Publications
69 results found
Beardmore-Gray A, Seed PT, Fleminger J, et al., 2022, Planned delivery or expectant management in preeclampsia: an individual participant data meta-analysis., American Journal of Obstetrics and Gynecology, Vol: 227, Pages: 218-230.e8, ISSN: 0002-9378
OBJECTIVE: Pregnancy hypertension is a leading cause of maternal and perinatal mortality and morbidity. Between 34+0 and 36+6 weeks gestation, it is uncertain whether planned delivery could reduce maternal complications without serious neonatal consequences. In this individual participant data meta-analysis, we aimed to compare planned delivery to expectant management, focusing specifically on women with preeclampsia. DATA SOURCES: We performed an electronic database search using a prespecified search strategy, including trials published between January 1, 2000 and December 18, 2021. We sought individual participant-level data from all eligible trials. STUDY ELIGIBILITY CRITERIA: We included women with singleton or multifetal pregnancies with preeclampsia from 34 weeks gestation onward. METHODS: The primary maternal outcome was a composite of maternal mortality or morbidity. The primary perinatal outcome was a composite of perinatal mortality or morbidity. We analyzed all the available data for each prespecified outcome on an intention-to-treat basis. For primary individual patient data analyses, we used a 1-stage fixed effects model. RESULTS: We included 1790 participants from 6 trials in our analysis. Planned delivery from 34 weeks gestation onward significantly reduced the risk of maternal morbidity (2.6% vs 4.4%; adjusted risk ratio, 0.59; 95% confidence interval, 0.36-0.98) compared with expectant management. The primary composite perinatal outcome was increased by planned delivery (20.9% vs 17.1%; adjusted risk ratio, 1.22; 95% confidence interval, 1.01-1.47), driven by short-term neonatal respiratory morbidity. However, infants in the expectant management group were more likely to be born small for gestational age (7.8% vs 10.6%; risk ratio, 0.74; 95% confidence interval, 0.55-0.99). CONCLUSION: Planned early delivery in women with late preterm preeclampsia provides clear maternal benefits and may reduce the risk of the infant being born small for gestational
Dallera G, Skopec M, Barlow J, et al., 2022, Review of a frugal cooling mattress to induce therapeutic hypothermia for treatment of hypoxic-ischaemic encephalopathy in the UK NHS, Globalization and Health, Vol: 18, ISSN: 1744-8603
Hypoxic ischaemic encephalopathy (HIE) is a major cause of neonatal mortality and disability in the United Kingdom (UK) and has significant human and financial costs. Therapeutic hypothermia (TH), which consists of cooling down the newborn’s body temperature, is the current standard of treatment for moderate or severe cases of HIE. Timely initiation of treatment is critical to reduce risk of mortality and disability associated with HIE. Very expensive servo-controlled devices are currently used in high-income settings to induce TH, whereas low-income settings rely on the use of low-tech devices such as water bottles, ice packs or fans. Cooling mattresses made with phase change materials (PCMs) were recently developed as a safe, efficient, and affordable alternative to induce TH in low-income settings. This frugal innovation has the potential to become a reverse innovation for the National Health Service (NHS) by providing a simple, efficient, and cost-saving solution to initiate TH in geographically remote areas of the UK where cooling equipment might not be readily available, ensuring timely initiation of treatment while waiting for neonatal transport to the nearest cooling centre. The adoption of PCM cooling mattresses by the NHS may reduce geographical disparity in the availability of treatment for HIE in the UK, and it could benefit from improvements in coordination across all levels of neonatal care given challenges currently experienced by the NHS in terms of constraints on funding and shortage of staff. Trials evaluating the effectiveness and safety of PCM cooling mattresses in the NHS context are needed in support of the adoption of this frugal innovation. These findings may be relevant to other high-income settings that experience challenges with the provision of TH in geographically remote areas. The use of promising frugal innovations such as PCM cooling mattresses in high-income settings may also contribute to challenge the dominant narrative that
