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Aim: To characterise parathyroid hormone (PTH) concentrations in infants at high risk for metabolic bone disease, in order to assist clinical decisions around the use of PTH for screening. Methods: Infants born under 28 weeks' postmenstrual age or with birthweight under 1.5 kg in a tertiary neonatal unit in the UK were included. Clinical guidance was to assess PTH concentration in the first 3 weeks after birth. Clinical information was extracted from prospective records. Results: Sixty‐four infants had mean birth gestation of 26 weeks and birthweight of 882 g. Median PTH (sent on median day 18 of life) was 9.2 pmol/L (interquartile range 5.3–17 pmol/L). Sixty‐seven per cent of infants had a PTH greater than 7 pmol/L. For 22% of the infants, raised PTH was not accompanied by abnormal phosphate or alkaline phosphatase. Eighty‐nine per cent of infants tested were insufficient or deficient for 25‐hydroxyvitamin D. Conclusions: Universal screening highlights the high frequency of high PTH in this high‐risk population, implying a need for calcium supplementation. A considerable number of infants would not be identified as showing potential signs of metabolic bone disease if the assessment excludes the use of PTH. The high level of 25‐hydroxyvitamin D deficiency may be a confounder. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants.Design: Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables. Bacteria and metabolite compositions of longitudinal stool and urine samples were analysed to investigate the impact of lactoferrin supplementation.Setting: Thirteen UK hospitals participating in a RCT of lactoferrin.Patients: 479 infants born <32 weeks' gestation between June 2016 and September 2017.Results: 10 990 stool and 22 341 urine samples were collected. Analyses of gut microbiome (1304 stools, 201 infants), metabolites (171 stools, 83 infants; 225 urines, 90 infants) and volatile organic compounds (314 stools, 117 infants) were performed. Gut microbiome Shannon diversity at 34 weeks corrected age was not significantly different between infants in the lactoferrin (mean=1.24) or placebo (mean=1.06) groups (p=0.11). Lactoferrin receipt explained less than 1% variance in microbiome compositions between groups. Metabolomic analysis identified six discriminative features between trial groups. Hospital site (16%) and postnatal age (6%) explained the greatest variation in microbiome composition.Conclusions: This multiomic study identified minimal impacts of lactoferrin but much larger impacts of hospital site and postnatal age. This may be due to the specific lactoferrin product used, but more likely supports the findings of the RCT in which this study was nested, which showed no impact of lactoferrin on reducing rates of sepsis. Multisite mechanistic studies nested within RCTs are feasible and help inform trial interpretation and future trial design. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the impact of a quality improvement project of the adoption of standard parenteral nutrition (SPN) in preterm infants., Design: Retrospective, multicentre, whole-population, non-concurrent control study using data from the UK National Neonatal Research Database between 1 January 2014 and 31 December 2020., Setting: Neonatal units in London UK organised by geographical network., Patients: Preterm infants <31 weeks' gestation., Interventions: Introduction of two SPN formulations previously tested in randomised controlled trials (NEON and SCAMP). SCAMP delivers a higher target macronutrient intake., Main Outcome Measures: The primary outcome was survival to discharge from neonatal care without major morbidities. Secondary outcomes included the individual components of the primary outcome and a comparison of outcomes between the NEON and the SCAMP formulations., Results: Of 6538 eligible infants, 4693 were admitted to neonatal care before and 1845 after the adoption of SPN. Morbidity-free survival decreased by an average of 8.6% (95% CI 5.8% to 11.4%, p<0.0001) following adoption. The effect varied by type of formulation; the cohort that adopted NEON showed no difference in morbidity-free survival, whereas the cohort that adopted SCAMP showed a statistically significant decrease in morbidity-free survival. Overall survival decreased by an average of 2.0% (95% CI 0.01% to 4.0%, p=0.048)., Conclusions: Research is urgently needed to identify the optimal composition of parenteral nutrition for preterm babies. This study also adds to the growing body of evidence that suggests that early and high intakes of macronutrients in preterm babies may be harmful., Competing Interests: Competing interests: Members of this research group (SNU and NM) were investigators of the NEON trial. SNU was a committee member of the UK NICE guideline on neonatal parenteral nutrition and the QI implementation programme of SPN that is the subject of this paper., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Universal screening for the psychological needs of families in neonatal care is internationally recommended, but is not routinely practiced in the United Kingdom (UK). The present quality improvement project explores the clinical and operational feasibility of a novel approach to universal screening on a neonatal intensive care unit in the UK. The approach to screening taken adopts collaborative, strengths-based and dialogical methods for recognising the psychological needs of families whose baby is in hospital. A novel screening tool, developed through consultation with families, is described. Over one month, 42 out of 80 eligible families engaged with the screening protocol either at admission to the unit, transition to the special care nursery within the unit, or discharge home, with completion rates higher at admission than discharge. This led to an eightfold increase in the number of families accessing targeted or specialist psychological intervention compared to the period prior to this pilot. This project demonstrates the need for adequate capacity in the workforce to carry out a screening programme and to respond to the needs identified., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Assess the relationship of time to first expression after very preterm birth and mothers' own milk quantity., Design: A cohort study (nested within a randomised trial)., Setting: Four neonatal units in the UK., Patients: 132 mothers of single or twin infants born at 23+0 to 31+6 weeks postmenstrual age., Exposures: Time to the first attempt to express after birth., Primary Outcomes: 24-hour mother's own milk yield on days 4, 14 and 21 after birth., Results: Median time to first expression attempt was 6 hours. 51.7% expressed within 6 hours of birth (62/120) and 48.3% expressed more than 6 hours after birth (58/120). Expressing within 6 hours of birth was associated with higher milk yield on day 4 (88.3 g, 95% CI 7.1 to 169.4) and day 14 (155.7 g, 95% CI 12.2 to 299.3) but not on day 21 (73.6 g, 95% CI -91.4 to 238.7). There was an interaction between expressing frequency and time to first expression (p<0.005), with increased expressing frequency being associated with higher yield only in those who expressed within 6 hours. Expressing within 2 hours of birth was not associated with further milk yield increase., Conclusions: Mothers who expressed within 6 hours of birth had higher milk yield, and a greater yield per expressing session, in the first 3 weeks after birth. This information will be highly motivating for families and the clinicians supporting them. There was no evidence of further benefit of extremely early expression (first 2 hours after birth)., Trial Registration Number: ISRCTN 16356650., Competing Interests: Competing interests: MF receives an unrestricted research donation from Philips for research in infant nutrition, unrelated to this work. IL was previously on the working group for the British Association of Perinatal Medicine Quality Improvement Toolkit on perinatal optimisation of breast milk. The study funder (NIHR) had no role in the design, conduct or analysis of the study, or of the decision to submit for publication., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Systematic reviews have reported conflicting evidence on whether macrolide antibiotics reduce rates of chronic lung disease of prematurity (CLD) in at-risk preterm infants born at less than 30 weeks' gestation, including in those colonised with pulmonary Ureaplasma spp. Since an adequately powered trial has been lacking, we aimed to assess if the macrolide azithromycin improved survival without the development of physiologically defined moderate or severe CLD in preterm infants., Methods: AZTEC was a multicentre, double-blind, randomised, placebo-controlled trial conducted in 28 tertiary neonatal intensive care units in the UK. Infants were eligible if they were born at less than 30 weeks' gestation and had received at least 2 h of either non-invasive (continuous positive airway pressure or humidified high flow nasal cannula therapy) or invasive respiratory support (via endotracheal tube) within 72 h of birth. Eligible infants were randomly allocated in a 1:1 ratio using random permuted blocks of four to receive either intravenous azithromycin at 20 mg/kg per day for 3 days followed by 10 mg/kg for 7 days, or to placebo. Allocation was stratified by centre and gestational age at birth (<28 weeks vs ≥28 weeks). Azithromycin and placebo vials were encased in tamper-evident custom cardboard cartons to ensure masking for clinicians, parents, and the research team. The primary outcome was survival without development of physiologically defined moderate or severe CLD at 36 weeks' postmenstrual age. Outcomes and safety were analysed on an intention-to-treat basis (all randomly allocated infants, regardless of any post-randomisation events). The study was registered with ISRCRN (11650227) and is closed., Findings: Infants were recruited between Oct 9, 2019, and March 22, 2022. 799 (53·1%) of 1505 eligible infants underwent random allocation; three infants were withdrawn, including consent to use their data, leaving 796 infants for analysis. Survival without moderate or severe CLD occurred in 166 (42%) of 394 infants in the intervention group and 179 (45%) of 402 in the placebo group (three-level adjusted OR [aOR] 0·84, 95% CI 0·55-1·29, p=0·43). Pulmonary Ureaplasma spp colonisation did not influence treatment effect. Overall, seven serious adverse events were reported for the azithromycin group (five graded as severe, two as moderate), and six serious adverse events were reported in the placebo group (two severe, two moderate, and two mild), as assessed by the local principal investigators., Interpretation: Since prophylactic use of azithromycin did not improve survival without development of physiologically-defined CLD, regardless of Ureaplasma spp colonisation, it cannot be recommended in clinical practice., Funding: UK National Institute for Health and Care Research., Competing Interests: Declaration of interests SK, JL, DG, KH, NK, ET-J, MT, JM, and JB received funding from NIHR HTA as coapplicants for this project. JM reports payments or honoraria for lectures from Institut Biochimique SA, support for attending meetings from Fred Hutchinson Cancer Centre, and patents issued and pending. SK reports receiving grant funding outside of this work from the Medical Research Council, Aspire Pharma, and Moulton Foundation; and consultancy fees from Aspire Pharma during the past 36 months. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Increasingly non-cardiac tertiary neonatal intensive care units (NCTNs) manage newborns with CHD prior to planned transfer to specialist cardiac surgical centres (SCSC). It improves patient flow in SCSCs, enables families to be nearer home, and improves psychological well-being Parker et al. (Evaluating models of care closer to home for children and young people who are ill: a systematic review, 2011) . This practice has gradually increased as the number of SCSCs has decreased. This study examines the effectiveness of this expanding practice. The management provided, length of stay in the NCTN and outcomes are described for one UK NCTN situated at a significant distance from its SCSC. A retrospective observational study of cardiac-related admissions to a NCTN between January 2010 and December 2019 was conducted. 190 neonates were identified: 41 had critical CHD; 64 had major CHD. The cohort includes babies with a wide range of cardiac conditions and additional complexities. 23.7% (n = 45) required transfer to a specialist center after a period of stabilization and growth ranging from several hours to 132 days. 68% (n = 130) were discharged home or repatriated to a local NICU. Of the remaining 15 babies, 13 were transferred to other specialties including the hospice. Two died on NICU. The mortality was consistent with the medical complexity of the group Best and Rankin (J Am Heart Assoc 5:e002846, 2016), Laas et al. (BMC Pediatr 17:124, 2017). 8.9% (n = 17) died before age 2. Nine babies had care redirected due to an inoperable cardiac condition or life-limiting comorbidities. Our study demonstrates a complex neonatal cohort with CHD can be managed effectively in a NCTN, supporting the current model of care. The NCTN studied was well supported by pediatricians with expertise in cardiology alongside visiting pediatric cardiologists., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Importance: Early detection and intervention of hearing loss may mitigate negative effects on children's development. Children who were admitted to the neonatal intensive care unit (NICU) as babies are particularly susceptible to hearing loss and risk factors are vital for surveillance., Design, Setting and Participants: This single-centre retrospective cohort study included data from 142 inborn infants who had been admitted to the NICU in a tertiary regional referral centre. Data were recorded for 71 infants with confirmed permanent congenital hearing loss hearing loss. To determine impact of NICU admission independently of prematurity, babies were individually matched with 71 inborn infants on gestational age, birthweight, and sex., Main Outcomes and Measures: Neonatal indicators were recorded for all children with permanent congenital hearing loss. Presence of UK and US risk factors for hearing loss were collected on the neonatal population with hearing loss and for the matched controls., Results: A fifth (21%) of babies with hearing loss had one or more UK risk factors whereas most (86%) had at least one US risk factor. False positives would be evident if US factors were used whereas the matched controls had no UK risk factors. Ten babies who at birth had no UK or US risk factors did not have any significant neonatal indicators identified in their records, one was ventilated for one day and two had a genetic anomaly., Conclusions and Relevance: Current risk factors for hearing loss we identified for follow-up in this high-risk group are highly specific for congenital hearing loss. UK risk factors were highly specific for hearing loss but not sensitive and conversely, US risk factors are sensitive but not specific so false positives would be recorded. A national study of neonatal indicators could provide the utility to test which combinations of risk factors provide high sensitivity without losing specificity., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Thornton et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Research has shown that many babies who die in neonatal units could have been potential tissue and/or organ donors. Despite the existence of guidelines supporting its implementation, the incidence of neonatal donation remains rare in the United Kingdom., Aim: The aim of this audit was to retrospectively determine potential eligibility for neonatal tissue and/or organ donation referral in infants who died in a single UK tertiary-level neonatal unit between 2012 and 2021. Cause of death and documentation of any discussions held regarding referral for donation were also explored., Study Design: An audit was undertaken to identify all neonatal deaths at a single tertiary-level NICU in London from 2012-2021. Infants who retrospectively could have been referred as potential tissue and/or organ donors were identified using current NHS Blood and Transplant inclusion and exclusion criteria., Results and Conclusion: A significant missed potential for neonatal tissue and/or organ donation referrals was identified, which is likely not just limited to the unit audited. Causes of death were as expected for a tertiary level neonatal unit and centre for therapeutic cooling of babies born with hypoxic perinatal brain injuries. Only one documented conversation was found regarding neonatal donation., Relevance to Clinical Practice: To enable conversations regarding neonatal donation to become a routine part of end-of-life care discussions with families as appropriate, good links between neonatal healthcare professionals and Specialist Nurses in Organ Donation need to be established. This will facilitate the referral of all suitable neonates as potential donors and ensure that neonatal staff feel supported to care for babies identified as potential donors., (© 2023 British Association of Critical Care Nurses.)

