 (35.0%) received at least one SARS-CoV-2 vaccine, with uptake higher among older, white CYP, from less deprived neighbourhoods. Of 8134 CYP followed up after a positive SARS-CoV-2 test, 1547 (19%) were vaccinated. Within 28 days of infection, 309 (4.7%) unvaccinated CYP were hospitalised with COVID-19 compared with 75 (4.8%) vaccinated CYP. Of 46 (0.7%) unvaccinated CYP were admitted to PICU compared with 10 (0.6%) vaccinated CYP. Of 20 CYP died within 28 days of SARS-CoV-2 infection, of which 13 were unvaccinated. Overall, adjusted hazard of hospitalisation for COVID-19 or admission to PICU did not vary by vaccination status. When the Alpha-Delta SARS-CoV-2 variants were dominant, hazard of hospitalisation with COVID-19 was significantly lower among vaccinated CYP (HR 0.26 (0.09 to 0.74)), with no difference seen during Omicron (HR 1.16 (0.74 to 1.81)). Conclusions SARS-CoV-2 vaccination was protective of COVID-19 hospitalisation among CYP with life-limiting neurodisability during Alpha-Delta, but not for other SARS-CoV-2 variants. Vaccine uptake was low and varied by ethnicity and deprivation.

Background: Preterm birth (before 37 completed weeks of gestation) is associated with an increased risk of adverse health and developmental outcomes relative to birth at term. Existing guidelines for data collection in cohort studies of individuals born preterm are either limited in scope, have not been developed using formal consensus methodology, or did not involve a range of stakeholders in their development. Recommendations meeting these criteria would facilitate data pooling and harmonisation across studies.Objectives: To develop a Core Dataset for use in longitudinal cohort studies of individuals born preterm.Methods: This work was carried out as part of the RECAP Preterm project. A systematic review of variables included in existing core outcome sets was combined with a scoping exercise conducted with experts on preterm birth. The results were used to generate a draft core dataset. A modified Delphi process was implemented using two stages with three rounds each. Three stakeholder groups participated: RECAP Preterm project partners; external experts in the field; people with lived experience of preterm birth. The Delphi used a 9‐point Likert scale. Higher values indicated greater importance for inclusion. Participants also suggested additional variables they considered important for inclusion which were voted on in later rounds.Results: An initial list of 140 data items was generated. Ninety‐six participants across 22 countries participated in the Delphi, of which 29% were individuals with lived experience of preterm birth. Consensus was reached on 160 data items covering Antenatal and Birth Information, Neonatal Care, Mortality, Administrative Information, Organisational Level Information, Socio‐economic and Demographic information, Physical Health, Education and Learning, Neurodevelopmental Outcomes, Social, Lifestyle and Leisure, Healthcare Utilisation and Quality of Life.Conclusions: This core dataset includes 160 data items covering antenatal care through outcomes in adulthood. Its use will guide data collection in new studies and facilitate pooling and harmonisation of existing data internationally.

Objective Neonatal infection with wildtype SARS-CoV-2 is rare and good outcomes predominate. We investigated neonatal outcomes using national population-level data to describe the impact of different SARS-CoV-2 variants. Design Prospective population-based cohort study. Setting Neonatal, paediatric and paediatric intensive care inpatient care settings in the UK. Patients Neonates (first 28 days after birth) with confirmed SARS-CoV-2 infection who received inpatient care, March 2020 to April 2022. Neonates were identified through active national surveillance with linkage to national SARS-CoV-2 testing data, routinely recorded neonatal data, paediatric intensive care data and obstetric and perinatal mortality surveillance data. Outcomes Presenting signs, clinical course, severe disease requiring respiratory support are presented by the dominant SARS-CoV-2 variant in circulation at the time. Results 344 neonates with SARS-CoV-2 infection received inpatient care; breakdown by dominant variant: 146 wildtype, 123 alpha, 57 delta and 18 omicron. Overall, 44.7% (153/342) neonates required respiratory support; short-term outcomes were good with 93.6% (322/344) of neonates discharged home. Eleven neonates died: seven unrelated to SARS-CoV-2 infection, four were attributed to neonatal SARS-CoV-2 infection (case fatality 4/344, 1.2% 95% CI 0.3% to 3.0%) of which three were born preterm due to maternal COVID-19. More neonates were born very preterm (23/54) and required invasive ventilation (27/57) when delta variant was predominant, and all four SARS-CoV-2-related deaths occurred in this period. Conclusions Inpatient care for neonates with SARS-CoV-2 was uncommon. Although rare, severe neonatal illness was more common during the delta variant period, potentially reflecting more severe maternal disease and associated preterm birth. Trial registration number ISRCTN60033461.