Greenbury SF, Angelini DE, Ougham K, et al., 2022, Post-natal growth of very preterm neonates, The Lancet Child & Adolescent Health, Vol: 6, Pages: E11-E11, ISSN: 2352-4642
Uthaya S, Longford N, Battersby C, et al., 2022, Early versus later initiation of parenteral nutrition for very preterm infants: a propensity score matched observational study, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 107, ISSN: 1359-2998
Background: A current standard of care based on expert opinion is to commence parenteral nutrition (PN) within hours of birth in very preterm infants. Trials in critically ill adults and children, including term infants have found short and long-term harms from early initiation of PN. Methods: We included all infants born below 31 weeks gestation between January 2008 and December 2019 and admitted to National Health Service neonatal units in England and Wales. The source of data was the National Neonatal Research Database. The exposure was PN initiated within the first two days after birth (early) versus after the second postnatal day (late). We used propensity matched analysis to balance the two groups on background variables. The primary outcome was survival to discharge without major morbidity. Findings: Of 65,033 infants included, 16,294 infants formed the matched cohort, 8147 in each group. There was no evidence of a difference in survival to discharge without major morbidity (absolute rate difference (ARD) between early versus late 0·50%; 95% Confidence Interval (CI), -1·45, 0·45; p=0·29). Survival to discharge was higher in the early group (ARD -3·25%; 95% CI, -3·82 to -2·68; p<0·001) but they also had higher rates of late-onset sepsis (ARD -0·84%; 95% CI, -1·20 to -0·48; p<0·001), bronchopulmonary dysplasia (ARD -1·24%; 95% CI, -2·17 to -0·30; p=0·01), treatment for retinopathy of prematurity (ARD (-0·5%; 95% CI, -0·84 to -0.17; p<0·001), surgical procedures (ARD -0·8%; 95% CI, -1·40 to -0·20; p=0·01) and greater drop in weight z-score between birth and discharge (absolute difference 0·019; 95% CI, 0·003 to 0·039; p=0·02). Among infants that died the median age (days) at death was shorter in the late group (ARD 6; 95% CI, 6; p<0.001). Interpretation: These o
Webbe J, Longford N, Battersby C, et al., 2022, Outcomes in relation to early parenteral nutrition use in preterm neonates born between 30 and 33 weeks gestation: a propensity score matched observational study, Archives of Disease in Childhood: Fetal and Neonatal Edition, Vol: 107, Pages: 131-136, ISSN: 1359-2998
ObjectiveTo evaluate whether in preterm neonates parenteral nutrition use in the first sevenpostnatal days, compared with no parenteral nutrition use, is associated withdifferences in survival and other important morbidities. Randomised trials in criticallyill older children show that harms, such as nosocomial infection, outweigh benefits ofearly parenteral nutrition administration; there is a paucity of similar data inneonates.DesignRetrospective cohort study using propensity matching including 35 maternal, infantand organisational factors to minimise bias and confounding.SettingNational, population-level clinical data obtained for all National Health Serviceneonatal units in England and Wales.PatientsPreterm neonates born between 30+0 and 32+6 weeks+days.InterventionsThe exposure was parenteral nutrition administered in the first seven days ofpostnatal life; the comparator was no parenteral nutrition.Main outcome measuresThe primary outcome was survival to discharge from neonatal care. Secondaryoutcomes comprised the neonatal core outcome set.Results16,292 neonates were compared in propensity score matched analyses. Comparedwith matched neonates not given parenteral nutrition in the first postnatal week, neonates who received parenteral nutrition had higher survival at discharge(absolute rate increase 0.91%; 95% CI 0.53% to 1.30%), but higher rates ofnecrotising enterocolitis (absolute rate increase 4.6%), bronchopulmonary dysplasia(absolute rate increase 3.9%), late-onset sepsis (absolute rate increase 1.5%) andneed for surgical procedures (absolute rate increase 0.92%).ConclusionsIn neonates born between 30+0 and 32+6 weeks gestation, those given parenteralnutrition in the first postnatal week had a higher rate of survival but higher rates ofimportant neonatal morbidities. Clinician equipoise in this area should be resolvedby prospective, randomised trials.
