Imperial College London

Dr Chris Gale

Faculty of MedicineSchool of Public Health

Reader in Neonatal Medicine
 
 
 
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Contact

 

+44 (0)20 3315 3519christopher.gale Website

 
 
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Location

 

Academic Neonatal Medicine, H4.4,Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Publication Type
Year
to

104 results found

Gale C, Quigley M, Placzek A, Knight M, Ladhani S, Draper E, Sharkey D, Doherty C, Mactier H, Kurinczuk Jet al., 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, ISSN: 2352-4642

Journal article

Bogiatzopoulou A, Mayberry H, Hawcutt DB, Whittaker E, Munro A, Roland D, Simba J, Gale C, Felsenstein S, Abrams E, Jones CB, Lewins I, Rodriguez-Martinez CR, Fernandes RM, Stilwell PA, Swann O, Bhopal S, Sinha I, Harwood Ret al., 2020, COVID-19 in children: what did we learn from the first wave?, Paediatrics and Child Health, ISSN: 1751-7222

A pandemic caused by the novel coronavirus, severe acute respiratory syndrome - coronavirus 2 (SARS-CoV-2), has caused high rates of mortality, predominantly in adults. Children are significantly less affected by SARS-CoV-2 with far lower rates of recorded infections in children compared to adults, milder symptoms in the majority of children and very low mortality rates. A suspected late manifestation of the disease, paediatric inflammatory multisystem syndrome - temporally associated with SARS-CoV-2 (PIMS-TS), has been seen in small numbers of children and has a more severe disease course than acute SARS-CoV-2. The pandemic has meant that children around the world have been kept off school, isolated from their extended family and friends and asked to stay inside. The UK has just been declared as being in an economic recession and unemployment rates are increasing. These indirect effects of SARS-CoV-2 are likely to have a significant impact on many children for years to come. Consolidating the knowledge that has accumulated during the first wave of this pandemic is essential for recognising the clinical signs, symptoms and effective treatment strategies for children; identifying children who may be at increased risk of severe SARS-CoV-2 infection; planning the safe delivery of healthcare and non-health related services that are important for childrens’ wellbeing; and engaging in, and developing, research to address the things that are not yet known. This article summarises the evidence that has emerged from the early phase of the pandemic and offers an overview for those looking after children or planning services.

Journal article

McLeish J, Alderdice F, Robberts H, Cole C, Dorling J, Gale Cet al., 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, 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.

Journal article

Webbe J, Gale C, 2020, NICE guidelines on neonatal parenteral nutrition: a step towards standardised care but evidence is scarce, The Lancet Child and Adolescent Health, Vol: 4, Pages: 645-646, ISSN: 2352-4642

Journal article

Dorling J, Tume LN, Arch B, Woolfall K, Latten L, Roper L, Deja E, Pathan N, Eccleson H, Hickey H, Brown M, Beissel A, Andrzejewska A, Valla FV, Gale Cet al., 2020, Gastric residual volume measurement in British neonatal intensive care units: a survey of practice, BMJ Paediatrics Open, Vol: 4, ISSN: 2399-9772

Objective: Despite little evidence, the practice of routine gastric residual volume (GRV) measurement to guide enteral feeding in neonatal units is widespread. Due to increased interest in this practice, and to examine trial feasibility, we aimed to determine enteral feeding and GRV measurement practices in British neonatal units.Design & Setting: An online survey was distributed via email to all neonatal units and networks in England, Scotland and Wales. A clinical nurse, senior doctor and dietitian were invited to collaboratively complete the survey and submit a copy of relevant guidelines. Results: 95/184 (51.6%) approached units completed the survey, 81/95 (85.3%) reported having feeding guidelines and 28 guidelines were submitted for review. The majority of units used intermittent (90/95) gastric feeds as their primary feeding method. 42/95 units reported specific guidance for measuring and interpreting GRV. 20/90 units measured GRV before every feed, 39/90 at regular time-intervals (most commonly 4-6 hourly 35/39) and 26/90 when felt to be clinically indicated. Most units reported uncertainty on the utility of aspirate volume for guiding feeding decisions; 13/90 reported that aspirate volume affected decisions ‘very much’. In contrast, aspirate colour was reported to affect decisions ‘very much’ by 37/90 of responding units. Almost half, 44/90, routinely returned aspirates to the stomach. Conclusions: Routine GRV measurement is part of standard practice in British neonatal units, although there was inconsistency in how frequently to measure or how to interpret the aspirate. Volume was considered less important than colour of the aspirate.

Journal article

Little M, Dupre S, Wormald J, Gardiner M, Gale C, Jain Aet al., 2020, Surgical intervention for paediatric infusion-related extravasation injury: a systematic review, BMJ Open, Vol: 10, Pages: 1-14, ISSN: 2044-6055

ObjectivesThis systematic review aims to assess the quality of literature supporting surgical interventions for paediatric extravasation injury and to determine whether there is sufficient evidence to support invasive techniques in children.MethodsWe performed a systematic review by searching Ovid MEDLINE and EMBASE as well as AMED, CINAHL, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews and clinicaltrials.gov from inception to February 2019. Studies other than case reports were eligible for inclusion if the population was younger than 18 years old, there was a surgical intervention aimed at treating extravasation injury and they reported on outcomes. Study quality was graded according to the National Institutes of Health (NIH) study quality assessment tools.Results26 studies involving 728 children were included – one before-and-after study and 25 case series. Extravasation injuries were mainly confined to skin and subcutaneous tissues but severe complications were also encountered, including amputation (one toe and one below elbow). Of the surgical treatments described, the technique of multiple puncture wounds and instillation of saline and/or hyaluronidase was the most commonly used. However, there were no studies in which its effectiveness was tested against another treatment or a control and details of functional and aesthetic outcomes were generally lacking. ConclusionSurgical management is commonly reported in the literature in cases where there is significant soft tissue injury but as there are no comparative studies, it is unclear whether this is optimal. Further observational and experimental research evaluating extravasation injuries, including a centralized extravasation register using a universal grading scheme and core outcome set with adequate follow-up, are required to provide evidence to guide clinician decision-making.