Objective: To study the current management practices of neonatal abstinence syndrome (NAS) throughout the UK and Ireland and identify changes in practice from the most recent survey in 2008., Design: Postal questionnaire to a consultant paediatrician or neonatologist in all 215 neonatal units in the UK and Ireland in January 2020., Results: Response rate was 62%. An objective scoring tool was used in 97% of units and the Finnegan score was favoured by 70%. Morphine sulfate use as first line for the treatment of opiate withdrawal was almost universal and 70% used a dose of 40 µg/kg every 4 hours (240 µg/kg/day). Phenobarbitone administration as a second-line agent for opiate withdrawal increased to 61% of units with significant reductions in chloral hydrate and chlorpromazine use compared with the previous survey. Morphine sulfate and phenobarbitone remain the preferred first-line and second-line agents, respectively, for polysubstance withdrawal. There was a significant increase in chlorpromazine use as first line for polydrug withdrawal (1.5-14.2%). The practice of units discharging infants' home on medication increased to 46% from 29%. All units now permit breastfeeding in mothers taking methadone, compared with 81% previously., Conclusion and Relevance: Compared with the previous survey, improvements in evidence-based practices were noted, highlighting the benefits of this type of research. Nonetheless, significant variation still exists in some aspects of the management of NAS. Post-discharge follow-up varies widely, with particular deficits in ophthalmology follow-up., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To perform a survey on postnatal corticosteroids usage in neonatal units in the United Kingdom and Ireland., Methods: An 18-item structured questionnaire was created asking for the level of neonatal care and corticosteroid prescribing practices. A consultant neonatologist or senor specialty training registrar/advanced neonatal nurse practitioner was contacted in every neonatal unit in the UK and Ireland between September and December 2022., Results: The response rate to the survey was 96% (203 of 211 units). Postnatal corticosteroids were prescribed in 48% of units: 5% of special care units, 43% of local neonatal units and 100% of neonatal intensive care units. Most units (90%) prescribed dexamethasone, which was prescribed to infants born at gestational ages less than 30 weeks in all those units prescribing postnatal corticosteroids, however, eight units also reported use in infants greater than 30 weeks of gestation. Dexamethasone regimens varied with starting doses from 50 to 500 μg/kg/day. Most tertiary units (97%) prescribed repeated courses of dexamethasone. In all levels of neonatal care, postnatal corticosteroids were prescribed to ventilated infants as well as those receiving non-invasive respiratory support., Conclusion: There is use of postnatal corticosteroids in all levels of neonatal care and much of the practice is not evidence based., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Objective: Increased incidence of neonatal Staphylococcus capitis bacteraemia in summer 2020, London, raised suspicion of widespread multidrug-resistant clone NRCS-A. We set out to investigate the molecular epidemiology of this clone in neonatal units (NNUs) across the UK., Methods: We conducted whole-genome sequencing (WGS) on presumptive S. capitis NRCS-A isolates collected from infants admitted to nationwide NNUs and from environmental sampling in two distinct NNUs in 2021. Previously published S. capitis genomes were added for comparison. Genetic clusters of NRCS-A isolates were defined based on core-genome single-nucleotide polymorphisms., Results: We analysed WGS data of 838 S. capitis isolates and identified 750 NRCS-A isolates. We discovered a possible UK-specific NRCS-A lineage consisting of 611 isolates collected between 2005 and 2021. We determined 28 genetic clusters of NRCS-A isolates, which covered all geographical regions in the UK, and isolates of 19 genetic clusters were found in ≥2 regions, suggesting inter-regional spread. Within the NRCS-A clone, strong genetic relatedness was identified between contemporary clinical and incubator-associated fomite isolates and between clinical isolates associated with inter-hospital infant transfer., Conclusions: This WGS-based study confirms the dispersion of S. capitis NRCS-A clone amongst NNUs across the UK and urges research on improving clinical management of neonatal S. capitis infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Aim: To explore the attitudes of parents and healthcare professionals (HCPs), and facilitators and barrier to implementation of Kangaroo Care (KC) in the United Kingdom., Methods: Online cross-sectional survey; distributed via the British Association of Perinatal Medicine, Bliss (UK-based charity), social media., Results: Sixty HCPs responded. 37 (62%) were nurses/nurse practitioners. 57 (95%) regularly implement KC. The most important factor that supported KC implementation was the team's belief in benefits of KC. Increased workload, staff shortage and fear about safely of KC in unwell infants were recognised as the challenges preventing implementation. Five hundred eighteen parents responded. 421 (81%) had a preterm baby within 3 years. 338 (80%) were familiar with KC. The main facilitator was the belief that their baby enjoyed it. Excess noise and crowding on the unit were the most frequently reported barriers. Lack of opportunity and limited staff support were the main reasons why they had been unable to practice KC., Conclusion: We found that most HCPs and parents believe that KC is beneficial and would like to practice it. Lack of resources to enable effective implementation is the main barrier. Service development and implementation research is required to ensure that KC is delivered in all UK neonatal units., (© 2023 The Authors. Acta Paediatrica published by John Wiley & Sons Ltd on behalf of Foundation Acta Paediatrica.)