Ashworth D, Battersby C, Green M, et al., 2022, Which antihypertensive treatment is better for mild to moderate hypertension in pregnancy?, BMJ: British Medical Journal, Vol: 376, Pages: 1-4, ISSN: 0959-535X
Stefani G, Skopec M, Battersby C, et al., 2021, Why is Kangaroo Mother Care not yet scaled in the UK? A systematic review and realist synthesis of a frugal innovation for newborn care, BMJ Innovations, Vol: 8, Pages: 9-20, ISSN: 2055-642X
Objective: Kangaroo Mother Care (KMC) is a frugal innovation improving newborn health at a reduced cost compared with incubator use. KMC is widely recommended; however, in the UK, poor evidence exists on KMC, and its implementation remains inconsistent.Design: This Systematic Review and Realist Synthesis explores the barriers and facilitators in the implementation of KMC in the UK.Data source: OVID databases, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Scopus and Google Scholar were searched.Eligibility criteria: Studies were UK based, in maternity/neonatal units, for full-term/preterm children. First screening included studies on (1) KMC, Kangaroo Care (KC) or skin-to-skin contact (SSC) or (2) Baby Friendly Initiative, Small Wonders Change Program or family-centred care if in relation to KMC/KC/SSC. Full texts were reviewed for evidence regarding KMC/KC/SSC implementation.Results: The paucity of KMC research in the UK did not permit a realist review. However, expanded review of available published studies on KC and SSC, used as a proxy to understand KMC implementation, demonstrated that the main barriers are the lack of training, knowledge, confidence and clear guidelines.Conclusion: The lack of KMC implementation research in the UK stands in contrast to the already well-proven benefits of KMC for stable babies in low-income contexts and highlights the need for further research, especially in sick and small newborn population. Implementation of, and research into, KC/SSC is inconsistent and of low quality. Improvements are needed to enhance staff training and parental support, and to develop guidelines to properly implement KC/SSC. It should be used as an opportunity to emphasise the focus on KMC as a potential cost-effective alternative to reduce the need for incubator use in the UK.
Kimpton J, Verma A, Thakkar D, et al., 2021, Comparison of NICE Guideline CG149 and the Sepsis Risk Calculator for the management of early onset sepsis on the postnatal ward, Neonatology: foetal and neonatal research, Vol: 118, Pages: 562-568, ISSN: 1661-7800
Introduction: NICE guideline CG149 has increased the number of well infants receiving antibiotics for suspected early onset sepsis (EOS). The Kaiser Permanente sepsis risk calculator (SRC) has safely and dramatically reduced investigations and antibiotics for suspected EOS in the USA. This study evaluates current management of suspected EOS against NICE guideline CG149 and the SRC. Methods: Prospective, multicentre, observational study across 13 neonatal units in London. Infants were born between June and August 2019 >34 weeks gestation and commenced on antibiotics for suspected EOS and cared for on postnatal/transitional care wards. Data were prospectively recorded: risk factors, clinical indicators, investigations and results. Outcome measures: 1) Incidence of EOS. 2) Proportion of infants recommended for antibiotics by NICE versus theoretical application of SRC. Results: 1066/8856 (12%) infants on postnatal/transitional care wards received antibiotics, 7 of whom had a positive blood culture (group B Streptococcus = 6, Escherichia coli = 1), making the EOS incidence 0.8/1000 infants. 601 infants had data for SRC analysis, which recommended “antibiotics” or “blood culture” for 130/601 (21.6%) infants using an EOS incidence of 0.5/1000 vs 527/601 (87.7%) if NICE was applied. Conclusions: Currently 12.0% of infants on postnatal/transitional care wards receive antibiotics for suspected EOS. The SRC could dramatically reduce antibiotic use but further prospective studies are required to evaluate safety of SRC implementation.
