Publications
197 results found
Ryan L, Ploetz FB, van den Hoogen A, et al., 2021, Neonates and COVID-19: state of the art Neonatal Sepsis series, Pediatric Research, Vol: 91, Pages: 432-439, ISSN: 0031-3998
The SARS-CoV-2 pandemic has had a significant impact worldwide, particularly in middle- and low-income countries. While this impact has been well-recognized in certain age groups, the effects, both direct and indirect, on the neonatal population remain largely unknown. There are placental changes associated, though the contributions to maternal and fetal illness have not been fully determined. The rate of premature delivery has increased and SARS-CoV-2 infection is proportionately higher in premature neonates, which appears to be related to premature delivery for maternal reasons rather than an increase in spontaneous preterm labor. There is much room for expansion, including long-term data on outcomes for affected babies. Though uncommon, there has been evidence of adverse events in neonates, including Multisystem Inflammatory Syndrome in Children, associated with COVID-19 (MIS-C). There are recommendations for reduction of viral transmission to neonates, though more research is required to determine the role of passive immunization of the fetus via maternal vaccination. There is now considerable evidence suggesting that the severe visitation restrictions implemented early in the pandemic have negatively impacted the care of the neonate and the experiences of both parents and healthcare professionals alike. Ongoing collaboration is required to determine the full impact, and guidelines for future management.
Mitchell E, Oddie SJ, Dorling J, et al., 2021, Implementing two-stage consent pathway in neonatal trials, Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN: 1359-2998
Perinatal trials sometimes require rapid recruitment processes to facilitate inclusion of participants when interventions are time-critical. A two-stage consent pathway has been used in some trials and is supported by national guidance. This pathway includes seeking oral assent for participation during the time-critical period followed by informed written consent later. This approach is being used in the fluids exclusively enteral from day one (FEED1) trial where participants need to be randomised within 3 hours of birth. There is some apprehension about approaching parents for participation via the oral assent pathway. The main reasons for this are consistent with previous research: lack of a written record, lack of standardised information and unfamiliarity with the process. Here, we describe how the pathway has been implemented in the FEED1 trial and the steps the trial team have taken to support sites. We provide recommendations for future trials to consider if they are considering implementing a similar pathway. Trial registration number: ISRCTN89654042.
Greenbury SF, Angelini ED, Ougham K, et al., 2021, Birthweight and patterns of postnatal weight gain in very and extremely preterm babies in England and Wales, 2008-19: a cohort study, The Lancet Child & Adolescent Health, Vol: 5, Pages: 719-728, ISSN: 2352-4642
BACKGROUND: Intrauterine and postnatal weight are widely regarded as biomarkers of fetal and neonatal wellbeing, but optimal weight gain following preterm birth is unknown. We aimed to describe changes over time in birthweight and postnatal weight gain in very and extremely preterm babies, in relation to major morbidity and healthy survival. METHODS: In this cohort study, we used whole-population data from the UK National Neonatal Research Database for infants below 32 weeks gestation admitted to neonatal units in England and Wales between Jan 1, 2008, and Dec 31, 2019. We used non-linear Gaussian process to estimate monthly trends, and Bayesian multilevel regression to estimate unadjusted and adjusted coefficients. We evaluated birthweight; weight change from birth to 14 days; weight at 36 weeks postmenstrual age; associated Z scores; and longitudinal weights for babies surviving to 36 weeks postmenstrual age with and without major morbidities. We adjusted birthweight for antenatal, perinatal, and demographic variables. We additionally adjusted change in weight at 14 days and weight at 36 weeks postmenstrual age, and their Z scores, for postnatal variables. FINDINGS: The cohort comprised 90 817 infants. Over the 12-year period, mean differences adjusted for antenatal, perinatal, demographic, and postnatal variables were 0 g (95% compatibility interval -7 to 7) for birthweight (-0·01 [-0·05 to 0·03] for change in associated Z score); 39 g (26 to 51) for change in weight from birth to 14 days (0·14 [0·08 to 0·19] for change in associated Z score); and 105 g (81 to 128) for weight at 36 weeks postmenstrual age (0·27 [0·21 to 0·33] for change in associated Z score). Greater weight at 36 weeks postmenstrual age was robust to additional adjustment for enteral nutritional intake. In babies surviving without major morbidity, weight velocity in all gestational age groups stabilised at around 34 weeks post
Rees P, Carter B, Gale C, et al., 2021, Cost of neonatal abstinence syndrome: an economic analysis of English national data held in the National Neonatal Research Database, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 106, Pages: 494-500, ISSN: 1359-2998
Objective To determine the incidence of neonatal abstinence syndrome (NAS) across neonatal units, explore healthcare utilisation and estimate the direct cost to the NHS.Design Population cohort study.Setting NHS neonatal units, using data held in the National Neonatal Research Database.Participants Infants born between 2012 and 2017, admitted to a neonatal unit in England, receiving a diagnosis of NAS (n=6411).Main outcome measures Incidence, direct annual cost of care (£, 2016–2017 prices), duration of neonatal unit stay (discharge HR), predicted additional cost of care, and odds of receiving pharmacotherapy.Results Of 524 334 infants admitted during the study period, 6411 had NAS. The incidence (1.6/1000 live births) increased between 2012 and 2017 (β=0.07, 95% CI (0 to 0.14)) accounting for 12/1000 admissions and 23/1000 cot days nationally. The direct cost of care was £62 646 661 over the study period. Almost half of infants received pharmacotherapy (n=2631; 49%) and their time-to-discharge was significantly longer (median 18.2 vs 5.1 days; adjusted HR (aHR) 0.16, 95% CI (0.15 to 0.17)). Time-to-discharge was longer for formula-fed infants (aHR 0.73 (0.66 to 0.81)) and those discharged to foster care (aHR 0.77 (0.72 to 0.82)). The greatest predictor of additional care costs was receipt of pharmacotherapy (additional mean adjusted cost of £8420 per infant).Conclusions This population study highlights the substantial cot usage and economic costs of caring for infants with NAS on neonatal units. A shift in how healthcare systems provide routine care for NAS could benefit infants and families while alleviating the burden on services.