Competing Interests: Competing interests: None declared.

Objective: Therapeutic hypothermia (TH) commenced soon after birth for neonatal hypoxic ischaemic encephalopathy (HIE) improves survival and reduces neurodisability. Availability of active TH at the place of birth (Immediate-TH) in the UK is unknown., Design: Population-based observational study., Setting: UK maternity centres., Patients: 5 975 056 births from 2011 to 2018., Intervention Methods: For each maternity centre, the year active Immediate-TH was available and the annual birth rates were established. Admission temperatures of infants with HIE transferred from non-tertiary centres with and without Immediate-TH were compared., Main Outcome Measures: Quantify the annual number of births with access to Immediate-TH. Secondary outcomes included temporal changes in Immediate-TH and admission temperatures for infants requiring transfer to tertiary centres., Results: In UK maternity centres, 75 of 194 (38.7%) provided Immediate-TH in 2011 rising to 95 of 192 (49.5%, p=0.003) in 2018 with marked regional variations. In 2011, 394 842 (51.2%) of 771 176 births had no access to Immediate-TH compared with 276 258 (39.3%) of 702 794 births in 2018 (p<0.001). More infants with HIE arrived in the therapeutic temperature range (76.5% vs 67.3%; OR 1.58, 95% CI 1.25 to 2.0, p<0.001) with less overcooling (10.6% vs 14.3%; OR 0.71, 95% CI 0.51 to 0.98, p=0.036) from centres with Immediate-TH compared with those without., Conclusions: Availability of active Immediate-TH has slowly increased although many newborns still have no access and rely on transport team arrival to commence active TH. This is associated with delayed optimal hypothermic management. Provision of Immediate-TH across all units, with appropriate training and support, could improve care of infants with HIE., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Neonatology is a relatively new specialty, in which much of the practice remains non-evidence based. Variation in the quality of care delivered is recognised but measuring this is challenging. One possible indicator of this is variation in practice. For more than a decade, the National Neonatal Audit Project (NNAP) has described variation in practice between UK neonatal units in relation to its annually reviewed audit measures. These are based on evidence based national standards or developed by a consensus method and have become de facto measures defining good quality of neonatal healthcare within the UK. In this article we explore the practicality of using the NNAP to look for associations between quality of care and outcomes. This would not be to validate the measures but could help towards a better understanding of the reasons underlying recognised variation in outcomes, even between neonatal units of the same designation., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Purpose: To describe the use of ciprofloxacin and fluconazole for the treatment of sepsis in European neonatal intensive care units (NICUs) in order to better orient research aimed at acquiring essential knowledge in this critical area. Methods: The survey consisted of an online questionnaire for all participating NICUs on treatment schemes employed, rationales behind drug choices and interest in participation in research involving the two drugs. Results: A total of 189 level II and III NICUs participated in the survey, representing 25 countries, with Italy, UK and France providing the greatest number of centres (54 % of total). Ciprofloxacin is used in 25 % of NICUs that responded, although the indications for administering it vary between centres and the dosage ranges vary considerably, with 25 % of NICUs giving ≤10 mg/kg/day and another 25 % giving ≥21 mg/kg/day. Factors given as affecting the decision to use ciprofloxacin are uncertainty about its safety and pharmacokinetics and level of penetration in the cerebrospinal fluid. Among the 70 % of responding units that use fluconazole to treat fungal infection, 45 % administer 6 mg/kg unit doses while 33 % administer 12 mg/kg; 41 % of NICUs use a 24-h interval between administrations while 20 % wait 72 h. Among the responding NICUs, 57 % were willing to participate in a project on ciprofloxacin and 59 % would consider participating in a randomized controlled trial evaluating fluconazole versus micafungin. Conclusions: Great variability in therapies exists within and between countries. Numerous centres are interested in participating in research on these drugs, highlighting the need for further knowledge on sepsis treatment and European centres' interest in off-patent medicine research. [ABSTRACT FROM AUTHOR]