Greenbury SF, Longford N, Ougham K, et al., 2021, Changes in neonatal admissions, care processes and outcomes in England and Wales during the COVID-19 pandemic: a whole population cohort study, BMJ Open, Vol: 11, ISSN: 2044-6055
Objectives: The COVID-19 pandemic instigated multiple societal and healthcare interventions with potential to affect perinatal practice. We evaluated population-level changes in preterm and full-term admissions to neonatal units, care processes and outcomes.Design: Observational cohort study using the UK National Neonatal Research Database.Setting: England and Wales.Participants: Admissions to National Health Service neonatal units from 2012 to 2020.Main outcome measures: Admissions by gestational age, ethnicity and Index of Multiple Deprivation, and key care processes and outcomes.Methods: We calculated differences in numbers and rates between April and June 2020 (spring), the first 3 months of national lockdown (COVID-19 period), and December 2019–February 2020 (winter), prior to introduction of mitigation measures, and compared them with the corresponding differences in the previous 7 years. We considered the COVID-19 period highly unusual if the spring–winter difference was smaller or larger than all previous corresponding differences, and calculated the level of confidence in this conclusion.Results: Marked fluctuations occurred in all measures over the 8 years with several highly unusual changes during the COVID-19 period. Total admissions fell, having risen over all previous years (COVID-19 difference: −1492; previous 7-year difference range: +100, +1617; p<0.001); full-term black admissions rose (+66; −64, +35; p<0.001) whereas Asian (−137; −14, +101; p<0.001) and white (−319; −235, +643: p<0.001) admissions fell. Transfers to higher and lower designation neonatal units increased (+129; −4, +88; p<0.001) and decreased (−47; −25, +12; p<0.001), respectively. Total preterm admissions decreased (−350; −26, +479; p<0.001). The fall in extremely preterm admissions was most marked in the two lowest socioeconomic quintiles.Conclusions: Our findings indicate substantia
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
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.
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.
Greenbury SF, Angelini ED, Ougham K, et al., 2021, Birthweight and Patterns of Postnatal Weight Gain in Very and Extremely Preterm Babies: A 12 Year, Whole Population Study, The Lancet Child & Adolescent Health, ISSN: 2352-4642
Lammons W, Moss R, Battersby C, et al., 2021, Incorporating parent, former patient, and clinician perspectives in the design of a national UK double-cluster, randomised controlled trial addressing uncertainties in preterm nutrition, BMJ Paediatrics Open, Vol: 5, ISSN: 2399-9772
Background: Comparative effectiveness randomised controlled trials are powerful tools to resolve uncertainties in existing treatments and care processes. We sought parent and patient perspectives on the design of a planned national, double-cluster randomised controlled trial (COLLABORATE) to resolve two longstanding uncertainties in preterm nutrition.Methods: We used qualitative focus groups and interviews with parents, former patients and clinicians. We followed the Consolidated Criteria for Reporting Qualitative Research checklist and conducted framework analysis, a specific methodology within thematic analysis.Results: We identified support for the trial’s methodology and vision, and elicited themes illustrating parents’ emotional needs in relation to clinical research. These were: relieving the pressure on mothers to breastfeed; opt-out consent as reducing parent stress; the desire for research to be a partnership between clinicians, parents and researchers; the value of presenting trial information in a collaborative tone; and in a format that allows assimilation by parents at their own pace. We identified anxiety and cognitive dissonance among some clinicians in which they recognised the uncertainties that justify the trial but felt unable to participate because of their strongly held views.Conclusions: The early involvement of parents and former patients identified the centrality of parents’ emotional needs in the design of comparative effectiveness research. These insights have been incorporated into trial enrolment processes and information provided to participants. Specific outputs were a two-sided leaflet providing very brief as well as more detailed information, and use of language that parents perceive as inclusive and participatory. Further work is warranted to support clinicians to address personal biases that inhibit trial participation.
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, 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
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, 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
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.
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.
Battersby C, Gale C, Modi N, 2020, CLINICAL TRIALS IN NEC RESEARCH: Advances, Perils, and Pitfalls, Necrotizing Enterocolitis: Insights into Pathogenesis, Diagnosis and Treatment, Editors: Hackham, Publisher: World Scientific, ISBN: 978-981-4725-94-1
Yeo KT, Oei JL, De Luca D, et 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, Vol: 109, Pages: 2192-2207, 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.