Ducey J, Kennedy A, Linsell L, et al., 2021, Timing of neonatal stoma closure: a survey of health professional perspectives and current practice, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 107, ISSN: 1359-2998
Optimal timing for neonatal stoma closure remains unclear. In this study we aimed to establish currentpractice and illustrate multidisciplinary perspectives on timing of stoma closure using an online survey sentto all 27 UK neonatal surgical units, as part of a research programme to determine feasibility of a clinical trialcomparing ‘early’ and ‘late’ stoma closure. 166 responses from all 27 units demonstrated concordance ofopinion in target time for closure (6 weeks most commonly stated across scenarios), although there washigh variability in practice. A sizeable proportion (41%) of respondents use weight, rather than time, todetermine when to close a neonatal stoma. Thematic analysis of free-text responses identified 9 key themesinfluencing decision making; most related to nutrition, growth and stoma complications. These data providean overview of current practice that is critical to informing an acceptable trial design.
Shipley L, Gale C, Sharkey D, 2021, Trends in the incidence and management of hypoxic-ischaemic encephalopathy in the therapeutic hypothermia era: a national population study, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 106, Pages: 529-534, ISSN: 1359-2998
Objective Hypoxic-ischaemic encephalopathy (HIE) remains a leading cause of neonatal mortality and neurodisability. We aimed to determine the incidence of HIE and management patterns against national guidelines.Design Retrospective cohort study using the National Neonatal Research Database.Setting Neonatal units in England and Wales.Patients Infants 34–42 weeks gestational age (GA) with a recorded diagnosis of HIE.Main outcomes Incidence of HIE, mortality and treatment with therapeutic hypothermia (TH) were the main outcomes. Temporal changes were compared across two epochs (2011–2013 and 2014–2016).Results Among 407 462 infants admitted for neonatal care, 12 195 were diagnosed with HIE. 8166 infants ≥36 weeks GA had moderate/severe HIE, 62.1% (n=5069) underwent TH and mortality was 9.3% (n=762). Of infants with mild HIE (n=3394), 30.3% (n=1027) underwent TH and 6 died. In late preterm infants (34–35 weeks GA) with HIE (n=635, 5.2%), 33.1% (n=210) received TH and 13.1% (n=83) died. Between epochs (2011–2013 vs 2014–2016), mortality decreased for infants ≥36 weeks GA with moderate/severe HIE (17.5% vs 12.3%; OR 0.69, 95% CI 0.59 to 0.81, p<0.001). Treatment with TH increased significantly between epochs in infants with mild HIE (24.9% vs 35.8%, p<0.001) and those born late preterm (34.3% vs 46.6%, p=0.002).Conclusions Mortality of infants ≥36 weeks GA with moderate/severe HIE has reduced over time, although many infants diagnosed with moderate/severe HIE do not undergo TH. Increasingly, mild HIE and late preterm infants with HIE are undergoing TH, where the evidence base is lacking, highlighting the need for prospective studies to evaluate safety and efficacy in these populations.
Hage L, Jeyakumaran D, Dorling J, et al., 2021, Changing clinical characteristics of infants treated for hypoxic ischaemic encephalopathy in England, Wales and Scotland: a population-based study using the National Neonatal Research Database, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 106, Pages: 501-508, ISSN: 1359-2998
Background Therapeutic hypothermia is standard of care for babies with moderate/severe hypoxic-ischaemic encephalopathy and is increasingly used for mild encephalopathy.Objective Describe temporal trends in the clinical condition of babies diagnosed with hypoxic-ischaemic encephalopathy who received therapeutic hypothermia.Design Retrospective cohort study using data held in the National Neonatal Research Database.Setting National Health Service neonatal units in England, Wales and Scotland.Patients Infants born from 1 January 2010 to 31 December 2017 with a recorded diagnosis of hypoxic-ischaemic encephalopathy who received therapeutic hypothermia for at least 3 days or died in this period.Main outcomes Primary outcomes: recorded clinical characteristics including umbilical cord pH; Apgar score; newborn resuscitation; seizures and treatment on day 1. Secondary outcomes: recorded hypoxic-ischaemic encephalopathy grade.Results 5201 babies with a diagnosis of hypoxic-ischaemic encephalopathy received therapeutic hypothermia or died; annual numbers increased over the study period. A decreasing proportion had clinical characteristics of severe hypoxia ischaemia or a diagnosis of moderate or severe hypoxic-ischaemic encephalopathy, trends were statistically significant and consistent across multiple clinical characteristics used as markers of severity.Conclusions Treatment with therapeutic hypothermia for hypoxic-ischaemic encephalopathy has increased in England, Scotland and Wales. An increasing proportion of treated infants have a diagnosis of mild hypoxic-ischaemic encephalopathy or have less severe clinical markers of hypoxia. This highlights the importance of determining the role of hypothermia in mild hypoxic-ischaemic encephalopathy. Receipt of therapeutic hypothermia is unlikely to be a useful marker for assessing changes in the incidence of brain injury over time.