Journal article

Yeo KT, Oei JL, De Luca D, Schmölzer GM, Guaran R, Palasanthiran P, Kumar K, Buonocore G, Cheong J, Owen LS, Kusuda S, James J, Lim G, Sharma A, Uthaya S, Gale C, Whittaker E, Battersby C, Modi N, Norman M, Naver L, Giannoni E, Diambomba Y, Shah PS, Gagliardi L, Harrison M, Pillay S, Alburaey A, Yuan Y, Zhang Het al., 2020, Review of guidelines and recommendations from 17 countries highlights the challenges that clinicians face caring for neonates born to mothers with COVID-19., Acta Paediatrica: Nurturing the Child, ISSN: 1651-2227

AIM: This review examined how applicable national and regional clinical practice guidelines and recommendations for managing neonates born to mothers with COVID-19 mothers were to the evolving pandemic. METHODS: A systematic search and review identified 20 guidelines and recommendations that had been published by 25 May 2020. We analysed documents from 17 countries: Australia, Brazil, Canada, China, France, India, Italy, Japan, Saudi Arabia, Singapore, South Africa, South Korea, Spain, Sweden, Switzerland, the UK and the USA. RESULTS: The documents were based on expert consensus with limited evidence and were of variable, low methodological rigour. Most did not provide recommendations for delivery methods or managing symptomatic infants. None provided recommendations for post-discharge assimilation of potentially-infected infants into the community. The majority encouraged keeping mothers and infants together, subject to infection control measures, but one-third recommended separation. Although breastfeeding or using breastmilk were widely encouraged, two countries specifically prohibited this. CONCLUSION: The guidelines and recommendations for managing infants affected by COVID-19 were of low, variable quality and may be unsustainable. It is important that transmission risks are not increased when new information is incorporated into clinical recommendations. Practice guidelines should emphasise the extent of uncertainty and clearly define gaps in the evidence.

Journal article

Ho A, Webster L, Bowen L, Creighton F, Findlay S, Gale C, Green M, Gronlund T, Magee LA, McManus RJ, Mistry HD, Singleton G, Thornton J, Whybrow R, Chappell Let al., 2020, Research priorities for pregnancy hypertension: a UK priority setting partnership with the James Lind Alliance., BMJ Open, Vol: 10, Pages: 1-8, ISSN: 2044-6055

OBJECTIVES: To identify research priorities for hypertensive disorders of pregnancy from individuals with lived experience and healthcare professionals. DESIGN: Prospective surveys and consensus meetings using principles outlined by the James Lind Alliance. SETTING: UK. METHODS: A steering group was established and 'uncertainties' were gathered using an online survey and literature search. An interim online survey ranked long-listed questions and the top 10 research questions were reached by consensus at a final prioritisation workshop. PARTICIPANTS: Women, partners, relatives and friends of those with lived experience of pregnancy hypertension, researchers and healthcare professionals. RESULTS: The initial online survey was answered by 278 participants (180 women with lived experience, 9 partners/relatives/friends, 71 healthcare professionals and 18 researchers). Together with a literature search, this identified 764 questions which were refined into 50 summary questions. All summary questions were presented in an interim prioritisation survey that was answered by 155 participants (87 women with lived experience, 4 partners/relatives/friends, 49 healthcare professionals and 15 researchers). The top 25 highest ranked questions were considered by the final prioritisation workshop. The top 10 uncertainties were identified by consensus and ranked as follows in order of priority: long-term consequences of pregnancy hypertension (for the woman and baby), short-term complications of pregnancy hypertension (for the woman and baby), screening tests for pre-eclampsia, prevention of long-term problems (for the woman and baby), causes of pregnancy hypertension, prevention of recurrent pregnancy hypertension, educational needs of healthcare professionals, diagnosis of pre-eclampsia, management of pregnancy hypertension, provision of support for women and families. CONCLUSIONS: Research priorities shared by those with lived experience of pregnancy hypertension and healthcare pro

Journal article

Rees P, Stilwell PA, Bolton C, Akillioglu M, Carter B, Gale C, Sutcliffe Aet al., 2020, Childhood Health and Educational Outcomes After Neonatal Abstinence Syndrome: A Systematic Review and Meta-analysis., The Journal of Pediatrics, ISSN: 0022-3476

OBJECTIVE: To systematically review and meta-analyze the association between neonatal abstinence syndrome (NAS) and adverse health or educational childhood outcomes. STUDY DESIGN: An all-language search was conducted across 11 databases between 1/1/75, and 9/3/19, and 5865 titles were identified. Observational studies of children between 28 days and 16 years of age, in whom a diagnosis of NAS was documented, were included. Outcomes included reasons for hospital admissions, childhood diagnoses, developmental outcomes, and academic attainment scores. All studies underwent independent review by two trained reviewers, who extracted study data and assessed risk of bias using the Newcastle Ottawa Tool. RESULTS: Fifteen studies were included comprising 10,907 children with previous NAS and 1,730,213 children without previous NAS, aged 0-16 years. There was a strong association between NAS and subsequent child maltreatment (aOR 6.49 (4.46, 9.45, I2=52%)), injuries and poisoning (aOR 1.34 (1.21, 1.49, I2= 0%)), and a variety of mental health conditions. Studies consistently demonstrated an increased incidence of strabismus and nystagmus among those with previous NAS. Children with NAS also had lower mean academic scores than the control group in every domain of testing across age groups. CONCLUSIONS: NAS is significantly associated with future child maltreatment, mental health diagnoses, visual problems and poor school performance. Due to the necessary inclusion of non-randomized studies, incomplete reporting among studies and likely unadjusted confounding, this review does not suggest causation. However, we highlight associations requiring further investigation and targeted intervention, to positively impact the life course trajectories of this growing population of children.