Johnson SM, Vasu V, Marseille C, et al., 2020, Validation of transcutaneous bilirubinometry during phototherapy for detection and monitoring of neonatal jaundice in a low-income setting, Paediatrics and International Child Health, Vol: 40, Pages: 25-29, ISSN: 2046-9047
Background Severe neonatal jaundice (SNJ) and associated long term health sequelae are a significant problem in low income countries (LIC) where measurement of total serum bilirubin (TSB) is often unavailable. Transcutaneous bilirubinometry (TcB) provides opportunity for non-invasive, point-of-care monitoring. Few studies have evaluated its agreement with TSB levels during phototherapy in LICs.AimTo determine agreement between TcB and TSB during phototherapy in a Haiti newborn population, and to establish if TcB can be safely used to guide treatment during photother-apy when TSB is unavailable. MethodsA single centre prospective study (February-May 2017) in Cap Haïtien, northern Haiti was conducted. Newborns with clinically detected jaundice, <7 days of age were eligible for inclusion. A TcB device (JM-103) was used to screen for newborn jaundice along with a parallel TSB. A strip of black tape was placed across the sternum during phototherapy and uncovered for subsequent TcB measurements. Phototherapy treatment decisions were based upon UK National Institute of Clinical Excellence (NICE) threshold criteria. Paired TSB and TcB measurements were compared using Bland Altman methods. Results The final analysis included 70 parallel TSB/TcB measurements from 35 infants within the first five days of life. 19 (54.3%) were male; 12 (34.3%) were <35 weeks. 32 (91.4%) were receiving phototherapy. There was good agreement between TSB and TcB. TcB tended to overestimate bilirubin in comparison to TSB; mean difference 11.1 µmol/L (95% CI -10.2, 32.5 µmol/L). However, at higher bilirubin levels (>250 µmol/L), TcB tended to underestimate bilirubin in comparison to TSB and the magnitude of the differ-ence increased. ConclusionIn a LIC setting where serum bilirubin testing is not commonly available, TcB demon-strates good agreement with TSB and can be safely used to guide jaundice treatment dur-ing phototherapy but may lead to overtreatment at lowe
Modi N, Ashby D, Battersby C, et al., 2019, Developing routinely recorded clinical data from electronic patient records as a national resource to improve neonatal health care: the Medicines for Neonates research programme, Programme Grants for Applied Research, Vol: 7, Pages: 1-396, ISSN: 2050-4322
BackgroundClinical data offer the potential to advance patient care. Neonatal specialised care is a high-cost NHS service received by approximately 80,000 newborn infants each year.Objectives(1) To develop the use of routinely recorded operational clinical data from electronic patient records (EPRs), secure national coverage, evaluate and improve the quality of clinical data, and develop their use as a national resource to improve neonatal health care and outcomes. To test the hypotheses that (2) clinical and research data are of comparable quality, (3) routine NHS clinical assessment at the age of 2 years reliably identifies children with neurodevelopmental impairment and (4) trial-based economic evaluations of neonatal interventions can be reliably conducted using clinical data. (5) To test methods to link NHS data sets and (6) to evaluate parent views of personal data in research.DesignSix inter-related workstreams; quarterly extractions of predefined data from neonatal EPRs; and approvals from the National Research Ethics Service, Health Research Authority Confidentiality Advisory Group, Caldicott Guardians and lead neonatal clinicians of participating NHS trusts.SettingNHS neonatal units.ParticipantsNeonatal clinical teams; parents of babies admitted to NHS neonatal units.InterventionsIn workstream 3, we employed the Bayley-III scales to evaluate neurodevelopmental status and the Quantitative Checklist of Autism in Toddlers (Q-CHAT) to evaluate social communication skills. In workstream 6, we recruited parents with previous experience of a child in neonatal care to assist in the design of a questionnaire directed at the parents of infants admitted to neonatal units.Data sourcesData were extracted from the EPR of admissions to NHS neonatal units.Main outcome measuresWe created a National Neonatal Research Database (NNRD) containing a defined extract from real-time, point-of-care, clinician-entered EPRs from all NHS neonatal units in England, Wales and Scotland (