Background: Concerns have been raised regarding a potential surge of COVID-19 in pregnancy, secondary to the rising numbers of COVID-19 in the community, easing of societal restrictions, and vaccine hesitancy. Although COVID-19 vaccination is now offered to all pregnant women in the United Kingdom; limited data exist on its uptake and safety., Objective: This study aimed to investigate the uptake and safety of COVID-19 vaccination among pregnant women., Study Design: This was a cohort study of pregnant women who gave birth at St George's University Hospitals National Health Service Foundation Trust, London, United Kingdom, between March 1, 2020, and July 4, 2021. The primary outcome was uptake of COVID-19 vaccination and its determinants. The secondary outcomes were perinatal safety outcomes. Data were collected on COVID-19 vaccination uptake, vaccination type, gestational age at vaccination, and maternal characteristics, including age, parity, ethnicity, index of multiple deprivation score, and comorbidities. Further data were collected on perinatal outcomes, including stillbirth (fetal death at ≥24 weeks' gestation), preterm birth, fetal and congenital abnormalities, and intrapartum complications. Pregnancy and neonatal outcomes of women who received the vaccine were compared with that of a matched cohort of women with balanced propensity scores. Effect magnitudes of vaccination on perinatal outcomes were reported as mean differences or odds ratios with 95% confidence intervals. Factors associated with antenatal vaccination were assessed with logistic regression analysis., Results: Data were available for 1328 pregnant women of whom 140 received at least 1 dose of the COVID-19 vaccine before giving birth and 1188 women who did not; 85.7% of those vaccinated received their vaccine in the third trimester of pregnancy and 14.3% in the second trimester of pregnancy. Of those vaccinated, 127 (90.7%) received a messenger RNA vaccine and 13 (9.3%) a viral vector vaccine. There was evidence of reduced vaccine uptake in younger women (P=.001), women with high levels of deprivation (ie, fifth quintile of the index of multiple deprivation; P=.008), and women of Afro-Caribbean or Asian ethnicity compared with women of White ethnicity (P<.001). Women with prepregnancy diabetes mellitus had increased vaccine uptake (P=.008). In the multivariable model the fifth deprivation quintile (most deprived) (adjusted odds ratio, 0.10; 95% confidence interval, 0.02-0.10; P=.003) and Afro-Caribbean ethnicity (adjusted odds ratio, 0.27; 95% confidence interval, 0.06-0.85; P=.044) were significantly associated with lower antenatal vaccine uptake, whereas prepregnancy diabetes mellitus was significantly associated with higher antenatal vaccine uptake (adjusted odds ratio, 10.5; 95% confidence interval, 1.74-83.2; P=.014). In a propensity score-matched cohort, the rates of adverse pregnancy outcomes of 133 women who received at least 1 dose of the COVID-19 vaccine in pregnancy were similar to that of unvaccinated pregnant women (P>.05 for all): stillbirth (0.0% vs 0.2%), fetal abnormalities (2.2% vs 2.5%), postpartum hemorrhage (9.8% vs 9.0%), cesarean delivery (30.8% vs 34.1%), small for gestational age (12.0% vs 12.8%), maternal high-dependency unit or intensive care admission (6.0% vs 4.0%), or neonatal intensive care unit admission (5.3% vs 5.0%). Intrapartum pyrexia (3.7% vs 1.0%; P=.046) was significantly increased but the borderline statistical significance was lost after excluding women with antenatal COVID-19 infection (P=.079). Mixed-effects Cox regression showed that vaccination was not significantly associated with birth at <40 weeks' gestation (hazard ratio, 0.93; 95% confidence interval, 0.71-1.23; P=.624)., Conclusion: Of pregnant women eligible for COVID-19 vaccination, less than one-third accepted COVID-19 vaccination during pregnancy, and they experienced similar pregnancy outcomes with unvaccinated pregnant women. There was lower uptake among younger women, non-White ethnicity, and lower socioeconomic background. This study has contributed to the body of evidence that having COVID-19 vaccination in pregnancy does not alter perinatal outcomes. Clear communication to improve awareness among pregnant women and healthcare professionals on vaccine safety is needed, alongside strategies to address vaccine hesitancy. These strategies include postvaccination surveillance to gather further data on pregnancy outcomes, particularly after first-trimester vaccination, and long-term infant follow-up., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Vancomycin is the most widely used antibiotic for neonatal Gram-positive sepsis, but clinical outcome data of dosing strategies are scarce. The NeoVanc programme comprised extensive preclinical studies to inform a randomised controlled trial to assess optimised vancomycin dosing. We compared the efficacy of an optimised regimen to a standard regimen in infants with late onset sepsis that was known or suspected to be caused by Gram-positive microorganisms., Methods: NeoVanc was an open-label, multicentre, phase 2b, parallel-group, randomised, non-inferiority trial comparing the efficacy and toxicity of an optimised regimen of vancomycin to a standard regimen in infants aged 90 days or younger. Infants with at least three clinical or laboratory sepsis criteria or confirmed Gram-positive sepsis with at least one clinical or laboratory criterion were enrolled from 22 neonatal intensive care units in Greece, Italy, Estonia, Spain, and the UK. Infants were randomly assigned (1:1) to either the optimised regimen (25 mg/kg loading dose, followed by 15 mg/kg every 12 h or 8 h dependent on postmenstrual age, for 5 ± 1 days) or the standard regimen (no loading dose; 15 mg/kg every 24 h, 12 h, or 8 h dependent on postmenstrual age for 10 ± 2 days). Vancomycin was administered intravenously via 60 min infusion. Group allocation was not masked to local investigators or parents. The primary endpoint was success at the test of cure visit (10 ± 1 days after the end of actual vancomycin therapy) in the per-protocol population, where success was defined as the participant being alive at the test of cure visit, having a successful outcome at the end of actual vancomycin therapy, and not having a clinically or microbiologically significant relapse or new infection requiring antistaphylococcal antibiotics for more than 24 h within 10 days of the end of actual vancomycin therapy. The non-inferiority margin was -10%. Safety was assessed in the intention-to-treat population. This trial is registered at ClinicalTrials.gov (NCT02790996)., Findings: Between March 3, 2017, and July 29, 2019, 242 infants were randomly assigned to the standard regimen group (n=122) or the optimised regimen group (n=120). Primary outcome data in the per-protocol population were available for 90 infants in the optimised group and 92 in the standard group. 64 (71%) of 90 infants in the optimised group and 73 (79%) of 92 in the standard group had success at test of cure visit; non-inferiority was not confirmed (adjusted risk difference -7% [95% CI -15 to 2]). Incomplete resolution of clinical or laboratory signs after 5 ± 1 days of vancomycin therapy was the main factor contributing to clinical failure in the optimised group. Abnormal hearing test results were recorded in 25 (30%) of 84 infants in the optimised group and 12 (15%) of 79 in the standard group (adjusted risk ratio 1·96 [95% CI 1·07 to 3·59], p=0·030). There were six vancomycin-related adverse events in the optimised group (one serious adverse event) and four in the standard group (two serious adverse events). 11 infants in the intention-to-treat population died (six [6%] of 102 infants in the optimised group and five [5%] of 98 in the standard group)., Interpretation: In the largest neonatal vancomycin efficacy trial yet conducted, no clear clinical impact of a shorter duration of treatment with a loading dose was demonstrated. The use of the optimised regimen cannot be recommended because a potential hearing safety signal was identified; long-term follow-up is being done. These results emphasise the importance of robust clinical safety assessments of novel antibiotic dosing regimens in infants., Funding: EU Seventh Framework Programme for research, technological development and demonstration., Competing Interests: Declaration of interests PTH is a member of the National Institute for Health and Care Excellence neonatal infection guideline development group. LR is an employee of Therakind. DD obtained a PhD that was funded by Fondazione Penta; the capacity and remit of this PhD was independent and unrelated to involvement with NeoVanc. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background: Hyperglycaemia and hypoglycaemia are common in preterm infants and have been associated with increased risk of mortality and morbidity. Interventions to reduce risk associated with these exposures are particularly challenging due to the infrequent measurement of blood glucose concentrations, with the potential of causing more harm instead of improving outcomes for these infants. Continuous glucose monitoring (CGM) is widely used in adults and children with diabetes to improve glucose control, but has not been approved for use in neonates. The REACT trial aimed to evaluate the efficacy and safety of CGM in preterm infants requiring intensive care., Methods: This international, open-label, randomised controlled trial was done in 13 neonatal intensive care units in the UK, Spain, and the Netherlands. Infants were included if they were within 24 h of birth, had a birthweight of 1200 g or less, had a gestational age up to 33 weeks plus 6 days, and had parental written informed consent. Infants were randomly assigned (1:1) to real-time CGM or standard care (with masked CGM for comparison) using a central web randomisation system, stratified by recruiting centre and gestational age (<26 or ≥26 weeks). The primary efficacy outcome was the proportion of time sensor glucose concentration was 2·6-10 mmol/L for the first week of life. Safety outcomes related to hypoglycaemia (glucose concentrations <2·6 mmol/L) in the first 7 days of life. All outcomes were assessed on the basis of intention to treat in the full analysis set with available data. The study is registered with the International Standard Randomised Control Trials Registry, ISRCTN12793535., Findings: Between July 4, 2016, and Jan 27, 2019, 182 infants were enrolled, 180 of whom were randomly assigned (85 to real-time CGM, 95 to standard care). 70 infants in the real-time CGM intervention group and 85 in the standard care group had CGM data and were included in the primary analysis. Compared with infants in the standard care group, infants managed using CGM had more time in the 2·6-10 mmol/L glucose concentration target range (mean proportion of time 84% [SD 22] vs 94% [11]; adjusted mean difference 8·9% [95% CI 3·4-14·4]), equivalent to 13 h (95% CI 5-21). More infants in the standard care group were exposed to at least one episode of sensor glucose concentration of less than 2·6 mmol/L for more than 1 h than those in the intervention group (13 [15%] of 85 vs four [6%] of 70). There were no serious adverse events related to the use of the device or episodes of infection., Interpretation: Real-time CGM can reduce exposure to prolonged or severe hyperglycaemia and hypoglycaemia. Further studies using CGM are required to determine optimal glucose targets, strategies to obtain them, and the potential effect on long-term health outcomes., Funding: National Institute for Health Research Efficacy and Mechanisms Evaluation Programme., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Clinical trials show that antimicrobial-impregnated central venous catheters reduce catheter-related bloodstream infection in adults and children receiving intensive care, but there is insufficient evidence for use in newborn babies., Objectives: The objectives were (1) to determine clinical effectiveness by conducting a randomised controlled trial comparing antimicrobial-impregnated peripherally inserted central venous catheters with standard peripherally inserted central venous catheters for reducing bloodstream or cerebrospinal fluid infections (referred to as bloodstream infections); (2) to conduct an economic evaluation of the costs, cost-effectiveness and value of conducting additional research; and (3) to conduct a generalisability analysis of trial findings to neonatal care in the NHS., Design: Three separate studies were undertaken, each addressing one of the three objectives. (1) This was a multicentre, open-label, pragmatic randomised controlled trial; (2) an analysis was undertaken of hospital care costs, lifetime cost-effectiveness and value of information from an NHS perspective; and (3) this was a retrospective cohort study of bloodstream infection rates in neonatal units in England., Setting: The randomised controlled trial was conducted in 18 neonatal intensive care units in England., Participants: Participants were babies who required a peripherally inserted central venous catheter (of 1 French gauge in size)., Interventions: The interventions were an antimicrobial-impregnated peripherally inserted central venous catheter (coated with rifampicin-miconazole) or a standard peripherally inserted central venous catheter, allocated randomly (1 : 1) using web randomisation., Main Outcome Measure: Study 1 - time to first bloodstream infection, sampled between 24 hours after randomisation and 48 hours after peripherally inserted central venous catheter removal. Study 2 - cost-effectiveness of the antimicrobial-impregnated peripherally inserted central venous catheter compared with the standard peripherally inserted central venous catheters. Study 3 - risk-adjusted bloodstream rates in the trial compared with those in neonatal units in England. For study 3, the data used were as follows: (1) case report forms and linked death registrations; (2) case report forms and linked death registrations linked to administrative health records with 6-month follow-up; and (3) neonatal health records linked to infection surveillance data., Results: Study 1, clinical effectiveness - 861 babies were randomised (antimicrobial-impregnated peripherally inserted central venous catheter, n  = 430; standard peripherally inserted central venous catheter, n  = 431). Bloodstream infections occurred in 46 babies (10.7%) randomised to antimicrobial-impregnated peripherally inserted central venous catheters and in 44 (10.2%) babies randomised to standard peripherally inserted central venous catheters. No difference in time to bloodstream infection was detected (hazard ratio 1.11, 95% confidence interval 0.73 to 1.67; p  = 0.63). Secondary outcomes of rifampicin resistance in positive blood/cerebrospinal fluid cultures, mortality, clinical outcomes at neonatal unit discharge and time to peripherally inserted central venous catheter removal were similar in both groups. Rifampicin resistance in positive peripherally inserted central venous catheter tip cultures was higher in the antimicrobial-impregnated peripherally inserted central venous catheter group (relative risk 3.51, 95% confidence interval 1.16 to 10.57; p  = 0.02) than in the standard peripherally inserted central venous catheter group. Adverse events were similar in both groups. Study 2, economic evaluation - the mean cost of babies' hospital care was £83,473. Antimicrobial-impregnated peripherally inserted central venous catheters were not cost-effective. Given the increased price, compared with standard peripherally inserted central venous catheters, the minimum reduction in risk of bloodstream infection for antimicrobial-impregnated peripherally inserted central venous catheters to be cost-effective was 3% and 15% for babies born at 23-27 and 28-32 weeks' gestation, respectively. Study 3, generalisability analysis - risk-adjusted bloodstream infection rates per 1000 peripherally inserted central venous catheter days were similar among babies in the trial and in all neonatal units. Of all bloodstream infections in babies receiving intensive or high-dependency care in neonatal units, 46% occurred during peripherally inserted central venous catheter days., Limitations: The trial was open label as antimicrobial-impregnated and standard peripherally inserted central venous catheters are different colours. There was insufficient power to determine differences in rifampicin resistance., Conclusions: No evidence of benefit or harm was found of peripherally inserted central venous catheters impregnated with rifampicin-miconazole during neonatal care. Interventions with small effects on bloodstream infections could be cost-effective over a child's life course. Findings were generalisable to neonatal units in England. Future research should focus on other types of antimicrobial impregnation of peripherally inserted central venous catheters and alternative approaches for preventing bloodstream infections in neonatal care., Trial Registration: Current Controlled Trials ISRCTN81931394., 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. 57. See the NIHR Journals Library website for further project information.