Journal article

Duffy JMN, Cairns AE, Magee LA, von Dadelszen P, van 't Hooft J, Gale C, Brown M, Chappell LC, Grobman WA, Fitzpatrick R, Karumanchi SA, Lucas DN, Mol B, Stark M, Thangaratinam S, Wilson MJ, Williamson PR, Ziebland S, McManus RJ, International Collaboration to Harmonise Outcomes for Pre-eclampsia iHOPEet al., 2020, Standardising definitions for the pre-eclampsia core outcome set: A consensus development study, Pregnancy Hypertension, Vol: 21, Pages: 208-217, ISSN: 2210-7789

OBJECTIVES: To develop consensus definitions for the core outcome set for pre-eclampsia. STUDY DESIGN: Potential definitions for individual core outcomes were identified across four formal definition development initiatives, nine national and international guidelines, 12 Cochrane systematic reviews, and 79 randomised trials. Eighty-six definitions were entered into the consensus development meeting. Ten healthcare professionals and three researchers, including six participants who had experience of conducting research in low- and middle-income countries, participated in the consensus development process. The final core outcome set was approved by an international steering group. RESULTS: Consensus definitions were developed for all core outcomes. When considering stroke, pulmonary oedema, acute kidney injury, raised liver enzymes, low platelets, birth weight, and neonatal seizures, consensus definitions were developed specifically for low- and middle-income countries because of the limited availability of diagnostic interventions including computerised tomography, chest x-ray, laboratory tests, equipment, and electroencephalogram monitoring. CONCLUSIONS: Consensus on measurements for the pre-eclampsia core outcome set will help to ensure consistency across future randomised trials and systematic reviews. Such standardization should make research evidence more accessible and facilitate the translation of research into clinical practice. Video abstract can be available at: www.dropbox.com/s/ftrgvrfu0u9glqd/6.%20Standardising%20definitions%20in%20teh%20pre-eclampsia%20core%20outcome%20set%3A%20a%20consensus%20development%20study.mp4?dl=0.

Journal article

Gale C, Knight M, Ladhani S, Draper ES, Sharkey D, Doherty D, Mactier H, Kurinczuk JJet al., 2020, National active surveillance to understand and inform neonatal care in COVID-19, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 105, Pages: 346-347, ISSN: 1359-2998

Journal article

Webbe J, Duffy JMN, Afonso E, Al-Muzaffar I, Brunton G, Greenough A, Hall NJ, Knight M, Latour JM, Lee-Davey C, Marlow N, Noakes L, Nycyk J, Richard-Löndt A, Wills-Eve B, Modi N, Gale Cet al., 2020, Core outcomes in neonatology: Development of a core outcome set for neonatal research, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 105, Pages: 425-431, ISSN: 1359-2998

BackgroundNeonatal research evaluates many different outcomes using multiple measures. This canprevent synthesis of trial results in meta-analyses and selected outcomes may not berelevant to former patients, parents and health professionals.ObjectiveTo define a core outcome set (COS) for research involving infants receiving neonatal care ina high income setting.DesignOutcomes reported in neonatal trials and qualitative studies were systematically reviewed.Stakeholders were recruited for a three-round international Delphi survey. A consensusmeeting was held to confirm the final COS, based upon the survey results.ParticipantsFour hundred and fourteen former patients, parents, healthcare professionals andresearchers took part in the eDelphi survey; 173 completed all 3 rounds. Sixteenstakeholders participated in the consensus meeting.ResultsThe literature reviews identified 104 outcomes; these were included in round one.Participants proposed ten additional outcomes; 114 outcomes were scored in round two andthree. Round one scores showed different stakeholder groups prioritised contrastingoutcomes. Twelve outcomes were included in the final COS: survival, sepsis, necrotisingenterocolitis, brain injury on imaging, general gross motor ability, general cognitive ability,quality of life, adverse events, visual impairment/blindness, hearing impairment /deafness,retinopathy of prematurity and chronic lung disease/bronchopulmonary dysplasia.6Conclusions and relevanceA COS for clinical trials and other research studies involving infants receiving neonatal carein a high-income setting has been identified. This COS for neonatology will help standardiseoutcome selection in clinical trials and ensure these are relevant to those most affected byneonatal care.

Journal article

Knight M, Bunch K, Vousden N, Morris E, Simpson N, Gale C, O'Brien P, Quigley M, Brocklehurst P, Kurinczuk JJ, UK Obstetric Surveillance System SARS-CoV-2 Infection in Pregnancy Collaborative Groupet al., 2020, Characteristics and outcomes of pregnant women admitted to hospital with confirmed SARS-CoV-2 infection in UK: national population based cohort study., BMJ, Vol: 369, Pages: m2107-m2107, ISSN: 1759-2151