Ojha S, Battersby C, Longford NT, et al., 2019, OPTIMISING NURTITION DURING THERAPEUTIC HYPOTHERMIA: AN OBSERVATIONAL STUDY USING PROPENSITY SCORE MATCHING, 3rd Congress of Joint European Neonatal Societies (jENS), Publisher: NATURE PUBLISHING GROUP, Pages: 20-21, ISSN: 0031-3998
Ojha S, Dorling J, Battersby C, et al., 2019, Optimising nutrition during therapeutic hypothermia, Archives of Disease in Childhood. Fetal and Neonatal Edition, Vol: 104, Pages: F230-F231, ISSN: 1359-2998
There is little evidence to inform provision of enteral or parenteral nutrition to infants with hypoxic ischaemic encephalopathy (HIE) during and soon after therapeutic hypothermia; as a consequence, clinical practice is both variable and changing. A 2014 UK survey found that 79% (33 of 42) of responding neonatal units routinely withheld enteral nutrition during cooling; 3 years later, a similar survey found that 41% (20 of 49) of responding units reported withholding enteral nutrition.1 The latter study also reports wide variation in how, when and how much to feed, and in the use of parenteral nutrition. Internationally, practice is even more variable: withholding enteral feeds is practised almost universally2 in some countries, while in others, milk feeding during hypothermia is routine.3 Here we discuss the limited evidence available to inform enteral and parenteral nutrition during therapeutic hypothermia.
Battersby C, Modi N, 2019, Challenges in advancing necrotizing enterocolitis research, Clinics in Perinatology, Vol: 46, Pages: 19-27, ISSN: 0095-5108
Progressing necrotizing enterocolitis research is difficult because the disease is variable in presentation, there are difficulties in making a precise diagnosis, a reliable agreed case-definition is currently lacking, and there is a paucity of preclinical research to identify etiologic targets. The major challenges of the cost of clinical trials and need for long-term outcome ascertainment could be eased through incorporation of novel randomization approaches and data collection into routine care, and collaboration between public-sector and industry funders.
Modi N, Ashby D, Battersby C, et al., 2018, Using routinely recorded clinical data for research: the Medicines for Neonates research programme, Programme Grants for Applied Research, ISSN: 2050-4322
Background: Clinical data offer potential to advance patient care. Neonatal specialised care is a high cost NHS service received by approximately 80,000 newborn infants each year. Objectives: To 1) develop the use of routinely recorded operational clinical data from Electronic Patient Records (EPR), secure national coverage, evaluate and improve the quality of clinical data, and develop their use as a national resource to improve neonatal healthcare and outcomes; test the hypotheses that 2) clinical and research data are of comparable quality; 3) routine NHS clinical assessment at age two-years reliably identifies children with neurodevelopmental impairment; and 4) trial-based economic evaluations of neonatal interventions can be reliably conducted using clinical data; 5) test methods to link NHS datasets; 6) evaluate parent views of personal data in research Design: Six interrelated work-streams; quarterly extractions of predefined data from neonatal EPR; approvals from the National Research Ethics Service, Health Research Authority Confidentiality Advisory Group, Caldicott Guardians and lead neonatal clinicians of participating NHS Trusts Setting: NHS neonatal unitsParticipants: Neonatal clinical teams; parents of babies admitted to NHS neonatal unitsInterventions: In work-stream 3 we employed the Bayley-III scales to evaluate neurodevelopmental status and the Quantitative Checklist of Autism in Toddlers (Q-CHAT) to evaluate social-communication skills. In work-stream 6 we recruited parents with previous experience of a child in neonatal care to assist in the design of a questionnaire directed at the parents of infants admitted to neonatal units. Data sources: Data extracted from the EPR of admissions to NHS neonatal units Main outcomes and results: We created a National Neonatal Research Database (NNRD) containing a defined extract from real-time, point-of-care, clinician-entered EPR from all NHS neonatal units in England, Wales and Scotland (n=200), establish