Objectives To determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour to be monitored. Design Population-based, observational study using congenital anomaly (CA) registration data for England curated by the National Congenital Anomaly and Rare Disease Registration Service (NCARDRS). Setting Regions of England with active registration in the time period. Participants Babies that were liveborn or stillborn and pregnancies that resulted in a termination of pregnancy or a late miscarriage (20–23 weeks’ gestation) with an NTD. Main outcome measures Total birth prevalence of anencephaly, spina bifida and all NTDs in England. Poisson regression analysis was used to evaluate time trends with regional register as a random effect. The progress of national registration across England was assessed. Results There were 4541 NTD pregnancies out of 3 637 842 births in England; 1982 anencephaly and 2127 spina bifida. NTD prevalence was 12.5 (95% CI 12.1 to 12.9) per 10 000 total births. NTD prevalence per 10 000 total births was significantly higher in 2015–2019 (13.6, 95% CI 12.9 to 14.4) compared with 2010–2014 (12.1, 95% CI 11.7 to 12.5). An increasing trend in NTDs overall was detected (incidence rate ratio (IRR) 1.01, 1.00 to 1.02), although further analysis determined this effect was confined to 2015–2019 (compared against 2000–2004, IRR 1.14, 1.04 to 1.24). The birth prevalence of anencephaly reflected this pattern. The prevalence of spina bifida remained relatively stable over time. Conclusions Baseline NTD prevalence for England has been established. National and standardised CA registration is in place, facilitating the systematic and consistent monitoring of pre-fortification and post-fortification NTD trends and evaluating the impact of fortification on NTD prevalence.

Background: Children born extremely preterm (EP) are at increased risk of neurocognitive and behavioural morbidity. Here, we investigate whether behavioural outcomes have changed over time concomitant with increasing survival following EP birth. Methods: Comparison of outcomes at 11 years of age for two prospective national cohorts of children born EP in 1995 (EPICure) and 2006 (EPICure2), assessed alongside term-born children. Behavioural outcomes were assessed using the parent-completed Strengths and Difficulties Questionnaire (SDQ), DuPaul Attention-Deficit/Hyperactivity Disorder Rating Scale (ADHD-RS), and Social Communication Questionnaire (SCQ). Results: In EPICure, 176 EP and 153 term-born children were assessed (mean age: 10.9 years); in EPICure2, 112 EP and 143 term-born children were assessed (mean age: 11.8 years). In both cohorts, EP children had higher mean scores and more clinically significant difficulties than term-born children on almost all measures. Comparing outcomes for EP children in the two cohorts, there were no significant differences in mean scores or in the proportion of children with clinically significant difficulties after adjustment for confounders. Using term-born children as reference, EP children in EPICure2 had significantly higher SDQ total difficulties and ADHD-RS hyperactivity impulsivity z-scores than EP children in EPICure. Conclusions: Behavioural outcomes have not improved for EP children born in 2006 compared with those born in 1995. Relative to term-born peers, EP children born in 2006 had worse outcomes than those born in 1995. There is an ongoing need for long-term clinical follow-up and psychological support for children born EP.