OBJECTIVES: To describe a national cohort of pregnant women admitted to hospital with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in the UK, identify factors associated with infection, and describe outcomes, including transmission of infection, for mothers and infants. DESIGN: Prospective national population based cohort study using the UK Obstetric Surveillance System (UKOSS). SETTING: All 194 obstetric units in the UK. PARTICIPANTS: 427 pregnant women admitted to hospital with confirmed SARS-CoV-2 infection between 1 March 2020 and 14 April 2020. MAIN OUTCOME MEASURES: Incidence of maternal hospital admission and infant infection. Rates of maternal death, level 3 critical care unit admission, fetal loss, caesarean birth, preterm birth, stillbirth, early neonatal death, and neonatal unit admission. RESULTS: The estimated incidence of admission to hospital with confirmed SARS-CoV-2 infection in pregnancy was 4.9 (95% confidence interval 4.5 to 5.4) per 1000 maternities. 233 (56%) pregnant women admitted to hospital with SARS-CoV-2 infection in pregnancy were from black or other ethnic minority groups, 281 (69%) were overweight or obese, 175 (41%) were aged 35 or over, and 145 (34%) had pre-existing comorbidities. 266 (62%) women gave birth or had a pregnancy loss; 196 (73%) gave birth at term. Forty one (10%) women admitted to hospital needed respiratory support, and five (1%) women died. Twelve (5%) of 265 infants tested positive for SARS-CoV-2 RNA, six of them within the first 12 hours after birth. CONCLUSIONS: Most pregnant women admitted to hospital with SARS-CoV-2 infection were in the late second or third trimester, supporting guidance for continued social distancing measures in later pregnancy. Most had good outcomes, and transmission of SARS-CoV-2 to infants was uncommon. The high proportion of women from black or minority ethnic groups admitted with infection needs urgent investigation and explanation. STUDY REGISTRATION: ISRCTN 4

Journal article

Webbe J, Gale C, A bag half full? NICE Guidelines on Neonatal Parenteral Nutrition, Lancet Child and Adolescent Health, ISSN: 2352-4642

Globally, neonatal conditions are the leading cause of reduced disability adjusted life years (1) and affect outcomes that extend throughout life. Providing neonatal care to optimise such long-term outcomes is challenging as short-term research outcomes may conflict even within individual trials (2). Evidence based guidelines are a welcome tool to translate research into practice and reduce variation in care. Such standardisation of care can improve outcomes for patients: for example, adherence to a standardised enteral feeding guideline is protective against necrotising enterocolitis (3) despite heterogeneity in the content of individual guidelines. The latest NICE guideline on neonatal parenteral nutrition (4) is a welcome addition to neonatal practice, and is particularly important given the deficiencies frequently found in the provision of neonatal nutritional care (5).

Journal article

Duffy JMN, Cairns AE, Richards-Doran D, van 't Hooft J, Gale C, Brown M, Chappell LC, Grobman WA, Fitzpatrick R, Karumanchi SA, Khalil A, Lucas DN, Magee LA, Mol BW, Stark M, Thangaratinam S, Wilson MJ, von Dadelszen P, Williamson PR, Ziebland S, McManus RJ, International Collaboration to Harmonise Outcomes for Pre-eclampsia iHOPEet al., 2020, A core outcome set for pre-eclampsia research: An international consensus development study, BJOG: an International Journal of Obstetrics and Gynaecology, ISSN: 1470-0328

OBJECTIVE: To develop a core outcome set for pre-eclampsia. DESIGN: Consensus development study. SETTING: International. POPULATION: Two hundred and eight one healthcare professionals, 41 researchers, and 110 patients, representing 56 countries, participated METHODS: Modified Delphi method and Modified Nominal Group Technique. RESULTS: A longlist of 116 potential core outcomes was developed, by combining the outcomes reported in 79 pre-eclampsia trials with those derived from thematic analysis of 30 in-depth interviews of women with lived experience of pre-eclampsia. Forty-seven consensus outcomes were identified from the Delphi process following which 14 maternal and eight offspring core outcomes were agreed at the consensus development meeting. Maternal core outcomes: death, eclampsia, stroke, cortical blindness, retinal detachment, pulmonary oedema, acute kidney injury, liver haematoma or rupture, abruption, postpartum haemorrhage, raised liver enzymes, low platelets, admission to intensive care required, and intubation and ventilation. Offspring core outcomes: stillbirth, gestational age at delivery, birth weight, small-for-gestational-age, neonatal mortality, seizures, admission to neonatal unit required, and respiratory support. CONCLUSIONS: The core outcome set for pre-eclampsia should underpin future randomised trials and systematic reviews. Such implementation should ensure future research holds the necessary reach and relevance to inform clinical practice, enhance women's care, and improve the outcomes of pregnant women and their babies.

Journal article

Tume LN, Woolfall K, Arch B, Roper L, Deja E, Jones AP, Latten L, Pathan N, Eccleson H, Hickey H, Parslow R, Preston J, Beissel A, Andrzejewska I, Gale C, Valla FV, Dorling Jet al., 2020, Routine gastric residual volume measurement to guide enteral feeding in mechanically ventilated infants and children: the GASTRIC feasibility study, Health Technology Assessment, Vol: 24, Pages: 1-122, ISSN: 1366-5278

BackgroundThe routine measurement of gastric residual volume to guide the initiation and delivery of enteral feeding is widespread in paediatric intensive care and neonatal units, but has little underlying evidence to support it.ObjectiveTo answer the question: is a trial of no gastric residual volume measurement feasible in UK paediatric intensive care units and neonatal units?DesignA mixed-methods study involving five linked work packages in two parallel arms: neonatal units and paediatric intensive care units. Work package 1: a survey of units to establish current UK practice. Work package 2: qualitative interviews with health-care professionals and caregivers of children admitted to either setting. Work package 3: a modified two-round e-Delphi survey to investigate health-care professionals’ opinions on trial design issues and to obtain consensus on outcomes. Work package 4: examination of national databases to determine the potential eligible populations. Work package 5: two consensus meetings of health-care professionals and parents to review the data and agree consensus on outcomes that had not reached consensus in the e-Delphi study.Participants and settingParents of children with experience of ventilation and tube feeding in both neonatal units and paediatric intensive care units, and health-care professionals working in neonatal units and paediatric intensive care units.ResultsBaseline surveys showed that the practice of gastric residual volume measurement was very common (96% in paediatric intensive care units and 65% in neonatal units). Ninety per cent of parents from both neonatal units and paediatric intensive care units supported a future trial, while highlighting concerns around possible delays in detecting complications. Health-care professionals also indicated that a trial was feasible, with 84% of staff willing to participate in a trial. Concerns expressed by junior nurses about the intervention arm of not measuring gastric residual volumes