A survey was conducted in UK regional children's hospitals with paediatric intensive care and paediatric infectious disease (PID) departments to describe the characteristics of paediatric antimicrobial stewardship (PAS) programmes. A structured questionnaire was sent to PAS coordinators. 'Audit and feedback' was implemented in 13 out of 17 centres. Microbiology-led services were more likely to implement antimicrobial restriction (75% vs 33% in PID-led services), to focus on broad-spectrum antibiotics, and to review patients with positive blood cultures. PID-led services were more likely to identify patients from e-prescribing or drug charts and review all antimicrobials. A PAS network has been established., (Crown Copyright © 2020. Published by Elsevier Ltd. All rights reserved.)

Background: Innovation is important to improve patient care, but few studies have explored the factors that initiate change in healthcare organizations., Methods: As part of the European project EPICE on evidence-based perinatal care, we carried out semi-structured interviews (N = 44) with medical and nursing staff from 11 randomly selected neonatal intensive care units in 6 countries. The interviews focused on the most recent clinical or organizational change in the unit relevant to the care of very preterm infants. Thematic analysis was performed using verbatim transcripts of recorded interviews., Results: Reported changes concerned ventilation, feeding and nutrition, neonatal sepsis, infant care, pain management and care of parents. Six categories of drivers to change were identified: availability of new knowledge or technology; guidelines or regulations from outside the unit; need to standardize practices; participation in research; occurrence of adverse events; and wish to improve care. Innovations originating within the unit, linked to the availability of new technology and seen to provide clear benefit for patients were more likely to achieve consensus and rapid implementation., Conclusions: Innovation can be initiated by several drivers that can impact on the success and sustainability of change.

Objective: To compare rates of necrotising enterocolitis (NEC), late-onset sepsis, and mortality in 5-year epochs before and after implementation of routine daily multistrain probiotics administration in high-risk neonates., Design: Single-centre retrospective observational study over the 10-year period from 1 January 2008 to 31 December 2017., Setting: Level 3 neonatal intensive care unit (NICU) of the Norfolk and Norwich University Hospital, UK., Patients: Preterm neonates at high risk of NEC: admitted to NICU within 3 days of birth at <32 weeks' gestation or at 32-36 weeks' gestation and of birth weight <1500 g., Intervention: Prior to 1 January 2013 probiotics were not used. Thereafter, dual-species Lactobacillus acidophilus and Bifidobacterium bifidum combination probiotics were routinely administered daily to high-risk neonates; from April 2016 triple-species probiotics ( L. acidophilus, B. bifidum, and B. longum subspecies infantis ) were used., Main Outcome Measures: Incidence of NEC (modified Bell's stage 2a or greater), late-onset sepsis, and mortality., Results: Rates of NEC fell from 7.5% (35/469 neonates) in the pre-implementation epoch to 3.1% (16/513 neonates) in the routine probiotics epoch (adjusted sub-hazard ratio=0.44, 95% CI 0.23 to 0.85, p=0.014). The more than halving of NEC rates after probiotics introduction was independent of any measured covariates, including breast milk feeding rates. Cases of late-onset sepsis fell from 106/469 (22.6%) to 59/513 (11.5%) (p<0.0001), and there was no episode of sepsis due to Lactobacillus or Bifidobacterium . All-cause mortality also fell in the routine probiotics epoch, from 67/469 (14.3%) to 47/513 (9.2%), although this was not statistically significant after multivariable adjustment (adjusted sub-hazard ratio=0.74, 95% CI 0.49 to 1.12, p=0.155)., Conclusions: Administration of multispecies Lactobacillus and Bifidobacterium probiotics has been associated with a significantly decreased risk of NEC and late-onset sepsis in our neonatal unit, and no safety issues. Our data are consistent with routine use of Lactobacillus and Bifidobacterium combination probiotics having a beneficial effect on NEC prevention in very preterm neonates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Objective: To assess if a computerised decision support system reliably identified abnormal fetal heart rate (FHR) patterns in fetuses with adverse neonatal outcomes in the INFANT trial, and whether its use reduced substandard care., Design: Prospective cohort study within a randomised controlled trial., Setting: Twenty-four maternity units in the UK and Ireland., Population or Sample: A total of 46 614 labours between January 6 2010 and August 31 2013 in the INFANT trial., Methods: Panel review of intrapartum and neonatal care in infants with adverse outcome, and an assessment of the effectiveness of computerised interpretation of fetal heart rate in reducing substandard care. Descriptive analysis of other factors associated with adverse outcome., Main Outcome Measures: Incidence and detection rate of abnormal fetal heart rate patterns, other characteristics associated with perinatal adverse outcome, and frequency of substandard care., Results: Computer interpretation of FHR patterns was deemed to be completely valid in only 24 of 71 (33.8%) cases of adverse outcome. On a scale of 0-10 (completely invalid to completely valid), 28 cases (39.4%) had a score of 6 or less, mainly due to lack of recognition of decelerations (15 cases), or reduced variability (seven cases), or failure to recognise tachysystole (five cases). There were multiple associated factors that modified the clinical assessment of FHR patterns. There was substandard care in 45/71 cases (63%)., Conclusion: A significant proportion of abnormal fetal heart rate patterns were not detected accurately by computer analysis, and its use did not reduce the incidence of substandard care., Funding: UK National Institute for Health Research Health Technology Assessment Programme (project number 06.38.01)., Tweetable Abstract: Improved recognition of abnormal fetal heart rate patterns is insufficient to reduce the incidence of substandard care., (© 2018 Royal College of Obstetricians and Gynaecologists.)

