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Background: Neonates undergoing emergency abdominal surgery frequently require a stoma; closing this stoma with a second operation is an essential part of recovery. Timing of closure varies. Optimal timing is unclear and would be best resolved through a randomised controlled trial; such a trial is likely to be challenging., Aim: To determine if it is feasible to conduct a clinical trial comparing 'early' versus 'late' stoma closure in neonates., Design: Mixed methods comprising three parallel workstreams incorporating: a clinician survey, prospective observational cohort study, parent interviews, focus groups, database analyses and consensus meeting., Setting: Specialist neonatal surgical centres across the United Kingdom., Participants and Data Sources: Neonatologists, neonatal surgeons, neonatal dietitians and neonatal nurses who care for neonates with stomas. Neonates with recent stoma, their parents and the clinicians looking after them. Three existing, overlapping clinical databases., Results: One hundred and sixty-six professionals from all 27 neonatal surgical centres completed the survey: 6 weeks was the most common target time for stoma closure across clinical scenarios, although there was wide variation. Timing of closure was influenced by nutrition, growth and stoma complications. The prospective cohort study enrolled 56 infants from 8 centres. Infants were mostly preterm with necrotising enterocolitis or intestinal perforation. Clinicians identified extreme preterm gestation and clinical conditions as reasons for not randomising babies into a hypothetical trial comparing early and late stoma closure. Parents and healthcare professionals identified that comparator arms needed more clinical flexibility in relation to timing of stoma closure. Analysis of existing databases revealed wide variation in current timing of stoma closure in neonates and identified approximately 300 eligible infants for a trial per annum in the United Kingdom., Conclusions: A trial of 'early' compared to 'late' stoma closure in neonates is feasible and is important to families and health professionals. The population of eligible babies in the United Kingdom is sufficient for such a trial. Challenges centre around lack of equipoise in certain scenarios, specifically: extremely preterm infants; infants waiting too long for stoma closure in the 'late' comparator; and logistical issues in closing a stoma at a trial-allocated time. These challenges are addressable by incorporating flexibility based on gestation at birth, communicating that both trial arms are standard practice and valid treatment options, and providing resources, for example, for operating lists., Future Work: We recommend the following population, intervention, comparator and outcome as a starting point to inform future trial design. Population: neonates with stomas (excluding those with a fixed treatment pathway). Intervention: stoma closure at 6 weeks and after 32 weeks post conceptual age. Comparator: expectant management with stoma closure undertaken when the clinical team determines is best for the infant. Primary outcomes: weight gain/growth or length of hospital stay., Study Registration: This study is registered as IRAS Project ID 278331, REC Reference 20/LO/1227., Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: NIHR128617) and is published in full in Health Technology Assessment ; Vol. 28, No. 71. See the NIHR Funding and Awards website for further award information.

Aims: Necrotising enterocolitis (NEC) is a disease associated with high mortality and morbidity, low birthweight and prematurity are risk factors. This study reports outcomes of babies having emergency laparotomy for NEC, examining institutional trends and exploring impact of multiple variables on mortality at 30 days and 1 year post‐operatively. Methods: Case records of babies with ICD coding for NEC were examined from 2000 to 2015. After exclusions, 243 cases were identified—confirmed by operative findings and histology. Cohort demographics and trends in mortality were investigated, and the relationship of common variables to mortality was modelled with univariate and multivariate logistic regression to generate a mortality prediction tool. Results: Mean gestational age was 28 + 4 weeks. A 30‐day mortality was 18.9%. Gestation, birthweight and area of bowel affected were significant of outcome (mortality), and the presence of pre‐operative pneumoperitoneum was strongly correlated. Year of surgery and congenital cardiac pathology requiring intervention were not significant. Using multivariate regression modelling, a mortality outcome prediction tool has been developed. Conclusion: Good survival following operation for NEC (>70%) is feasible, even in those babies born extremely premature (<28 weeks) and post‐operatively re‐located to tertiary NICUs. With increasing gestational age (>32 weeks), mortality is uncommon. [ABSTRACT FROM AUTHOR]