Pinchefsky EF, Schneider J, Basu S, et al., 2021, Nutrition and management of glycemia in neonates with neonatal encephalopathy treated with hypothermia, Seminars in Fetal and Neonatal Medicine, Vol: 26, ISSN: 1084-2756
Adequate nutrition and glycemic homeostasis are increasingly recognized as potentially neuroprotective for the developing brain. In the context of hypoxia-ischemia, evidence is scarce regarding optimal nutritional support and administration route, as well as the short- and long-term consequences of such interventions. In this review, we summarize current knowledge on disturbances of brain metabolism of glucose and substrates by hypoxia-ischemia, and compound effects of these mechanisms on brain injury characterized by specific patterns on EEG and MRI. Risks and benefits of nutrition delivery via parenteral or enteral routes are examined. Nutrition could mitigate adverse neurodevelopmental outcomes, and the impact of nutritional strategies and specific nutritional interventions are reviewed. Limited literature highlights the need for further studies to understand the changes in energy metabolism during and after hypoxic-ischemic injury, to optimize nutritional regimens and glucose management, and to inform the neuroprotective role of nutrition.
Fleming PF, Gale C, Molloy EJ, et al., 2021, Paediatric research in the times of COVID-19, Pediatric Research, Vol: 90, Pages: 267-271, ISSN: 0031-3998
The COVID-19 pandemic poses many direct and indirect consequences for children’s health and associated research. Direct consequences include participation of children in COVID-19 research trials, pausing other research in children and the potential implications of a global economic downturn on future research funding. Collaborative and networked research together with streamlined research processes and use of remote technology have been central to efforts by clinicians and scientists around the world and have proved essential for reducing COVID-19 morbidity and mortality.
McCarthy M, O'Keeffe L, Williamson PR, et al., 2021, A study protocol for the development of a SPIRIT extension for trials conducted using cohorts and routinely collected data (SPIRIT-ROUTINE) [version 1; peer review: 2 approved], HRB Open Research, Vol: 4, ISSN: 2515-4826
Background: Protocols are an essential document for conducting randomised controlled trials (RCTs). However, the completeness of the information provided is often inadequate. To help improve the content of trial protocols, an international group of stakeholders published the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Initiative in 2013. Presently, there is increasing use of cohorts and routinely collected data (RCD) for RCTs because these data have the potential to improve efficiencies by facilitating recruitment, simplifying, and reducing the cost of data collection. Reporting guidelines have been shown to improve the quality of reporting, but there is currently no specific SPIRIT guidance on protocols for trials conducted using cohorts and RCD. This protocol outlines steps for developing SPIRIT-ROUTINE, which aims to address this gap by extending the SPIRIT guidance to protocols for trials conducted using cohorts and RCD. Methods: The development of the SPIRIT-ROUTINE extension comprises five stages. Stage 1 consists of a project launch and a meeting to finalise the membership of the steering group and scope of the extension. In Stage 2, a rapid review will be performed to identify possible modifications to the original SPIRIT 2013 checklist. Other key reporting guidelines will be reviewed to identify areas where additional items may be needed, such as the Consolidated Standards of Reporting Trials (CONSORT) extension for trials conducted using cohorts and RCD (CONSORT-ROUTINE). Stage 3 will involve an online Delphi exercise, consisting of two rounds and involving key international stakeholders to gather feedback on the preliminary checklist items. In Stage 4, a consensus meeting of the SPIRIT-ROUTINE steering group will finalise the items to include in the extension. Stage 5 will involve the publication preparation and dissemination of
Gale C, Longford N, Jeyakumaran D, et al., 2021, Feeding during neonatal therapeutic hypothermia: a retrospective population-based cohort study using routinely collected data held in the National Neonatal Research Database, The Lancet Child and Adolescent Health, Vol: 5, ISSN: 2352-4642
Background: There is limited evidence to inform feeding during neonatal therapeutic hypothermia; practice is variable. We aimed assess the association between feeding during therapeutic hypothermia and clinically important outcomes.Methods: Retrospective, population-based cohort study using the National Neonatal Research Database. We included all babies admitted to NHS neonatal units in England, Scotland or Wales, 1 January 2010 – 31 December 2017, that received therapeutic hypothermia for 72 hours or died during treatment. We formed matched groups for analysis using propensity scores and compared outcomes in babies fed during therapeutic hypothermia to those that were not. The primary outcome was severe necrotising enterocolitis confirmed at surgery or causing death; we also described pragmatically defined necrotising enterocolitis including lower severity disease, infection, survival, hypoglycaemia, parenteral nutrition and central line days, measures of breastmilk feeding, length of stay and weight. Pre-registered ISRCTN47404296.Findings: 6030 babies received therapeutic hypothermia and 1873 (31%) were fed during hypothermia. Seven babies (0·1%) were diagnosed with severe necrotising enterocolitis. 3236 babies were selected for the matched feeding analysis (1618 pairs) and good balance was achieved for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare both fed and not fed groups (0·6% and 1·1% respectively). Higher survival to discharge (difference 5·2%; 95% CI: 3·9, 6·6; p<0·0001) and breastfeeding at discharge (difference 8·0%; 95% CI: 5·1, 10·8; p<0·0001) were seen in fed babies, who also had shorter neonatal stays (difference -2·2 days, 95% CI: -3·0, -1·2; p<0.0001). Interpretation: Necrotising enterocolitis is rare in babies receiving therapeutic hypothermia. Feeding during hypothermia is associated with l