Introduction: Preterm babies are among the highest users of parenteral nutrition (PN) of any patient group, but there is wide variation in commencement, duration, and composition of PN and uncertainty around which groups will benefit from early introduction. Recent studies in critically unwell adults and children suggest that harms, specifically increased rates of nosocomial infection, outweigh the benefits of early administration of PN. In this study, we will describe early PN use in neonatal units in England, Wales and Scotland. We will also evaluate if this is associated with differences in important neonatal outcomes in neonates born between 30 +0 and 32 +6 weeks +days gestation., Methods and Analysis: We will use routinely collected data from all neonatal units in England, Wales and Scotland, available in the National Neonatal Research Database (NNRD). We will describe clinical practice in relation to any use of PN during the first 7 postnatal days among neonates admitted to neonatal care between 1 January 2012 and 31 December 2017. We will compare outcomes in neonates born between 30 +0 and 32 +6 weeks +days gestation who did or did not receive PN in the first week after birth using a propensity score-matched approach. The primary outcome will be survival to discharge home. Secondary outcomes will include components of the neonatal core outcome set: outcomes identified as important by former patients, parents, clinicians and researchers., Ethics and Dissemination: We have obtained UK National Research Ethics Committee approval for this study (Ref: 18/NI/0214). The results of this study will be presented at academic conferences; the UK charity Bliss will aid dissemination to former patients and parents., Trial Registration Number: NCT03767634., Competing Interests: Competing interests: JW has received support from Chiesi Pharmaceuticals to attend an educational conference and has received a research grant from Mason Medical Research Foundation. SU has received funding from the National Institute of Health Research, the Department of Health and Prolacta Life Sciences. SU has been on the Advisory Board of Fresenius Kabi and received honoraria and travel expenses for speaking at study days organised by Fresenius Kabi. SU is a member of the National Institute for Health and Care Excellence Parenteral Nutrition Guideline Development Committee. NM is Director of the Neonatal Data Analysis Unit at Imperial College London. In the last five years, NM has served on the Board of Trustees of the Royal College of Paediatrics and Child Health, David Harvey Trust, Medical Women’s Federation and Medact; and is a member of the Nestle Scientific Advisory Board. NM has received research grants from the British Heart Foundation, Medical Research Council, National Institute of Health Research, Westminster Research Fund, Collaboration for Leadership in Applied Health and Care Northwest London, Healthcare Quality Improvement Partnership, Bliss, Prolacta Life Sciences, Chiesi, Shire and HCA International; travel and accommodation expenses from, Nutricia, Prolacta, Nestle and Chiesi; honoraria from Ferring Pharmaceuticals and Alexion Pharmaceuticals for contributions to expert advisory boards, and Chiesi for contributing to a lecture programme. CG is part of an international team developing reporting guidance (a CONSORT extension) for clinical trials using cohorts and routinely collected health data. He has received support from Chiesi Pharmaceuticals to attend an educational conference; in the past 5 years he been investigator on received research grants from Medical Research Council, National Institute of Health Research, Canadian Institute of Health Research, Department of Health in England, Mason Medical Research Foundation, Westminster Medical School Research Trust and Chiesi Pharmaceuticals., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Background: A significant proportion of hospital deaths occur in intensive care units (ICU) and often follow a decision to limit or withdraw life-sustaining treatment. Facilitating the preferred choice in place of death for babies/children is increasingly being advocated, although the literature on a home death is often limited to case reports., Aims and Objectives: To examine (a) health care professionals' (HCPs) views and experience of transferring babies/children home to die from intensive care, (b) patient clinical characteristics that HCPs would consider transferring home and (c) barriers to transferring home., Design: A cross-sectional descriptive web-based survey., Methods: A total of 900 HCPs from paediatric and neonatal ICU across the United Kingdom were invited to participate., Results: A total of 191 (22%) respondents completed the survey; 135 (70.7%) reported being involved in transferring home to die. However, most (58.4%) had just transferred one or two patients in the last 3 years. Overall, respondents held positive views towards transfer, although there was some evidence of divided opinion. Patients identified as unsuitable for transfer included unstable patients (57.6%) and those in need of cardiovascular support (56%). There was statistically significant difference in views between those with and without experience, in that those with experience had more positive views. The most significant barrier was the lack of access to care in the community., Conclusions: HCPs view the concept of transferring critically ill babies/children home to die positively but have infrequent experience. Views held about transfers are influenced by previous experience. The clinical instability of patients and access to community care are central to decision-making., Relevance to Clinical Practice: A home death for critically ill babies/children is occurring in the United Kingdom but infrequently. Experience of a transfer home positively influences views and increases confidence. Improved multi-organizational collaboration between ICU and community care teams would assist decision-making and facilitation for a transfer home., (© 2019 British Association of Critical Care Nurses.)

An unusually high number of positive adenovirus stool antigen tests were observed in neonatal samples from a large tertiary referral unit over a 10-week period, prompting the declaration of an outbreak and escalation of infection control precautions. Subsequent testing of original samples by alternative methods revealed a series of false-positive results. This is the first adenovirus pseudo-outbreak to be reported in the United Kingdom and the first to involve the Proflow Rotavirus-Adenovirus Combi test., (Copyright © 2018 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: To define levels of mean arterial blood pressure (MABP) where cerebrovascular reactivity is strongest (MABP OPT ) during the early transitional circulation in extremely preterm infants and to investigate the association between deviations above and below MABP OPT with intraventricular hemorrhage (IVH) and mortality., Study Design: A total of 44 infants born at a median gestational age 25 (23-27) weeks with indwelling arterial catheter were studied at a median 5.5 (3.1-12.6) hours within the first 24 hours of life. Cerebrovascular reactivity (tissue oxygenation heart rate reactivity index) was estimated by the moving correlation coefficient between heart rate and near-infrared spectroscopy tissue oxygenation index. MABP OPT was defined as the MABP where tissue oxygenation heart rate reactivity index reaches minimum value. Deviations below or above MABP OPT values were calculated along with MABP OPT values during retrospective data analysis., Results: MABP OPT was detected in all infants. The mean (SD) MABP OPT was 31.3 (±4.7) mm Hg. MABP OPT increased with increasing gestational age, R = 0.424; P = .004. Deviations below MABP OPT were greater in the IVH group (mean 2.7 mm Hg; 95% CI 2.0-3.5) compared with no-IVH (mean 1.7 mm Hg; 1.1-2.2), P = .006. In infants who died, the deviation below MABP OPT was greater (mean 3.3; 95% CI 1.9-4.8) compared with those who survived (mean 1.9 mm Hg; 95% CI 1.4-2.3), P = .015., Conclusions: Defining optimal MABP based on the strength of cerebrovascular reactivity within the first 24 hours of life is feasible and can provide an individualized approach to the care of extremely preterm infants. Deviations below MABP OPT were significantly associated with IVH and death., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Invasive Group B streptococcus (GBS) is a major cause of serious neonatal infection. Current strategies to reduce early-onset GBS disease have no impact on late-onset disease (LOD). Although GBS LOD is viewed as a sporadic event in the community, LOD arising within the neonatal intensive care unit (ICU) raises questions about mode of acquisition., Methods: Following a cluster of 4 GBS LOD cases, enhanced surveillance for all GBS LOD was undertaken over 2 years in the neonatal ICU supported by neonatal rectal screening. GBS isolates were serotyped and genome-sequenced., Results: Twelve late -onset invasive GBS episodes were identified (incidence 0.6/1000 live births). Genomic analysis revealed that 11/12 GBS isolates (92%) were linked to at least one other LOD isolate. Isolates from the first cluster were serotype V, resistant to macrolides and lincosamides, and sequencing confirmed isolates were indistinguishable, or distinguishable by only one SNP difference, from each other. Rectal carriage was rare. Prospective surveillance identified three further clusters of LOD due to serotypes Ia (3 cases), Ib (2 cases), and III (2 cases), that would not have been identified without surveillance and genome sequencing, leading to a re-evaluation of interventions required to prevent GBS LOD., Conclusion: Acquisition routes for LOD GBS in the neonatal ICU are poorly understood; cases may not necessarily be sporadic. Within this neonatal ICU, our data suggest that a single case of LOD GBS sepsis should be considered a potential nosocomial transmission event warranting prompt investigation, heightened infection prevention vigilance and action where required.

Competing Interests: Competing interests: None declared.

The relationship between health care expenditure and health outcomes has been the subject of recent academic inquiry in order to inform cost-effectiveness thresholds for health technology assessment agencies. Previous studies in public health systems have relied upon data aggregated at the national or regional level; however, there remains debate about whether the supply side effect of changes to expenditure are identifiable using data at this level of aggregation. We use detailed patient data derived from electronic neonatal records across England along with routinely available cost data to estimate the effect of changes to patient expenditure on clinical health outcomes in a well-defined patient population. A panel of 32 neonatal intensive care units for the period 2009-2013 was constructed. Accounting for the potential endogeneity of expenditure a £100 increase in the cost per intensive care cot day (sample average cost: £1,127) is estimated to reduce the risk of mortality of 0.38 percentage points (sample average mortality: 11.0%) in neonatal intensive care. This translates into a cost per life saved in neonatal intensive care of approximately £420,000., (Copyright © 2017 John Wiley & Sons, Ltd.)