Abstract In the last decade preterm birth rates have continued to rise hand in hand with improving neonatal care. Unfortunately rates of severe disability have remained static. National benchmarking of key outcomes shows significant variations in adaptation of best practices across United Kingdom (UK). While emerging technologies give us a glimpse of fascinating possibilities, widespread adoption of evidence-based interventions should remain a priority. In this article we have attempted to outline mechanisms of preterm brain injury and identify the most promising strategies currently available to minimize it. Quality improvement strategies (QI) that can help perinatal teams adopt best practices and promising new therapies are discussed. [ABSTRACT FROM AUTHOR]

Results from previous studies have suggested that supplemental bovine lactoferrin (BLF) given to preterm infants (<32 weeks gestation) reduces late-onset sepsis (LOS) and necrotising enterocolitis (NEC). The Enteral Lactoferrin in Neonates (ELFIN) study, performed in the UK, aimed to further address this issue with a well powered double-blind placebo controlled trial of >2200 preterm infants. The results from ELFIN did not demonstrate a reduction in LOS or NEC, or several other clinically important measures. Of the 1093 infants, 316 (29%) in the intervention group developed late-onset sepsis versus 334 (31%) of 1089 in the control group, with an adjusted risk ratio of 0.95 (95% CI = 0.86-1.04; p  = 0.233). Reasons for the differences in ELFIN trial results and other studies may include population differences, the routine use of antifungal prophylaxis in the UK, timing of administration of the lactoferrin in relation to disease onset, or specific properties of the lactoferrin used in the different trials. The UK National Institutes for Health Research funded "Mechanisms Affecting the Guts of Preterm Infants in Enteral feeding trials" (MAGPIE) study is further exploring the use of lactoferrin, and the results should be available soon.