Gale C, Longford NT, Jeyakumaran D, et al., 2021, Feeding during neonatal therapeutic hypothermia, assessed using routinely collected National Neonatal Research Database data: a retrospective, UK population-based cohort study, The Lancet Child and Adolescent Health, Vol: 5, Pages: 408-416, ISSN: 2352-4642
Background:Therapeutic hypothermia is standard of care in high-income countries for babies born with signs of hypoxic ischaemic encephalopathy, but optimal feeding during treatment is uncertain and practice is variable. This study aimed to assess the association between feeding during therapeutic hypothermia and clinically important outcomes.Methods:We did a population-level retrospective cohort study using the UK National Neonatal Research Database. We included all babies admitted to National Health Service neonatal units in England, Scotland, and Wales between Jan 1, 2010, and Dec 31, 2017, who received therapeutic hypothermia for 72 h or died during this period. For analysis, we created matched groups using propensity scores and compared outcomes in babies who were fed versus unfed enterally during therapeutic hypothermia. The primary outcome was severe necrotising enterocolitis, either confirmed at surgery or causing death. Secondary outcomes include pragmatically defined necrotising enterocolitis (a recorded diagnosis of necrotising enterocolitis in babies who received at least 5 consecutive days of antibiotics while also nil by mouth during their neonatal unit stay), late-onset infection (pragmatically defined as 5 consecutive days of antibiotic treatment commencing after day 3), survival to discharge, measures of breastmilk feeding, and length of stay in neonatal unit.Findings:6030 babies received therapeutic hypothermia, of whom 1873 (31·1%) were fed during treatment. Seven (0·1%) babies were diagnosed with severe necrotising enterocolitis and the number was too small for further analyses. We selected 3236 (53·7%) babies for the matched feeding analysis (1618 pairs), achieving a good balance for all recorded background variables. Pragmatically defined necrotising enterocolitis was rare in both groups (incidence 0·5%, 95% CI 0·2–0·9] in the fed group vs 1·1% [0·7–1·4] in the unfed grou
Gale C, Jeyakumaran D, Battersby C, et al., 2021, Nutritional management in newborn babies receiving therapeutic hypothermia: two retrospective observational studies using propensity score matching, Health Technology Assessment, Vol: 25, Pages: 1-106, ISSN: 1366-5278
BACKGROUND: Therapeutic hypothermia is standard of care for babies with moderate to severe hypoxic-ischaemic encephalopathy. There is limited evidence to inform provision of nutrition during hypothermia. OBJECTIVES: To assess the association during therapeutic hypothermia between (1) enteral feeding and outcomes, such as necrotising enterocolitis and (2) parenteral nutrition and outcomes, such as late-onset bloodstream infection. DESIGN: A retrospective cohort study using data held in the National Neonatal Research Database and applying propensity score methodology to form matched groups for analysis. SETTING: NHS neonatal units in England, Wales and Scotland. PARTICIPANTS: Babies born at ≥ 36 gestational weeks between 1 January 2010 and 31 December 2017 who received therapeutic hypothermia for 72 hours or who died during treatment. INTERVENTIONS: Enteral feeding analysis - babies who were enterally fed during therapeutic hypothermia (intervention) compared with babies who received no enteral feeds during therapeutic hypothermia (control). Parenteral nutrition analysis - babies who received parenteral nutrition during therapeutic hypothermia (intervention) compared with babies who received no parenteral nutrition during therapeutic hypothermia (control). OUTCOME MEASURES: Primary outcomes were severe and pragmatically defined necrotising enterocolitis (enteral feeding analysis) and late-onset bloodstream infection (parenteral nutrition analysis). Secondary outcomes were survival at neonatal discharge, length of neonatal stay, breastfeeding at discharge, onset of breastfeeding, time to first maternal breast milk, hypoglycaemia, number of days with a central line in situ, duration of parenteral nutrition, time to full enteral feeds and growth. RESULTS: A total of 6030 babies received therapeutic hypothermia. Thirty-one per cent of babies received enteral feeds and 25% received parenteral nutrition. Seven babies (0.1%) were diagnosed with severe necrotising e
Mohamed M, Curzen N, Ludman P, et al., 2021, TRENDS OF IN-HOSPITAL AND 30-DAY MORTALITY AFTER PERCUTANEOUS CORONARY INTERVENTION IN ENGLAND BEFORE AND AFTER THE COVID-19 ERA, 70th Annual Scientific Session and Expo of the American-College-of-Cardiology (ACC), Publisher: ELSEVIER SCIENCE INC, Pages: 3160-3160, ISSN: 0735-1097
Vousden N, Bunch K, Morris E, et al., 2021, The incidence, characteristics and outcomes of pregnant women hospitalized with symptomatic and asymptomatic SARS-CoV-2 infection in the UK from March to September 2020: A national cohort study using the UK Obstetric Surveillance System (UKOSS), PLoS One, Vol: 16, ISSN: 1932-6203