Away from the media spotlight, nurses in neonatal and intensive care units across the UK continue to do their jobs. Difficult ethical cases in these units, such as the one at the centre of the High Court challenge by the parents of baby Charlie Gard (pictured), are more common than people might think.

Organ transplantation offers children in acute or chronic severe organ failure similar opportunities to adults. However, while the number who might benefit is relatively low, significantly fewer cadaveric donors exist for any given child compared with an adult. Incompatible organ size and relatively low donation rates mean that despite living parental donation and innovations to reduce donated organ size, children die before organs become available. The severity of the UK situation is compounded by restrictions on paediatric living donation, uncertainties over the application of brain death criteria, and ethical concerns about the use of donation after circulatory death. The UK Department of Health's Organ Donation Task Force suggested the means by which the adult donor pool might be increased, recommending that outstanding ethical and legal issues be resolved, but made no specific recommendations about children. [ABSTRACT FROM AUTHOR]

Bordetella pertussis, the cause of whooping cough, is highly contagious. A female, twin 1, born at 34 weeks of gestation and present on a neonatal intensive care unit for 19 days, became apnoeic and bradycardic. A pernasal swab, sent when pertussis was clinically suspected, grew B. pertussis. Twin 2 had similar symptoms. The mother admitted having a prolonged cough. Polymerase chain reaction of pernasal swabs was positive for both twins, and the mother had positive pertussis serology. An incident management committee was convened. Fifty neonates and 117 healthcare workers were identified as contacts and were offered information, azithromycin chemoprophylaxis and/or pertussis vaccination according to UK national guidelines., (Copyright © 2012 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.)

Between December 2007 and July 2008, three neonates in a neonatal intensive care unit (NICU) in Salford, UK, were diagnosed with primary cutaneous aspergillosis (PCA) due to Aspergillus fumigatus. The first PCA case, in December 2007, developed multi-organ failure leading to death within a short time frame: the other two cases survived after treatment with intravenous antifungal therapy followed by oral posaconazole. Air, surface, and water samples were collected within the NICU and from the incubators that were occupied by the neonates. All recovered fungal isolates were confirmed as A. fumigatus by sequencing the beta-tubulin region. Microsatellite strain typing demonstrated genotypically related A. fumigatus isolates from the neonates and the humidity chambers (HCs) of the neonates' incubators, suggesting that the source of the infection may have been the HCs/incubators used in the NICU. Aspergillus strain typing may be a useful tool in clinical outbreak settings to help understand the source of exposure and to design targeted environmental interventions to prevent future infections., (Published by Elsevier Ltd.)

Pertussis carries a high risk of mortality in very young infants. The mechanism of refractory cardio-respiratory failure is complex and not clearly delineated. We aimed to examine the clinico-pathological features and suggest how they may be related to outcome, by multi-center review of clinical records and post-mortem findings of 10 patients with fulminant pertussis (FP). All cases were less than 8 weeks of age, and required ventilation for worsening respiratory symptoms and inotropic support for severe hemodynamic compromise. All died or underwent extra corporeal membrane oxygenation (ECMO) within 1 week. All had increased leukocyte counts (from 54 to 132 x 10(9)/L) with prominent neutrophilia in 9/10. The post-mortem demonstrated necrotizing bronchitis and bronchiolitis with extensive areas of necrosis of the alveolar epithelium. Hyaline membranes were present in those cases with viral co-infection. Pulmonary blood vessels were filled with leukocytes without well-organized thrombi. Immunodepletion of the thymus, spleen, and lymph nodes was a common feature. Other organisms were isolated as follows; 2/10 cases Para influenza type 3, 2/10 Moraxella catarrhalis, 1/10 each with respiratory syncytial virus (RSV), a coliform organism, methicillin-resistant Staphylococcus aureus (MRSA), Haemophilus influenzae, Stenotrophomonas maltophilia, methicillin-sensitive Staphylococcus aureus (MSSA), and candida tropicalis. We postulate that severe hypoxemia and intractable cardiac failure may be due to the effects of pertussis toxin, necrotizing bronchiolitis, extensive damage to the alveolar epithelium, tenacious airway secretions, and possibly leukostasis with activation of the immunological cascade, all contributing to increased pulmonary vascular resistance. Cellular apoptosis appeared to underlay much of these changes. The secondary immuno-compromise may facilitate co-infection.

Background: Neonatal intensive care requires adequate numbers of trained neonatal nurses to provide safe, effective care, but existing research into the relationship between nurse numbers and the care needs of babies is over 10 years old. Since then, the preterm population and treatment practices have changed considerably., Aims: To validate the dependency categories of the British Association of Perinatal Medicine (BAPM, 2001) and to revalidate the Northern Region categories (NR, 1993) in relation to contemporary nursing workload., Setting: Three tertiary neonatal intensive care services in England., Methods: Nursing activity around each baby was captured every 10 min by direct observations by trained observers. Time spent on each nursing activity was related to the baby's dependency category and the nurse's grade., Results: Both scales detected differences between categories. Discrimination between individual categories was improved when nasal continuous positive airway pressure (nCPAP) was distinguished from ventilation and combined with BAPM2/NRA. On this revised four-point scale, babies in BAPM1/NRA occupied nursing time for a median of 56 min per hour (IQR 48-70), those on nCPAP or in BAPM2/NRB for 36 min, (27-42), those in BAPM3/NRC for 20-22 min (15-33) and those in BAPM4/NRD for 31-32 min (24-36). The NR scale was easier to apply and had greater interobserver agreement (98.5%) than the BAPM scale (93%). All categories attracted more time compared to 1993., Conclusions: Both scales predict average nursing workload. A revised categorisation which separates nCPAP from ventilation is more robust and practical. Nursing time attracted in all categories has increased since 1993.

The principal objective of the EPICure studies was to determine both short- and long-term outcomes of extremely preterm birth. Data were collected for all births before 26 completed weeks of gestation in the UK and Republic of Ireland for 10 months in 1995. Of 811 infants admitted to neonatal units, 314 (39%) survived. Of these, 283 (92%) were assessed at 2.5 years and 241 (78%) at 6 years, together with a comparator group selected from classmates in normal schools. At 6 years, 32 (13%) of those assessed had disabling cerebral palsy and 31 (13%) had severe sensory impairment. Cognitive impairment was a more frequent adverse outcome: the mean intelligence quotient (IQ) was 82 (SD 19). Fifty children (21%) had IQs > 3 SD less than that of the comparator group, and in 48 children (20%), IQ was 2-3 SD less than that of the comparator group. Infants whose mothers had received antenatal steroids had fewer severely abnormal head scan findings. In this population, abnormal head scan findings are independent predictors of reduced, severe motor disability at 2.5 years. Using step-wise logistic regression analysis, postnatal transfer was associated with severe motor disability; prolonged membrane rupture with reduced Mental Development Index (MDI) and antenatal steroid with increased MDI. It is clear that factors around the time of birth are critical in determining outcome, irrespective of later complications during neonatal intensive care. Since 1995, there is good evidence of improved survival, but it is not clear whether or not the number of survivors with severe adverse outcomes has changed. A new cohort of births <27 completed weeks is currently being collected in English maternity units. Data collection around the time of birth is more detailed than in 1995 in order to better explore the relationship between perinatal factors and later outcomes.