Journal article

Gale C, McGuire W, Juszczak E, 2020, Randomised controlled trials for informing perinatal care, Neonatology, Vol: 117, Pages: 8-14, ISSN: 1661-7800

BACKGROUND: Randomised controlled trials provide the best evidence for the effects of interventions and are a key tool in the effort to improve the care and outcomes for newborn infants. METHODS: We discuss the role of randomisation for minimising selection bias in clinical trials and describe examples of seminal trials that have shaped the development of modern perinatal care. We consider the challenges inherent in designing and delivering large, simple, and pragmatic trials, and the need for the development and adoption of core outcome sets to ensure that trials provide high-quality evidence of sufficient validity and applicability to guide policy and practice. RESULTS: Since the earliest days of modern neonatology, the randomised controlled trial has been recognised as the best method for assessing treatments and practices. While many strategies that reduce mortality and morbidity have been introduced following randomised trials, there are, however, important examples of ineffective or potentially harmful practices that have been adopted in the absence of trial-based evidence. Typically, randomised controlled trials in perinatal care need to recruit several thousand participants to be able to detect modest but potentially important effects of new interventions on the most important but rare outcomes. Given the concerns about the financial burden and regulatory complexity of standard trial designs, innovative "efficient" trial designs are being evaluated to streamline processes while safeguarding participants. CONCLUSIONS: Well-conducted randomised controlled trials provide the most robust evaluation of interventions aimed at improving outcomes for newborn infants and their families. Increasingly, these trials will need to be large and multicentre (often international) and use a simple and pragmatic protocol, incorporating meticulous follow-up procedures and assessment of long-term outcomes.

Journal article

Medvedev MM, Brotherton H, Gai A, Tann C, Gale C, Waiswa P, Elbourne D, Lawn JE, Allen Eet al., 2020, Development and validation of a simplified score to predict neonatal mortality risk among neonates weighing 2000 g or less (NMR-2000): an analysis using data from the UK and The Gambia., Lancet Child and Adolescent Health, Vol: 4, Pages: 299-311, ISSN: 2352-4642

BACKGROUND: 78% of neonatal deaths occur in sub-Saharan Africa and southern Asia, among which, more than 80% are in low birthweight babies. Existing neonatal mortality risk scores have primarily been developed for high-resource settings. The aim of this study was to develop and validate a score that is practicable for low-income and middle-income countries to predict in-hospital mortality among neonates born weighing 2000 g or less using datasets from the UK and The Gambia. METHODS: This analysis used retrospective data held in the UK National Neonatal Research Database from 187 neonatal units, and data from the Edward Francis Small Teaching Hospital (EFSTH), Banjul, The Gambia. In the UK dataset, neonates were excluded if birthweight was more than 2000 g; if the neonate was admitted aged more than 6 h or following discharge; if the neonate was stillborn; if the neonate died in delivery room; or if they were moribund on admission. The Gambian dataset included all neonates weighing less than 2000 g who were admitted between May 1, 2018, and Sept 30, 2019, who were screened for but not enrolled in the Early Kangaroo Mother Care Trial. 18 studies were reviewed to generate a list of 84 potential parameters. We derived a model to score in-hospital neonatal mortality risk using data from 55 029 admissions to a random sample of neonatal units in England and Wales from Jan 1, 2010, to Dec 31, 2016. All candidate variables were included in a complete multivariable model, which was progressively simplified using reverse stepwise selection. We validated the new score (NMR-2000) on 40 329 admissions to the remaining units between the same dates and 14 818 admissions to all units from Jan 1, to Dec 31, 2017. We also validated the score on 550 neonates admitted to the EFSTH in The Gambia. FINDINGS: 18 candidate variables were selected for inclusion in the modelling process. The final model included three parameters: birthweight, admission oxygen saturation, and highest level of r

Journal article

Sakonidou S, Andrzejewska I, Webbe J, Modi N, Bell D, Gale Cet al., 2020, Interventions to improve quantitative measures of parent satisfaction in neonatal care: a systematic review, BMJ Paediatrics Open, Vol: 4, ISSN: 2399-9772

Objective: Interventions improving parent satisfaction can reduce parent stress, may improve parent-infant bonding and infant outcomes. Our objective was to systematically review neonatal interventions relating to parents of infants of all gestations where an outcome was parent satisfaction. Methods: We searched the databases MEDLINE, EMBASE, PsychINFO, Cochrane Central Register of Controlled Trials, CINAHL, HMIC, Maternity and Infant Care between 1 January 1946 and 1 October 2017. Inclusion criteria were randomised controlled trials (RCT), cohort studies and other non-randomised studies if participants were parents of infants receiving neonatal care, interventions were implemented in neonatal units (of any care level) and ≥1 quantitative outcome of parent satisfaction was measured. Included studies were limited to the English language only. We extracted study characteristics, interventions, outcomes and parent involvement in intervention design. Included studies were not sufficiently homogenous to enable quantitative synthesis. We assessed quality with the Cochrane Collaboration risk of bias tool (randomised) and the ROBINS-I tool (Risk Of Bias In Non-randomised Studies - of Interventions) (non-randomised studies). Results: We identified 32 studies with satisfaction measures from over 2800 parents and grouped interventions into 5 themes. Most studies were non-randomised involving preterm infants. Parent satisfaction was measured by 334 different questions in 29 questionnaires (only 6/29 fully validated). 18/32 studies reported higher parent satisfaction in the intervention group. The intervention theme with most studies reporting higher satisfaction was parent involvement (10/14). Five (5/32) studies reported involving parents in intervention design. All studies had high risk of bias. Conclusions: Many interventions, commonly relating to parent involvement, are reported to improve parent satisfaction. Inconsistency in satisfaction measurements and high risk of b