BACKGROUND: There is a lack of population level data on risk factors, incidence and impact of SARS-CoV-2 infection in pregnant women and their babies. The primary aim of this study was to describe the incidence, characteristics and outcomes of hospitalized pregnant women with symptomatic and asymptomatic SARS-CoV-2 in the UK compared to pregnant women without SARS-CoV-2. METHODS AND FINDINGS: We conducted a national, prospective cohort study of all hospitalized pregnant women with confirmed SARS-CoV-2 from 01/03/2020 to 31/08/2020 using the UK Obstetric Surveillance System. Incidence rates were estimated using national maternity data. Overall, 1148 hospitalized women had confirmed SARS-CoV-2 in pregnancy, 63% of which were symptomatic. The estimated incidence of hospitalization with symptomatic SARS-CoV-2 was 2.0 per 1000 maternities (95% CI 1.9-2.2) and for asymptomatic SARS-CoV-2 was 1.2 per 1000 maternities (95% CI 1.1-1.4). Compared to pregnant women without SARS-CoV-2, women hospitalized with symptomatic SARS-CoV-2 were more likely to be overweight or obese (adjusted OR 1.86, (95% CI 1.39-2.48) and aOR 2.07 (1.53-2.29)), to be of Black, Asian or Other minority ethnic group (aOR 6.24, (3.93-9.90), aOR 4.36, (3.19-5.95) and aOR 12.95, (4.93-34.01)), and to have a relevant medical comorbidity (aOR 1.83 (1.32-2.54)). Hospitalized pregnant women with symptomatic SARS-CoV-2 were more likely to be admitted to intensive care (aOR 57.67, (7.80-426.70)) but the absolute risk of poor outcomes was low. Cesarean births and neonatal unit admission were increased regardless of symptom status (symptomatic aOR 2.60, (1.97-3.42) and aOR 3.08, (1.99-4.77); asymptomatic aOR 2.02, (1.52-2.70) and aOR 1.84, (1.12-3.03)). The risks of stillbirth or neonatal death were not significantly increased, regardless of symptom status. CONCLUSIONS: We have identified factors that increase the risk of symptomatic and asymptomatic SARS-CoV-2 in pregnancy. Clinicians can be reassured that the maj
Gale C, Jeyakumaran D, Longford N, et al., 2021, Administration of parenteral nutrition during therapeutic hypothermia: a population level observational study using routinely collected data held in the National Neonatal Research Database, Archives of Disease in Childhood: Fetal and Neonatal Edition, ISSN: 1359-2998
Imran M, Kwakkenbos L, McCall SJ, et al., 2021, Methods and results used in the development of a consensus-driven extension to the Consolidated Standards of Reporting Trials (CONSORT) statement for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE), BMJ Open, Vol: 11, ISSN: 2044-6055
Objectives: Randomised controlled trials conducted using cohorts and routinely collected data, including registries, electronic health records and administrative databases, are increasingly used in healthcare intervention research. A Consolidated Standards of Reporting Trials (CONSORT) statement extension for trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE) has been developed with the goal of improving reporting quality. This article describes the processes and methods used to develop the extension and decisions made to arrive at the final checklist.Methods: The development process involved five stages: (1) identification of the need for a reporting guideline and project launch; (2) conduct of a scoping review to identify possible modifications to CONSORT 2010 checklist items and possible new extension items; (3) a three-round modified Delphi study involving key stakeholders to gather feedback on the checklist; (4) a consensus meeting to finalise items to be included in the extension, followed by stakeholder piloting of the checklist; and (5) publication, dissemination and implementation of the final checklist.Results: 27 items were initially developed and rated in Delphi round 1, 13 items were rated in round 2 and 11 items were rated in round 3. Response rates for the Delphi study were 92 of 125 (74%) invited participants in round 1, 77 of 92 (84%) round 1 completers in round 2 and 62 of 77 (81%) round 2 completers in round 3. Twenty-seven members of the project team representing a variety of stakeholder groups attended the in-person consensus meeting. The final checklist includes five new items and eight modified items. The extension Explanation & Elaboration document further clarifies aspects that are important to report.Conclusion: Uptake of CONSORT-ROUTINE and accompanying Explanation & Elaboration document will improve conduct of trials, as well as the transparency and completeness of reporting of trials conducted using coh
Kwakkenbos L, Imran M, McCall SJ, et al., 2021, CONSORT extension for the reporting of randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE): checklist with explanation and elaboration, BMJ: British Medical Journal, Vol: 373, ISSN: 0959-535X
Randomised controlled trials are increasingly conducted as embedded, nested, or using cohorts or routinely collected data, including registries, electronic health records, and administrative databases, to assess if participants are eligible for the trial and to facilitate recruitment, to deliver an embedded intervention, to collect trial outcome data, or a combination of these purposes. This report presents the Consolidated Standards of Reporting Trials (CONSORT) extension for randomised controlled trials conducted using cohorts and routinely collected data (CONSORT-ROUTINE). The extension was developed to look at the unique characteristics of trials conducted with these types of data with the goal of improving reporting quality in the long term by setting standards early in the process of uptake of these trial designs. The extension was developed with a sequential approach, including a Delphi survey, a consensus meeting, and piloting of the checklist. The checklist was informed by the CONSORT 2010 statement and two reporting guidelines for observational studies, the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement and the REporting of studies Conducted using Observational Routinely collected Data (RECORD) statement. The extension includes eight items modified from the CONSORT 2010 statement and five new items. Reporting items with explanations and examples are provided, including key aspects of trials conducted using cohorts or routinely collected data that require specific reporting considerations.