Background: Observational data suggest that slowly advancing enteral feeds in preterm infants may reduce necrotising enterocolitis but increase late-onset sepsis. The Speed of Increasing milk Feeds Trial (SIFT) compared two rates of feed advancement., Objective: To determine if faster (30 ml/kg/day) or slower (18 ml/kg/day) daily feed increments improve survival without moderate or severe disability and other morbidities in very preterm or very low-birthweight infants., Design: This was a multicentre, two-arm, parallel-group, randomised controlled trial. Randomisation was via a web-hosted minimisation algorithm. It was not possible to safely and completely blind caregivers and parents., Setting: The setting was 55 UK neonatal units, from May 2013 to June 2015., Participants: The participants were infants born at < 32 weeks' gestation or a weight of < 1500 g, who were receiving < 30 ml/kg/day of milk at trial enrolment., Interventions: When clinicians were ready to start advancing feed volumes, the infant was randomised to receive daily feed increments of either 30 ml/kg/day or 18 ml/kg/day. In total, 1400 infants were allocated to fast feeds and 1404 infants were allocated to slow feeds., Main Outcome Measures: The primary outcome was survival without moderate or severe neurodevelopmental disability at 24 months of age, corrected for gestational age. The secondary outcomes were mortality; moderate or severe neurodevelopmental disability at 24 months corrected for gestational age; death before discharge home; microbiologically confirmed or clinically suspected late-onset sepsis; necrotising enterocolitis (Bell's stage 2 or 3); time taken to reach full milk feeds (tolerating 150 ml/kg/day for 3 consecutive days); growth from birth to discharge; duration of parenteral feeding; time in intensive care; duration of hospital stay; diagnosis of cerebral palsy by a doctor or other health professional; and individual components of the definition of moderate or severe neurodevelopmental disability., Results: The results showed that survival without moderate or severe neurodevelopmental disability at 24 months occurred in 802 out of 1224 (65.5%) infants allocated to faster increments and 848 out of 1246 (68.1%) infants allocated to slower increments (adjusted risk ratio 0.96, 95% confidence interval 0.92 to 1.01). There was no significant difference between groups in the risk of the individual components of the primary outcome or in the important hospital outcomes: late-onset sepsis (adjusted risk ratio 0.96, 95% confidence interval 0.86 to 1.07) or necrotising enterocolitis (adjusted risk ratio 0.88, 95% confidence interval 0.68 to 1.16). Cost-consequence analysis showed that the faster feed increment rate was less costly but also less effective than the slower rate in terms of achieving the primary outcome, so was therefore found to not be cost-effective. Four unexpected serious adverse events were reported, two in each group. None was assessed as being causally related to the intervention., Limitations: The study could not be blinded, so care may have been affected by knowledge of allocation. Although well powered for comparisons of all infants, subgroup comparisons were underpowered., Conclusions: No clear advantage was identified for the important outcomes in very preterm or very low-birthweight infants when milk feeds were advanced in daily volume increments of 30 ml/kg/day or 18 ml/kg/day. In terms of future work, the interaction of different milk types with increments merits further examination, as may different increments in infants at the extremes of gestation or birthweight., Trial Registration: Current Controlled Trials ISRCTN76463425., Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 18. See the NIHR Journals Library website for further project information., Competing Interests: Jane Abbott, Janet Berrington, Elaine Boyle, Ursula Bowler, Jon Dorling, Nicholas Embleton, Kenny McCormick, William McGuire, Edmund Jaszczuk, Samantha Johnson, Madeleine Hurd, Oliver Hewer, Andrew King, Alison Leaf, Louise Linsell, Christopher Partlett, David Murray, Ben Stenson, Judith Rankin and Tracy Roberts report funding from the National Institute for Health Research (NIHR) for the trial. Jon Dorling, Janet Berrington, Elaine Boyle, Nicholas Embleton, Edmund Jaszczuk, Samantha Johnson, Andrew King, Louise Linsell, William McGuire, Christopher Partlett and Tracy Roberts report receipt of funding from NIHR, outside the submitted work. Jon Dorling reports grants from Nutrinia (Nazareth, Israel) outside the submitted work; specifically, he was funded for part of his salary to work as an expert advisor on a trial of enteral insulin. Furthermore, he was a member of the NIHR Health Technology Assessment (HTA) General Board (2017–18) and the NIHR HTA Maternity, Newborn and Child Health Panel (2013–18). Elaine Boyle reports grants from the Medical Research Council and East Midlands Specialised Commissioning Group outside the submitted work. Janet Berrington reports grants and personal fees from Danone Early Life Nutrition (Paris, France) and grants from Prolacta Biosciences US (Duarte, CA, USA) outside the submitted work. Nicholas Embleton reports grants from Prolacta Biosciences US and Danone Early Life Nutrition and personal fees from Nestlé Nutrition Institute (Vevey, Switzerland), Baxter (Deerfield, IL, USA) and Fresenius Kabi (Bad Homburg vor der Höhe, Germany) outside the submitted work. Samantha Johnson reports grants from Action Medical Research (Horsham, UK), EU Horizon 2020 (Brussels, Belguim), the Medical Research Council (London, UK), Sparks (London, UK) and the Nuffield Foundation (London, UK) outside the submitted work. William McGuire is a member of the NIHR HTA Commissioning Board (2013 to present) and the HTA and Efficacy and Mechanism Evaluation Editorial Board (2012 to present). Edmund Juszczak was a member of the NIHR HTA General Board from 2016 to 2017 and the HTA funding committee (commissioning) from 2013 to 2016.

Background Small for gestational age (SGA) infants are less likely to develop respiratory distress syndrome (RDS), but more likely to develop bronchopulmonary dysplasia (BPD) and have a higher mortality. Our aim was to focus on outcomes of those with a birth weight less than or equal to 750 g. Methods The mortality, BPD severity, necrotising enterocolitis (NEC), home oxygen requirement and length of hospital stay were determined according to SGA status of all eligible infants in a 5-year period admitted within the first 24 h after birth. Results The outcomes of 84 infants were assessed, and 35 (42%) were SGA. The SGA infants were more mature (P<0.001), had a lower birth weight centile (P<0.001) and a greater proportion exposed to antenatal corticosteroids (P=0.022). Adjusted for gestational age (GA), there was no significant difference in mortality between the two groups (P=0.242), but a greater proportion of the SGA infants developed severe BPD (P=0.025). The SGA infants had a lower weight z-score at discharge (-3.64 vs. -1.66) (P=0.001), but a decrease in z-score from birth to discharge was observed in both groups (median -1.53 vs. -1.07, P=0.256). Conclusion Despite being more mature, the SGA infants had a similar mortality rate and a greater proportion developed severe BPD.