Journal article

Tume L, Arch B, Woolfall K, Roper L, Deja E, Jones A, Latten L, Eccleston H, Nazima P, Preston J, Beissel A, Andrzejewska I, Gale C, Valla F, Dorling Jet al., 2020, Determining optimal outcome measures in a trial investigating no routine gastric residual volume measurement in critically ill children, Journal of Parenteral and Enteral Nutrition, ISSN: 0148-6071

BackgroundChoosing trial outcome measures is important. When outcomes are not clinically relevant or important to parents/patients, trial evidence is less likely to be implemented into practice. This study aimed to determine optimal outcome measures for a trial of no routine gastric residual volume (GRV) measurement in critically ill children.MethodsA mixed‐methods approach was used: a focused literature review, parent and clinician interviews, a modified 2‐round Delphi, and a stakeholder consensus meeting.ResultsThe review generated 13 outcomes. Fourteen pediatric intensive care unit (PICU) parents proposed 3 additional outcomes; these 16 were then rated by 28 clinicians in Delphi round 1. Six further outcomes were proposed, and 22 outcomes were rated in the second round. No items were voted “consensus out.” The 18 “no‐consensus” items were voted in a face‐to‐face meeting by 30 participants. The final 12 outcome measures were time to reach energy targets, ventilator‐associated pneumonia, vomiting, time enteral feeds withheld per 24 hours, necrotizing enterocolitis, length of invasive ventilation, PICU length of stay, mortality, change in weight and markers of feed intolerance (parenteral nutrition administered), feed formula altered, and change to postpyloric feeds all secondary to feed intolerance.ConclusionWe have identified 12 outcomes for a trial of no GRV measurement through a multistage process, seeking views of parents and clinicians.

Journal article

Helenius K, Longford N, Lehtonen L, Modi N, Gale Cet al., 2020, Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matching, Obstetrical and Gynecological Survey, Vol: 75, Pages: 145-147, ISSN: 0029-7828

Approximately 1 in 20 preterm infants in high-income countries are born at less than 28 weeks' gestation with increased risk of death and morbidity. Previous studies have shown improved outcomes when care is provided in tertiary hospitals as compared with nontertiary hospitals; this study aims to examine the rate of adverse outcomes for those preterm infants who underwent postnatal transfer to a tertiary facility in England.

Journal article

Brunton G, Webbe J, Oliver S, Gale Cet al., 2020, Adding value to core outcome set development using multi-method systematic reviews, Research Synthesis Methods, Vol: 11, Pages: 248-259, ISSN: 1759-2879

Trials evaluating the same interventions rarely measure or report identical outcomes. This limits the possibility of aggregating effect sizes across studies to generate high quality evidence through systematic reviews and meta-analyses. To address this problem, Core Outcome Sets (COS) establish agreed sets of outcomes to be used in all future trials. When developing COS, potential outcome domains are identified by systematically reviewing the outcomes of trials, and increasingly, through primary qualitative research exploring the experiences of key stakeholders, with relevant outcome domains subsequently determined through transdisciplinary consensus development. However, the primary qualitative component can be time consuming with unclear impact. We aimed to examine the potential added value of a qualitative systematic review alongside a quantitative systematic review of trial outcomes to inform COS development in neonatal care using case analysis methods.We compared the methods and findings of a scoping review of neonatal trial outcomes and a scoping review of qualitative research on parents', patients' and professional caregivers' perspectives of neonatal care. Together, these identified a wider range and greater depth of health and social outcome domains, some unique to each review, which were incorporated into the subsequent Delphi process and informed the final set of core outcome domains. Qualitative scoping reviews of participant perspectives research, used in conjunction with quantitative scoping reviews of trials, could identify more outcome domains for consideration and could provide greater depth of understanding to inform stakeholder group discussion in COS development. This is an innovation in the application of research synthesis methods. This article is protected by copyright. All rights reserved.

Journal article

Oliver S, Uhm S, Duley L, Crowe S, David AL, James CP, Chivers Z, Gyte G, Gale C, Turner M, Chambers B, Dowling I, McNeill J, Alderdice F, Shennan A, Deshpande Set al., 2019, Top research priorities for preterm birth: results of a prioritisation partnership between people affected by preterm birth and healthcare professionals, BMC Pregnancy and Childbirth, Vol: 19, ISSN: 1471-2393

BACKGROUND: We report a process to identify and prioritise research questions in preterm birth that are most important to people affected by preterm birth and healthcare practitioners in the United Kingdom and Republic of Ireland. METHODS: Using consensus development methods established by the James Lind Alliance, unanswered research questions were identified using an online survey, a paper survey distributed in NHS preterm birth clinics and neonatal units, and through searching published systematic reviews and guidelines. Prioritisation of these questions was by online voting, with paper copies at the same NHS clinics and units, followed by a decision-making workshop of people affected by preterm birth and healthcare professionals. RESULTS: Overall 26 organisations participated. Three hundred and eighty six people responded to the survey, and 636 systematic reviews and 12 clinical guidelines were inspected for research recommendations. From this, a list of 122 uncertainties about the effects of treatment was collated: 70 from the survey, 28 from systematic reviews, and 24 from guidelines. After removing 18 duplicates, the 104 remaining questions went to a public online vote on the top 10. Five hundred and seven people voted; 231 (45%) people affected by preterm birth, 216 (43%) health professionals, and 55 (11%) affected by preterm birth who were also a health professional. Although the top priority was the same for all types of voter, there was variation in how other questions were ranked. Following review by the Steering Group, the top 30 questions were then taken to the prioritisation workshop. A list of top 15 questions was agreed, but with some clear differences in priorities between people affected by preterm birth and healthcare professionals. CONCLUSIONS: These research questions prioritised by a partnership process between service users and healthcare professionals should inform the decisions of those who plan to fund research. Priorities of people affecte