McLeish J, Alderdice F, Robberts H, et al., 2021, Challenges of a simplified opt-out consent process in a neonatal randomised controlled trial: a qualitative study of parents’ and health professionals’ views and experiences, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 106, Pages: 244-250, ISSN: 1359-2998
Background: More effective recruitment strategies like alternative approaches to consent are needed to facilitate adequately powered trials. WithHolding Enteral feeds Around Transfusion (WHEAT) was a multicentre, randomised, pilot trial that compared withholding and continuing feeds around transfusion. The primary clinical outcome was necrotising enterocolitis (NEC). The trial used simplified opt-out consent with concise parent information and no consent form.Objective: To explore the views and experiences of parents and health professionals on the acceptability and feasibility of opt-out consent in randomised comparative effectiveness trials.Methods: A qualitative, descriptive interview-based study nested within a randomised trial. Semi-structured interview transcripts were analysed using inductive thematic analysis.Setting: Eleven neonatal units in England.Participants: Eleven parents and ten health professionals with experience of simplified consent. Results: Five themes emerged: ‘Opt-out consent operationalised as verbal opt-in consent’, ‘Opt-out consent normalises participation while preserving parental choice’, ‘Opt-out consent as an ongoing process of informed choice’, ‘Consent without a consent form’ and ‘Choosing to opt out of a comparative effectiveness trial’, with two subthemes: ‘Wanting “normal care”’ and ‘A belief that feeding is better’. Conclusions: Introducing a novel form of consent proved challenging in practice. The principle of simplified, opt-out approach to consent was generally considered feasible and acceptable by health professionals for a neonatal comparative effectiveness trial. The priority for parents was having the right to decide about trial participation, and they did not see opt-out consent as undermining this. Describing a study as ‘opt-out’ can help to normalise participation and emphasise that parents can withdraw consent.
Gale C, Dorling J, Arch B, et al., 2021, Optimal outcome measures for a trial of not routinely measuring gastric residual volume in neonatal care: a mixed methods consensus process, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 106, Pages: 292-297, ISSN: 1359-2998
BACKGROUND: Routine measurement of gastric residual volume to guide feeding is widespread in neonatal units but not supported by high-quality evidence. Outcome selection is critical to trial design. OBJECTIVE: To determine optimal outcome measures for a trial of not routinely measuring gastric residual volume in neonatal care. DESIGN: A focused literature review, parent interviews, modified two-round Delphi survey and stakeholder consensus meeting. PARTICIPANTS: Sixty-one neonatal healthcare professionals participated in an eDelphi survey; 17 parents were interviewed. 19 parents and neonatal healthcare professionals took part in the consensus meeting. RESULTS: Literature review generated 14 outcomes, and parent interviews contributed eight additional outcomes; these 22 outcomes were then ranked by 74 healthcare professionals in the first Delphi round where four further outcomes were proposed; 26 outcomes were ranked in the second round by 61 healthcare professionals. Five outcomes were categorised as 'consensus in', and no outcomes were voted 'consensus out'. 'No consensus' outcomes were discussed and voted on in a face-to-face meeting by 19 participants, where four were voted 'consensus in'. The final nine consensus outcomes were: mortality, necrotising enterocolitis, time to full enteral feeds, duration of parenteral nutrition, time feeds stopped per 24 hours, healthcare-associated infection; catheter-associated bloodstream infection, change in weight between birth and neonatal discharge and pneumonia due to milk aspiration. CONCLUSIONS AND RELEVANCE: We have identified outcomes for a trial of no routine measurement of gastric residual volume to guide feeding in neonatal care. This outcome set will ensure outcomes are important to healthcare professionals and parents.