Battersby C, Longford N, Patel M, et al., 2018, Study Protocol: Optimising newborn nutrition during and after neonatal therapeutic hypothermia in the United Kingdom: Observational study of routinely collected data using propensity matching, BMJ Open, Vol: 8, ISSN: 2044-6055
ntroduction Therapeutic hypothermia is standard of care for infants born ≥36 weeks gestation with hypoxic ischaemic encephalopathy (HIE); consensus on optimum nutrition during therapeutic hypothermia is lacking. This results in variation in enteral feeding and parenteral nutrition (PN) for these infants. In this study, we aim to determine the optimum enteral nutrition and PN strategy for newborns with HIE during therapeutic hypothermia.Methods and analysis We will undertake a retrospective cohort study using routinely recorded electronic patient data held on the United Kingdom (UK) National Neonatal Research Database (NNRD). We will extract data from infants born ≥36 weeks gestational age between 1 January 2008 and 31 December 2016, who received therapeutic hypothermia for at least 72 hours or died during therapeutic hypothermia, in neonatal units in England, Wales and Scotland. We will form matched groups in order to perform two comparisons examining: (1) the risk of NEC between infants enterally fed and infants not enterally fed, during therapeutic hypothermia; (2) the risk of late-onset blood stream infections between infants who received intravenous dextrose without any PN and infants who received PN, during therapeutic hypothermia. The following secondary outcomes will also be examined: survival, length of stay, breast feeding at discharge, hypoglycaemia, time to full enteral feeds and growth. Comparison groups will be matched on demographic, maternal, infant and organisational factors using propensity score matching.Ethics and dissemination In this study, we will use deidentifed data held in the NNRD, an established national population database; parents can opt out of their baby’s data being held in the NNRD. This study holds study-specific Research Ethics Committee approval (East Midlands Leicester Central, 17/EM/0307). These results will help inform optimum nutritional management in infants with HIE receiving therapeutic hypothermia; resul
Battersby C, Statnikov Y, Santhakumaran S, et al., 2018, The United Kingdom National Neonatal Research Database: a validation study, PLoS ONE, Vol: 13, ISSN: 1932-6203
BackgroundThe National Neonatal Research Database (NNRD) is a rich repository of pre-defined clinical data extracted at regular intervals from point-of-care, clinician-entered electronic patient records on all admissions to National Health Service neonatal units in England, Wales, and Scotland. We describe population coverage for England and assess data completeness and accuracy.MethodsWe determined population coverage of the NNRD in 2008–2014 through comparison with data on live births in England from the Office for National Statistics. We determined the completeness of seven data items on the NNRD. We assessed the accuracy of 44 data items (16 patient characteristics, 17 processes, 11 clinical outcomes) for infants enrolled in the multi-centre randomised controlled trial, Probiotics in Preterm Study (PiPs). We compared NNRD to PiPs data, the gold standard, and calculated discordancy rates using predefined criteria, and sensitivity, specificity and positive predictive values (PPV) of binary outcomes.ResultsThe NNRD holds complete population data for England for infants born alive from 25+0 to 31+6 (completed weeks) of gestation; and 70% and 90% for those born at 23 and 24 weeks respectively. Completeness of patient characteristics was over 90%. Data were linked for 2257 episodes of care received by 1258 of the 1310 babies recruited to PiPs. Discordancy rates were <5% for 13/16 patient characteristics (exceptions: mode of delivery 8.7%; maternal ethnicity 10.2%, Lower layer Super Output Area 16.5%); <5% for 9/16 processes (exceptions: medical treatment for Patent ductus arteriosus 6.1%, high-dependency days 10.2%, central line days 11.2%, type of first milk 22.3%; and during first 14 days, summary of types of milk 13.8%; number of days of antibiotics 9.0%; whether antacid given 5.1%); and <5% for 10/11 clinical outcomes (exception: Bronchopulmonary dysplasia, defined as oxygen dependency at 36 weeks postmenstrual age 3.3%). The specificity of NNRD dat
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