Journal article

Webbe J, Ali S, Sakonidou S, Webbe T, Duffy J, Brunton G, Modi N, Gale Cet al., 2019, Inconsistent outcome reporting in large neonatal trials: a systematic review, Archives of Disease in Childhood. Fetal and Neonatal Edition, Vol: 105, Pages: 69-75, ISSN: 1359-2998

ObjectiveInconsistent outcome selection and reporting in clinical trials are important sources of research waste; it is not known how common this problem is in neonatal trials. Our objective was to determine whether large clinical trials involving infants receiving neonatal care report a consistent set of outcomes, how composite outcomes are used and whether parents or former patients were involved in outcome selection.DesignA literature search of CENTRAL, CINAHL, EMBASE and Medline was conducted; randomised trials published between July 1st 2012 and July 1st 2017 and involving at least 100 infants in each arm were included. Outcomes and outcome measures were extracted and categorised by physiological system; reported former patient and parent involvement in outcome selection was extracted.ResultsSeventy six trials involving 43126 infants were identified; 216 different outcomes with 889 different outcome measures were reported. Outcome reporting covered all physiological systems but was variable between individual trials: only 67/76 (88%) of trials reported survival and 639 outcome measures were only reported in a single trial. Thirty three composite outcomes were used in 41 trials. No trials reported former patient or parent involvement in outcome selection.ConclusionsInconsistent outcome reporting and a lack of parent and former patient involvement in outcome selection in neonatal clinical trials limits the ability of such trials to answer clinically meaningful questions. Developing and implementing a core outcome set for future neonatal trials, with input from all stakeholders, should address these issues.

Journal article

Jawad S, Modi N, Prevost AT, Gale Cet al., 2019, A systematic review identifying common data items in neonatal trials and assessing their completeness in routinely recorded United Kingdom national neonatal data, Trials, Vol: 20, ISSN: 1745-6215

BackgroundWe aimed to test whether a common set of key data items reported across high impact neonatal clinical trials could be identified, and to quantify their completeness in routinely recorded United Kingdom neonatal data held in the National Neonatal Research Database (NNRD). MethodsWe systematically reviewed neonatal clinical trials published in four high impact medical journals over 10 years (2006-2015) and extracted baseline characteristics, stratification items, and potential confounders used to adjust primary outcomes. Completeness was examined using data held in the NNRD for identified data items, for infants admitted to neonatal units in 2015. The NNRD is a repository of routinely recorded data extracted from neonatal Electronic Patient Records (EPR) of all admissions to National Health Service (NHS) Neonatal Units in England, Wales and Scotland. We defined missing data as an empty field or an implausible value. We reported common data items as frequencies and percentages alongside percentages of completeness. ResultsWe identified 44 studies involving 32,095 infants and 126 data items. Fourteen data items were reported by more than 20% of studies (table 2). Gestational age (95%), sex (93%) and birth weight (91%) were the most common baseline data items. The completeness of data in the NNRD was high for these data with greater than 90% completeness found for 9 of the 14 most common items.Conclusion High impact neonatal clinical trials share common data items. In the United Kingdom, these items can be obtained at a high level of completeness from routinely recorded data held in the NNRD. The feasibility and efficiency using routinely recorded EPR data, such as that held in the NNRD, for clinical trials, rather than collecting these items anew, should be examined.

Journal article

Kwok TC, Dorling J, Gale C, 2019, Early enteral feeding in preterm infants, Seminars in Perinatology, Vol: 43, Pages: 1-11, ISSN: 0146-0005

Early enteral feeding is a potentially modifiable risk factor for necrotising enterocolitis (NEC) and late onset sepsis (LOS), however enteral feeding practices for preterm infants are highly variable. High-quality evidence is increasingly available to guide early feeding in preterm infants. Meta-analyses of randomised trials indicate that early trophic feeding within 48 h after birth and introduction of progressive enteral feeding before 4 days of life at an advancement rate above 24 ml/kg/day can be achieved in clinically stable very preterm and very low birthweight (VLBW) infants, without higher mortality or incidence of NEC. This finding may not be generalisable to high risk infants such as those born small for gestational age (SGA) or following absent/reversed end diastolic flow velocity (AREDFV) detected antenatally on placental Doppler studies, due to the small number of such infants in existing trials. Trials targeting such high-risk preterm infants have demonstrated that progressive enteral feeding started in the first 4 days is safe and does not lead to higher NEC or mortality; however, there is a paucity of data to guide feeding advancement in such infants. There is little trial evidence to support bolus or continuous gavage feeding as being superior in clinically stable preterm infants. Trials that examine enteral feeding are commonly unblinded for technical and practical reasons, which increases the risk of bias in such trials, specifically when considering potentially subjective outcome such as NEC and LOS; future clinical trials should focus on objective, primary outcome measures such as all-cause mortality, long term growth and neurodevelopment. Alternatively, important short-term outcomes such as NEC could be used with blinded assessment.

Journal article

Duffy JMN, Hirsch M, Ziebland S, McManus RJ, Duffy JMN, Brown M, Gale C, Grobman W, Fitzpatrick R, Karumanchi SA, Lucas N, Magee L, Mol B, Stark M, Thangaratinam S, Wilson M, Hooft JV, von Dadelszen P, Williamson PR, Khan KS, Ziebland S, McManus RJet al., 2019, Methodological decisions influence the identification of potential core outcomes in studies related to pre-eclampsia: an analysis informing the development of recommendations for future core outcome set developers, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 126, Pages: 1482-1490, ISSN: 1470-0328

Journal article

Jawad S, Modi N, Prevost AT, Gale Cet al., A systematic review identifying common data items in neonatal trials and assessing their completeness in routinely recorded United Kingdom national neonatal data, Trials, ISSN: 1745-6215