Greenbury SF, Ougham K, Wu J, et al., 2021, Identification of variation in nutritional practice in neonatal units in England and association with clinical outcomes using agnostic machine learning, Scientific Reports, Vol: 11, ISSN: 2045-2322
We used agnostic, unsupervised machine learning to cluster a large clinical database of information on infants admitted to neonatal units in England. Our aim was to obtain insights into nutritional practice, an area of central importance in newborn care, utilising the UK National Neonatal Research Database (NNRD). We performed clustering on time-series data of daily nutritional intakes for very preterm infants born at a gestational age less than 32 weeks (n = 45,679) over a six-year period. This revealed 46 nutritional clusters heterogeneous in size, showing common interpretable clinical practices alongside rarer approaches. Nutritional clusters with similar admission profiles revealed associations between nutritional practice, geographical location and outcomes. We show how nutritional subgroups may be regarded as distinct interventions and tested for associations with measurable outcomes. We illustrate the potential for identifying relationships between nutritional practice and outcomes with two examples, discharge weight and bronchopulmonary dysplasia (BPD). We identify the well-known effect of formula milk on greater discharge weight as well as support for the plausible, but insufficiently evidenced view that human milk is protective against BPD. Our framework highlights the potential of agnostic machine learning approaches to deliver clinical practice insights and generate hypotheses using routine data.
Gale C, Quigley MA, Placzek A, et al., 2021, The ability of the neonatal immune response to handle SARS-CoV-2 infection - Authors' reply, The Lancet Child and Adolescent Health, Vol: 5, Pages: e8-e8, ISSN: 2352-4642
Rees P, Stilwell PA, Bolton C, et al., 2021, Childhood Morbidity After Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis, American-Academy-of-Pediatrics (AAP) Virtual National Conference and Exhibition - Section on Emergency Medicine, Publisher: AMER ACAD PEDIATRICS, ISSN: 0031-4005
Duhig KE, Myers JE, Gale C, et al., 2021, Placental growth factor measurements in the assessment of women with suspected preeclampsia: a stratified analysis of the PARROT trial, Pregnancy Hypertension, Vol: 23, Pages: 41-47, ISSN: 2210-7789
ObjectivePlacental growth factor testing decreases time to recognition of preeclampsia and may reduce severe maternal adverse outcomes. This analysis aims to describe the clinical phenotype of women by PlGF concentration, and to determine the mechanism(s) underpinning the reduction in severe maternal adverse outcomes in the PARROT trial, in order to inform how PlGF testing may be optimally used within clinical management algorithms.Study designThis was a planned secondary analysis from the PARROT trial that compared revealed PlGF testing and management guidance with usual care in the assessment of women with suspected preterm preeclampsia.Main outcome measuresMaternal and perinatal outcomes following stratification of women by trial group, and measured PlGF concentration.Results1006 women were included. PlGF < 100 pg/ml identified women with more marked hypertension, increased adverse maternal outcomes and preterm delivery rates, and higher rates of small for gestational age infants. There was a reduction in adverse maternal outcomes in women whose results were revealed when PlGF levels were 12–100 pg/ml compared to usual care (3.8% vs 6.9%; aOR 0.15(95% CI 0.03–0.92). There was no significant difference in gestation at delivery between concealed or revealed groups in any PlGF categories.ConclusionLow PlGF concentrations are associated with severe preeclampsia. The reduction in severe adverse maternal outcomes may be mediated through quicker diagnosis and intensive surveillance, as recommended by the management algorithm for those at increased risk. PlGF is particularly beneficial in those who test 12–100 pg/ml, as these may be women with silent multi-organ disease who otherwise may go undetected.
Rees P, Carter B, Gale C, et al., 2021, The Cost of Neonatal Abstinence Syndrome To The National Health Service: An Economic Analysis Of A National Database, Publisher: AMER ACAD PEDIATRICS, ISSN: 0031-4005
Nimish S, Jawad S, Ougham K, et al., 2021, Increasing use of inhaled nitric oxide in neonatal intensive care units in England: a retrospective population study, BMJ Paediatrics Open, Vol: 5, ISSN: 2399-9772
Objective To describe temporal changes in inhaled nitric oxide (iNO) use in English neonatal units between 2010 and 2015.Design Retrospective analysis using data extracted from the National Neonatal Research Database.Setting All National Health Service neonatal units in England.Patients Infants of all gestational ages born 2010–2015 admitted to a neonatal unit and received intensive care.Main outcome measures Proportion of infants who received iNO; age at initiation and duration of iNO use.Results 4.9% (6346/129 883) of infants received iNO; 31% (1959/6346) were born <29 weeks, 18% (1152/6346) 29–33 weeks and 51% (3235/6346)>34 weeks of gestation. Between epoch 1 (2010–2011) and epoch 3 (2014–2015), there was (1) an increase in the proportion of infants receiving iNO: <29 weeks (4.9% vs 15.9%); 29–33 weeks (1.1% vs 4.8%); >34 weeks (4.5% vs 5.0%), (2) increase in postnatal age at iNO initiation: <29 weeks 10 days vs 18 days; 29–33 weeks 2 days vs 10 days, (iii) reduction in iNO duration: <29 weeks (3 days vs 2 days); 29–33 weeks (2 days vs 1 day).Conclusions Between 2010 and 2015, there was an increase in the use of iNO among infants admitted to English neonatal units. This was most notable among the most premature infants with an almost fourfold increase. Given the cost of iNO therapy, limited evidence of efficacy in preterm infants and potential for harm, we suggest that exposure to iNO should be limited, ideally to infants included in research studies (either observational or randomised placebo-controlled trial) or within a protocolised pathway. Development of consensus guidelines may also help standardise practice.