<jats:title>Abstract</jats:title> <jats:p>BackgroundWe aimed to test whether a common set of key data items reported across high impact neonatal clinical trials could be identified, and to quantify their completeness in routinely recorded United Kingdom neonatal data held in the National Neonatal Research Database (NNRD). MethodsWe systematically reviewed neonatal clinical trials published in four high impact medical journals over 10 years (2006-2015) and extracted baseline characteristics, stratification items, and potential confounders used to adjust primary outcomes. Completeness was examined using data held in the NNRD for identified data items, for infants admitted to neonatal units in 2015. The NNRD is a repository of routinely recorded data extracted from neonatal Electronic Patient Records (EPR) of all admissions to National Health Service (NHS) Neonatal Units in England, Wales and Scotland. We defined missing data as an empty field or an implausible value. We reported common data items as frequencies and percentages alongside percentages of completeness.ResultsWe identified 44 studies involving 32,095 infants and 126 data items. Fourteen data items were reported by more than 20% of studies. Gestational age (95%), sex (93%) and birth weight (91%) were the most common baseline data items. The completeness of data in the NNRD was high for these data with greater than 90% completeness found for 9 of the 14 most common items.ConclusionHigh impact neonatal clinical trials share common data items. In the United Kingdom, these items can be obtained at a high level of completeness from routinely recorded data held in the NNRD. The feasibility and efficiency using routinely recorded EPR data, such as that held in the NNRD, for clinical trials, rather than collecting these items anew, should be examined.RegistrationPROSPERO registration number CRD42016046138, registered prospectively 17 th August 2016</jats:p>

Journal article

Helenius K, Longford N, Lehtonen L, Modi N, Gale C, Babirecki M, Kamalanathan A, Wickham T, Aucharaz K, Gupta A, Paul N, Wong LM, Mittal A, Broggio P, Surana P, Singh A, Seal S, Hassan A, Schwarz K, Thomas M, Foo A, Anderson J, Whincup G, Brearey S, Chang J, Gad K, Hasib A, Garbash M, Allwood A, Adiotomre P, Brooke N, Deketelaere A, Khader KA, Shephard R, Rekha S, Abuzgia B, Jain M, Pirie S, Surana P, Zengeya S, Watts T, Balal S, Seagrave C, Bate T, Dixon H, Aladangady N, Gaili H, James M, Lal M, Ambadkar P, Pandey P, Hickey A, Rhodes S, Pai V, Lama M, Miall L, Cusack J, Kairamkonda V, Grosdenier M, Kollipara L, Kefas J, Yoxall B, Birch J, Whitehead G, Krishnamurthy R, Sashikumar P, Misra I, Pillay T, Ali I, Thiagarajan P, Dyke M, Selter M, Kamath P, Alsford L, Spencer V, Gupta S, Nicholl R, Wardle S, Chakrabarti S, Adams E, McDevitt K, Reddy A, Gibson D, Khashu M, Reddy C, Pearson F, Amess P, Deshpande S, Sleight E, Groves C, Godambe S, Bosman D, Rewitzky G, Banjoko O, Kumar N, Muogbo D, Lopez W, D'Amore A, Mattara S, Zipitis C, De Halpert P, Settle P, Munyard P, McIntyre J, Bartle D, Pain K, Fedee J, Maddock N, Gupta R, Moore A, Godden C, Amess P, Jones S, Fenton A, Mahadevan S, Brown N, Mack K, Adiotomre P, Bolton R, Khan A, Mannix P, Huddy C, Yasin S, Butterworth S, Godambe S, Nedungadi S, Cairns P, Reynolds P, Brennan N, Heal C, Salgia S, Abu-Harb M, Birch J, Knight C, Clark S, Theron M, Murthy V, Paul S, Kisat H, Kendall G, Blake K, Obi O, Garbash M, Kumar H, Rawlingson C, Webb D, Bird S, Narayanan S, Eyre E, Evans I, Sanghavi R, Sullivan C, Garr R, Leith W, Vasu V, Harry L, Vamvakiti K, Vemuri G, Eaton M, Samy Met al., 2019, Association of early postnatal transfer and birth outside a tertiary hospital with mortality and severe brain injury in extremely preterm infants: observational cohort study with propensity score matching, BMJ: British Medical Journal, Vol: 367, Pages: 1-11, ISSN: 0959-535X

Objective To determine if postnatal transfer or birth in a non-tertiary hospital is associated with adverse outcomes.Design Observational cohort study with propensity score matching.Setting National health service neonatal care in England; population data held in the National Neonatal Research Database.Participants Extremely preterm infants born at less than 28 gestational weeks between 2008 and 2015 (n=17 577) grouped based on birth hospital and transfer within 48 hours of birth: upward transfer (non-tertiary to tertiary hospital, n=2158), non-tertiary care (born in non-tertiary hospital; not transferred, n=2668), and controls (born in tertiary hospital; not transferred, n=10 866). Infants were matched on propensity scores and predefined background variables to form subgroups with near identical distributions of confounders. Infants transferred between tertiary hospitals (horizontal transfer) were separately matched to controls in a 1:5 ratio.Main outcome measures Death, severe brain injury, and survival without severe brain injury.Results 2181 infants, 727 from each group (upward transfer, non-tertiary care, and control) were well matched. Compared with controls, infants in the upward transfer group had no significant difference in the odds of death before discharge (odds ratio 1.22, 95% confidence interval 0.92 to 1.61) but significantly higher odds of severe brain injury (2.32, 1.78 to 3.06; number needed to treat (NNT) 8) and significantly lower odds of survival without severe brain injury (0.60, 0.47 to 0.76; NNT 9). Compared with controls, infants in the non-tertiary care group had significantly higher odds of death (1.34, 1.02 to 1.77; NNT 20) but no significant difference in the odds of severe brain injury (0.95, 0.70 to 1.30) or survival without severe brain injury (0.82, 0.64 to 1.05). Compared with infants in the upward transfer group, infants in the non-tertiary care group had no significant difference in death before discharge (1.10, 0.84

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