Deja E, Roper L, Tume L, et al., 2021, Can they stomach it? Parent and practitioner acceptability of a trial comparing Gastric Residual Volume measurement versus no Gastric Residual Volume in UK NNU and PICU’s: a feasibility study, Pilot and Feasibility Studies, Vol: 7, ISSN: 2055-5784
BackgroundRoutine measurement of gastric residual volume (GRV) to guide feeding in neonatal and paediatric intensive care is widespread. However, this practice is not evidence based and may cause harm. As part of a feasibility study, we explored parent and practitioner views on the acceptability of a trial comparing GRV measurement or no GRV measurement.MethodsA mixed-methods study involving interviews and focus groups with practitioners and interviews with parents with experience of tube feeding in neonatal and/or paediatric intensive care. A voting system recorded closed question responses during practitioner data collection, enabling the collection of quantitative and qualitative data. Data were analysed using thematic analysis and descriptive statistics.ResultsWe interviewed 31 parents and nine practitioners and ran five practitioner focus groups (n=42). Participants described how the research question was logical, and the intervention would not be invasive and potential benefits of not withholding the child’s feeds. However, both groups held concerns about the potential risk of not measuring GRV, including delayed diagnosis of infection and gut problems, increased risk of vomiting into lungs and causing discomfort or pain. Parent’s views on GRV measurement and consent decision making were influenced by their views on the importance of feeding in the ICU, their child’s prognosis and associated comorbidities or complications.ConclusionsThe majority of parents and practitioners viewed the proposed trial as acceptable. Potential concerns and preferences were identified that will need careful consideration to inform the development of the proposed trial protocol and staff training.
Vasu V, Gale C, 2021, Understanding the impact of size at birth and prematurity on biological ageing: the utility and pitfalls of a life-course approach, Pediatric Research, Vol: 89, Pages: 411-412, ISSN: 0031-3998
Gale C, Quigley M, Placzek A, et al., 2021, Characteristics and outcomes of neonatal SARS-CoV-2 infection in the United Kingdom: a prospective national cohort study using active surveillance, The Lancet Child and Adolescent Health, Vol: 5, Pages: 113-121, ISSN: 2352-4642
Background: Babies differ in their exposure to SARS-CoV-2relative to older children. There are limited data describing the impact of SARS-CoV-2 in this group and guidance is variable. Methods: ProspectiveUKpopulation-based cohort study of babies with confirmed SARS-CoV-2 infection in the first28 days that received inpatient care, 1st March 2020to30thApril 2020. Babies were identified through active national surveillance with linkage to national testing, paediatric intensive care audit and obstetric surveillance data. Outcomes included incidence per10,000 live births of inpatient hospital care with confirmed SARS-CoV-2 infection, severe disease, suspected vertically and nosocomially acquired infection. Findings: Sixty-six babies had SARS-CoV-2 infection and received inpatient care, an incidence of 5·6(95% CI 4·3, 7·1); 28 (42%) babies had severe neonatal SARS-CoV-2 infection, incidence 2·4 (95% CI 1·6, 3·4). Twenty-nine babies (45%) were from black, Asian or minority ethnic groups, an incidence of 11·1(95% CI 7·4, 15·9); incidence in white group 4·6(95% CI 3·2, 6·4). Sixteen(24%) babies were born preterm. Seventeen(26%) babies with confirmed infection were born to mothers with known perinatal SARS-CoV-2 infection. Two babies had possible vertically acquired infection and eight (12%) babies had suspected no socomial infection. Most babies (58, 88%) have been discharged home; one baby died of a cause unrelated to SARS-CoV-2 infection.Interpretation: Inpatient care in babies with neonatal SARS-CoV-2 infection is uncommon.Babies in hospital with SARS-CoV-2 infection were more likely to have severe disease than older children, although outcomes were good. Infection with neonatal admission following birth to a mother with perinatal SARS-CoV-2 infection was unlikely and possible vertical transmission rare, supporting international guidance to avoid separation of mother and baby. The high pro
Gale C, Jeyakumaran D, Ougham K, et al., 2021, Correction to: Brain injury occurring during or soon afterbirth: annual incidence and rates of brain injuries to monitorprogress against the national maternity ambition. 2016 and 2017 data, Correction to: Brain injury occurring during or soon afterbirth: annual incidence and rates of brain injuries to monitorprogress against the national maternity ambition. 2016 and 2017 data, London, UK, Publisher: The Neonatal Data Analysis Unit, Imperial College London, 2
Correction to the following report: https://doi.org/10.25561/87336
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